Heart and Stroke Foundation of Canada, Ottawa, Canada.
Framework Convention Alliance: building support for global tobacco control.

Framework Convention on Tobacco Control, Tobacco-Free Initiative, World Health Organization, Geneva, Switzerland.
Tobacco control in an era of trade liberalisation.

The Synar Amendment requires states and territories to enact a law prohibiting the sale of tobacco to minors and to enforce that law in a manner that could reasonably be expected to decrease the availability of tobacco to minors.To determine if the Department of Health and Human Services (DHHS) and applicant states and territories are complying with the Synar Amendment.Block grant applications from 59 states and territories describing activities during the federal fiscal year 1998.Whether applicants had enacted a tobacco sales law without loopholes, conducted enforcement inspections, penalized violators, and conducted a valid statewide survey with violation rates below the permissible threshold, and whether DHHS actions were consistent with the statutory requirements of the Synar Amendment.Three applicants had laws containing loopholes, 6 failed to conduct enforcement inspections, 7 failed to prosecute violators, 2 failed to conduct a valid survey, and 10 failed to demonstrate compliance with violation rate goals. Fifteen applicants failed 1 or more criteria and 8 were ultimately penalized by DHHS. No measurable progress in reducing violation rates was reported by 30 states, with 16 reporting an increase during the previous year. Twenty-four applicants were granted delays.States that demonstrated remarkable progress were balanced by states with worsening performance; as a whole there was no significant national progress toward reducing the availability of tobacco to youths. This failure can be attributed to inadequate resources devoted to enforcement and reliance on merchant education in lieu of bona fide law enforcement.
Department of Family Medicine and Community Health, 55 Lake Ave, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Archives of pediatrics & adolescent medicine
State and federal compliance with the Synar Amendment: federal fiscal year 1998.

European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP)

Boston University School of Public Health, MA 02118, USA.
Tobacco, the Food and Drug Administration, and Congress.

This study assessed the exposure of adolescent girls to cigar images in women's magazines from 1992 to 1998.Data were obtained from the 5 women's magazines with the highest readership of adolescent girls.We found a significant upward trend in cigar images portrayed in women's magazines and a significant increase in the portrayal of women cigar smokers over the period observed. Cigar images were less likely than cigarette images to promote tobacco or nontobacco products. Among advertisements, nearly all those that featured cigars promoted nontobacco products; advertisements featuring cigarettes overwhelmingly promoted tobacco products.Between 1992 and 1998, adolescent readers of women's magazines were increasingly exposed to images of cigars.
Mailman School of Public Health, Columbia University, New York, NY, USA. monicafeit@yahoo.com
Exposure of adolescent girls to cigar images in women's magazines, 1992-1998.

West Virginia University Voice and Swallowing Center, Morgantown, USA.

The purpose of this study was to examine print media coverage of cigars during the period 1987 to 1997.A content analysis of 790 cigar-focused newspaper and magazine articles was conducted.Cigar-focused articles increased substantially over the study period, paralleling increased cigar consumption. Articles focused on cigar business (39%) and events (19%). Only 4% of articles focused on health effects. Sixty-two percent portrayed cigars favorably. The tobacco industry was mentioned in 54% of articles and portrayed positively in 78%. Forty-two percent of the individuals quoted or described in articles were affiliated with the tobacco industry; only 5% were government/public health figures.Print coverage of cigars failed to communicate health risk messages and contributed to positive images of cigars.
Institute for Health Policy Studies, School of Medicine, Box 0936, University of California, San Francisco, CA 94143, USA. lynndee@itsa.ucsf.edu
The cigar revival and the popular press: a content analysis, 1987-1997.

Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco

To assess the prevalence and characteristics of tobacco sales and point-of-sale promotions and advertising in predominantly Latino business districts, and in comparison districts; and the economic importance of tobacco sales and marketing to Latino owned small businesses.Observational surveys of retail establishments and interviews with store managers.Demographically contrasting business districts of eastern Massachusetts.Percentage of businesses selling tobacco, numbers and characteristics of exterior and interior tobacco advertisements per store, merchant reports of promotional allowances received from tobacco distributors.The proportion of businesses selling tobacco, and hence having storefront tobacco advertising, is strongly negatively correlated with per capita income in the census tracts where businesses are located (Spearman's rho = -0.794, p = 0.006). Mentholated brands are marketed disproportionately in low income, urban communities. Latino merchants are highly dependent on tobacco sales, but would require relatively modest compensation to forego tobacco promotional allowances.Storefront tobacco advertising is far more prevalent in predominantly minority, low income communities than in non-minority, higher income communities, principally because of the differing mix of kinds of businesses in the two types of communities, and the greater prevalence of tobacco vendors in lower income neighbourhoods. Tobacco companies obtain this advertising at little cost.
The Center for Research on Culture and Health, Latin American Health Institute, 95 Berkeley Street, Boston, MA 02116, USA. Bart@lhi.org
Tobacco availability and point of sale marketing in demographically contrasting districts of Massachusetts.

The nation's largest tobacco age-restriction enforcement program is described. Between 1997 and 2000, the U.S. Food and Drug Administration--working with state agencies--conducted nearly 200,000 compliance checks in 123,000 establishments in 44 states, 1 territory, and Washington, D.C. The overall violation rate was 26 percent (more than 40,000 violations), ranging from 9 percent in Maine to 54 percent in the Virgin Islands. Due to the recent Supreme Court ruling, the FDA has stopped conducting these checks and is shutting down its tobacco program. The protocol described in this article will prove useful to others conducting compliance checks and seeking to keep tobacco out of the hands of children.
American Legacy Foundation, Washington, DC, USA.
Journal of public health management and practice : JPHMP
J Public Health Manag Pract. 2001-05;7(3):1-10.
The FDA's enforcement of age restrictions on the sale of cigarettes and smokeless tobacco.

Journal of the Indian Society of Pedodontics and Preventive Dentistry
J Indian Soc Pedod Prev Dent. 2002-06;20(2):v.

The devastating link between tobacco products and human cancers results from a powerful alliance of two factors - nicotine and carcinogens. Without either one of these, tobacco would be just another commodity, instead of being the single greatest cause of death due to preventable cancer. Nicotine is addictive and toxic, but it is not carcinogenic. This addiction, however, causes people to use tobacco products continually, and these products contain many carcinogens. What are the mechanisms by which this deadly combination leads to 30% of cancer-related deaths in developed countries, and how can carcinogen biomarkers help to reveal these mechanisms?
University of Minnesota Cancer Center, Mayo Mail Code 806, 420 Delaware Street SE, Minneapolis, Minnesota 55455, USA. hecht002@umn.edu
Tobacco carcinogens, their biomarkers and tobacco-induced cancer.

In oral squamous cell carcinoma (SCC), the presence of lymph node metastasis is one of the most important prognostic factors, correlating locoregional spread, recurrence, distant metastasis and survival. However, the biological factors implicated and the mechanisms underlying these events are not completely elucidated. We reported Ets-1 expression in oral SCC and proposed that it may serve as a plausible marker of invasive potential and lymph node metastasis. Herein, we investigate the prognostic significance of Ets-1 expression in oral cancer. One hundred oral SCCs assessed for Ets-1 expression showed significant association with tumor stage (P = .027), lymph node involvement (P < 10(-6)) and distant organ metastasis (P = .007). The transcription factor Ets-1 regulates the expression of several genes involved in extracellular matrix remodeling that may account for its association with lymph node and distant organ metastasis. Kaplan-Meier survival analysis entailed significant association of Ets-1 expression in oral SCCs with reduced disease free survival (P = .0041), suggesting its utility as a prognosticator for oral cancer. In conclusion, these findings underscore the role of Ets-1 in oral tumor invasion and metastasis and may thus account for its association with diminished disease free survival.
Department of Biochemistry, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi.
Prognostic impact of Ets-1 overexpression in betel and tobacco related oral cancer.

Why we need an international agreement on tobacco control.

This study evaluated merchant compliance with laws prohibiting the sale of tobacco to minors in Massachusetts.Stratified cluster sampling was used to select outlets from which youths aged 13 to 17 years attempted to purchase tobacco.Illegal sales were more common when the youth purchasing the tobacco was older, when the clerk was male, and when tobacco was obtained from a self-service display or unlocked vending machine. Failure to request proof of age was the strongest predictor of illegal sales.Measured compliance rates are strongly influenced by the age of the youths used to purchase tobacco.
Department of Family Medicine and Community Health, University of Massachusetts Medical Center, Worcester, MA 01655, USA. difranzj@ummhc.org
Measuring statewide merchant compliance with tobacco minimum age laws: the Massachusetts experience.

This report summarises a workshop on evaluation of tobacco control interventions convened in Santa Fe, New Mexico in June 2001 by the Institute for Global Tobacco Control at the Johns Hopkins Bloomberg School of Public Health. The evaluation of such interventions is filled with complexities which intensify as the scope of tobacco control programmes increase. Evaluators are charged with the task of determining the effect of interventions in terms of magnitude of change, the relative contribution of programme components, and the relative impact for different populations. The report explores the theoretical foundations of tobacco control evaluation and provides a conceptual framework for capturing elements necessary for evaluating interventions. It then provides two case studies of challenges encountered when evaluating large scale tobacco control initiatives. The report summarises the discussions and recommendations of the workshop's three working groups. Participants were certain and unanimous that the current state of evaluation research must be improved to evaluate accurately the dynamic nature of comprehensive tobacco control programmes. Hierarchical or multilevel modelling approaches were seen as promising for further research. Coordinated evaluation will provide a better understanding of local, state, and national tobacco control efforts.
Evaluating comprehensive tobacco control interventions: challenges and recommendations for future action. Report of a workshop convened by the Institute for Global Tobacco Control, Johns Hopkins Bloomberg School of Public Health.

Oral cancers in India constitute a major portion of all cancers. With a population of 1,000 million, this cancer poses many challenges. More than 90% of cases are tobacco-related, and hence eminently amenable to primary prevention. The progress made in these cancers is helping us to address the problem in a better way, bringing hope to overcome the misery. Semin Oncol 28:169-173.
Copyright 2001 by W.B. Saunders Company.
Kidwai Memorial Institute of Oncology, Bangalore, India.

Observations of 246 children and the adults accompanying them were carried out in supermarkets. Of those arriving and leaving by automobile (n = 194), 36% of adults used safety belts, and 51.1% of children used safety belts or restraining seats. While shopping, 79% of adults lost sight of the children in their care at least once, and 73.2% were 10 feet or more from their children at least once. 48% of children climbed or attempted to climb from carts; 27% stood in carts, and 23.6% handled hazardous products. 24% of adults purchased tobacco products. Poor adult supervision of children was related to adult's nonuse of safety belts and the child's and adult's ages. Climbing from the cart was related in a logistic regression to both poor adult supervision and child's age. Tobacco purchases were related to handling of hazards by children and standing in carts. Child's age and adult's safety belt use related to the restraint of children in vehicles.
University of Alberta, Centre for Experimental Sociology, Edmonton, Canada. aharrell@gpu.srv.ualberta.ca
Safety of children in grocery carts: adults' personal health and safety habits.

Maternal use of social drugs in pregnancy continues to increase--worldwide. Although a great deal has been learned regarding the implications of illicit drug abuse in pregnancy (cocaine, amphetamines, hallucinogens), the use of social drug in pregnancy has received far less attention. This article reviews the consequences of the social drug use in pregnancy including ethanol, tobacco and caffeine and offers recommendation for anaesthetic management of these potentially complicated pregnancies.
Departments of Anaesthesiology and Reproductive Medicine, University of California San Diego, San Diego, California, USA.
Social drug use in the parturient: implications for the management of obstetrical anaesthesia.

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi
Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2003-06;21(3):202.

University of Massachusetts Medical School, Worcester 01655, USA. difranza@banyan.ummed.edu
A gadget can't fix what's wrong with the tobacco distribution system.

A specific and rapid liquid chromatographic/tandem mass spectrometric (LC/MS/MS) method was developed and validated for NNAL, a metabolite of the tobacco-specific nitrosamine metabolite NNK. The metabolite was detected in smokers' urine with a limit of quantitation (LOQ) of 20 pg ml(-1) and a linear range up to 1000 pg ml(-1). The method features a single solid-phase extraction step and MS/MS monitoring following electrospray ionization. Fragmentation pathways for the protonated molecular ion are proposed. The sample preparation is simpler than that for gas chromatographic methods reported in the literature and maintains sensitivity adequate for determining NNAL in smokers' urine. By using enzyme hydrolysis to determine total NNAL in urine, the amount of NNAL-glucuronide was calculated. A standard pooled smokers' urine sample used for development gave values of 176 +/- 8 pg ml(-1) free NNAL and 675 +/- 26 pg ml(-1) total NNAL following enzyme hydrolysis. The method was applied to a group of seven smokers; the free NNAL level for the group was 101-256 pg ml(-1) with NNAL-glucuronides at 247-566 pg ml(-1). The ratio of conjugated to free NNAL was in the range 0.98-2.95. The variability in total daily amount of NNAL excreted (ng per 24 h) had RSDs of 6-21% for free NNAL, 7-22% for conjugated NNAL and 6-20% for total NNAL excreted. When normalized to the number of cigarettes smoked, the amounts of NNAL excreted per cigarette smoked were in the range of amounts of NNK yields reported for cigarettes in the literature.
R. J. Reynolds Tobacco Company, Biological Chemistry Division, Winston-Salem, North Carolina 27102, USA. byrdg@rjrt.com
Liquid chromatographic/tandem mass spectrometric method for the determination of the tobacco-specific nitrosamine metabolite NNAL in smokers' urine.

Vegetable consumption, including cruciferous vegetables, is protective against lung cancer, but the mechanisms are poorly understood. The purpose of this study was to investigate the effects of cruciferous vegetable consumption on the metabolism of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in smokers. The study was carried out in Singapore Chinese, whose mean daily intake of cruciferous vegetables is three times greater than that of people in the United States. Eighty-four smokers provided urine samples and were interviewed about dietary habits using a structured questionnaire, which included questions on consumption of nine commonly consumed cruciferous vegetables. Samples of these vegetables obtained in Singapore markets at three different times of year were analyzed for glucosinolates. Urine was analyzed for metabolites of NNK: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides (NNAL-Glucs). Glucobrassicins, which release indole-3-carbinols on chewing, were the major glucosinolates in seven of the nine cruciferous vegetables, accounting for 70.0% to 93.2% of all glucosinolates in these vegetables. There was a significant correlation (P = 0.01) between increased consumption of glucobrassicins and decreased levels of NNAL in urine after adjustment for number of cigarettes smoked per day; similar trends were observed for NNAL-Glucs (P = 0.08) and NNAL plus NNAL-Glucs (P = 0.03). These results are consistent with those of previous studies, which demonstrate that indole-3-carbinol decreases levels of urinary NNAL probably by inducing hepatic metabolism of NNK. The results are discussed with respect to the known chemopreventive activity of indole-3-carbinol against lung tumorigenesis by NNK in mice and the effects of isothiocyanates, which are also formed on consumption of cruciferous vegetables, on NNK metabolism. The results of this study demonstrate the complexities in assessing effects of cruciferous vegetables on carcinogen metabolism.
University of Minnesota Cancer Center, Mayo Mail Code 806, 420 Delaware St. SE, Minneapolis, MN 55455, USA. hecht002@umn.edu
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Cancer Epidemiol Biomarkers Prev. 2004-06;13(6):997-1004.
Effects of cruciferous vegetable consumption on urinary metabolites of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in singapore chinese.

UCSF School of Nursing, San Francisco, CA 94118, USA. pjones@itsa.ucsf.edu
Nurses speak out against the marketing of tobacco.

[Tobacco and murder--the first case of nicotine poisoning proved in a homicide].

Most of the methods of tobacco are use linked to the oral cavity where the taste receptors, a primary site for stimulation of salivary secretion, are constantly exposed to tobacco. It is generally believed that repeated exposure of a receptor to a stimulus results in inactivation (suppression) of the receptor. The present study was designed to document changes in salivary concentrations of sodium (Na+) and potassium (K+) in response to this effect in chronic tobacco users.Subjects of the study were divided into smokers, pan (tobacco-betel-lime quid) chewers, niswar (moist oral snuff) differs and non tobacco users as controls. The saliva of each subject was collected under resting condition and following application of crude nicotine and citric acid solutions to the tip of his tongue.After stimulation with nicotine all groups exhibited an increase in sodium concentration but the increase was significant (p < 0.05) in pan chewers only. However all groups showed a highly significant (p < 0.005) increase in sodium concentration after citric acid stimulation. No statistically significant (p > 0.05) decrease in potassium concentration was observed in any group after nicotine stimulation but all chronic tobacco user groups showed a highly significant (p < 0.005) decrease after citric acid stimulation.We conclude the sodium concentration increases and that of potassium decreases with the increase in salivary flow rates and this observation in chronic tobacco users was not much different from that in non tobacco users.
Department of Physiology, Khyber Medical College, Peshawar.
Journal of Ayub Medical College, Abbottabad : JAMC
J Ayub Med Coll Abbottabad. ;15(1):41-4.
Effect of chronic tobacco use on salivary concentrations of sodium and potassium.

Head and neck squamous cell carcinomas (HNSCC) have been causally associated with tobacco and alcohol exposure. However, 10-15% of HNSCC develop in absence of significant carcinogen exposure. Several lines of evidence suggest that the genetic composition of HNSCC varies based on the extent of tobacco/alcohol exposure, however, no genome wide measures have been applied to address this issue. We used comparative genomic hybridization (CGH) to screen for the genetic aberrations in 71 patients with head and neck squamous cell carcinoma and stratified the findings by the status of tobacco/alcohol exposure.Although the median number of abnormalities (9), gains (6) and losses (2) per case and the overall pattern of abnormalities did not vary significantly by the extent of tobacco/alcohol exposure, individual abnormalities segregating these patients were identified. Gain of 1p (p = 0.03) and 3q amplification (p = 0.05) was significantly more common in patients with a history of tobacco/alcohol exposure.This data suggests that the overall accumulated chromosomal aberrations in head and neck squamous cell carcinoma are not significantly influenced by the severity of tobacco/alcohol exposure with limited exceptions.
Laboratory of Epithelial Cancer Biology, Biology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York, USA. singhb@mskcc.org
Chromosomal aberrations in patients with head and neck squamous cell carcinoma do not vary based on severity of tobacco/alcohol exposure.

L'Ecole nationale de la santé publique, Rennes.
Sante publique (Vandoeuvre-les-Nancy, France)
[Educating through fear, an anti-tobacco campaign].

Executive functioning in cocaine/polydrug (marijuana, alcohol, tobacco) exposed infants was assessed in a single session, occurring between 9.5 and 12.5 months of age. In an A-not-B task, infants searched, after performance-adjusted delays, for an object hidden in a new location. Overall, the cocaine-exposed (CE) infants did not differ from non-CE controls recruited from the same at-risk population. However, comparison of heavier-CE (n = 9) to the combined group of lighter-CE (n = 10) and non-CE (n = 32) infants revealed significant differences on A-not-B performance, as well as on global tests of mental and motor development. Covariates investigated included socioeconomic status, marital status, race, maternal age, years of education, weeks of gestation, birth weight, as well as severity of prenatal marijuana, alcohol, and tobacco exposure. The relationship of heavier-CE status to motor development was mediated by length of gestation, and the relationship of heavier-CE status to mental development was confounded with maternal gestational use of cigarettes. The relationship of heavier-CE status to A-not-B performance remained significant after controlling for potentially confounded variables and mediators, but was not statistically significant after controlling for the variance associated with global mental development.
Department of Pediatrics and General Medical Sciences, Case Western Reserve University, USA. jsn4@po.cwru.edu
Prenatal cocaine/polydrug exposure and infant performance on an executive functioning task.

The purpose of this study was to assess the prevalence of the use of alcohol, tobacco, coffee, and various medications among flying crew and clerks working in a ministry in Kuwait.In a cross-sectional study, a self-administered questionnaire was filled in by 277 flying crew and 302 clerks of a comparable age and gender ratio.Frequencies of using alcohol, tobacco, coffee, and various medications were much higher among flying crew as compared to clerks. Flying crew were a very homogenous group in terms of exposure to the substances studied with only two exceptions: younger people were more likely to drink alcohol abroad (but not in Kuwait), and cabin crew relied on herbal medicine more than pilots.Flying crew differ very much from a socially comparable segment of the local population, but it is not possible to discern the impact of occupational risks (jet leg and night shifts) from exposure to foreign influences and, as for alcohol and sedatives, from easier availability.
Faculty of Medicine, Health Science Center, Kuwait University, Hawally, Kuwait. monisbasheer@hotmail.com
Aviation, space, and environmental medicine
Middle East aircrew use of alcohol, tobacco, coffee, and medicaments.

Department of Public Health Sciences, Texas A & M University System Health Science Center, Baylor College of Dentistry, Dallas, USA.
Tobacco: what your patients know, what you should know, what's on the horizon.

Smoking Cessation Leadership Center, University of California, San Francisco, USA.

We investigated the promotor hypermethylation status of multiple genes in 49 oral squamous cell carcinomas (OSCC), using the methylation-specific PCR (MSP) assay. The genes examined included p16INK4a, p14ARF, RB1, p21Waf1, p27Kip1, PTEN, p73, 0(6)-MGMT, and GST-P. Detailed clinicopathological data, such as patient age, sex, tobacco use, alcohol consumption, lesion site, degree of tumor differentiation, tumor size, presence of lymph node metastasis, and clinical stage, were collected for all 49 samples. Overall, gene methylation was detected in 46.9% (23/49) of samples and was closely correlated with tobacco use or/and alcohol consumption. Of the genes investigated, p16INK4a, p14ARF, 0(6)-MGMT, RB1, PTEN, and p27Kip1 were found to be methylated in 34.7%, 20.4%, 12.2%, 10.2%, 6.1%, and 4.1% of these 49 tumors, respectively, but methylation of p21Waf1, p73, and GST-P was not detected at all. Methylation frequencies were much higher for each gene when computed among informative cases only. Concurrent promotor hypermethylation of p16INK4a and p14ARF correlated significantly with tumor size, lymph node metastasis, and stage III/IV advanced OSCC; p14ARF hypermethylation, in particular, was significantly associated with both lymph node metastasis and late clinical stage. Our results suggest that DNA methylation of multiple genes, especially hypermethylation of the p14ARF promoter, is common in OSCC and is associated with the use of tobacco and/or alcohol consumption. For this type of cancer, the data further implicates gene methylation as playing an important role in tumor progression.
Departments of Pathology, Nara Medical University School of Medicine, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan.
Promotor hypermethylation of p14ARF is a key alteration for progression of oral squamous cell carcinoma.

In support of the efforts to combat smuggling, as well as illegal sale and distribution of cigarettes, an analytical approach for the characterization of tobacco has been proposed and evaluated. It involves aqueous extraction of the filler tobaccos followed by direct analysis of the extracts by electrospray ionization-ion trap mass spectrometry (ESI-ITMS) in the negative mode. Typically, the deprotonated ions, [M - H](-), of organic acids (malic, citric, caffeic, quinic acid) and polyphenols (chlorogenic acid, rutin, scopoletin) were detected. MS/MS spectra of the ion at m/z 191, which is the [M - H](-) of quinic acid, citric acid, and scopoletin, and a fragment ion of chlorogenic acid were acquired. Significant differences in the MS and MS/MS spectra were observed between counterfeit samples and the corresponding authentic brand name cigarettes. Analysis of 25 commercial cigarettes showed that straight Virginia blends were readily distinguished from the blended products containing different tobacco types (Virginia, burley, and Oriental). The former exhibited consistently higher relative abundances of m/z 353 (chlorogenic acid) to m/z 133 (malic acid) in the MS spectra (0.9-1.2 vs 0.4-0.6) and higher intensity ratios of m/z 176 (scopoletin) to m/z 173 (0.4-0.8 vs 0.1-0.3) and of m/z 127 (quinic acid) to m/z 173 (0.7-1.0 vs 0.3-0.5) in the MS/MS spectra. Evidence is presented to demonstrate that the spectral differences were related not only to the tobacco type (Virginia, burley and Oriental) but also to the tobacco part (stem, lamina) used in the manufacture of the cigarettes.
Laboratory and Scientific Services Directorate, Canada Border Services Agency, 79 Bentley Avenue, Ottawa, Ontario, Canada K1A 0L8. Rachel.Ng@ccra-adrc.gc.ca
Journal of agricultural and food chemistry
Characterization of cigarette tobacco by direct electrospray ionization-ion trap mass spectrometry (ESI-ITMS) analysis of the aqueous extract--a novel and simple approach.

Efforts to prohibit the sales of tobacco and alcohol products to minors are widespread. Electronic Age Verification (EAV) devices are one possible means to improve compliance with sales to minors laws. The purpose of this study was to evaluate the implementation and effectiveness of EAV devices in terms of the frequency and accuracy of age verification, as well as to examine the impact of EAV's on the retailer environment. Two study locations were selected: Tallahassee, Florida and Iowa City, Iowa. Retail stores were invited to participate in the study, producing a self-selected experimental group. Stores that did not elect to test the EAV's comprised the comparison group. The data sources included: 1) mystery shopper inspections: two pre- and five post-EAV installation mystery shopper inspections of tobacco and alcohol retailers; 2) retail clerk and manager interviews; and 3) customer interviews. The study found that installing EAV devices with minimal training and encouragement did not increase age verification and underage sales refusal. Surveyed clerks reported positive experiences using the electronic ID readers and customers reported almost no discomfort about being asked to swipe their IDs. Observations from this study support the need for a more comprehensive system for responsible retailing.
Heller School of Management and Health Policy, Brandeis University, Waltham, Massachusetts 02454-9110, USA. krevor@brandeis.edu
Preventing illegal tobacco and alcohol sales to minors through electronic age-verification devices: a field effectiveness study.

With the extent of international usage and the critical role phosphine gas (PH3) plays in commercial pest control, identification of the residual components deposited during fumigation is mandatory. It has been postulated that these infrequent residues are primarily composed of phosphoric acid or reduced forms of phosphoric acid [hypophosphorous acid (H3PO2) and phosphorous acid (H3PO3)], due to the oxidative degradation of phosphine. Using environmental scanning electron microscopy, gas phase Fourier transform infrared spectroscopy, and X-ray fluorescence spectroscopy, the structural elucidation and formation mechanism of the yellow amorphous polyhydric phosphorus polymers (P(x)H(y)) that occur in addition to the lower oxyacids of phosphorus in residues deposited during PH3 fumigations of select tobacco commodities are explored. This research determined that nitric oxide gas (or nitrogen dioxide) initiates residue formation of phosphorus hydride polymers and phosphorus oxyacids during PH3 fumigations of stored products.
Research Center, Philip Morris USA, 4201 Commerce Road, Richmond, Virginia 23234, USA. jason.w.flora@pmusa.com
Residue formations of phosphorus hydride polymers and phosphorus oxyacids during phosphine gas fumigations of stored products.

The TGF-beta signaling pathway is a key organizer of injury and immune responses, and recent studies suggest it fulfills critical roles in CNS function and maintenance. TGF-beta receptor activation results in phosphorylation of Smad proteins, which subsequently translocate to the nucleus to regulate gene transcription by binding to Smad binding elements (SBE). Using SBE-luciferase reporter mice, we recently discovered that the brain has the highest Smad baseline activity of any major organ in the mouse, and we now demonstrate that this signal is primarily localized to pyramidal neurons of the hippocampus. In vivo excitatory stimulation with kainic acid (KA) resulted in an increase in luciferase activity and phosphorylated Smad2 (Smad2P), and nuclear translocation of Smad2P in hippocampal CA3 neurons correlated significantly with luciferase activity. Although this activation was most prominent at 24 h after KA administration in neurons, Smad2P immunoreactivity gradually increased in astrocytes and microglial cells at 3 and 5 days, consistent with reactive gliosis. Bioluminescence measured over the skull in living mice peaked at 12-72 h and correlated with the extent of microglial activation and pathological markers of neurodegeneration 5 days after injury. Treatment with the glutamate receptor antagonist MK-801 strongly reduced bioluminescence and pathology. These results show that Smad2 signaling is a sensitive marker of neuronal activation and CNS injury that can be used to monitor KA-induced neuronal degeneration. This and related mouse models may provide valuable tools to study mechanisms and treatments for neurodegeneration.
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
Proceedings of the National Academy of Sciences of the United States of America
Bioluminescence imaging of Smad signaling in living mice shows correlation with excitotoxic neurodegeneration.

Pinney Associates and Johns Hopkins University School of Medicine, Baltimore, MD 20814, USA. jhenning@pinneyassociates.com
Guidance for research and testing to reduce tobacco toxicant exposure.

There is much debate about the future of tobacco regulation. Some have argued that to achieve maximum possible reduction in the harm tobacco causes, new regulatory models that involve fundamental institutional change must be adopted. The tobacco industry will continue to undermine tobacco control, and, so it is argued, we must change the way in which it operates if we are to be able to make the necessary progress. Such proposals may have an immediate appeal, especially for those frustrated that progress in tobacco control is not as rapid as they would hope--with all the avoidable loss of life and livelihoods that that entails--but they need to be carefully analysed and assessed, and much thought must be applied before spending time and resources advocating for them. One such proposal, advanced by Borland, involves the establishment of a monopsonistic statutory purchasing agency and wholesale distributor of tobacco products. Borland argues the relative benefits of such a model as compared to a more conventional model. On close examination, the benefits of the Borland proposal, as compared to the conventional model, appear overstated, and the Borland proposal introduces significant regulatory problems. There is still much that can be achieved in tobacco regulation through more conventional approaches, and within the existing system . We should be wary of allowing the understandable allure of new or radical approaches to distract us from this reality.
VicHealth Centre for Tobacco Control, The Cancer Council Victoria, 100 Drummond Street, Carlton 3053, Victoria, Australia. jonathan.liberman@cancervic.org.au
The future of tobacco regulation: a response to a proposal for fundamental institutional change.

Frequent users of smokeless tobacco (ST) have an increased risk for developing oral cancer. Nicotine and its derivatives may contribute to tumorigenesis through stimulation of nicotinic acetylcholine receptors (nAChRs) in target cells. Emerging evidence indicates that nAChRs can be stimulated by the nicotine-derived nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) that can induce oral cavity tumors in laboratory animals. This study was designed to elucidate the receptor-mediated mechanisms of the initiation and progression of NNK-, and NNN-induced oral cancers. We used Het-1A cells that were found to express alpha3, alpha5, alpha7, alpha9, beta2 and beta4 nAChR subunits. Both NNK and NNN competed with nicotinic radioligands for binding to Het-1A cells. NNK showed a higher than NNN affinity to the [3H]nicotine-labeled binding sites, and NNN-to the [3H]epibatidine-sensitive nAChRs. NNK and NNN increased proliferative potential of Het-1A cells and produced an anti-apoptotic effect, which was alleviated by antagonists. alpha-Bungarotoxin was most effective against NNK and mecamylamine against NNN. Treatment of Het-1A cells with either NNK or NNN led to acquisition of capability of anchorage independent growth and ability to produce tumors in nude mice, both of which can be by inhibited by antagonists. To elucidate the signaling mechanisms, we studied transcription of the genes encoding the cell cycle, apoptosis and signal transduction regulators at both the mRNA and protein levels. The Het-1A cells stimulated with nitrosamines showed multifold increases of the mRNA transcripts encoding PCNA and Bcl-2, and upregulated expression of the transcription factors GATA3, nuclear factor-kappaB, and STAT-1. The STAT-1 protein-binding activity induced by NNK and NNN correlated with elevated gene expression. The obtained results establish the role of specific nAChR subtypes in tobacco-related carcinogenesis and open a novel avenue for oral cancer chemoprevention.
Department of Dermatology, University of California at Davis, Davis, California, USA.
Nicotinic receptors mediate tumorigenic action of tobacco-derived nitrosamines on immortalized oral epithelial cells.

Bulletin of the World Health Organization
[The carcinogenic effects of tobacco. Monatsschrift für Krebsbekämpfung Vol. 8, Issue 5, 1940].

Establishing more sensible measures to treat cocaine-addicted mothers and their children is essential for improving U.S. drug policy. Favorable post-natal environments have moderated potential deleterious prenatal effects. However, since cocaine is an illicit substance having long been demonized, we hypothesized that attitudes toward prenatal cocaine exposure would be more negative than for licit substances, alcohol, nicotine and caffeine. Further, media portrayals about long-term outcomes were hypothesized to influence viewers' attitudes, measured immediately post-viewing. Reducing popular crack baby stigmas could influence future policy decisions by legislators. In Study 1, 336 participants were randomly assigned to 1 of 4 conditions describing hypothetical legal sanction scenarios for pregnant women using cocaine, alcohol, nicotine or caffeine. Participants rated legal sanctions against pregnant women who used one of these substances and risk potential for developing children. In Study 2, 139 participants were randomly assigned to positive, neutral and negative media conditions. Immediately post-viewing, participants rated prenatal cocaine-exposed or non-exposed teens for their academic performance and risk for problems at age 18.Participants in Study 1 imposed significantly greater legal sanctions for cocaine, perceiving prenatal cocaine exposure as more harmful than alcohol, nicotine or caffeine. A one-way ANOVA for independent samples showed significant differences, beyond .0001. Post-hoc Sheffe test illustrated that cocaine was rated differently from other substances. In Study 2, a one-way ANOVA for independent samples was performed on difference scores for the positive, neutral or negative media conditions about prenatal cocaine exposure. Participants in the neutral and negative media conditions estimated significantly lower grade point averages and more problems for the teen with prenatal cocaine exposure than for the non-exposed teen beyond .0001 alpha level. The positive media program closed estimated grade point average differences and risks of later problems to a non-statistically significant margin, p >.05.Ratings for prenatal cocaine were more negative than comparable ratings for alcohol, nicotine or caffeine exposure. Stereotypes can be reduced, showing viewers that positive postnatal environments ameliorate potential teratogenic effects of cocaine. Reducing negative stereotypes for crack babies may be a requisite for substantive changes in current policy.
Department of Psychology, Texas State University - San Marcos, San Marcos, Texas 78666, USA. hg01@txstate.edu
Substance abuse treatment, prevention, and policy
Subst Abuse Treat Prev Policy. 2006-02-01;1():4.
Comparing attitudes about legal sanctions and teratogenic effects for cocaine, alcohol, tobacco and caffeine: a randomized, independent samples design.

Despite an intensive national campaign of information, the drugs most frequently consumed by young adults undoubtedly continue to be alcohol, tobacco and cannabis. If the impact of these drugs on the health of the consumers can be evaluated in conjunction with the clinical and epidemiologic data, the consequences on the embryo due to their consumption by the pregnant women can be appreciated thanks to the abundant literature describing their effects in the gravid animal. Taking into account the abundant literature available in multiple animal species, the zero drug recommendation should be widely diffused to pregnant women.
Animal toxicology and safety, Novexel SA, parc Biocitech, 102, route de Noisy, 93230 Romainville, France. francois.spezia@novexel.com
[Alcohol, tobacco and cannabis: Review of teratogenicity studies in animals].

The global cigarette: origins and evolution of British American Tobacco, 1880-1945. [Review of: Cox, H. The global cigarette: origins and evolution of British American Tobacco, 1880-1945. New York: Oxford U. Pr., 2000].

Altered states: opium and tobacco compared.

Acetaldehyde is generated in the mainstream tobacco smoke mainly from the pyrolysis (and oxidative pyrolysis) of carbohydrates that are present in tobacco plant, cigarette paper, and also used as additives in tobacco. Acetaldehyde has been classified as an animal carcinogen, and may be cytotoxic or genetoxic. Owing to its high volatility and reactivity, it is difficult to accurately measure it, especially on site. In this work, a novel analytical method based on collection and simultaneous derivatization in water, solid-phase microextraction (SPME), and portable gas chromatography (GC) analysis has been developed for the field and rapid analysis of acetaldehyde in the mainstream tobacco smoke. In the proposed method, acetaldehyde in mainstream tobacco smoke was collected in 1 ml water, and derivatizated with O-2,3,4,5,6-(pentafluorobenzyl)hydroxylamine. The formed acetaldehyde oximes were headspace extracted by a divinylbenzene/carboxen/polydimethylsiloxane fiber at 30 degrees C for 10 min, with a stirring rate of 1100 rpm. The acetaldehyde oximes extracted on the fiber were desorbed and analyzed rapidly by portable GC. The method validations including detection limit, recovery, precision and linearity were studied. It was found that the proposed method required the whole analysis time 27 min, and provided low detection limit of 0.04774 mg/ml, good recovery of 85%, RSD value 6.7%, and linear range 0.0716-0.7160 mg/ml (r(2)=0.997). The obtained results demonstrated that SPME-portable GC is a simple, rapid and solvent-free method for the field analysis of acetaldehyde. Finally, the proposed method was further applied to the quantification of acetaldehyde in mainstream tobacco smoke of five different brands.
Department of Chemistry, Fudan University, Shanghai 200433, China.
Field analysis of acetaldehyde in mainstream tobacco smoke using solid-phase microextraction and a portable gas chromatograph.

After the digestion of cigarettes and its ash are digested with concentrated nitric acid and perchloric acid, the change in mineral elements (Ca, Mg, Cu, Fe, Zn, Mn, Ni, Co, Cr, Pb and Cd) content in the cigarette and its ash were determined by flame atomic absorptionspectrophotometry. The experimental results showed that there were differences between the cigarette (tobacco) and its ash, especially, the contents of Pb and Cd harmful to human health in the ash are lowed 26.4% and 44.2%, respectively. It is concluded that a part of Pb and Cd in the cigarette passes through the human lung respiration and air environment.
Center for Experiment Teaching, School of Chemistry and Chemical Engineering, Shandong University, Ji'nan 250100, China. Naixingwang@163.com
Guang pu xue yu guang pu fen xi = Guang pu
Guang Pu Xue Yu Guang Pu Fen Xi. 2007-09;27(9):1845-7.
[Change of the trace elements content from cigarettes (tobacco) to its ash and to look at harm of stuck cigarette].

Contact dermatitis caused by tobacco is rare and poorly understood. In this paper, we report what is to our knowledge, the first case of tobacco contact dermatitis with identification of the causative agent.A 46-year-old man was hospitalised for diffuse dermatitis originating in the left leg. Subsequent epicutaneous tests indicated that this dermatitis was ascribable to sensitisation to the sorbic acid present in Fucidin cream applied around a chronic wound. A persistent plaque of eczema observed on the day of examination opposite the patient's right trouser pocket suggested the implication of tobacco powder with which the pocket was soiled. An epicutaneous test using tobacco (moistened in water) proved positive (++ at 48 and 72 h). This tobacco contained sorbic acid, used as a preservative.The positive test for sorbic acid was relevant not only regarding the lesions on the patient's legs (application of a topical cream containing sorbic acid) but also for the lesion on the patient's thigh and for palmar dyshidrosis (through contact with strands of loose rolling tobacco). To our knowledge, this is the first recorded case of contact dermatitis caused by sorbic acid in tobacco.
Service de dermatologie, hôpital Robert-Debré, CHU de Reims, avenue du Général-Koenig, 51092 Reims cedex, France. agrange@chu-reims.fr
Annales de dermatologie et de venereologie
[Tobacco contact dermatitis caused by sensitivity to sorbic acid].

Tobacco is implicated in multisystemic carcinogenesis through more than fifty identified carcinogenic metabolites that produce mutations responsible for alterations in cell cycle, immune response and endocrine regulation. Is one of nine risk factors identified in one third of cancer deaths together with obesity, sedentary, alcohol consumption, sexual promiscuity, drug addiction, and open and closed air contamination. Answering for cardiovascular diseases as the first cause of death in civilized world, tobacco is also pointed as the major factor implicated in the development of COPD (chronic obstructive pulmonary disease), RB-ILD (respiratory bronchiolitis and interstitial lung disease), DIP (desquamative interstitial pneumonia), bronchiolitis and bronchiolocentric interstitial fibrosis, Langerhans cells histiocytosis, eosinophilic pneumonia, sarcoidosis, epidermoid metaplasia in respiratory epithelium and lung cancer. The chronic tobacco induced inflammatory state is the basis for the acquisition of genetic alterations dependent on the tobacco contaminants.
Faculdade de Medicina da Universidade de Coimbra, Coimbra.
[Tobacco and morphology: pulmonary diseases].

Big tobacco and moto-GP: why no warnings on the motorcycles?

To identify alterations in genes and molecular functional pathways in esophageal cancer in a high incidence region of India where there is a widespread use of tobacco and betel quid with fermented areca nuts.Total RNA was isolated from tumor and matched normal tissue of 16 patients with esophageal squamous cell carcinoma. Pooled tumor tissue RNA was labeled with Cy3-dUTP and pooled normal tissue RNA was labeled with Cy5-dUTP by direct labeling method. The labeled probes were hybridized with human 10K cDNA chip and expression profiles were analyzed by Genespring GX V 7.3 (Silicon Genetics).Nine hundred twenty three genes were differentially expressed. Of these, 611 genes were upregulated and 312 genes were downregulated. Using stringent criteria (P < or = 0.05 and > or = 1.5 fold change), 127 differentially expressed genes (87 upregulated and 40 downregulated) were identified in tumor tissue. On the basis of Gene Ontology, four different molecular functional pathways (MAPK pathway, G-protein coupled receptor family, ion transport activity, and serine or threonine kinase activity) were most significantly upregulated and six different molecular functional pathways (structural constituent of ribosome, endopeptidase inhibitor activity, structural constituent of cytoskeleton, antioxidant activity, acyl group transferase activity, eukaryotic translation elongation factor activity) were most significantly downregulated.Several genes that showed alterations in our study have also been reported from a high incidence area of esophageal cancer in China. This indicates that molecular profiles of esophageal cancer in these two different geographic locations are highly consistent.
Institute of Pathology, Indian Council of Medical Research, Safdarjang Hospital Campus, Post Box No. 4909, New Delhi 110029, India.
Gene expression profile of esophageal cancer in North East India by cDNA microarray analysis.

To examine the associations among cigarette design features and tar yields of leading cigarette brands sold in the United States, Canada, Australia and the United Kingdom.Government reports and numbers listed on packs were used to obtain data on International Organization for Standardization (ISO)/Federal Trade Commission (FTC) yields for the tar of 172 cigarette varieties sold in the United States, Canada, Australia and the United Kingdom. We used standardised methods to measure the following 11 cigarette design parameters: filter ventilation, cigarette pressure drop, filter pressure drop, tobacco rod length, filter length, cigarette diameter, tipping paper length, tobacco weight, filter weight, rod density and filter density.Filter ventilation was found to be the predominant design feature accounting for the variations between brands in ISO/FTC tar yields in each of the four countries. After accounting for filter ventilation, design parameters such as overwrap length, tobacco weight and rod density played comparatively minor roles in determining tar yields.Variation in ISO/FTC tar yields are predicted by a limited set of cigarette design features, especially filter ventilation, suggesting that governments should consider mandatory disclosure of cigarette design parameters as part of comprehensive tobacco product regulations.
Department of Health Behavior, Division of Cancer Prevention and Population Sciences, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA. richard.oconnor@roswellpark.org
How do different cigarette design features influence the standard tar yields of popular cigarette brands sold in different countries?

The World Health Organization Tobacco Product Regulation (TobReg) study group has proposed emissions level performance standards for nine toxicants (NNN, NNK, acetaldehyde, acrolein, 1,3-butadiene, CO, BaP, benzene and formaldehyde, all expressed as micrograms per milligram nicotine as measured under the Canadian intensive method) in cigarette smoke for parties to the FCTC in conjunction with regular monitoring of emissions of nine other toxicants of interest, nicotine and nicotine-free dry particulate matter (NFDPM, or tar ).We examined the published literature and publicly available tobacco industry documents to determine the extent to which existing available technologies can be applied to reduce the emissions of the specified toxicants in cigarette smoke.Agricultural practices (for example, fertilisers, curing), plant characteristics (for example, protein content, nicotine content), tobacco blending (for example, American blend vs Virginia blend) and cigarette design (for example, additives, filters, paper) issues all have roles in the generation and reduction of specific smoke toxicants. The tobacco industry has explored a number of technologies, including selective filtration, changes to curing practices and rod additives to reduce specific toxicants.Technologies exist to reduce the toxicants identified by TobReg. The extent to which the industry is able to simultaneously reduce toxicants, however, is unknown.
Department of Health Behavior, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, New York 14263, USA. Richard.Oconnor@roswellpark.org
Existing technologies to reduce specific toxicant emissions in cigarette smoke.

The inhibitor of apoptosis protein survivin is selectively expressed in tumor cells. The tobacco component nicotine increases the transcription of the survivin gene in non-small cell lung cancer cells. However, the role of survivin expression induced by tobacco component is not clear during lung carcinogenesis. We investigated the effects of the tobacco components nicotine and its related carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) on survivin expression in normal human bronchial epithelial (NHBE) cells and examined the role of survivin in the malignant transformation of normal human bronchial epithelial (HBE) cells induced by these components. We found that survivin messenger RNA (mRNA) expression was detected in 41% (7 of 17) of bronchial brush specimens from heavy smokers. Nicotine and NNK increased survivin mRNA and protein expression levels in primary cultured NHBE cells and immortalized HBE cells. Bronchial epithelium in mice administered NNK also showed increased staining for survivin. Nicotine and NNK stimulated the Akt-mammalian target of rapamycin (mTOR) pathway in NHBE cells, leading to increased de novo synthesis of survivin protein. Induced survivin expression increased the survival potential of the cells, which was blocked by transfection with survivin-specific small interfering RNA (siRNA). siRNA-induced down-regulation of survivin expression also suppressed the tumorigenic potential of premalignant and malignant HBE cells exposed to the tobacco components. These findings suggest that NNK and nicotine induce survivin protein synthesis in NHBE cells by activating the Akt-mTOR pathway and thus blockade of the pathway effectively inhibits the tobacco-induced malignant transformation of HBE cells.
Department of Thoracic/Head and Neck Medical Oncology, Unit 432, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Survivin expression in normal human bronchial epithelial cells: an early and critical step in tumorigenesis induced by tobacco exposure.

Oral cancer is the leading cancer type among Southeast Asian men and is causally associated with the use of tobacco. Genetic polymorphisms in xenobiotic-metabolizing enzymes modify the effect of environmental exposures, thereby playing a significant role in gene-environment interactions and hence contribute to the high degree of variance in individual susceptibility to cancer risk. This study investigates the role of polymorphisms at CYP1A1, GSTM1 and GSTT1 to oral squamous cell carcinoma (OSCC) in a case-control study involving 155 patients with precancerous lesions, 458 cancer patients and 729 age and habit-matched controls. Genotypes at these loci were determined by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism performed on genomic DNA extracted from peripheral blood lymphocytes. Risk to oral cancer was estimated among different tobacco exposure groups and doses using logistic regression analysis. GSTM1 null genotype conferred 1.29-fold increased risk [95% confidence interval (CI), 1.04-1.65] to OSCC. GSTT1 null genotype, however, conferred 0.57 times reduced risk to OSCC (95% CI, 0.39-0.83), specifically among tobacco chewers (odds ratio 0.27; 95% CI, 0.14-0.53). This risk was further reduced to 0.13 times (95% CI, 0.04-0.46) with increase in lifetime exposure to tobacco. We also investigated risk conferred by these genotypes at two different intra-oral sites, buccal mucosa and tongue. We found increased susceptibility to buccal mucosa cancer among individuals carrying these genetic markers. These results support the finding that GSTM1 null genotype is a risk factor to OSCC among Indian tobacco habits; GSTT1 null genotype, however, emerged as a protective factor.
Cancer Research Institute, Advanced Center for Treatment, Research and Education in Cancer, Tata Memorial Center, Kharghar, Navi Mumbai 410 208, India.
Susceptibility to oral cancer by genetic polymorphisms at CYP1A1, GSTM1 and GSTT1 loci among Indians: tobacco exposure as a risk modulator.

Folate has been hypothesized to protect against aero-digestive cancers although the evidence is not yet conclusive due to possible confounding by other dietary factors. Sequence variants in folate pathway were suggested to be associated with plasma folate levels and are unlikely to be confounded by other lifestyle factors. We therefore investigated the effects of key folate genetic variants on the risk of aero-digestive cancers and their potential effect modification by folate intake in a multicenter study in Central Europe. A total of 2250 lung cases, 811 upper aero-digestive tract cases and 2899 controls were recruited with blood samples. The methylenetetrahydrofolate reductase (MTHFR) C677T variant was associated with an increased risk of lung cancer with an odds ratio (OR) for homozygote variant of 1.37 [95% confidence interval (CI) = 1.10-1.71]. The two MTHFR variants were in strong linkage disequilibrium, and 677T-1298A appeared to be the primary haplotype associated with cancer risk. The risk estimates for MTHFR 677T/677T genotype was more prominent among lung cancer patients with young onset (OR = 1.92, 95% CI = 1.12-3.29). When stratified by dietary intake of folate, the effect of the MTHFR 677T variant was more prominent among subjects with low intake of folate: the ORs for 677T/677T genotype among subjects with the lowest decile were 2.60 (95% CI = 1.39-4.88) and 4.14 (95% CI = 1.47-11.7) for lung and upper aero-digestive tract cancer, respectively. In conclusion, we identified a moderate effect of MTHFR C677T on lung cancer risk and a possible effect modification by folate intake that is consistent with the functional data. These results support an important role of folate in protecting against tobacco-related cancers.
International Agency for Research on Cancer, 150 cours Albert Thomas, F-69372, 69008, Lyon Cedex 08, France. hung@iarc.fr
Folate-related genes and the risk of tobacco-related cancers in Central Europe.

Nutritional deficiency may be the cause of a genuine optic neuropathy, sometimes associated with involvement of the peripheral nervous system. Nutritional optic neuropathies are usually bilateral, painless, chronic, insidious and slowly progressive. Most often, they present as a non-specific retrobulbar optic neuropathy. The differential diagnosis with other causes of optic nerve involvement, in particular of toxic origin, may be particularly difficult. Nutritional deficits are often associated with toxic effects from alcohol and tobacco; therefore, the separation of the nutritional and toxic components is often illusory and artificial. The pathophysiological mechanisms involved in nutritional -- and toxic -- optic neuropathies affect biochemical pathways involved in cell energetic production, correction of oxidative stress and quenching of free radicals. The recognition of these mechanisms could provide future therapeutic alternatives. Currently, the treatment is limited to the intensive use of vitamins with variable results in individual cases, and to the implementation of preventive measures, when feasible.
Department of Ophthalmology, Hôpital Européen Georges Pompidou, Assistance Publique Hôpitaux de Paris, 20, Rue Leblanc, 75015, Paris, France. christophe.orssaud@hop.egp.ap-hop-paris.fr

The plant powder maras powder (MP) has been used widely instead of cigarettes in the southeastern region of Turkey. The aim of this study was to assess the impacts of MP and cigarette smoking on the methylation and micronuclei (MN) formation in buccal cells of humans with a comparison to blood lymphocytes. DNA samples from 80 subjects (40 MP users, 20 tobacco smokers, 20 healthy volunteers) were analyzed for their genomic methylation status using Hpa II and Msp I digestions followed by a simple gel electrophoresis and ethidium bromide staining. A densitometric method was developed to measure the methylation in genomic DNA samples and the results were evaluated using a software program designed for this purpose. Buccal epithelial cells were collected from the same groups and examined for MN formation. The results indicated that a general genomic hypomethylation was present in almost all of the samples that were obtained from MP users and tobacco smokers. This hypomethylation was significant in MP users compared to smokers and healthy volunteers. The percentage of cells containing MN was 1.93 in MP users, 0.95 in healthy volunteers, and 1.82 in smokers. The MN frequency was significantly higher in MP users and smokers than in healthy volunteers. There was no statistical difference between smokers and MP users. Evidence indicates that MP usage induces DNA hypomethylation and increase frequency of MN formation.
Department of Medical Genetics, Erciyes University Medical Faculty, Kayseri, Turkey. csaatci@erciyes.edu.tr
Journal of toxicology and environmental health. Part A
J Toxicol Environ Health A. 2008;71(6):396-404.
The effect of maras powder on DNA methylation and micronucleus formation in human buccal tissue.

Urinary tobacco alkaloid measurement in patients having thromboangiitis obliterans.

To describe and identify factors associated with tobacco sales in a metropolitan county.King County, Washington is the largest county in Washington State with an estimated population of 1.8 million or about 30% of the state's population.The data analysis is based on compliance checks in King County between January 2001 and March 2005. The 8879 checks were conducted by 91 youth operatives aged 14-17. Analysis of data was completed in 2006.The outcome variable for this analysis was whether a sale was made to a youth operative during a compliance check. Associations between independent variables and the outcome variable were examined using 2 x 2 tables, univariate (unadjusted) logistic regression, and multivariate (adjusted) logistic regression analysis.Overall tobacco sales during the 4-year and 3-month period was 7.7%. Convenience stores selling gas were significantly more likely to sell tobacco products to minors, whereas restaurants, bars, and tobacco discount stores were less likely to sell to minors. Other factors that were significantly associated with sales are described.In a county that has adopted many of the required youth access laws, opportunities still exist to reduce sales of tobacco products to minors. Asking for age and photo identification still appears to be an effective strategy in reducing sales of tobacco products to minors.
Angulo-Group Health Community Foundation, Seattle, Washington 98012, USA. pearson.d@ghc.org
Youth tobacco sales in a metropolitan county: factors associated with compliance.

To summarize current knowledge about the health and social consequences of tobacco production and to outline research needed to better understand these effects.The literature documenting the effects of tobacco production is scattered, and not always published in peer-reviewed sources. We undertook a systematic search using (1) a literature file based on over a decade of research on the health effects of tobacco work, (2) searches of computerized data bases (Medline, Science Citation Index, Agricola), (3) a review of new sources cited in literature uncovered through data base searches, and (4) professional contacts with others working on the effects of tobacco production.The health effects of tobacco production include nicotine poisoning (green tobacco sickness), pesticide exposure, respiratory effects, musculoskeletal and other injuries. Most research has focused on nicotine poisoning. Social effects of tobacco production include social disruption for communities in which tobacco production is declining (unemployment, economic loss), and for communities in which tobacco production is being introduced (loss of local food production and local autonomy).Research is needed on the effects of tobacco work on the health of women and children through exposure to nicotine and pesticides, the effects of chronic nicotine exposure on all tobacco workers, the neurotoxic effects of pesticide exposure and its relationship with mental health, and the effects of growing tobacco on using tobacco. Greater effort is needed to document the social disruption in communities that are economically dependent on tobacco production, particularly those in developing countries.
Department of Family and Community Medicine, Wake Forest University School of Medicine , Winston-Salem, NC 27157-1084, USA. tarcury@wfubmc.edu
Health and social impacts of tobacco production.

Illicit tobacco: an international problem with an international solution.

K-Ras mutations are characteristic of human lung adenocarcinomas and occur almost exclusively in smokers. In preclinical models, K-Ras mutations are necessary for tobacco carcinogen-driven lung tumorigenesis and are sufficient to cause lung adenocarcinomas in transgenic mice. Because these mutations confer resistance to commonly used cytotoxic chemotherapies and targeted agents, effective therapies that target K-Ras are needed. Inhibitors of mTOR such as rapamycin can prevent K-Ras-driven lung tumorigenesis and alter the proportion of cytotoxic and Foxp3+ regulatory T cells, suggesting that lung-associated T cells might be important for tumorigenesis.Lung tumorigenesis was studied in three murine models that depend on mutant K-Ras; a tobacco carcinogen-driven model, a syngeneic inoculation model, and a transgenic model. Splenic and lung-associated T cells were studied using flow cytometry and immunohistochemistry. Foxp3+ cells were depleted using rapamycin, an antibody, or genetic ablation.Exposure of A/J mice to a tobacco carcinogen tripled lung-associated Foxp3+ cells prior to tumor development. At clinically relevant concentrations, rapamycin prevented this induction and reduced lung tumors by 90%. In A/J mice inoculated with lung adenocarcinoma cells resistant to rapamycin, antibody-mediated depletion of Foxp3+ cells reduced lung tumorigenesis by 80%. Likewise, mutant K-Ras transgenic mice lacking Foxp3+ cells developed 75% fewer lung tumors than littermates with Foxp3+ cells.Foxp3+ regulatory T cells are required for K-Ras-mediated lung tumorigenesis in mice. These studies support clinical testing of rapamycin or other agents that target Treg in K-Ras driven human lung cancer.
Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
A central role for Foxp3+ regulatory T cells in K-Ras-driven lung tumorigenesis.

Among all carcinogenic substances contained in tobacco smoke, Polonium 210 (Po-210), with a half-life of 138 days, is one of the most dangerous, by exerting a devastating, chronic, slow and progressive carcinogenesis activity. The main source of Po-210 in tobacco is represented by fertilizers (polyphosphates) containing radium-226 (Ra-222) which decades to plumb 210 (Pb-210). Through the thricomes Pb-210 is concentrated in the tobacco leaves, where it turns to Po-210, which at the cigarette combustion temperature (800-900 degrees C) reaches the gaseous state and it is absorbed by the micro particles released into tobacco smoke. Thus, smoke becomes radioactive in both its gaseous and corpuscular components and reaches the airways, where, particularly at the branches level and together with other substances, it exerts its carcinogenic activity, especially in those subjects with impaired respiratory mucosal clearance. The carcinogenic risk/one year lifetime of a smoker of 20 cigarettes per day is equivalent to that of undertaking 300 chest x-rays. It is calculated that Po-210 may be independently responsible of 4 lung cancers every 10,000 smokers. During cigarette's combustion, tobacco smoke is also released in the air, contributing to serious health risks for those exposed to passive smoke.
AUSL di Bologna, Italia. vincenzo.zaga@ausl.bo.it
[Polonium: the radioactive killer from tobacco smoke].

Canadian Ophthalmological Society Glaucoma Clinical Practice Guideline Expert CommitteeCanadian Ophthalmological Society
Canadian journal of ophthalmology. Journal canadien d'ophtalmologie
Can J Ophthalmol. 2009;44 Suppl 1():S7-93.
Canadian Ophthalmological Society evidence-based clinical practice guidelines for the management of glaucoma in the adult eye.

Semmelweis Museum, Library and Archives for the History of Medicine, Budapest, Hungary. orvostortenet@t-online.hu
[Contribution to the history of tobacco use].

A reliable method for measuring (15)N/(14)N and (2)H/(1)H ratios of nicotine in cigarette tobacco has been developed. It involves a simple procedure for extracting nicotine from tobacco using methanol. The extract is directly analyzed on a gas chromatography isotope ratio mass spectrometer (GC-IRMS). The method is reproducible with 4% RSD for delta(2)H and delta(15)N. Brand name cigarettes manufactured in Canada (N = 47) and in China (N = 23) have been analyzed. The results show that nicotine from Canadian cigarettes has a higher (2)H/(1)H ratio and a lower (15)N/(14)N ratio than the Chinese cigarettes. The delta(2)H values for Canadian cigarettes range from -232.7 per thousand to -203.4 per thousand with an average of -222.1 per thousand; the delta(2)H values for Chinese cigarettes range from -262.6 per thousand to -219.9 per thousand with an average of -243.8 per thousand. The delta(15)N values for Canadian cigarettes range from -7.7 per thousand to -6.3 per thousand with an average of -7.1 per thousand; the delta(15)N values for Chinese cigarettes range from -7.6 per thousand to -5.7 per thousand with an average of -6.3 per thousand. The combined measurements of (2)H/(1)H and (15)N/(14)N have been shown to be useful in identifying counterfeits of Canadian cigarettes analyzed in this study.
Laboratory and Scientific Services Directorate, Canada Border and Services Agency, 79 Bentley Avenue, Ottawa, Ontario K2E 6T7, Canada. Marie-Josee.Binette@cbsa-asfc.gc.ca
Characterization of Canadian cigarettes using multi-stable isotope analysis by gas chromatography-isotope ratio mass spectrometry.

Public health. Expanded U.S. drug agency to control tobacco.

Nutt and colleagues' 'rational' scale to assess the harms of commonly used drugs was based on ratings by a panel of experts. This survey aimed to assess drug users' views of the harms of drugs using the same scale. As users' drug choices are not solely based on harms, we additionally assessed perceived benefits. The survey was hosted at http://www.nationaldrugsurvey.org. UK residents reported their experience of 20 commonly used substances; those with direct experience of a substance rated its physical, dependence-related and social harms as well as benefits. A total of 1501 users completed the survey. There was no correlation between the classification of the 20 drugs under the Misuse of Drugs Act and ranking of harms by users. Despite being unclassified substances, alcohol, solvents and tobacco were rated within the top ten most harmful drugs. There was a remarkably high correlation (r = 0.896) overall between rankings by users' and by experts. Ecstasy, cannabis and LSD were ranked highest by users on both acute and chronic benefits. These findings imply that users are relatively well informed about the harms associated with the drugs they use. They also suggest that the current UK legal classification system is not acting to inform users of the harms of psychoactive substances.
Clinical Psychopharmacology Unit, University College London, London, UK. c.morgan@ucl.ac.uk
Journal of psychopharmacology (Oxford, England)
Harms associated with psychoactive substances: findings of the UK National Drug Survey.

4-Methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK) is a tobacco-specific procarcinogen. We have investigated whether NNK causes inflammatory upheaval in the brain by activation of resident microglia and astrocyte and result in bystander neuronal damage. We have carried out the work in both in vitro and in vivo models. We have found that treatment with NNK causes significant activation of mouse microglial (BV2) cell line as evident by increase in reactive oxygen species and nitric oxide level. Western blot analysis has showed increase in proinflammatory signaling proteins, proinflammatory effector proteins, and other stress-related proteins. Interestingly, increased levels of proinflammatory cytokines like interleukin (IL)-6, tumor necrosis factor-alpha, monocyte chemoattractant protein 1 (MCP1), and IL-12p70 are also detected. Work from our in vivo studies has demonstrated similar increase in proinflammatory signaling and effector molecules along with the proinflammatory cytokine levels, following NNK treatment. Immunohistochemical staining of the brain sections of NNK-treated mice reveals massive microglial and astrocyte activation along with distinct foci of neuronal damage. Both in vitro and in vivo results provide strong indication that NNK causes significant upheaval of the inflammatory condition of brain and inflicts subsequent neuronal damage.
National Brain Research Centre, Manesar, Haryana, India.
Tobacco carcinogen induces microglial activation and subsequent neuronal damage.

Drug policy makers continuously face a changing pattern of drug use, i.e. new drugs appear on the market, the popularity of certain drugs changes or drugs are used in another way or another combination. For legislative purposes, drugs have mostly been classified according to their addictive potency. Such classifications, however, lack a scientific basis. The present study describes the results of a risk assessment study where 19 recreational drugs (17 illicit drugs plus alcohol and tobacco) used in the Netherlands have been ranked by a Dutch expert panel according to their harm based on the scientific state of the art. The study applies a similar approach as recently applied by Nutt et al. [Lancet 2007;369:1047-1053], so that the results of both studies could be compared. The harm indicators scored are acute and chronic toxicity, addictive potency and social harm. The aim of this study is to evaluate whether the legal classification of drugs in the Netherlands corresponds with the ranking of the drugs according to their science-based ranking of harm. Based on the results, recommendations are formulated about the legal classification of recreational drugs at national and international level which serves a rational approach for drug control.
Laboratory for Health Protection Research, RIVM, Bilthoven, The Netherlands. jan.van.amsterdam@rivm.nl
Ranking the harm of alcohol, tobacco and illicit drugs for the individual and the population.

A majority of modern war wounds are caused by blasts and high-energy ballistics. Extremity injuries predominate since modern body armor does not protect these areas due to mobility limitations. A less known and more insidious mechanism of enemy attack among our soldiers involves treachery by the local populace posing as noncombatants. One such recent event involved the contamination of tobacco with cyanide (CN). We describe a case of a soldier with CN intoxication due to ingestion of tobacco purchased from a local merchant. The soldier developed a complex neuropathic pain syndrome and was successfully treated with an inpatient high-dose intravenous ketamine infusion in combination with continuous peripheral nerve blockade.
Army Regional Anaesthesia and Pain Management Initiative, Anaesthesia and Operative Service, Walter Reed Army Medical Center, Building 2, Ward 44, Room 4418, Washington, DC 20307-5001, USA.
Development of a complicated pain syndrome following cyanide poisoning in a U.S. soldier.

Your company has spent months designing a compliance program and training your sales representatives. They know never to mention the off-label uses of your product. If they are asked about the off-label uses by the physician they are detailing, they know to forward those inquiries to the scientific liaisons at headquarters. But, could your company still be in legal jeopardy simply because it knows that the product is being used for an off-label purpose? This article attempts to track the Food and Drug Administration's (FDA's) shifting interpretation of its intended use regulations, from focusing entirely on the statements of the manufacturers to focusing on the knowledge of the industry, indeed, of the consumers of products, in determining the true intended use of a product. It will look at several recent attempts by FDA to use that new interpretation of the regulations to expand its power: to regulate tobacco and to require pediatric indications for any new drug. Finally, it will look at several recent examples of how this new interpretation has manifested in actions by FDA and the Department of Justice (DOJ).
Morrison Mahoney, LLP, Boston, Massachusetts, USA.
Criminalizing knowledge: the perverse implications of the intended use regulations of off-label promotion prosecutions.

Upwards of 400,000 Americans will die that year from the effects of cigarettes, which FDA will now regulate very gently, with its hands tied by a slick statutory protection for the largest existing tobacco marketers. Career FDA professionals will be criticized as enablers of mega-marketers' continued sales, working at the margins, arranging the paperwork for protection of megafirms' market share, and sitting by as the deaths and addictive behaviors continue. Join the Public Health Service, inspired by a public health mission, they were told, and yet they will be unable to do much regulating of the addictive and fatal products for which they now have titular responsibility. This essay observes that these fine FDA professionals are handed the sticky remains of a messy bargain, negotiated in a distracted Congress by expensive lawyers with clients who were potent contributors to political action committees. The only formula that is not secret about the 2009 law is the way in which industry purchased sufficient allegiance to gather the votes for its adoption. The remaining mystery is how FDA could be expected to do these tasks without losing its best and brightest professionals to other fields.
College of Law, University of Cincinnati, Cincinnati, OH, USA.
FDA regulation of tobacco: blessing or curse for FDA professionals?

FDA exercises new authority to regulate tobacco products, but some limits remain.

We previously showed different effects of tobacco and nicotine on fracture healing, but due to pump reservoir limits, maximum exposure period was 4 weeks. To allow flexibility in pre- and post-fracture exposure periods, the objective of this study was to compare a new oral administration route for nicotine to the established pump method. Four groups were studied: (1) pump saline, (2) pump saline + oral tobacco, (3) pump saline/nicotine + oral tobacco, and (4) pump saline + oral nicotine/tobacco. Sprague-Dawley rats (n = 84) received a transverse femoral fracture stabilized with an intramedullary pin 1 week after initiating dosing. After 3 weeks, no difference was found in torsional strength or stiffness between oral nicotine/tobacco or pump nicotine + tobacco, while energy absorption with oral nicotine/tobacco was greater than pump nicotine + tobacco (p < 0.05). Compared to saline control, strength for oral nicotine/tobacco was higher than control (p < 0.05), and stiffnesses for pump nicotine + tobacco and oral nicotine/tobacco were higher than control (p < 0.05). No differences in energy were found for either nicotine-tobacco group compared to saline control. Mean serum cotinine (stable nicotine metabolite) was different between pump and oral nicotine at 1 and 4 weeks, but all groups were in the range of 1-2 pack/day smokers. In summary, relevant serum cotinine levels can be reached in rats with oral nicotine, and, in the presence of tobacco, nicotine can influence mechanical aspects of fracture healing, dependent on administration method. Caution should be exercised when comparing results of fracture healing studies using different methods of nicotine administration.
(c) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Aarhus University Hospital, Norrebrogade 44, Building 1A, 8000 Aarhus C, Denmark. d022340@dadlnet.dk
Journal of orthopaedic research : official publication of the Orthopaedic Research Society
Effect of nicotine and tobacco administration method on the mechanical properties of healing bone following closed fracture.

All researchers agree that individuals can become intoxicated by and dependent on alcohol, tobacco, and other psychoactive drugs. But they have disagreed over whether, and to what extent, drug pathologies comprise a unitary medical problem. Most critically, does addiction have a biological common denominator? Consensus on this question has shifted back and forth. In the late nineteenth and early twentieth centuries, physicians often studied and treated various drug addictions together, working under the inebriety paradigm. By the mid-twentieth century the inebriety paradigm had collapsed. Tobacco and alcohol had split off, both in the medical research community and in western popular culture. This article argues that neuroscientific, genetic, epidemiological, and historical evidence helped to reunify the addiction field in the late twentieth century. A new unifying paradigm emerged, variously called chemical dependency, substance abuse, or simply ATOD -- alcohol, tobacco, and other drugs.
Soc Hist Alcohol Drugs. 2005;20(1):105-40.
Mr. ATOD's wild ride: what do alcohol, tobacco, and other drugs have in common?

If tobacco-related carcinogens are not inactivated or extruded from the cell, they can damage the DNA. Single nucleotide polymorphisms (SNPs) in genes involved in tobacco metabolism, DNA repair, and multidrug resistance have been related to lung cancer susceptibility. We examined 13 SNPs in 10 of these genes and correlated the results with time to progression (TTP) and overall survival (OS) in 71 smoker or former smoker patients with resected non-small-cell lung cancer (NSCLC).DNA was obtained from paraffin-embedded tumor. SNP analysis of the candidate genes was performed by allelic discrimination assay. Log-rank test, Kaplan-Meier plots, and Cox multivariate analysis were used to evaluate the association of TTP and survival with the SNPs evaluated.Patients with wild-type (wt) XPC rs2228001, wt CYP2C8 rs10509681, or non-wt NAT2 rs1799930 had a longer TTP. Patients with wt ERCC1 showed a nonsignificant trend towards longer TTP. No other relation between SNPs and TTP were observed. Patients harboring at least two unfavorable genotypes in these four genes had a shorter TTP and OS than patients with either one or no unfavorable genotypes. In the multivariate analysis, non-wt XPC rs2228001 and the presence of at least two unfavorable genotypes emerged as independent markers for shorter TTP.SNPs in tobacco metabolism and DNA repair genes may influence the clinical outcome of resected NSCLC.
Copyright © 2011 Elsevier Inc. All rights reserved.
Department of Medical Oncology, ICMHO, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
Single nucleotide polymorphisms in tobacco metabolism and DNA repair genes and prognosis in resected non-small-cell lung cancer.

Genomic alterations such as chromosomal amplifications, deletions and loss of heterozygosity play an important role in the pathogenesis and progression of cancer. Environmental risk factors contribute to the development and progression of tumors by facilitating the loss of tumor suppressor genes and amplification of oncogenes. In this current study, Affymetrix 10K single nucleotide polymorphism (SNP) arrays were used to evaluate genomic alterations in 20 pairs of matched germ-line and tumor DNA obtained from patients with esophageal squamous cell carcinoma (ESCC) from high-risk area of India where tobacco, betel quid and alcohol use are widespread. Twenty-two amplified regions and 16 deleted regions identified across chromosomal arms were biologically relevant. The candidate genes located at amplified regions of chromosomes or low-level gain regions such as PLA2G5 (1p36-p34), COL11A1 (1p21), KCNK2 (1q41), S100A3 (1q21), ENAH (1q42.12), RGS1 (1q31), KCNH1 (1q32-q41), INSIG2 (2q14.1), FGF12 (3q28), TRIO (5p15.2), RNASEN (5p15.2), FGF10 (5p13-p12), EDN1(6p24.1-p22.3), SULF1 (8q13.2-13.3), TLR4 (9q32-q33), TNC (9q33), NTRK2 (9q22.1), CD44 (11p13), NCAM1 (11q23.1), TRIM29 (11q22-q23), PAK1 (11q13-q14) and RAB27A (15q15-q21.1), are found to be associated with cellular migration and proliferation, tumor cell metastasis and invasion, anchorage independent growth and inhibition of apoptosis. The candidate genes located at deleted regions of chromosomes, such as FBLN2 (3p25.1), WNT7A (3p25), DLC1 (8p22), LZTS1 (8p22), CDKN2A (9p21), COL4A1 (13q34), CDK8 (13q12) and DCC (18q21.3), are found to be associated with the suppression of tumor. The suggested candidate genes were mostly involved in potential signaling pathways such as focal adhesion (COL4A1), tight junction (CLDN10), MAPK signaling pathway (FGF12) and neuroactive ligand receptor interaction pathway (CCKAR). Expression of FGF12 and COL4A1 was validated by tissue microarray. These unique copy number alteration profiles should be taken into consideration when developing biomarkers for the early detection of ESCC in high-risk areas of India in association with tobacco and betel quid use.
Copyright © 2010 Elsevier B.V. All rights reserved.
Institute of Pathology, New Delhi 110029, India.
Genome-wide analysis of chromosomal alterations in patients with esophageal squamous cell carcinoma exposed to tobacco and betel quid from high-risk area in India.

CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne
The federal government's senseless policy change on tobacco warning labels.

In this work, we have conducted a case-control study in order to assess the effect of tobacco and three genetic polymorphisms in XPC, ERCC2 and ERCC5 genes (rs2228001, rs13181 and rs17655) in bladder cancer development in Tunisia. We have also tried to evaluate whether these variants affect the bladder tumor stage and grade.The patients group was constituted of 193 newly diagnosed cases of bladder tumors. The controls group was constituted of non-related healthy subjects. The rs2228001, rs13181 and rs17655 polymorphisms were genotyped using a polymerase chain reaction-restriction fragment length polymorphism technique.Our data have reported that non smoker and light smoker patients (1-19PY) are protected against bladder cancer development. Moreover, light smokers have less risk for developing advanced tumors stage. When we investigated the effect of genetic polymorphisms in bladder cancer development we have found that ERCC2 and ERCC5 variants were not implicated in the bladder cancer occurrence. However, the mutated homozygous genotype for XPC gene was associated with 2.09-fold increased risk of developing bladder cancer compared to the control carrying the wild genotype (p = 0.03, OR = 2.09, CI 95% 1.09-3.99). Finally, we have found that the XPC, ERCC2 and ERCC5 variants don't affect the tumors stage and grade.These results suggest that the mutated homozygous genotype for XPC gene was associated with increased risk of developing bladder. However we have found no association between rs2228001, rs13181 and rs17655 polymorphisms and tumors stage and grade.
Laboratory of Genetic, Immunology and Human Pathology, Faculty of Sciences of Tunis, University of El Manar I. Tunis, Tunisia.
The effect of tobacco, XPC, ERCC2 and ERCC5 genetic variants in bladder cancer development.

To determine the influence of alcohol and tobacco consumption on serum prostate-specific antigen (PSA) levels. 59 men participated in this study: 20 with prostate tumors (PT) and 39 without tumor diagnosis (prostate controls, PC) (mean 66 and 58 years, respectively). PSA was analyzed in serum samples and its values were compared through the Kruskal-Wallis nonparametric test. Alcohol and tobacco consumption was also considered. PSA mean value was higher than 4 ng/ml in PT, whereas in PC it was lower than that value. Statistically significant differences were found when comparing PSA between PT and PC (P < 0.05). PSA was higher in alcohol and tobacco consumers than in non-consumers in PT group (P < 0.05). For PC, PSA mean values were higher in non-smokers than in smokers. Statistically significant differences were observed for serum PSA when compared between PT and PC groups considering alcohol and tobacco consumption (P < 0.05). Serum PSA values appear to be influenced by alcohol and tobacco consumption.
Cátedra de Anatomía, Facultad de Odontología, Universidad Nacional de Córdoba, Av. Pueyrredón 2335, Bº Alto Alberdi, 5003 Córdoba, Argentina. escandriolojorge@odo.unc.edu.ar
Medical oncology (Northwood, London, England)
Prostate-specific antigen: its relationship with alcohol intake and tobacco.

In the half century since the 1959 Cuban Revolution, El Habano remains the premium cigar the world over; but both before and since 1959, the seed, agricultural and industrial know-how, and human capital have been transplanted to replicate that cigar in a process accentuated by upheavals and out-migration. The focus here is on a little-known facet of the interconnected island and offshore Havana cigar history, linking Cuba with Connecticut and Indonesia: from when tobacco was taken from the Americas to Indonesia and gave rise to the famed Sumatra cigar wrapper leaf; through the rise and demise of its sister shade wrapper in Connecticut, with Cuban and Sumatra seed, ultimately overshadowed by Indonesia; and the resulting challenges facing Cuba today. The article highlights the role of Dutch, U.S., British, and Swedish capital to explain why in 2009 the two major global cigar corporations, British Imperial Tobacco and Swedish Match, were lobbying Washington, respectively, for and against the embargo on Cuba. As the antismoking, antitobacco lobby gains ground internationally, the intriguing final question is whether the future lies with El Habano or smokeless Swedish snus.
El Habano and the world it has shaped: Cuba, Connecticut, and Indonesia.

Some concentrated natural tobacco aromatizers (FL-Marwal, FL-Achshe, FL-Vlakot) and casings (CC-Catjas, CC-Wenget, CC-Krawat) from British American Tobacco Germany GmbH (Germany) imported into the Republic of Uzbekistan to be used in the manufacture of cigarettes were tested. The author's toxicological studies have revealed that the test agents may be recommended for use in the manufacture of cigarettes as safe tobacco aromatizers and casings. The normal life span reduction caused by the test natural concentrated tobacco aromatizers and casings in the hygienic range will be expected to be 3-6 days a year.
[Assessment health damage from use of tobacco aromatizers].

Multiple myelomas are a less frequent cancer site among both sexes. On a worldwide scale, it is estimated that about 86 000 incident cases occur annually, accounting for about 0.8% of all new cancer cases. About 63 000 subjects are reported to die from the disease each year, accounting for 0.9% of all cancer deaths. Geographically, the frequency is very unevenly distributed in the world with the highest incidence in the industrialised regions of Australia / New Zealand, Europe and North America. Incidence and mortality seem to be stable in Asian countries and to increase slowly over the decades among whites in the western countries. The etiology is poorly understood. This depends partly upon the fact that the risk factors which play a major role for malignant diseases in general, such as tobacco consumption and diet have not been found strongly involved into multiple myeloma etiology. Nevertheless, some consistency seems to be in the findings about a risk elevation with obesity and a slightly decreased risk with high fruit consumption. Despite some contradicting results, indications to a role of ionising radiation persist. Finally, infections with HIV and hepatitis C virus appear related to an elevated multiple myeloma risk. Currently, large efforts are undertaken to unravel the etiology of malignant lymphoma including those of multiple myeloma.
German Cancer Research Center, Im Neuenheimer Feld 581, D-69120, Heidelberg, Germany. n.becker@dkfz.de
Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer
Recent Results Cancer Res. 2011;183():25-35.

O(2)-[4-(3-Pyridyl)-4-oxobut-1-yl]thymidine (O(2)-POB-dThd) is the most persistent adduct detected in the lung and liver of rats treated with tobacco specific nitrosamines: N'-nitrosonornicotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and its metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). It is an important biomarker to assess the human exposure to these carcinogens. The only synthetic method reported for O(2)-POB-dThd requires repeated HPLC purifications and could only be used to prepare an analytical standard due to very low yield (0.4%). We have developed for the first time a regioselective and efficient method for the total synthesis of O(2)-POB-dThd and its site-specifically adducted oligonucleotides. The main step in the synthesis of O(2)-POB-dThd was achieved by a novel method. The treatment of O(2)-5'-anhydrothymidine with the sodium salt of 4-(1,3-dithian-2-yl)-4-(3-pyridyl)butan-1-ol gave exclusively the O(2)-alkylated adduct, which was deprotected in one step to furnish the desired O(2)-POB-dThd in excellent yield. The product was characterized by NMR ((1)H and (13)C), high-resolution MS, and HPLC analysis. This work provided for the first time a reliable method for large scale total synthesis of O(2)-POB-dThd that allowed for solid state site-specifically adducted oligomer synthesis. The O(2)-POB-dThd was converted to its phosphoramidite and subsequently used for the synthesis of oligodeoxynucleotides by standard methods. The oligomers were characterized by MS and HPLC analysis. These oligomers will facilitate the elucidation of the mutagenic potential of the O(2)-POB-dThd adduct, which will provide further insight into the role of tobacco-specific nitrosamines in inducing cancers in smokers.
Department of Pharmacology, Penn State College of Medicine, Hershey, Pennsylvania 17033, United States.
Facile syntheses of O(2)-[4-(3-pyridyl-4-oxobut-1-yl]thymidine, the major adduct formed by tobacco specific nitrosamine 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK) in vivo, and its site-specifically adducted oligodeoxynucleotides.

Lung tumors from smokers as well as lung tumors from mice exposed to tobacco carcinogens such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), often carry mutations in K-ras, which activates downstream-signaling pathways such as PI3K/AKT/mTOR pathway. Mice with genetic deletion of one of three isoforms of AKT were used to investigate the role of AKT in mutant K-ras-induced lung tumorigenesis in mice. Although deletion of Akt1 or Akt2 decreased NNK-induced lung tumor formation by 90%, deletion of Akt2 failed to decrease lung tumorigenesis in two other mouse models driven by mutant K-ras. Genetic mapping showed that Akt2 was tightly linked to the cytochrome P450 Cyp2a locus on chromosome 7. Consequently, targeted deletion of Akt2 created linkage to a strain-specific Cyp2a5 polymorphism that decreased activation of NNK in vitro. Mice with this Cyp2a5 polymorphism had decreased NNK-induced DNA adduct formation in vivo and decreased NNK-induced lung tumorigenesis. These studies support human epidemiological studies linking CYP2A polymorphisms with lung cancer risk in humans and highlight the need to confirm phenotypes of genetically engineered mice in multiple mouse strains.
Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
A Cyp2a polymorphism predicts susceptibility to NNK-induced lung tumorigenesis in mice.

Studies of the spirometric profiles of narghile smokers are few, have some methodological limits (i.e. small sample size), and present contradictory conclusions.(i) To determine the percentage of narghile smokers with obstructive ventilatory defect (OVD) and/or restrictive ventilatory defect (RVD) or static hyperinflation (SHI); (ii) to compare the chronological and estimated lung ages.men aged 20 to 60 years, narghile smokers (>1 narghile-year [NY]).cigar or cigarette smokers and comorbidity. Narghile use quantification: NY and kg of cumulative tobacco use (1 NY=9.125 kg of cumulative tobacco use).Large airway obstructive ventilatory defect (OVD): forced expired volume in one second (FEV(1))/forced vital capacity (FVC) less than lower limit of normal (LLN). Small airway OVD: FVC more than LLN and decrease (less than LLN) of one or more peripheral flows. RVD: total lung capacity (TLC) less than LLN. SHI: residual volume (RV) more than upper limit of normal. SPIROMETRIC MEASURES: (Vmax 22 Series/6200 Autobox, SensorMedics, Yorba Linda, California, USA with measurement of functional residual capacity by nitrogen washout). Measurements were made according to international recommendations.One hundred and ten narghile smokers were included (34±10 years; 1.76±0.07m; 84±14kg). Thirty-six percent of the subjects had SHI; 14% had small airway OVD; 14% had RVD, and 6% had large airway OVD. Estimated lung age was higher than chronological lung age (47±18 years vs. 34±10 years, P<0.05).Narghile use accelerates lung ageing. This study provides the health authorities with valid arguments to fight this blight on society, which increasingly involves children and pregnant women.
Copyright © 2011 SPLF. Published by Elsevier Masson SAS. All rights reserved.
Service de physiologie et des explorations fonctionnelles, EPS Farhat Hached, Sousse, Tunisia. helmi.bensaad@rns.tn
Spirometric profile of narghile smokers.

Melbourne Law School, University of Melbourne, 207 Bouverie St, Parkville, Victoria 3052, Australia.
Plain packaging of tobacco products in Australia: a novel regulation faces legal challenge.

This study was aimed to explore the therapeutic effect of sodium ferulate (SF) on rats with intrauterine growth retardation (IUGR), and then to clarify the corresponding mechanism. Pregnant rats were divided into normal group, tobacco/alcohol exposure group, and tobacco/alcohol+SF groups. Fetal developmental indices, placental weight, histological alteration, oxidative and antioxidative-function (e.g. MDA, SOD, CAT) and Mdr1 levels were assayed. Results showed exposure to tobacco/alcohol resulted in reduced fetal developmental indices and placental histological alteration, as well as the increased MDA content, decreased SOD and CAT activities and decreased Mdr1a level. After SF treatment, fetal developmental indices, and placental weight, histological alteration, oxidative and antioxidative-function and mdr1a levels were reversed. Our study indicated SF may be effective in reversing IUGR production, and its underlying mechanism may be due to enhanced placental antioxidative function and P-gp expression, which may be related to IUGR formation by tobacco/alcohol exposure.
Copyright © 2011 Elsevier B.V. All rights reserved.
Department of Pharmacology of Basic Medical College, Wuhan University, Wuhan 430071, China.
Environmental toxicology and pharmacology
Environ Toxicol Pharmacol. 2011-11;32(3):465-71.
Enhancement of placental antioxidative function and P-gp expression by sodium ferulate mediated its protective effect on rat IUGR induced by prenatal tobacco/alcohol exposure.

Fagerström Consulting, Jordkull 3670, 26878 Kagerod, Sweden. karl.fagerstrom@swipnet.se
Determinants of tobacco use and renaming the FTND to the Fagerstrom Test for Cigarette Dependence.

Graphene oxide was found to be a highly efficient, reusable and cost-effective organocatalyst for the aza-Michael addition of amines to activated alkenes to furnish corresponding β-amino compounds in excellent yields.
Chemical Sciences Division, Indian Institute of Petroleum, Mohkampur, Dehradun-248005, India.
Chemical communications (Cambridge, England)
Graphene oxide: an efficient and reusable carbocatalyst for aza-Michael addition of amines to activated alkenes.

The aim of this study was to compare the socioeconomic profile and social habits of oral cancer patients and those of control subjects in order to investigate the relative importance of these risk factors in the occurrence of oral cancer.Thirty-two histologically diagnosed oral carcinoma patients and 30 normal patients were recruited at the dental centre University College Hospital, Ibadan. A 33-item questionnaire was administered to the two groups. The data obtained was analyzed using student t test and chi square as appropriate as well as odds ratio.Incomes less than 50,000 naira per annum, absence of fruit in every diet and tobacco use, were associated with 5.7, 3.0 and 4.05 increased risk of oral cancer respectively.Low income, fruit depleted diet and tobacco use seems to be the most important risk factors for oral cancer development in the studied environment.
Department of Oral Pathology, College of Medicine, University of Ibadan, Ibadan, Nigeria. toytoy219@yahoo.com
African journal of medicine and medical sciences
Social profile and habits of oral cancer patients in Ibadan.

Searching for an indicator of the influence of the tobacco lobby on politicians.

The utility of thiourea dioxide as an efficient organocatalyst for the library synthesis of novel heterocyclic compounds via one-pot multicomponent coupling reactions is disclosed. Thiourea dioxide is an inexpensive and readily accessible catalyst, resulting in better product yields as compared to the corresponding thiourea as catalyst. Thiourea dioxide is found to be insoluble in various organic solvents and therefore at the end of the reaction products can be separated by extraction with diethyl ether and the recovered catalyst can be used several times with consistent catalytic activity.
Chemical Sciences Division, Indian Institute of Petroleum, Dehradun, India 248005.
Thiourea dioxide promoted efficient organocatalytic one-pot synthesis of a library of novel heterocyclic compounds.

To determine the tobacco industry's policy and action with respect to radioactive polonium 210 ((210)Po) in cigarette smoke and to assess the long-term risk of lung cancer caused by alpha particle deposits in the lungs of regular smokers.Analysis of major tobacco industries' internal secret documents on cigarette radioactivity made available online by the Master Settlement Agreement in 1998.The documents show that the industry was well aware of the presence of a radioactive substance in tobacco as early as 1959. Furthermore, the industry was not only cognizant of the potential cancerous growth in the lungs of regular smokers but also did quantitative radiobiological calculations to estimate the long-term (25 years) lung radiation absorption dose (rad) of ionizing alpha particles emitted from the cigarette smoke. Our own calculations of lung rad of alpha particles match closely the rad estimated by the industry. According to the Environmental Protection Agency, the industry's and our estimate of long-term lung rad of alpha particles causes 120-138 lung cancer deaths per year per 1,000 regular smokers. Acid wash was discovered in 1980 to be highly effectively in removing (210)Po from the tobacco leaves; however, the industry avoided its use for concerns that acid media would ionize nicotine converting it into a poorly absorbable form into the brain of smokers thus depriving them of the much sought after instant nicotine kick sensation.The evidence of lung cancer risk caused by cigarette smoke radioactivity is compelling enough to warrant its removal.
Translational Arrhythmia Research Section, Cardiovascular Research Laboratories, Department of Medicine, David Geffen School of Medicine at University of California Los Angeles, 675 Charles E. Young Drive South, MRL 1630, Mail Code: 176022, Los Angeles, CA 90095, USA. hkaragueuzian@mednet.ucla.edu
Cigarette smoke radioactivity and lung cancer risk.

The cross-drug relationship of subjective experiences between alcohol, tobacco, and marijuana and problem drug use behaviors were examined. Data were drawn from 3853 individuals between the ages of 11 and 30 years of age participating in the Colorado Center on Antisocial Drug Dependence [CADD]. Subjective experiences were assessed using a 13-item questionnaire that included positive and negative responses for alcohol, tobacco, and marijuana. Lifetime abuse and dependence on these three drugs was assessed using the Composite International Diagnostic Interview, Substance Abuse Module [CIDI-SAM].Positive and negative subjective experience scales were similar for alcohol, tobacco, and marijuana, although the hierarchical ordering of items differed by drug. Subjective experience scales for each of the three drugs examined correlated significantly, with the strongest relationship being for alcohol and marijuana experiences. Significant associations were identified between how a person experienced a drug and abuse and dependence status for the same or different drug.Cross-drug relationships provide evidence for a common liability or sensitivity towards responding in a similar manner to drugs of abuse within and across different pharmacological classes.
Institute for Behavioral Genetics, University of Colorado, Campus Box 447, Boulder, CO 80309-0447, USA.
Drug Alcohol Depend. 2012-06;123 Suppl 1():S52-8.
Subjective effects for alcohol, tobacco, and marijuana association with cross-drug outcomes.

This review assesses published literature related to frequency and outcomes associated with accidental ingestion of tobacco and pharmaceutical nicotine products among young children. Twenty-seven years of annual reports by American Association of Poison Control Centers (AAPCC) were analyzed for occurrence and outcomes associated with accidental ingestion events involving tobacco and pharmaceutical nicotine products among young children. Over a 27-year period, and of >50 million contacts for all categories combined, 217,340 contacts involving ingestion of tobacco products were reported. Approximately 89% involved children <6 years old. One fatality was reported, however the co-ingestion of both cigarettes and diazepam complicates an assessment of a contributory role of tobacco. The rate of major, non-fatal, outcomes was <0.1%. Data from AAPCC reports and other sources indicate the frequency of accidental poisoning events is relatively low for tobacco products compared with other products such as drugs, dietary supplements, cleaning products, and personal care products. These findings, along with those for pharmaceutical nicotine products, are consistent with published case reports and reviews, indicating that the frequency and severity of outcomes associated with accidental ingestion of tobacco products by young children appear to be relatively low. However, adults should keep tobacco products out of the reach of children.
Altria Client Services, 601 East Jackson Street, Richmond, VA 23219, USA. Scott.Appleton@altria.com
Regulatory toxicology and pharmacology : RTP
Regul Toxicol Pharmacol. 2011-11;61(2):210-4.
Frequency and outcomes of accidental ingestion of tobacco products in young children.

This work evaluates the characteristics of short-term release of volatile and semi-volatile organic chemicals from clothing fabrics that are exposed to environmental tobacco smoke (ETS). Various fabrics were concurrently exposed to ETS in a controlled facility, and the chemicals off-gassed were sampled using solid phase micro-extraction coupled with GC/MS analysis. Toluene-reference concentration (TRC) was calculated for nine selected chemicals and compared. The number of chemicals identified from ETS-exposed fabrics ranged from 13 (polyester and acetate) to 32 (linen). All fabrics off-gassed formaldehyde, tetradecanoic acid and n-hexadecanoic acid, while seven out of eight fabrics emitted furfural, benzonitrile, naphthalene and decanal. Natural fibers of plant origin (cotton and linen) off-gassed higher concentrations (TRC>100 μg/l) of chemicals that have low molecular weight (~100 or less) than did natural fibers of animal origin (wool and silk) and synthetic fibers. Conversely, wool and silk off-gassed more chemicals that are of high molecular weight (>200), such as TDA (TRC>100 μg/l) and n-HDA (TRC>500 μg/l), than did other fabrics. Fabric structure (for a particular material) significantly affects chemical off-gassing. Cotton typically used for polo shirt (knitted) off-gassed significantly (p<0.05) higher TRC for chemicals with molecular weight of ~100 (such as furfural) than did other cottons of woven style. The dyeing of fabric (white vs. black) had a limited effect on emission, while increasing contact time with ETS increased the intensity of chemical emissions. The mean TRC for cotton exposed for 12 min was nearly doubled than those exposed for 8min, but no difference existed for polyester.
Copyright © 2011. Published by Elsevier B.V.
Department of Safety, Health and Environmental Engineering, Hungkuang University, Taichung, Taiwan. ycchien@yuntech.edu.tw
Volatile organics off-gassed among tobacco-exposed clothing fabrics.

In this study, we have analyzed clinically, histopathologically and immunohistochemically a total of 34 cases of oral squamous carcinoma in 11 of the cases being identified adjacent epithelial dysplastic lesions. Carcinomas were diagnosed in patients aged 40-60 years, males, with chronic exposure to tobacco and/or alcohol, being located especially on the lips. Well-differentiated carcinomas have been predominant (52.9%) in stage I/II tumoral (88.3%). Immunoexpression analysis of p53, p16 and Ki67 did not reveal statistically significant differences between the expression of markers and clinical or histopathological parameters, except Ki67 whose increased expression was associated to the decrease of the degree of tumoral differentiation and with high degree dysplasia. The positivity index and the intensity of reaction were increased at the level of dysplasic epithelium for p16 and at the level of tumoral invasion front for the p53 and Ki67. The study highlights the value of the immunostain for p16 in identifying dysplasic lesions and predictive importance of p53 and Ki67 markers in identifying the aggressive forms of oral carcinomas.
Department of Occlusology Dental Prosthetics, University of Medicine and Pharmacy of Craiova, Romania.
Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie
Rom J Morphol Embryol. 2012;53(1):89-93.
P53, p16 and Ki67 immunoexpression in oral squamous carcinomas.

Revue d'epidemiologie et de sante publique
Rev Epidemiol Sante Publique. 2012-04;60(2):79-80.
[Tobacco: the taxation is also a tool of public health].

Autophagy is a physiologically regulated and evolutionary conserved process that plays a critical role in degradation of cytoplasmic proteins and other macromolecules within the lysosomes. Beclin-1, the mammalian orthologue of yeast Atg6, is an important mediator of autophagy that has been studied in many human cancers. However, the expression of Beclin-1 has not yet been investigated in oral cancer. We for the first time investigated the expression of Beclin-1 in serum and tissues and correlated it with the clinic-pathological features of oral cancer patients. m-RNA expression of Beclin-1 was evaluated in tumor and normal areas of surgical specimens from 10 oral cancer patients by real-time PCR. Approximately, 8-fold lower expression (p<0.001) of Beclin-1 mRNA was observed in tumor tissue as compared to the normal tissue. Serum levels of Beclin-1 were evaluated by SPR and ELISA. No significant difference was observed in serum Beclin-1 levels in patients as compared to healthy subjects, similarly no correlation was found between serum levels and clinic-pathological parameters such as stage, lymph node involvement and tumor size. Our results demonstrate that down-regulation of Beclin-1 may play an important role in the development and progression of oral cancer possibly by dysregulation of autophagy in tumor cells.
Copyright © 2012 Elsevier Inc. All rights reserved.
Department of Biotechnology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India. kapoor.vaishali@gmail.com
Biochemical and biophysical research communications
Deregulation of Beclin 1 in patients with tobacco-related oral squamous cell carcinoma.

Polymorphisms in the genes that code for metabolic enzymes involved in either the activation (Phase I) or detoxication (Phase II) of chemical carcinogens in tobacco, may alter expression or function of carcinogenic compounds and hence alter risk of oral cancer. The present study investigates whether polymorphisms at CYP1A1 and GSTM1 gene loci act as risk factors for oral precancerous lesions and cancer.For the present study, histopathologically confirmed cases of 90 oral precancerous lesions, 150 oral squamous cell carcinoma (SCC) and 150 control subjects were selected. Polymerase chain reaction and restriction fragment length polymorphism were performed using DNA from blood samples to determine the polymorphic genotypes at CYP1A1 and GSTM1 loci.CYP1A1 C (m2/m2) genotype conferred a 12.0 fold-increased risk (OR=12.0; 95% CI, 2.40-60.05) to oral SCC. GSTM1 null showed no significant association but the frequency was higher in oral SCC cases. Patients with genotype C and/or GSTM1 deficiency developed carcinoma after less tobacco consumption than those of other genotypes though the difference was not statistically significant. The frequency of the combined genotypes C and GSTM1 null was found to be 14% among oral SCC patients. On comparing the susceptibility of intraoral sites it was found that in the majority of cases (64%) in the study groups they were the buccal mucosa.Hence it was concluded that metabolic enzymes reported in the present study: CYP1A1 significantly alter oral cancer risk. GSTM1 null and CYP1A1 C (m2m2) show a predisposition to premalignant lesions and cancer of the buccal mucosa than other sites.
Department of Oral Pathology and Microbiology, Faculty of Dentistry, Jamia Millia Islamia, Delhi, India.
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub
Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2012-09;156(3):253-9.
Genetic polymorphism of drug metabolizing enzymes (GSTM1 and CYP1A1) as risk factors for oral premalignant lesions and oral cancer.

Children prenatally exposed to tobacco exhibit higher rates of learning and emotional-behavioral problems related to worse working memory performance. Brain function, however, among tobacco exposed children while performing a working memory task has not previously been examined. This study compared the brain function of tobacco-exposed (n = 7) and unexposed (n = 11) 12-year-olds during a number N-back working memory task using an event-related functional magnetic resonance imaging (fMRI) design. Prenatal alcohol exposure, neonatal medical problems, environmental risk, and sex were statistically controlled. Tobacco-exposed children showed greater activation in inferior parietal regions, whereas unexposed children showed greater activation in inferior frontal regions. These differences were observed in the context of correct responses, suggesting that exposed and unexposed children use different brain regions and approaches to succeed in working memory tasks. Implications for future research and intervention are discussed.
GLAD Program, Drexel University College of Medicine, Building C, Box 118, 4700 Wissahickon Avenue, Philadelphia, PA 19144, USA. David.Bennett@DrexelMed.edu
Prenatal tobacco exposure predicts differential brain function during working memory in early adolescence: a preliminary investigation.

Tobacco and tea habit are very common in world wide. In the present study, an attempt was made to evaluate the effect of regular drinking of black tea on reactive oxygen species (ROS) generation and DNA damage in buccal cells of normal subjects with or without tobacco habit. Expression of ROS associated proteins IκB, NF-κB as well as DNA repair associated proteins p53, MLH1 were also analyzed. Exfoliated buccal cells were collected from 308 healthy individuals and classified according to age, tobacco and tea habits. In all age groups, comparatively high ROS level and significantly high DNA damage frequency were seen in individuals with tobacco habit than the subjects without tea and tobacco habits. Tea habit effectively lowered ROS level and restrict DNA damage in tobacco users irrespective of ages. The DNA damage seen in the subjects was not associated with apoptosis. Moreover, tea habit effectively lowered the expression of IκB, NF-κB, p53 and MLH1 in tobacco users in all age groups. It seems that regular black tea habit could have anti-genotoxic effect as revealed by reduced tobacco associated ROS generation and DNA damage in buccal cells.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Department of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700 026, India.
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
Regular black tea habit could reduce tobacco associated ROS generation and DNA damage in oral mucosa of normal population.

The objective of the present study was to examine the influence of prenatal drug exposure (PDE) on memory performance and supporting brain structures (i.e., hippocampus) during adolescence. To achieve this goal, declarative memory ability and hippocampal volume were examined in a well-characterized sample of 138 adolescents (76 with a history of PDE and 62 from a non-exposed comparison group recruited from the same community, mean age=14 years). Analyses were adjusted for: age at time of the assessments, gender, IQ, prenatal exposure to alcohol and tobacco, and indices of early childhood environment (i.e., caregiver depression, potential for child abuse, and number of caregiver changes through 7 years of age). Results revealed that adolescents with a history of PDE performed worse on the California Verbal Learning Test-Child Version (CVLT-C), and story recall from the Children's Memory Scale (CMS), and had larger hippocampal volumes, even after covariate adjustment. Hippocampal volume was negatively correlated with memory performance on the CVLT-C, with lower memory scores associated with larger volumes. These findings provide support for long-term effects of PDE on memory function and point to neural mechanisms that may underlie these outcomes.
University of Maryland, College Park, USA. riggins@umd.edu
Memory ability and hippocampal volume in adolescents with prenatal drug exposure.

Leber hereditary optic neuropathy (LHON) is regarded as the most common mitochondrial disease. We have previously reported comprehensive population-based epidemiological data on common mitochondrial DNA (mtDNA) mutations including m.3243A>G, m.8344A>G and large-scale mtDNA deletions in Northern Finland. Our aim was to investigate the prevalence of primary LHON mutations and mutations in the four mtDNA genes considered hot spots for LHON in the same population.The study population consisted of 42 adult patients with an aetiologically undefined bilateral optic atrophy. The major LHON mutations m.3460G>A, m.11778G>A and m.14484T>C were analysed by restriction fragment length polymorphism (RFLP), and MTND1, MTND6 and MTATP6 genes were sequenced. MTND5 gene was analysed by conformation-sensitive gel electrophoresis (CSGE).No major LHON mutations were found in the population of the province of Northern Ostrobothnia giving the prevalence of these mutations 0-1.36:100 000 (95% CI). However, two main mutations were found elsewhere in Northern Finland, homoplasmic m.11778G>A from Kainuu and heteroplasmic m.3460G>A from Central Ostrobothnia. Furthermore, tobacco-alcohol amblyopia was diagnosed in five patients in the study population and one of them had m.11778G>A.The prevalence of the three major LHON mutations is lower in Northern Finland than elsewhere in Finland or in Western Europe. As LHON and tobacco-alcohol amblyopia have a similar phenotype, we recommend analysing the known LHON-associated mutations before setting tobacco-alcohol amblyopia diagnosis.
© 2012 The Authors. Acta Ophthalmologica © 2012 Acta Ophthalmologica Scandinavica Foundation.
Department of Ophthalmology, Institute of Clinical Medicine, University of Oulu and Clinical Research Center, Oulu University Hospital, Oulu, FinlandDepartment of Neurology, Institute of Clinical Medicine, University of Oulu and Clinical Research Center, Oulu University Hospital, Oulu, FinlandDepartment of Pediatrics, Institute of Clinical Medicine, University of Oulu and Clinical Research Center, Oulu University Hospital, Oulu, FinlandDepartment of Neurology, Institute of Clinical Medicine, University of Eastern, FinlandDepartment of Neurology, Kuopio University Hospital, Finland.
Prevalence of the primary LHON mutations in Northern Finland associated with bilateral optic atrophy and tobacco-alcohol amblyopia.

The phosphatidylinositol 3-kinase (PI3K) signaling regulates several cellular functions such as motility, proliferation, angiogenesis and survival.Since there is no information on expression of PI3K isoforms in oral cancer, we studied the expression of different isoforms of PI3K (p110α, p110γ, PI3K-C2, Vps34p and p85α) in tumor samples and PBMC by RT and q-RTPCR and serum levels of PI3K p110α by SPR and ELISA techniques in 108 patients with tobacco-related oral squamous cell carcinoma (OSCC) and 46 normal subjects.We observed significantly higher PI3K p110α (p<0.0001) and lower (p<0.0001) vesicular sorting protein 34p (Vps34p) mRNA both in PBMC and tissue samples of oral cancer patients as compared to the normal controls. Other PI3K isoforms did not show such change. Circulating PI3K p110α levels were higher in patients (p<0.0001) as compared to healthy subjects, the SPR data showed direct correlation with advancing stage of the disease. PI3K p110α was overexpressed in tumor samples but not in the normal buccal mucosa.Upregulation of circulating PI3K p110α isoform and its direct correlation with increasing tumor load in OSCC patients indicates that it may be a significant prognostic indicator and a suitable target for therapeutic/chemo-preventive strategies for tobacco-related OSCC.
Copyright © 2012 Elsevier B.V. All rights reserved.
Department of Biotechnology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi-110029, India.
Clinica chimica acta; international journal of clinical chemistry
Abnormal expression of PI3K isoforms in patients with tobacco-related oral squamous cell carcinoma.

The aim of this study was to investigate the effect of environmental factors, such as tobacco, alcohol and folic acid intake, obesity, stressful events, low blood levels of zinc and fever during pregnancy, on the incidence of cleft lip and/or palate (CL±P). An electronic search was performed in the Cochrane Reviews, the ISI Web of Knowledge, PubMed and Scopus, along with a manual search to identify other relevant case-control and cohort studies. Quality assessments and an evaluation of publication bias were undertaken. Statistical heterogeneity was examined, and odds ratios (ORs) and 95% confidence intervals (CI) estimated using the random effects model. Of 372 articles initially retrieved, 28 studies were selected as eligible for meta-analysis. No evidence of publication bias was found using funnel plot analysis and the Egger linear regression method. Many studies were classified as low quality due to inadequate case-control data. On the basis of this research, maternal factors most associated with CL±P were: tobacco (OR 1.48), alcohol (OR 1.28), folic acid intake (OR 0.77), obesity (OR 1.26), stressful events (OR 1.41), low blood zinc levels (OR 1.82), and fever during pregnancy (OR 1.30). Folic acid intake by the mother reduced the risk of CL±P in offspring (OR 0.77).
Copyright © 2013 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
School of Dentistry, University of Seville, Spain.
International journal of oral and maxillofacial surgery
Int J Oral Maxillofac Surg. 2013-02;42(2):177-84.
Current concepts on the effect of environmental factors on cleft lip and palate.

Department of Ophthalmology, Poznan City Hospital, Poznan, PolandChair of Ophthalmology, University of Warmia and Mazury, Olsztyn, PolandDepartment of Ophthalmology, Wroclaw Medical University, Wroclaw, Poland.
Tobacco-alcohol amblyopia does not exist.

Tobacco contains agents which generate various potent DNA adducts that can cause gene mutations. Production of DNA adducts may be neutralized by glutathione S transferase (GST) along with other phase I and phase II enzyme systems. The existence of null type of GST among the population increases the susceptibility to various disorders and diseases. The present study focuses on the impact of high tobacco usage and possible null type mutation in GST loci.Genotypes of GST were detected by multiplex polymerase chain reaction in unrelated 504 volunteers of high tobacco using natives of Gujarat. Allelic frequencies were calculated using Statistical Package for Social Studies-16 software. Hardy Weinberg Equilibrium (HWE) was calculated using Chi square test. Two sided Fisher's significance test was used to compare allelic frequencies of different populations.The frequency of homozygous null genotype of GSTM1 and GSTT1 were 20% (95% CI 16.7-23.9) and 35.5% (95% CI 31.4-39.9) respectively. The GSTM1 and GSTT1 null allele frequency distribution in the Gujarat population was significantly deviating from HWE. GSTT1 null frequency of Gujaratians was significantly higher and different to all reported low tobacco using Indian ethnics, while GSTM1 was not differing significantly.Tobacco usage significantly influences the rate of mutation and frequency of GSTT1 and M1 null types among the habituates. The rate of mutation in GSTT1 loci was an undeviating response to the dose of tobacco usage among the population. This mutational impact of tobacco on GSTT1 postulates the possible gene - environment interaction and selection of null genotype among the subjects to prone them under susceptible status for various cancers and even worst to cure the population with GSTT1 dependent drugs.
Department of Zoology, The Madura College (Autonomous), Madurai, India.
Asian Pacific journal of cancer prevention : APJCP
Impact of tobacco on glutathione S transferase gene loci of Indian ethnics.

Oral health is fundamental to general health and well being. Schools can provide a supportive environment for promoting oral health. School policies and education on health-related matters are imperative for the attainment of good oral health and control of related risk behaviors.This study was conducted to assess oral health-related knowledge, attitude, and practices among 12-year-old schoolchildren studying in rural areas of Panchkula, India. The ultimate goal was to implement an oral health-promotion program in this area.A total of 440 children (216 males and 224 females) from 12 schools were included in this study. All the participants were requested to complete a 13-question closed-ended questionnaire. The statistical significance of any difference between the two genders was determined using the Chi-square test.Only 25% of the participants said that they cleaned their teeth more than once in a day. Thirty-two percent did not clean their teeth daily. Over the preceding 1 year, 45.5% of the childern had had some problem with their teeth and/or gums, but only 35.9% visited the dentist. Among these children, 8.2% used tobacco in some form. Oral health-related knowledge of girls was significantly better than that of boys.Based upon the findings of the present study, the knowledge, attitude, and practices of the surveyed children with regard to oral health is poor. Hence, there is a need for regular oral health education of the children, as well as their parents and school teachers.
Department of Public Health Dentistry, Dr. HS Judge Institute of Dental Sciences and Hospital, Panjab University, Chandigarh (UT), India.
Indian journal of dental research : official publication of Indian Society for Dental Research
Oral health-related knowledge, attitude, and practices among 12-year-old schoolchildren studying in rural areas of Panchkula, India.

Research has shown that chemoprevention may be effective against the development of lung cancer. The purpose of the present study was to evaluate the effect of oral chemoprevention in a mouse model of tobacco carcinogen-induced lung tumor.A total of 60 A/J mice were randomized to a normal diet, a diet with low calcium, or a chemoprevention diet with acetylsalicylic acid, 1-α 25(0H)2-vitamin D3 and calcium. In addition to the diet, mice received carcinogens by oral gavage for ten weeks.The chemoprevention diet significantly reduced the number of animals with tumors [1 vs. 13, (p<0.001)] and the median number (range) of tumors [0 (0-1) vs. 1 (0-4), (p<0.001)] compared to controls. No signs of toxicity in relation to the diets were observed.The chemoprevention diet had a protective effect against tumor development in the mouse lungs.
Herlev Hospital - University of Copenhagen, Department of Surgery, Herlev Ringvej 75 - DK-2730 Herlev, Denmark. hcpommergaard@gmail.com.
Chemoprevention with acetylsalicylic acid, vitamin D and calcium reduces risk of carcinogen-induced lung tumors.

In 2003, we simultaneously quantified 27 metals by inductively coupled plasma-mass spectrometry (ICP-MS) in the whole blood, plasma and urine of 100 healthy volunteers. We again determined the metallic profile in whole blood and plasma during 2012. ICP-MS validated multielementary method was performed for metals in whole blood and plasma. Whole blood vanadium and chromium were quantified using ICP-MS collision cell technology. The aims of the study were to compare and assess any changes in this profile, particularly due to the environment. Healthy male/female staff volunteers (n = 106) with no professional exposure to metals, or medication containing lithium, strontium; or food supplements with trace elements and vitamins and with no metal prosthesis were included. Tobacco consumption and the number of dental amalgams were recorded. Our results demonstrated a blood lead level that had drastically decreased, i.e. reduced by half, during this period (12.5 versus 26.3 µg/L, P < 0.0001). Known differences were observed between males and females for copper and zinc; cadmium and lead were higher in smokers. Median plasmatic mercury, a specific test for dental amalgam exposure, did not significantly increase (0.38 versus 0.28 µg/L, P = 0.11). The ICP-MS metallic profile is a very practical concept that is useful for clinical, forensic and environmental toxicology, including industrial hygiene monitoring.
Laboratoire de Pharmacocinétique et de Toxicologie Cliniques, Groupe Hospitalier du Havre, Le Havre, France.
Metallic profile of whole blood and plasma in a series of 106 healthy volunteers.

The nicotine metabolites, cotinine and trans-3'-hydroxycotinine (3HC) are considered as superior biomarkers for identifying tobacco exposure. More importantly, the ratio of 3HC to cotinine is a good indicator to phenotype individuals for cytochrome P450 2A6 activity and to individualize pharmacotherapy for tobacco addiction. In this paper, a simple, robust and novel method based on surface-enhanced Raman spectroscopy coupled with thin-layer chromatography (TLC) was developed to directly quantify the biomarkers in human urine samples. This is the first time surface-enhanced Raman spectroscopy (SERS) was used to detect cotinine and 3HC in urine samples. The linear dynamic range for the detection of cotinine is from 40 nM to 8 μM while that of 3HC is from 1 μM to 15 μM. The detection limits are 10 nM and 0.2 μM for cotinine and 3HC, respectively. The proposed method was further validated by quantifying the concentration of both cotinine and 3HC in smokers' urine samples. This TLC-SERS method allows the direct detection of cotinine in the urine samples of both active and passive smokers and the detection of 3HC in smokers.
Department of Chemistry, University of South Florida, 4202 E. Fowler Ave CHE205, Tampa, FL 33620, USA.
Detection of tobacco-related biomarkers in urine samples by surface-enhanced Raman spectroscopy coupled with thin-layer chromatography.

Bladder cancer is a common urological malignancy with high recurrence rate, which may be reduced by chemoprevention. The aim was to evaluate chemoprevention in a mouse model of tobacco carcinogen-induced bladder tumors. A total of 60 A/J mice were randomized to normal diet, diet with low calcium, and diet with chemoprevention (acetyl salicylic acid, 1-alpha 25(OH)2-vitamin D3 and calcium). There were significantly fewer tumors (0 (0-0) vs. 0 (0-2), p = .045) and fewer animals with tumors (0/20 vs. 5/20, p = .045) in the chemoprevention group compared with controls. Thus, chemoprevention diet effectively reduced the tumor promoting effect of tobacco carcinogens in the mouse bladder.
Department of Surgery, Herlev Hospital, University of Copenhagen, Herlev, Denmark. hcpommergaard@gmail.com
Oral chemoprevention with acetyl salicylic Acid, vitamin D and calcium reduces the risk of tobacco carcinogen-induced bladder tumors in mice.

Nanocrystalline starch produced from the acid hydrolysis of gelatinized starch has been used for the first time to support palladium(II) ethylenediamine complex. The nanocrystalline starch supported Pd(II) complex was found to be an efficient and efficiently recycled catalyst for the Mizoroki-Heck reaction of furans and thiophenes with styrenes under mild reaction conditions.
Chemical Sciences Division, CSIR-Indian Institute of Petroleum, Dehradun-248005, India. suman@iip.res.in.
Dalton transactions (Cambridge, England : 2003)
Nanocrystalline starch grafted palladium(II) complex for the Mizoroki-Heck reaction.

The maintenance cytosine DNA methyltransferase DNMT1 and de novo methyltransferase DNMT3b cooperate to establish aberrant DNA methylation and chromatin complexes to repress gene transcription during cancer development. The expression of DNMT3b was constitutively increased 5-20-fold in hTERT/CDK4-immortalized human bronchial epithelial cells (HBECs) before treatment with low doses of tobacco carcinogens. Overexpression of DNMT3b increased and accelerated carcinogen-induced transformation. Genome-wide profiling of transformed HBECs identified 143 DNMT3b-target genes, many of which were transcriptionally regulated by the polycomb repressive complex 2 (PRC2) complex and silenced through aberrant methylation in non-small-cell lung cancer cell lines. Two genes studied in detail, MAL and OLIG2, were silenced during transformation, initially through enrichment for H3K27me3 and H3K9me2, commonly methylated in lung cancer, and exert tumor suppressor effects in vivo through modulating cancer-related pathways. Re-expression of MAL and OLIG2 to physiological levels dramatically reduced the growth of lung tumor xenografts. Our results identify a key role for DNMT3b in the earliest stages of initiation and provide a comprehensive catalog of genes targeted for silencing by this methyltransferase in non-small-cell lung cancer.
Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, NM, USA.
Global identification of genes targeted by DNMT3b for epigenetic silencing in lung cancer.

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), one of the most prevalent and procarcinogenic compounds in tobacco, is bioactivated by respiratory cytochrome P450 (CYP) 2A13, forming DNA adducts and initiating lung cancer. CYP2A13 inhibition offers a novel strategy for chemoprevention of tobacco-associated lung cancer.Twenty-four analogs of a 4-benzylmorpholine scaffold identified by high throughput screening were evaluated for binding and inhibition of both functional human CYP2A enzymes, CYP2A13 and the 94%-identical hepatic CYP2A6, whose inhibition is undesirable. Thus, selectivity is a major challenge in compound design.A key feature resulting in CYP2A13-selective binding and inhibition was substitution at the benzyl ortho position, with three analogs being >25-fold selective for CYP2A13 over CYP2A6.Two such analogs were negative for genetic and hERG toxicities and metabolically stable in human lung microsomes, but displayed rapid metabolism in human liver and in mouse and rat lung and liver microsomes, likely due to CYP2B-mediated degradation. A specialized knockout mouse mimicking the human lung demonstrates compound persistence in lung and provides an appropriate test model. Compound delivered by inhalation may be effective in the lung but rapidly cleared otherwise, limiting systemic exposure.
Department of Medicinal Chemistry, University of Kansas, 1251 Wescoe Hall Dr., Lawrence, Kansas 66045, USA.
Benzylmorpholine analogs as selective inhibitors of lung cytochrome P450 2A13 for the chemoprevention of lung cancer in tobacco users.

Tobacco-specific nitrosamines (TSNA) have implications in the pathogenesis of various lung diseases and conditions are prevalent even in non-smokers. N-nitrosonornicotine (NNN) and 4-(methyl nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are potent pulmonary carcinogens present in tobacco product and are mainly responsible for lung cancer. TSNA reacts with pulmonary surfactants, and alters the surfactant phospholipid. The present study was undertaken to investigate the in vitro exposure of rat lung tissue slices to NNK or NNN and to monitor the phospholipid alteration by [(32)P]orthophosphate labeling. Phospholipid content decreased significantly in the presence of either NNK or NNN with concentration and time dependent manner. Phosphatidylcholine (PC) is the main phospholipid of lung and significant reduction was observed in PC ∼61%, followed by phosphatidylglycerol (PG) with 100μM of NNK, whereas NNN treated tissues showed a reduction in phosphatidylserine (PS) ∼60% and PC at 250μM concentration. The phospholipase A2 assays and expression studies reveal that both compounds enhanced phospholipid hydrolysis, thereby reducing the phospholipid content. Collectively, our data demonstrated that both NNK and NNN significantly influenced the surfactant phospholipid level by enhanced phospholipase A2 activity.
Copyright © 2014 Elsevier Ltd. All rights reserved.
Biomembrane Lab, Department of Biochemistry, School of Life Sciences, Bharathidasan University, Tiruchirappalli, India.
Biochemistry Department, Indian Institute of Science, Bangalore 560012, India.
Biomembrane Lab, Department of Biochemistry, School of Life Sciences, Bharathidasan University, Tiruchirappalli, India. Electronic address: vasanthibch@gmail.com.
Toxicology in vitro : an international journal published in association with BIBRA
In vitro exposure of tobacco specific nitrosamines decreases the rat lung phospholipids by enhanced phospholipase A2 activity.

Genome integrity is essential for normal cellular functions and cell survival. Its instability can cause genetic aberrations and is considered as a hallmark of most cancers. To investigate the carcinogenesis process induced by tobacco-specific carcinogen NNK, we studied the dynamic changes of two important protectors of genome integrity, p53 and MMR system, in malignant transformation of human bronchial epithelial cells after NNK exposure. Our results showed that the expression of MLH1, one of the important MMR proteins, was decreased early and maintained the downregulation during the transformation in a histone modification involved and DNA methylation-independent manner. Another MMR protein PMS2 also displayed a declined expression while being in a later stage of transformation. Moreover, we conducted p53 mutation analysis and revealed a mutation at codon 273 which led to the replacement of arginine by histidine. With the mutation, DNA damage-induced activation of p53 was significantly impaired. We further reintroduced the wild-type p53 into the transformed cells, and the malignant proliferation can be abrogated by inducing cell cycle arrest and apoptosis. These findings indicate that p53 and MMR system play an important role in the initiation and progression of NNK-induced transformation, and p53 could be a potential therapeutic target for tobacco-related cancers.
Department of Clinical Medicine, Zhejiang Medical College, Hangzhou 310053, China.
Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou 310058, China.
Department of Pulmonology, Sir Run Run Shaw Hospital, Hangzhou 310016, China.
Involvement of p53 mutation and mismatch repair proteins dysregulation in NNK-induced malignant transformation of human bronchial epithelial cells.

An efficient photo-induced reduction of CO2 using magnetically separable Ru-CoPc@TiO2@SiO2@Fe3O4 as a heterogeneous catalyst in which CoPc and Ru(bpy)2phene complexes were attached to a solid support via covalent attachment under visible light is described. The as-synthesized catalyst was characterized by a series of techniques including FTIR, UV-Vis, XRD, SEM, TEM, etc. and subsequently tested for the photocatalytic reduction of carbon dioxide using triethylamine as a sacrificial donor and water as a reaction medium. The developed photocatalyst exhibited a significantly higher catalytic activity to give a methanol yield of 2570.78 μmol per g cat after 48 h.
Chemical Sciences Division, CSIR-Indian Institute of Petroleum, Mohkampur, Dehradun-248005, India. suman@iip.res.in.
Photo-induced reduction of CO2 using a magnetically separable Ru-CoPc@TiO2@SiO2@Fe3O4 catalyst under visible light irradiation.

To characterize the extent to which state and national professional pharmacy associations have implemented formal policies addressing the sale of tobacco and alcohol products in community pharmacies.To determine existence of tobacco and alcohol policies, national professional pharmacy associations (n = 10) and state-level pharmacy associations (n = 86) affiliated with the American Pharmacists Association (APhA) and/or the American Society of Health-System Pharmacists (ASHP) were contacted via telephone and/or e-mail, and a search of the association websites was conducted.Of 95 responding associations (99%), 14% have a formal policy opposing the sale of tobacco products in pharmacies and 5% have a formal policy opposing the sale of alcohol in pharmacies. Of the associations representing major tobacco-producing states, 40% have a formal policy against tobacco sales in pharmacies, significantly more than the 8% of non-tobacco state associations with such policies.Among national professional pharmacy associations, only APhA and ASHP have formal policy statements opposing the sale of both tobacco and alcohol in pharmacies. Most state-level professional pharmacy associations affiliated with these two national organizations have no formal policy statement or position.
Journal of the American Pharmacists Association : JAPhA
Tobacco and alcohol sales in community pharmacies: policy statements from U.S. professional pharmacy associations.

Oral cancer in the form of squamous cell carcinoma (OSCC) is typically detected in advanced stages when treatment is complex and may not be curative. The need for surgical biopsy may contribute to delays in diagnosis and impede early detection. Multiple studies of RNA from surgically obtained tumor samples have revealed many genes differentially expressed with this disease. We sought to determine whether the identified mRNAs could be used as markers by a non-invasive detection system for OSCC using RNA from brush cytology.Levels of mRNAs from 21 genes known to be differentially expressed in head and neck squamous cell carcinoma surgical samples, compared with controls, were shown to be quantifiable in oral brush cytology samples. These mRNAs were quantified in a training set of 14 tumor and 20 non-malignant brush cytology samples from tobacco/betel nut users. With the measurement of two additional mRNAs and analysis using support vector machines algorithm for class prediction of these cancers was produced.This OSCC classifier based on the levels of 5 mRNAs in RNA from brush cytology initially showed 0.93 sensitivity and 0.91 specificity in differentiating OSCC from benign oral mucosal lesions based on leave-one-out cross-validation. When used on a test set of 19 samples from 6 OSCCs and 13 non-malignant oral lesions, we found misclassification of only one OSCC and one benign lesion.This shows the promise of using RNA from brush cytology for early OSCC detection and the potential for clinical usage of this non-invasive classifier.
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Department of Oral and Maxillofacial Surgery, College of Dentistry, University of Illinois at Chicago, Chicago, IL, USA.
Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology
A prototype tobacco-associated oral squamous cell carcinoma classifier using RNA from brush cytology.

Small and detrimental, albeit inconsistent, effects of prenatal cocaine exposure (PCE) during early childhood have been reported. The teratogenic effects of prenatal alcohol (PAE) and tobacco exposure (PTE) on neurobehavior are more firmly established than PCE. We tested if co-exposure to all three drugs could be related to greater differences in brain structure than exposure to cocaine alone. Participants (n=42, PCE=27; age range=14-16 years) received an executive function battery prior to a T1-weighted 3T structural MRI scan. Cortical thickness was measured using FreeSurfer (v5.1). Fetal drug exposure was quantified through maternal self-reports usage during pregnancy. Using general linear modeling, we found no main effects of PCE on cortical thickness, but significant main effects of PAE and PTE in superior and medial frontal regions, after co-varying for the effects of age, sex, and each drug of exposure. Significant alcohol-by-tobacco interactions, and significant cocaine-by-alcohol interactions on cortical thickness in medial parietal and temporal regions were also observed. Poly-drug exposure and cognitive function also showed significant interactions with cortical thickness: lower cortical thickness was associated with better performance in PCE-exposed adolescents. Results suggest that although children with PCE have subtle but persistent brain cortical differences until mid-to-late adolescence.
Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
Department of Pediatrics, Keck School of Medicine, University of Southern California, Children's Hospital of Los Angeles, Los Angeles, CA, United States.
Department of Pediatrics, University of Florida, Gainesville, FL, United States.
Department of Pediatrics, Keck School of Medicine, University of Southern California, Children's Hospital of Los Angeles, Los Angeles, CA, United States; Department of Neurology, University of California at Los Angeles, Los Angeles, CA, United States. Electronic address: esowell@chla.usc.edu.
Executive function and cortical thickness in youths prenatally exposed to cocaine, alcohol and tobacco.

In the past decade, the number of epidemiological publications addressing environmental chemical exposures and autism has grown tremendously. These studies are important because it is now understood that environmental factors play a larger role in causing autism than previously thought and because they address modifiable risk factors that may open up avenues for the primary prevention of the disability associated with autism. In this review, we covered studies of autism and estimates of exposure to tobacco, air pollutants, volatile organic compounds and solvents, metals (from air, occupation, diet, dental amalgams, and thimerosal-containing vaccines), pesticides, and organic endocrine-disrupting compounds such as flame retardants, non-stick chemicals, phthalates, and bisphenol A. We included studies that had individual-level data on autism, exposure measures pertaining to pregnancy or the 1st year of life, valid comparison groups, control for confounders, and adequate sample sizes. Despite the inherent error in the measurement of many of these environmental exposures, which is likely to attenuate observed associations, some environmental exposures showed associations with autism, especially traffic-related air pollutants, some metals, and several pesticides, with suggestive trends for some volatile organic compounds (e.g., methylene chloride, trichloroethylene, and styrene) and phthalates. Whether any of these play a causal role requires further study. Given the limited scope of these publications, other environmental chemicals cannot be ruled out, but have not yet been adequately studied. Future research that addresses these and additional environmental chemicals, including their most common routes of exposures, with accurate exposure measurement pertaining to several developmental windows, is essential to guide efforts for the prevention of the neurodevelopmental damage that manifests in autism symptoms.
Copyright © 2014 Mosby, Inc. All rights reserved.
Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, WI.
Department of Public Health Sciences, University of California Davis School of Medicine, Davis, CA; Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California Davis, Sacramento, CA.
Current problems in pediatric and adolescent health care
Curr Probl Pediatr Adolesc Health Care. 2014-11;44(10):277-318.
Environmental chemical exposures and autism spectrum disorders: a review of the epidemiological evidence.

Recent studies have challenged the idea that illegal substances are necessarily associated with more harm than those that are legal. This study investigates perceived drug harm among students at the University of Oslo (UO) and at a smaller university located on Norway's coast in a more conservative and religious region, called 'Coastal University' (CU).This study consisted of surveys (n=458) about perceived physical harm, mental health conditions, dependence, injuries and social consequences that may be associated with the use of tobacco, alcohol and cannabis. Information about substance use was also collected. Analyses of variance and multiple regression analyses were used to examine whether harm ratings differed for different drugs, whether drug type, gender and university site interacted in predicting harm ratings, and what role the participants' own substance use played in their harm ratings.UO students rated cannabis as overall less harmful than alcohol, while the opposite was true for CU students. Tobacco received the highest physical harm score. Alcohol was rated as most harmful with regard to injuries; cannabis was rated as most harmful with regard to mental health consequences. Use of the substance in question was associated with a reduced harm rating. This was particularly true for cannabis.Norwegian students rate the harm of substances differently from previous reports from the Norwegian general population. Most importantly, their relative ratings of cannabis harm were lower. However, the pattern was most evident among students from the urban Oslo area.
© 2015 the Nordic Societies of Public Health.
Department of Sociology and Human Geography, University of Oslo, Norway willy.pedersen@sosgeo.uio.no.
Department of Psychology, University of Oslo and Norwegian Social Research (NOVA), Norway.
Which substance is most dangerous? Perceived harm ratings among students in urban and rural Norway.

Oral leukoplakia is a morphological alteration of tissue that is an early indicator for malignancy. Tenascin (TN) is a large hexameric extracellular matrix (ECM) protein with anti-adhesive properties that fosters cell migration during development, wound healing and tissue remodeling; it is present in small amounts in adult tissues. Overexpression of TN in a pathological condition may be either a cause or a consequence of the disease. We evaluated the efficacy of TN for early prediction of tobacco-associated oral cancers. We studied retrospectively 95 cases of oral leukoplakia, including mild, moderate and severe cases, using immunohistochemistry for TN. We evaluated the intensity, area and pattern of TN expression. Greater intensity and area of TN expression was observed in mild and severe dysplasia than in moderate dysplasia. Most cases showed a reticular pattern of expression, especially in mild and moderate dysplasia; a fibrillar pattern was more evident in severe dysplasia. We also observed homogeneous expression pattern in some cases. TN is a marker for dysplastic changes in epithelium and its expression may be helpful for predicting the malignancy potential of tobacco-associated oral leukoplakia.
a Department of Oral Pathology and Microbiology , KLE VK Institute of Dental Sciences and Hospital , Belgaum, Karnataka , India.
b Basic Science Research Laboratory, KLE VK Institute of Dental Sciences and Hospital , Belgaum, Karnataka , India.
Biotechnic & histochemistry : official publication of the Biological Stain Commission
Immunoexpression of tenascin as a predictor of the malignancy potential of oral leukoplakia associated with a tobacco habit.

Parkinson's disease (PD) is a neurodegenerative disease characterized by the loss of mainly the nigrostriatal dopaminergic neurons, which leads to motor dysfunction. Although, most of the drugs are currently used for symptomatic treatment, there are at least three FDA-approved drugs for the treatment of PD that have been suggested preclinically to have neuroprotective effects. Among these drugs are monoamine oxidase (MAO) type B inhibitors such as selegiline and rasagiline, and non-ergot derivative dopamine agonist, pramipexole. In this review article, we focused on the potential uses of non-selective reversible MAO inhibitor, 2,3,6-trimethyl-1,4-naphthoquinone, from flue-cured tobacco leaves extract and two β- carboline alkaloids (harman and norharman) as potent, reversible and non-selective MAO inhibitors for the treatment of PD. In addition, we discussed the potential uses of farnesol as a potent inhibitor of MAO-B and farnesylacetone as a less potent selective MAO-B inhibitor. Furthermore, adducts of 1,2,3,4-tetrahydroisoquinoline have shown to have competitive inhibitory effects for both MAO-A and MAO-B. These inhibitors have potential neuroprotective effects, which might be mediated at least through nerve growth factor, neurotrophin 3, brain derived neurotrophic factor, and glial-cell-line-derived neurotrophic factor. We suggest here the neuroprotective implication of extracted MAO inhibitors from smoke tobacco; however, it is important to note that there are several existing compounds in tobacco smoke that have toxic effects in the brain, these include and not limited to the induction of neuropathological features observed in individuals suffering from Alzheimer's disease and dementia.
University of Toledo, College of Pharmacy and Pharmaceutical Sciences, Department of Pharmacology, Health Science Campus, 3000 Arlington Avenue, HEB282G, Toledo, OH 43614. USA. youssef.sari@utoledo.edu.
Qatar University, College of Pharmacy, Pharmaceutical Sciences Section, Doha, Qatar. akhalil@qu.edu.qa.
CNS & neurological disorders drug targets
CNS Neurol Disord Drug Targets. 2015;14(6):777-85.
Monoamine Oxidase Inhibitors Extracted from Tobacco Smoke as Neuroprotective Factors for Potential Treatment of Parkinson's Disease.

The present paper describes the results of a rating study performed by a group of European Union (EU) drug experts using the multi-criteria decision analysis model for evaluating drug harms.Forty drug experts from throughout the EU scored 20 drugs on 16 harm criteria. The expert group also assessed criteria weights that would apply, on average, across the EU. Weighted averages of the scores provided a single, overall weighted harm score (range: 0-100) for each drug.Alcohol, heroin and crack emerged as the most harmful drugs (overall weighted harm score 72, 55 and 50, respectively). The remaining drugs had an overall weighted harm score of 38 or less, making them much less harmful than alcohol. The overall weighted harm scores of the EU experts correlated well with those previously given by the UK panel.The outcome of this study shows that the previous national rankings based on the relative harms of different drugs are endorsed throughout the EU. The results indicates that EU and national drug policy measures should focus on drugs with the highest overall harm, including alcohol and tobacco, whereas drugs such as cannabis and ecstasy should be given lower priority including a lower legal classification.
Department of Psychiatry, University of Amsterdam, Amsterdam, the Netherlands jan.van.amsterdam@amc.uva.nl.
Centre for Neuropychopharmacology, Imperial College London, London, UK.
Department of Management, London School of Economics and Political Science, London, UK.
Department of Psychiatry, University of Amsterdam, Amsterdam, the Netherlands Amsterdam Institute for Addiction Research, Academic Medical Centre, Amsterdam, the Netherlands.

The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK, 1) is a potent lung carcinogen in laboratory animals and is believed to play a key role in the development of lung cancer in smokers. Metabolic activation of NNK leads to the formation of pyridyloxobutyl DNA adducts, a critical step in its mechanism of carcinogenesis. In addition to DNA nucleobase adducts, DNA phosphate adducts can be formed by pyridyloxobutylation of the oxygen atoms of the internucleotidic phosphodiester linkages. We report the use of a liquid chromatography-nanoelectrospray ionization-high-resolution tandem mass spectrometry technique to characterize 30 novel pyridyloxobutyl DNA phosphate adducts in calf thymus DNA (CT-DNA) treated with 4-(acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone (NNKOAc, 2), a regiochemically activated form of NNK. A (15)N3-labeled internal standard was synthesized for one of the most abundant phosphate adducts, dCp[4-oxo-4-(3-pyridyl)butyl]dC (CpopC), and this standard was used to quantify CpopC and to estimate the levels of other adducts in the NNKOAc-treated CT-DNA. Formation of DNA phosphate adducts by NNK in vivo was further investigated in rats treated with NNK acutely (0.1 mmol/kg once daily for 4 days by subcutaneous injection) and chronically (5 ppm in drinking water for 10, 30, 50, and 70 weeks). This study provides the first comprehensive structural identification and quantitation of a panel of DNA phosphate adducts of a structurally complex carcinogen and chemical support for future mechanistic studies of tobacco carcinogenesis in humans.
Masonic Cancer Center, University of Minnesota , 2231 6th St SE, Minneapolis, Minnesota 55455, United States.
Comprehensive High-Resolution Mass Spectrometric Analysis of DNA Phosphate Adducts Formed by the Tobacco-Specific Lung Carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone.

Part of the large group of nutritional and toxic optic neuropathies, tobacco-alcohol optic neuropathy is a disease often underdiagnosed or detected at a stage when the full recovery of vision is not possible. This article summarizes its signs and symptoms, describes the pathophysiological processes involved and provides the necessary information for diagnosis and treatment of the entity previously known as tobacco-alcohol amblyopia, reporting in the end, a challenging case along with its findings.
Nicolae Malaxa Clinical Hospital, Bucharest.
Carol Davila University of Medicine and Pharmacy, Bucharest.
Clinical Ophthalmological Emergency Hospital.
Tobacco-alcohol optic neuropathy--clinical challenges in diagnosis.

Chitosan coated magnetic nanoparticles were synthesized and used as a support for the immobilization of the cobalt(II) acetylacetonate complex [Co(acac)2] and quaternary triphenylphosphonium bromide [P(+)Ph3Br(-)] targeting -NH2 and -OH moieties located on the surface of chitosan. The synthesized material was used as a catalyst for one pot direct synthesis of cyclic carbonates from olefins via an oxidative carboxylation approach with carbon dioxide using isobutyraldehyde as the sacrificial reductant and molecular oxygen as the oxidant. After the reaction, the catalyst was recovered by applying an external magnet and reused for several runs without significant loss in catalytic activity and no leaching was observed during this course.
Chemical Sciences Division, CSIR-Indian Institute of Petroleum, Dehradun 248005, India. suman@iip.res.in.
Dual catalysis with magnetic chitosan: direct synthesis of cyclic carbonates from olefins with carbon dioxide using isobutyraldehyde as the sacrificial reductant.

Alcohol, Tobacco, Triggers, and Headache Disorders.

Understanding behavioral resilience among at-risk adolescents may guide public policy decisions and future programs. We examined factors predicting behavioral resilience following intrauterine substance exposure in a prospective longitudinal birth-cohort study of 136 early adolescents (ages 12.4-15.9 years) at risk for poor behavioral outcomes. We defined behavioral resilience as a composite measure of lack of early substance use initiation (before age 14), lack of risky sexual behavior, or lack of delinquency. Intrauterine substance exposures included in this analysis were cocaine, tobacco, alcohol, and marijuana. We recruited participants from Boston Medical Center as mother-infant dyads between 1990 and 1993. The majority of the sample was African American/Caribbean (88%) and 49% female. In bivariate analyses, none and lower intrauterine cocaine exposure level predicted resilience compared with higher cocaine exposure, but this effect was not found in an adjusted model. Instead, strict caregiver supervision (adjusted odds ratio [AOR] = 6.02, 95% confidence interval (CI) [1.90, 19.00], p = .002), lower violence exposure (AOR = 4.07, 95% CI [1.77, 9.38], p < .001), and absence of intrauterine tobacco exposure (AOR = 3.71, 95% CI [1.28, 10.74], p = .02) predicted behavioral resilience. In conclusion, caregiver supervision in early adolescence, lower violence exposure in childhood, and lack of intrauterine tobacco exposure predicted behavioral resilience among a cohort of early adolescents with significant social and environmental risk. Future interventions should work to enhance parental supervision as a way to mitigate the effects of adversity on high-risk groups of adolescents. (PsycINFO Database Record
Clinical Addiction Research and Education Unit, Boston Medical Center.
Department of Family Medicine, Boston Medical Center.
Department of Pediatrics, Boston Medical Center.
Department of Biostatistics, Boston University School of Public Health.
Data Coordinating Center, Boston University School of Public Health.
Psychology of addictive behaviors : journal of the Society of Psychologists in Addictive Behaviors
Prenatal substance exposure: What predicts behavioral resilience by early adolescence?

Among smokers, the presence of tobacco stains on fingers has recently been associated with a high prevalence of tobacco related conditions and alcohol abuse.we aimed to explore tobacco stains as a marker of death and hospital readmission.Seventy-three smokers presenting tobacco-tar staining on their fingers and 70 control smokers were followed during a median of 5.5 years in a retrospective cohort study. We used the Kaplan-Meier survival analysis and the log-rank test to compare mortality and hospital readmission rates among smokers with and smokers without tobacco stains. Multivariable Cox models were used to adjust for confounding factors: age, gender, pack-year unit smoked, cancer, harmful alcohol use and diabetes. The number of hospital admissions was compared through a negative binomial regression and adjusted for the follow-up time, diabetes, and alcohol use.Forty-three patients with tobacco-stained fingers died compared to 26 control smokers (HR 1.6; 95%CI: 1.0 to 2.7; p 0.048). The association was not statistically significant after adjustment. Patients with tobacco-stained fingers needed a readmission earlier than smokers without stains (HR 2.1; 95%CI: 1.4 to 3.1; p<0.001), and more often (incidence rate ratio (IRR) 1.6; 95%CI: 1.1 to 2.1). Associations between stains and the first hospital readmission (HR 1.6; 95%CI: 1.0 to 2.5), and number of readmissions (IRR 1.5; 95%CI: 1.1 to 2.1) persisted after adjustment for confounding factors.Compared to other smokers, those presenting tobacco-stained fingers have a high unadjusted mortality rate and need early and frequent hospital readmission even when controlling for confounders.
Department of Internal Medicine, Hôpital neuchâtelois, 2300, La Chaux-de-Fonds, Switzerland; Department of Internal medicine geriatrics and rehabilitation, Geneva University Hospitals (HUG), Gabrielle-Perret-Gentil 4, CH-1205, Geneva, Switzerland.
Department of Internal Medicine, Hôpital neuchâtelois, 2300, La Chaux-de-Fonds, Switzerland.
Department of Internal Medicine, Centre Hospitalier de Bienne, 2501, Bienne, Switzerland.
Tobacco Stained Fingers and Its Association with Death and Hospital Admission: A Retrospective Cohort Study.

Oral tongue squamous cell carcinoma (OTSCC) is the most common oral cancer subtype with a maximum propensity for regional spread. Our objective was to study if p53 expression might have any correlation with aggressive patterns of invasion within oral tongue cancers as well as with the histologically identified degree of oral tongue dysplasia. p53 immunoexpression was studied using immunohistochemistry in early staged OTSCCs (n=155), oral tongue dysplasias, (n=29) and oral tongue normal specimens (n=10) and evaluated for correlations with histological and clinicopathological parameters. Our study (n=194) showed a pattern of p53 expression increasing with different grades of tongue dysplasia to different grades of invasive OTSCC (p=0.000). Among the OTSCC tumours, positive p53 expression was seen in 43.2% (67/155) and a higher p53 labelling index was significantly associated with increased Bryne's grade of the tumour invasive front (p=0.039) and increased tumour depth (p=0.018). Among the OTSCC patients with tobacco habits, (n=91), a higher p53 labelling index was significantly associated with increased risk of local recurrence (p=0.025) and with lymphovascular space involvement (p=0.014). Evaluation of p53 through varying degrees of dysplasia to oral tongue cancer indicates that p53 expression is linked to aggressive features of oral tongue cancers and tongue precancers entailing a closer monitoring in positive cases. Among the OTSCCs, p53 expression is associated with tumour aggressiveness correlating with increased grading of invasive tumour front and tumour depth.
Department of Preventive Oncology, Cancer Institute (WIA), Adyar, India E-mail : vijiciwia@gmail.com.
Asian Pac J Cancer Prev. 2016;17(1):189-95.
p53 Expression Helps Identify High Risk Oral Tongue Pre- malignant Lesions and Correlates with Patterns of Invasive Tumour Front and Tumour Depth in Oral Tongue Squamous Cell Carcinoma Cases.

Nicotine is the most abundant alkaloid in tobacco accounting for 95% of the alkaloid content. There are also several minor tobacco alkaloids; among these are nornicotine, anatabine, and anabasine. We developed and applied a 96 well plate-based capillary LC-tandem mass spectrometry method for the analysis of nornicotine, anatabine, and anabasine in urine. The method was validated with regard to accuracy and precision. Anabasine was quantifiable to low levels with a limit of quantitation (LOQ) of 0.2 ng/mL even when nicotine, which is isobaric, is present at concentrations >2500-fold higher than anabasine. This attribute of the method is important since anatabine and anabasine in urine have been proposed as biomarkers of tobacco use for individuals using nicotine replacement therapies. In the present study, we analyzed the three minor tobacco alkaloids in urine from 827 smokers with a wide range of tobacco exposures. Nornicotine (LOQ 0.6 ng/mL) was detected in all samples, and anatabine (LOQ, 0.15 ng/mL) and anabasine were detected in 97.7% of the samples. The median urinary concentrations of nornicotine, anatabine, and anabasine were 98.9, 4.02, and 5.53 ng/mL. Total nicotine equivalents (TNE) were well correlated with anatabine (r(2) = 0.714) and anabasine (r(2) = 0.760). TNE was most highly correlated with nornicotine, which is also a metabolite of nicotine. Urine samples from a subset of subjects (n = 110) were analyzed for the presence of glucuronide conjugates by quantifying any increase in anatabine and anabasine concentrations after β-glucuronidase treatment. The median ratio of the glucuronidated to free anatabine was 0.74 (range, 0.1 to 10.9), and the median ratio of glucuronidated to free anabasine was 0.3 (range, 0.1 to 2.9). To our knowledge, this is the largest population of smokers for whom the urinary concentrations of these three tobacco alkaloids has been reported.
Department of Biochemistry Molecular Biology and Biophysics and Masonic Cancer Center, University of Minnesota , Minneapolis, Minnesota 55455, United States.
Department of Psychology, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.
Masonic Cancer Center and Department of Psychiatry, University of Minnesota , Minneapolis, Minnesota 55455, United States.
Quantitation of the Minor Tobacco Alkaloids Nornicotine, Anatabine, and Anabasine in Smokers' Urine by High Throughput Liquid Chromatography-Mass Spectrometry.

National Drug Dependence Treatment Centre, All India Institute of Medical Sciences, New Delhi 110 029, India.
Putting tobacco harm reduction in perspective: is it a viable alternative?

Stellenbosch University/University of Cape Town Medical Research Council Unit on Anxiety and Stress Disorders, Department of Psychiatry, Stellenbosch University, Cape Town, South Africa.
Division of Developmental Paediatrics, Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital and University of Cape Town, Cape Town, South Africa.
Refining the Understanding of the Effects of Prenatal Methamphetamine and Tobacco Exposure on the Developing Brain.

N'-Nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are carcinogenic tobacco-specific nitrosamines believed to play a vital role in the initiation of tobacco-related cancers. For their carcinogenicities to be exhibited, both NNN and NNK must be metabolically activated by cytochrome P450s, specifically P450 2A6 and P450 2A13, respectively. Prior research has focused on α-hydroxylation, which leads to the formation of several DNA adducts that have been identified and quantified in vivo. However, some studies indicate that P450s can retain substrates within their active sites and perform processive oxidation. For nitrosamines, this would oxidize the highly unstable α-hydroxynitrosamines to potentially more stable nitrosamides, which could also alkylate DNA. Thus, we hypothesized that both NNN and NNK are processively oxidized in vitro to nitrosamides by P450 2A6 and P450 2A13, respectively. To test this hypothesis, we synthesized the NNN- and NNK-derived nitrosamides, determined their half-lives at pH 7.4 and 37 °C, and monitored for nitrosamide formation in an in vitro P450 system with product analysis by LC/NSI+-HRMS/MS. Half-lives of the nitrosamides were determined by HPLC-UV and ranged from 7-35 min, which is more than 40 times longer than the corresponding α-hydroxynitrosamines. Incubation of NNN in the P450 2A6 system resulted in the formation of the nitrosamide N'-nitrosonorcotinine (NNC) at low levels. Similarly, the nitrosamide 4-(methylnitrosamino)-1-(3-pyridyl)-1,4-butanedione (CH2-oxo-NNK) was detected in low amounts in the incubation of NNK with the P450 2A13 system. The other possible NNK-derived nitrosamide, 4-(nitrosoformamido)-1-(3-pyridyl)-1-butanone (CH3-oxo-NNK), was not observed in the P450 2A13 reactions. CH2-oxo-NNK readily formed O6meGua in reactions with dGuo and calf thymus DNA. These results demonstrate that NNC and CH2-oxo-NNK are novel metabolites of NNN and NNK, respectively. Though low-forming, their increased stability may allow for mutagenic DNA damage in vivo. More broadly, this study provides the first account of a cytochrome P450-mediated conversion of nitrosamines to nitrosamides, which warrants further studies to determine how general this phenomenon is in nitrosamine metabolism.
Masonic Cancer Center, University of Minnesota , 2231 Sixth Street SE, 2-210 CCRB, Minneapolis, Minnesota 55455, United States.Department of Pharmacology, University of Minnesota Medical School , 321 Church Street SE, 6-120 Jackson Hall, Minneapolis, Minnesota 55455, United States.
Masonic Cancer Center, University of Minnesota , 2231 Sixth Street SE, 2-210 CCRB, Minneapolis, Minnesota 55455, United States.
Evaluation of Nitrosamide Formation in the Cytochrome P450-Mediated Metabolism of Tobacco-Specific Nitrosamines.

Advanced persistent threats (APT) combine a variety of different attack forms ranging from social engineering to technical exploits. The diversity and usual stealthiness of APT turns them into a central problem of contemporary practical system security, since information on attacks, the current system status or the attacker's incentives is often vague, uncertain and in many cases even unavailable. Game theory is a natural approach to model the conflict between the attacker and the defender, and this work investigates a generalized class of matrix games as a risk mitigation tool for an advanced persistent threat (APT) defense. Unlike standard game and decision theory, our model is tailored to capture and handle the full uncertainty that is immanent to APTs, such as disagreement among qualitative expert risk assessments, unknown adversarial incentives and uncertainty about the current system state (in terms of how deeply the attacker may have penetrated into the system's protective shells already). Practically, game-theoretic APT models can be derived straightforwardly from topological vulnerability analysis, together with risk assessments as they are done in common risk management standards like the ISO 31000 family. Theoretically, these models come with different properties than classical game theoretic models, whose technical solution presented in this work may be of independent interest.
Universität Klagenfurt, Institute of Applied Informatics, Klagenfurt, Austria.
Austrian Institute of Technology, Safety & Security Department, Klagenfurt, Austria.
Defending Against Advanced Persistent Threats Using Game-Theory.

Prenatal psychoactive substance exposure has significant impact on neonatal health and child development and the development of reliable biomarkers is critical. Meconium presents several advantages for detecting prenatal exposure to psychoactive substances, as it is easy to collect and provides a broad time frame of exposure (third trimester). The aim of our study was to compare the prevalence of alcohol, tobacco and/or cannabis use during the third trimester of pregnancy (using maternal self-reports) with the results of meconium testing of their metabolites in newborns (cotinine, ethyl-glucuronide (EtG) and cannabinoid metabolites). Among all deliveries (993) that occurred in all maternities in Rouen (Normandy) during a defined time period (5 consecutive weeks in August, 2010 and August, 2011), 724 mothers were included and 645 meconium samples were collected. Maternal self-reports, using the Addiction Severity Index (5th edition), and meconium samples were collected within 72 h of delivery. Cotinine detection appears highly correlated to maternal self-reports (Kappa value: 0.79; [95%CI: 0.73-0.85]). Moreover, detection in meconium seems more accurate in the prediction of neonatal consequences of prenatal tobacco exposure as compared to maternal self-reports. In contrast, we have found a lower concordance between maternal self-reports and meconium testing for EtG and cannabinoid metabolites (Kappa value: 0.13; [95%CI: 0.04-0.22] and: 0.30; [95%CI: -0.03-0.63], respectively); however the total number of EtG- and cannabinoid-positive meconium samples was small. Interestingly, meconium samples with the highest levels of EtG mainly corresponded to negative maternal self-reports. Fetal exposure to alcohol, tobacco or cannabis may also considerably differ as displayed in our pairs of dizygotic twins. Finally, a polyconsumption of these psychoactive substances was not frequently observed according to meconium testing. In conclusion, cotinine detection appears as a valuable meconium biomarker. EtG measurement in meconium samples seems interesting if there is any risk of high fetal exposure, whereas assessment of prenatal cannabis exposure, using meconium testing, needs to be improved.
Copyright © 2017 Elsevier Ltd. All rights reserved.
Department of Addictology, Ramsay- General de Santé, SSR Petit Colmoulins, Harfleur, France; University Hospital Cochin (site Tarnier), University Sorbonne Paris-Cité (Paris V), Faculty of Medicine Paris Descartes, INSERM U894, Centre Psychiatry and Neurosciences, Paris, France. Electronic address: sandrine.lamy74@gmail.com.
CHU Lille, Service de Toxicologie-Génopathies, F-59000 Lille, France. Electronic address: benjamin.hennart@chru-lille.fr.
Department of Biostatistics, University Hospital Rouen, Centre d'Investigation Clinique et de Ressources Biologiques, INSERM CIC-CRB, 1404 Rouen, France. Electronic address: Estelle.Houivet@chu-rouen.fr.
Laboratoire de Pharmacologie, Toxicologie et Pharmacovigilance, Hôpital Dupuytren, CHU de Limoges, France. Electronic address: sylvain.dulaurent@unilim.fr.
Department of Psychiatry, Faculty of Medicine, Federal University of Minas Gerais, Brazil. Electronic address: heloise.delavenne@gmail.com.
Department of Biostatistics, University Hospital Rouen, Centre d'Investigation Clinique et de Ressources Biologiques, INSERM CIC-CRB, 1404 Rouen, France. Electronic address: Jacques.Benichou@chu-rouen.fr.
CHU Lille, Service de Toxicologie-Génopathies, F-59000 Lille, France; Univ.Lille, EA 4483-IMPECS- IMPact de l'Environnement Chimique sur la Santé humaine, F-59000 Lille, France. Electronic address: delphine.allorge@chru-lille.fr.
Department of Neonatal Medicine-Neuropediatrics, Rouen University Hospital and INSERM U 1245, Neovasc Team, Perinatal neurological handicap and Neuroprotection, Institute of Biomedical Research and Innovation, School of Medicine, Normandy University, France. Electronic address: stephane.marret@chu-rouen.fr.
University Hospital Cochin (site Tarnier), University Sorbonne Paris-Cité (Paris V), Faculty of Medicine Paris Descartes, INSERM U894, Centre Psychiatry and Neurosciences, Paris, France. Electronic address: florence.thibaut@aphp.fr.
Assessment of tobacco, alcohol and cannabinoid metabolites in 645 meconium samples of newborns compared to maternal self-reports.

Use of narcotic or recreational drugs has been associated with adverse pregnancy outcomes such as preterm delivery. However, the associations might be confounded by other factors related to high-risk behaviours. This is the first study to investigate the association between traditional opium use during pregnancy and risk of preterm delivery.We performed a population-based cohort study in the rural areas of the Golestan province, Iran between 2008 and 2010. We randomly selected 920 women who used (usually smoked) opium during pregnancy and 920 women who did not. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the associations between the opium use during pregnancy and preterm delivery and adjustment was made for potential confounding factors. This study shows compared with non-use of opium and tobacco, use of only opium during pregnancy was associated with an increased risk of preterm delivery (OR = 1.56; 95% CI 1.05-2.32), and the risk was more than two-fold increased among dual users of opium and tobacco (OR = 2.31; 95% CI 1.37-3.90). We observed that opium use only was associated with a doubled risk for preterm caesarean delivery (OR = 2.05; 95% CI 1.10-3.82) but not for preterm vaginal delivery (OR = 1.25; 95% CI 0.75-2.07). Dual use of opium and tobacco was associated with a substantially increased risk of vaginal preterm delivery (OR = 2.58; 95% CI 1.41-4.71).Opium use during pregnancy among non-tobacco smokers is associated with an increased risk of preterm caesarean delivery, indicating an increased risk of a compromised foetus before or during labour. Women who use both opium and smoked during pregnancy have an increased risk of preterm vaginal delivery, indicating an increased risk of spontaneous preterm delivery.
Clinical Epidemiology Unit, Department of Medicine, Karolinska Institute, Solna, Sweden.
Clinical Epidemiology Unit, Department of Medicine, Karolinska Institute, Solna, Sweden.Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden.Department of Epidemiology and Public Health, University College London, United Kingdom.
Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran.
Clinical Epidemiology Unit, Department of Medicine, Karolinska Institute, Solna, Sweden.Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
Clinical Epidemiology Unit & Centre for Pharmacoepidemiology, Department of Medicine, Karolinska Institute, Solna, Sweden.
Opium use during pregnancy and risk of preterm delivery: A population-based cohort study.

The emergence of electronic nicotine delivery systems (ENDS, or e-cigarettes ) has resulted in nicotine and tobacco scientists committing increased resources to studying these products. Despite this surge of research on various topics related to e-cigarettes, it is important to characterize the evolving e-cigarette research landscape as a way to identify important future research directions. The purpose of this review was to broadly categorize published scholarly work on e-cigarettes using a structured, multi-level coding scheme.A systematic literature search was conducted to collect articles on e-cigarettes that were published in peer-reviewed journals from 2006 through 2014. Studies were classified through 3 coding waves. Articles were first divided into research reports, literature reviews and opinions/editorials. Research reports were further categorized to determine the proportion of these studies using human participants. Finally, human studies were classified based on their methodologies: descriptive, predictive, explanatory, and intervention.Research reports (n=224) and opinions/editorials (n=248) were published at similar rates during this time period. All types of articles showed exponential rates of increase in more recent years. 76.4% of human research studies were descriptive in nature, with very little research employing experimental (6.8%) or intervention-based methodologies (5.4%).This review reinforces the idea that e-cigarettes are a disruptive technology exerting substantial influence on nicotine and tobacco science. This review also suggests that opinions on e-cigarettes may be outpacing our scientific understanding of these devices. Our findings highlight the need for more e-cigarette research involving experimental, intervention, and longitudinal designs.
Copyright Â© 2016 Elsevier Ltd. All rights reserved.
Department of Psychology, University of South Florida, 4202 East Fowler Avenue, Tampa, FL 33620, USA; Tobacco Research & Intervention Program, H. Lee Moffitt Cancer Center, 4115 East Fowler Avenue, Tampa, FL 33617, USA.
Department of Psychology, University of South Florida, 4202 East Fowler Avenue, Tampa, FL 33620, USA; Tobacco Research & Intervention Program, H. Lee Moffitt Cancer Center, 4115 East Fowler Avenue, Tampa, FL 33617, USA. Electronic address: thomas.brandon@moffitt.org.
Documenting the emergence of electronic nicotine delivery systems as a disruptive technology in nicotine and tobacco science.

Activated carbon (AC)/CoFe2O4 nanocomposites, MAC-1 and MAC-2, were prepared by a simple pyrolytic method using a mixture of iron(III)/cobalt(II) benzoates and iron(III)/cobalt(II) oxalates, respectively, and were used as efficient adsorbents for the removal of amoxicillin (AMX) and paracetamol (PCT) of aqueous effluents. The synthesized nanocomposites were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), vibrating sample magnetometry (VSM), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX) and transmission electron microscopy (TEM). The sizes of cobalt ferrite nanoparticles formed from benzoates of iron(III)/cobalt(II) and oxalates of iron(III)/cobalt(II) precursors were in the ranges of 5-80 and 6-27 nm, respectively. The saturation magnetization (M s), remanence (M r) and coercivity (H c) of the MAC-2 nanocomposites were found to be 3.07 emu g-1, 1.36 emu g-1 and 762.49 Oe; for MAC-1, they were 0.2989 emu g-1, 0.0466 emu g-1 and 456.82 Oe. The adsorption kinetics and isotherm studies were investigated, and the results showed that the as-prepared nanocomposites MAC-1 and MAC-2 could be utilized as an efficient, magnetically separable adsorbent for environmental cleanup. The maximum sorption capacities obtained were 280.9 and 444.2 mg g-1 of AMX for MAC-1 and MAC-2, respectively, and 215.1 and 399.9 mg g-1 of PCT using MAC-1 and MAC-2, respectively. Both adsorbents were successfully used for simulated hospital effluents, removing at least 93.00 and 96.77% for MAC-1 and MAC-2, respectively, of a mixture of nine pharmaceuticals with high concentrations of sugars, organic components and saline concentrations.
Institute of Chemistry, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
Department of Chemistry, Kongunadu Arts and Science College, Coimbatore, Tamil Nadu, 641029, India.
Institute of Chemistry, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil. glaydsonambiental@mail.com.Department of Metallurgy, Federal University of Rio Grande do Sul (UFRGS), Engineering School, Av. Bento Gonçalves, 9500, Agronomia, Porto Alegre, 91501-970, Brazil. glaydsonambiental@mail.com.
Department of Metallurgy, Federal University of Rio Grande do Sul (UFRGS), Engineering School, Av. Bento Gonçalves, 9500, Agronomia, Porto Alegre, 91501-970, Brazil.
Environmental science and pollution research international
Efficient removal of amoxicillin and paracetamol from aqueous solutions using magnetic activated carbon.

The aim of this work was to evaluate the prevalence of TP53Arg72Pro mutations and their possible relationship with oral carcinoma and oral potentially malignant disorders in Argentine patients. A cross-sectional study was performed on 111 exfoliated cytologies from patients with oral cancer (OC), oral potentially malignant disorders (OPMD) and controls. The TP53Arg72Pro mutations were determined using conventional PCR. We evaluated univariate and multivariate study variables, setting p < 0.05. We found: (a) a low frequency of Pro72 variant in control group and a high frequency in OC and OPMD, as well in OC and oral leukoplakia (OL) diagnosis; (b) multivariate association among the TP53CC genotype and females over 45 years with no tobacco nor alcohol habits with oral lichen planus pathology; (c) multivariate association between the TP53GC genotype and males with alcohol and tobacco habits and OC and OL pathologies. Our results showed that the wild-type Arg72variant was related to control patients and Pro72variant was related to OC and OPMD, in Argentine patients.
1 Departamento de Biología Bucal, Facultad de Odontología, Universidad Nacional de Córdoba, Córdoba, Argentina.
2 Departamento de Patología Bucal, Facultad de Odontología, Universidad Nacional de Córdoba, Córdoba, Argentina.
3 Facultad de Ciencias Químicas, CIQUIBIC-CONICET, Universidad Nacional de Córdoba, Córdoba, Argentina.
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine
Study of the TP53 codon 72 polymorphism in oral cancer and oral potentially malignant disorders in Argentine patients.

The possibility of association between ABO blood groups and malignancy was first discussed by Anderson DE & Haas C. The association between blood group and oral cancer is least explored and hence this study was undertaken to evaluate relationship of ABO blood groups with an increased risk for oral cancer.The present study was conducted at various cancer hospitals in Kanpur. The study samples comprised 100 oral cancer patients and 50 controls with tobacco chewing habit. The information regarding the socio demographic profile, history on tobacco habits, type of oral cancer and ABO blood group profile was obtained from the case sheets of the patients.The frequency of squamous cell carcinoma was significantly higher in men (78%) than women (22%) and mostly found in the age range of 45-65 years and also consuming chewing type of tobacco. It was found that out of 100 patients, 53 were of blood group B+ve, 28 of O +ve, 16 of A+ve and 3 had the blood group AB+ve. The high potential risk of developing OSCC was more in B+ve blood group (1.96 times), and relative frequency (%) in blood group O+ve (1.64 times) than in the control group Among locations of oral cancers, squamous cell carcinoma of tongue (25%) and buccal mucosa (15%) was more common in B+ve and Carcinoma of floor of mouth (11%) was more common in O+ve blood group cases. It was found that people with blood group B+ve, followed by O+ve had increased risk of developing OSCC with most prevalent being Well Differentiated OSCC as compared to people of other blood groups.The present study reveals that there is an inherited element in the susceptibility against different types of oral cancers. The people with blood group B+ve and O+ve having tobacco chewing habits can be appraised that they are more at risk to develop oral cancer than people with other blood groups.
Department of Oral and Maxillofacial Pathology, Rama Dental College Hospital and Research Centre, Kanpur, 208024, Uttar Pradesh, India.
Dept. of Public Health Dentistry, Institute of Dental Sciences, Bhubaneswar, Odisha, India.
Department of Periodontics, Rama Dental College Hospital and Research Center, Kanpur, 208024, Uttar Pradesh, India.
Journal of experimental therapeutics & oncology
Assessment of relationship of ABO blood groups among tobacco induced oral cancer patients of Kanpur Population, Uttar Pradesh.

Latin America makes progress on tobacco control.

Electronic Nicotine Delivery Systems (ENDS) were introduced into the US market in 2007, and until recently these devices were unregulated at the federal level. In 2014, the US Food and Drug Administration (FDA) published a Notice of Proposed Rulemaking asserting its intention to regulate ENDS and requesting public comments on numerous related issues, including potential limits on the sale of flavored ENDS. This article analyzes key comments submitted to the FDA on the issue of flavor regulation in ENDS and examines the weight and credibility of the evidence presented by both supporters and opponents of regulation. It also describes the final deeming rule, published in May 2016, and the FDA's response to the evidence submitted. This is the first study to examine public comments submitted to the FDA's Center for Tobacco Products, and it concludes that opponents of regulation were more likely to rely on sources that were not peer reviewed and that were affected by conflicts of interest. In light of these findings, the FDA and the research community should develop processes to carefully and critically analyze public comments submitted to the FDA on issues of tobacco regulation.
Copyright © 2017 by Duke University Press.
Journal of health politics, policy and law
Evidentiary Support in Public Comments to the FDA's Center for Tobacco Products.

Faculty of Health Sciences, Simon Fraser University, Burnaby, BC V5A 1S6, Canada. Electronic address: kelley_lee@sfu.ca.
Department of Politics, University of York, York, UK.
Looming threat of Asian tobacco companies to global health.

There is widespread concern about the nature, extent and impacts of lobbying by industries selling unhealthy commodities, which threatens public health and undermines important democratic processes. In the last decade, all Australian jurisdictions (except the Northern Territory) have established lobbyist registers with the stated objective of increasing the capacity of government and the public to scrutinise lobbying. Our aim was to assess whether the registers are fulfilling this objective.We conducted web searches of registers in Australian jurisdictions in 2014 and 2015 to determine what type of information they collected and whether data were accessible. We supplemented searches with e-mails and phone calls to registrars to clarify policies and seek additional information.We found that the data were lacking in critical details and historical information was difficult or impossible to obtain. None of the registers required in-house lobbyists to register or to be bound by the Lobbying Codes of Conduct. None required that informal lobbying (e.g. by government relations staff within a company) be recorded, and none provided detailed information about the nature and extent of lobbying activities.The registers do not meet the stated objective of making lobbying activity transparent to the Australian public. Timely access to comprehensive information is essential to help promote the rational development of policy concerning tobacco, alcohol and gambling problems. There is an urgent need to reform lobbyist registers to ensure that they are comprehensive and transparent.
© 2017 Australasian Professional Society on Alcohol and other Drugs.
School of Psychology Deakin University, Geelong, Australia.
School of Medicine and Public Health, Newcastle University, Newcastle, Australia.
Faculty of Health Sciences, Curtin University, Perth, Australia.
Australian lobbyist registers are not serving the purposes they were designed for.

Tanshinone IIA (Tan IIA), as a bioactive compound extracted from the dried roots of Salvia miltiorrhiza (also known as Danshen), is known to inhibit cancer cell proliferation and induce apoptosis. However, the mechanisms underlying the function of Tan IIA in cancer cell apoptosis remain to be elucidated The aim of the present study was to identify the molecular mechanisms underlying the anti‑cancer effects of Tan IIA in p53‑deficient H1299 cells. Tan IIA was demonstrated to suppress murine double minute 4 (MDM4) expression in a time‑ and dose‑dependent manner through the inhibition of MDM4 mRNA synthesis. Tan IIA‑induced downregulation of MDM4 resulted in an increase of P73α and a decrease of inhibitor of apoptosis 3 (IAP3). However, P73α was not activated as two P73α target genes, BCL2 binding component 3 and phorbol‑12‑myristate‑13‑acetate‑induced protein 1, were not significantly induced. Tan IIA‑induced inhibition of IAP3 expression may be involved in Tan IIA‑induced apoptosis and inhibition of H1299 cell viability. Notably, a combination of Tan IIA and doxorubicin (DOX) exposure resulted in further MDM4 overexpression in H1299 cells, indicating that Tan IIA sensitized p53‑deficient and MDM4‑overexpressing H1299 cells to DOX‑induced apoptosis.
Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
Tan IIA inhibits H1299 cell viability through the MDM4‑IAP3 signaling pathway.

Claude Bernard (1813-1878) was fascinated by the pharmacological mechanisms of poisons. In particular, using a huge amount of ingenious and robust experiments, he demonstrated the peripheral toxic action of the natural compound curare. His work generated controversies in a period where scientific methodology and technical development followed the progression of concepts and ideas. From his intense debates with Albert Vulpian emerged the location of curare's toxicity at the neuromuscular junction. These two fascinating scientists could not imagine how important were these discoveries which allowed John Langley to propose the concept of receptor early in the 20th century. At the same time, the German immunologist Paul Ehrlich suggested that these receptors could be targeted by so-called magic bullets , i.e., drugs that act on receptors, in order to treat patients. The molecular substrate of curare's activity was identified many years later as the nicotinic receptor of the motor end-plate. We now have curare molecules belonging to various chemical families that block receptors during anaesthesia. Suggamadex is the antidote for two of them, a drug that Claude Bernard perhaps dreamt of. We also have the recently marketed varenicline that acts as a partial agonist of nicotinic receptors in the central nervous system to treat patients from tobacco addiction. This rich story shows that biomedical research needs collaborations, imagination, perspicacity but also all results that it can have many years later, therefore challenging researchers about consequences of their discoveries.
Laboratoire de Neurobiologie et Pharmacologie Cardiovasculaire, Fédération de Médecine Translationnelle, Université et CHU de Strasbourg, 11 rue Humann, 67085 Strasbourg, France.
[Claude Bernard and nicotinic receptors: from the neuromuscular junction to tobacco weaning].

The intriguing molecular pathways involved in oral carcinogenesis are still ambiguous. The oral squamous cell carcinoma (OSCC) ranks as the most common type constituting more than 90% of the globally diagnosed oral cancers cases. The elevation in the OSCC incidence rate during past 10 years has an alarming impression on human healthcare. The major challenges associated with OSCC include delayed diagnosis, high metastatic rates, and low 5-year survival rates. The present work foundations on reverse genetic strategy and involves the identification of genes showing expressional variability in an OSCC case lacking addictive proclivities for tobacco, betel nut, and/or alcohol, major etiologies. The expression modulations in the identified genes were analyzed in 16 patients comprising oral pre-cancer and cancer histo-pathologies. The genes SCCA1 and KRT1 were found to down regulate while DNAJC13, GIPC2, MRPL17, IG-Vreg, SSFA2, and UPF0415 upregulated in the oral pre-cancer and cancer pathologies, implicating the genes as crucial players in oral carcinogenesis.
Department of Biotechnology, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi, India.
Molecular Diagnostics, Genetix Biotech Asia (P) Ltd., New Delhi, India.
Department of ENT, Hamdard Institute of Medical Sciences and Research, Jamia Hamdard, New Delhi, India.
Department of Biotechnology, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi, India.Department of Biochemistry, Hamdard Institute of Medical Sciences and Research, Jamia Hamdard, New Delhi, India.
Assessment of cellular and serum proteome from tongue squamous cell carcinoma patient lacking addictive proclivities for tobacco, betel nut, and alcohol: Case study.

A hormonal role in NSCLC development is well documented. We previously showed that the aromatase inhibitor (AI) anastrozole decreased development of tobacco carcinogen-induced lung tumors in a murine lung cancer prevention model and that aromatase and estrogen receptor were expressed in pulmonary inflammatory cells.We utilized a tobacco carcinogen-induced lung tumor mouse model by treatment with 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK), to determine whether an AI combined with nonsteroidal anti-inflammatory drugs results in greater lung tumor prevention effects compared to single-agent treatment.Combination of anastrozole (0.1 mg/kg/d) with aspirin (25 mg/kg/d) after NNK exposure resulted in significantly fewer and smaller lung tumors than did single-agent treatments and was accompanied by maximum decreases in circulating β-estradiol (E2) and interleukin-6, tumor-infiltrating macrophages, and tumoral Ki67, phospho-mitogen-activated protein kinase, phospho-signal transducer and activator of transcription 3, and interleukin-17A expression. Preneoplasia arising after combination treatment showed the lowest Sox-2 expression, suggesting an inhibitory effect on proliferative capacity in the airways by blocking both E2 and inflammation. Anastrozole combined with ibuprofen instead of aspirin also showed enhanced antitumor effects. Moreover, male mice treated with NNK that received E2 in their drinking water showed greater levels of pulmonary macrophages and inflammatory markers than did the control, confirming an E2 effect on inflammation in the microenvironment.Our results suggest a benefit to joint targeting of the estrogen and inflammatory pathways for NSCLC prevention. Combining AIs with nonsteroidal anti-inflammatory drugs reduces circulating E2, proinflammatory cytokines, and macrophage recruitment in the lung microenvironment after tobacco exposure. This strategy could be particularly effective in women who have underlying pulmonary inflammatory diseases.
Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania; UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania. Electronic address: stabilela@upmc.edu.
Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota.
UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania.
Department of Biostatistics, University of Pittsburgh School of Public Health, Pittsburgh, Pennsylvania.
UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania; Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pennsylvania.
Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota.
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
Preclinical Evidence for Combined Use of Aromatase Inhibitors and NSAIDs as Preventive Agents of Tobacco-Induced Lung Cancer.

Lung cancer is the most common cause of cancer-related deaths in humans worldwide. There is strong evidence that the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) play an important role in carcinogenesis caused by tobacco products. NNK and racemic NNAL are reported to induce lung and pancreatic tumors in rats. The carcinogenicity in Fischer 344 rats of NNK, NNAL, and its enantiomers ( R)-NNAL and ( S)-NNAL has been studied recently, and all test compounds induced significant numbers of lung tumors. We report here the detailed histopathological and immunohistochemical characterization of these tumors and their aggressive nature as shown by their metastasis locally and to the pancreas. The spectrum of treatment-related histopathological findings comprised pulmonary alveolar/bronchiolar (A/B) epithelial hyperplasia, A/B adenomas, and A/B carcinomas. A/B carcinomas frequently exhibited local invasion/metastasis within the mediastinum and thoracic cavity and distant metastasis to the pancreas that was confirmed by immunohistochemistry using the lung-specific markers prosurfactant protein-C and club (Clara) cell-10. Our observation regarding metastasis to the pancreas was an important, and unexpected, finding in this study both for the experimental animal model and potential human relevance.
1 Department of Veterinary Population Medicine, University of Minnesota, St. Paul, Minnesota, USA.2 Masonic Cancer Center, University of Minnesota, St. Paul, Minnesota, USA.3 Experimental Pathology Laboratories, Inc. (EPL Inc.)/Cellular and Molecular Pathology Branch, NIEHS, Research Triangle Park, North Carolina, USA.
1 Department of Veterinary Population Medicine, University of Minnesota, St. Paul, Minnesota, USA.2 Masonic Cancer Center, University of Minnesota, St. Paul, Minnesota, USA.
2 Masonic Cancer Center, University of Minnesota, St. Paul, Minnesota, USA.
Metastasis to the F344 Rat Pancreas from Lung Cancer Induced by 4-(Methylnitrosamino)- 1-(3-pyridyl)-1-butanone and Enantiomers of Its Metabolite 4-(Methylnitrosamino)-1-(3-pyridyl)- 1-butanol, Constituents of Tobacco Products.

Tobacco shops, medical marijuana dispensaries (MMD), and off-sale alcohol outlets are legal and prevalent in South Los Angeles, California-a high-crime, low-income urban community of color. This research is the first to explore the geographic associations between these three legal drug outlets with surrounding crime and violence in a large low-income urban community of color. First, spatial buffer analyses were performed using point-location and publically accessible January-December 2014 crime data to examine the geography of all felony property and violent crimes occurring within 100, 200, 500, and 1000-foot buffers of these three legal drug outlet types across South Los Angeles. Next, spatial regression analyses explored the geographic associations between density of these outlets and property and violent crimes at the census tract level. Results indicated that mean property and violent crime rates within 100-foot buffers of tobacco shops and alcohol outlets-but not MMDs-substantially exceeded community-wide mean crime rates and rates around grocery/convenience stores (i.e., comparison properties licensed to sell both alcohol and tobacco). Spatial regression analyses confirmed that tobacco shops significantly positively associated with property and violent crimes after controlling for key neighborhood factors (poverty, renters, resident mobility, ethnic/racial heterogeneity). Thus, study findings provide the first empirical evidence that tobacco shops may constitute public health threats that associate with crime and violence in U.S. low-income urban communities of color. Implementing and enforcing control policies that regulate and monitor tobacco shops in these communities may promote community health by improving public safety.
Copyright © 2017 Elsevier Inc. All rights reserved.
University of California Riverside, School of Medicine, Riverside, CA, United States. Electronic address: asubica@medsch.ucr.edu.
San Jose State University, Environmental Studies, San Jose, CA, United States.
University of Kansas, School of Social Welfare, Lawrence, KS, United States.
Loyola Marymount University, Psychology Applied Research Center, Los Angeles, CA, United States.
The geography of crime and violence surrounding tobacco shops, medical marijuana dispensaries, and off-sale alcohol outlets in a large, urban low-income community of color.

Although epidemiological data and results from rodent studies support an inverse relationship between nicotine consumption and body weight, the molecular mechanisms are poorly understood. CD-1 mice were fed a basal diet or a basal diet containing low or high dose smokeless tobacco blend or high dose nicotine tartrate for 14 weeks. High dose tobacco blend and nicotine tartrate diets vs. basal diet reduced mouse body weight (16.3% and 19.7%, respectively), epididymal (67.6% and 72.5%, respectively) and brown adipose weight (42% and 38%, respectively), epididymal adipocyte size (46.4% and 41.4%, respectively), and brown adipose tissue lipid droplet abundance, with no elevation of adipose tissue inflammation. High dose tobacco blend and nicotine diets also increased mouse physical activity and decreased respiratory exchange ratio, suggesting that high dose nicotine intake induces adipose tissue triglyceride lipolysis to provide fatty acids as an energy source. Both low and high dose tobacco blend and nicotine diet feeding vs. basal diet increased plasma insulin levels (2.9, 3.6 and 4.3-fold, respectively) and improved blood glucose disposal without affecting insulin sensitivity. Feeding of the high dose tobacco blend or nicotine feeding in mice induces body weight loss likely by increasing physical activity and stimulating adipose tissue triglyceride lipolysis.
Copyright © 2018. Published by Elsevier Ltd.
Departments of Internal Medicine, Section on Molecular Medicine, Winston-Salem, NC 27157, USA. Electronic address: mliu@wakehealth.edu.
Departments of Internal Medicine, Section on Molecular Medicine, Winston-Salem, NC 27157, USA.
RAI Services Company, Scientific and Regulatory Affairs, Winston-Salem, NC 27101, USA.
Departments of Internal Medicine, Section on Molecular Medicine, Winston-Salem, NC 27157, USA; RAI Services Company, Scientific and Regulatory Affairs, Winston-Salem, NC 27101, USA.
Departments of Internal Medicine, Section on Molecular Medicine, Winston-Salem, NC 27157, USA; Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA. Electronic address: jparks@wakehealth.edu.
Feeding of tobacco blend or nicotine induced weight loss associated with decreased adipocyte size and increased physical activity in male mice.

This Commentary forms a response to Nikogosian's and Kickbusch's forward-looking perspective about the legal strength of international health instruments. Building on their arguments, in this commentary we consider what we can learn from the Framework Convention on Tobacco Control (FCTC) for the adoption of new legal international health instruments.
© 2018 The Author(s); Published by Kerman University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Department of International Law/Global Health Law Groningen, Faculty of Law, University of Groningen, Groningen, The Netherlands.
Global Health Law Groningen Research Centre, Faculty of Law, University of Groningen, Groningen, The Netherlands.
International journal of health policy and management
Adopting New International Health Instruments - What Can We Learn From the FCTC? Comment on The Legal Strength of International Health Instruments - What It Brings to Global Health Governance?

Heavy metals intoxication is known to be risk factors for various diseases, including cancer. These metals may be presented in food and soil as well as in leaf and tobacco smoke. The aim of this study was to correlate the exposure to heavy metals stemming from tobacco and head and neck squamous cell carcinoma carcinogenesis. Analysis of lead, copper, manganese, arsenic, chromium, and cadmium by atomic absorption spectrophotometry was performed in whole blood samples from 91 patients: 68 smokers with oral cavity, pharynx, or laryngeal cancer; 8 non-smokers with oral or larynx cancer; and 15 non-cancer smokers with tobacco-related diseases (control group). No differences were found in metals quantifications, except a significant difference was observed (p = 0.0223) with higher mean in copper levels for non-smokers with cancer. The present study concluded, for the groups evaluated, it was not possible to prove the relationship between the studied metals in the development of the neoplasm. On the other hand, the results of copper demonstrated a correlation with smokers with cancer and lower levels of circulating copper.
Department of Biosciences and Oral Diagnosis, Sao Paulo State University (Unesp), Institute of Science and Technology, Av. Eng. Francisco José Longo 777, Sao Jose dos Campos, SP, Brazil.
Mogi das Cruzes, University Braz Cubas, Sao Paulo, Brazil.
Center of Toxicological Assistance (CEATOX), Sao Paulo State University (Unesp), Institute of Biosciences of Botucatu, Botucatu, SP, Brazil.
Department of Pharmacology, Sao Paulo State University (Unesp), Institute of Biosciences of Botucatu, Botucatu, SP, Brazil.
Department of Head and Neck Surgery, Medical Sciences College, Irmandade daSanta Casa de Misericordia de Sao Paulo (ISCMSP), Sao Paulo, SP, Brazil.
Department of Biosciences and Oral Diagnosis, Sao Paulo State University (Unesp), Institute of Science and Technology, Av. Eng. Francisco José Longo 777, Sao Jose dos Campos, SP, Brazil. janete@ict.unesp.br.
Tobacco influence in heavy metals levels in head and neck cancer cases.

Lung cancer is the principal cause of cancer-associated deaths. HMGB1 has been reported to be associated with tumorigenesis. This study aimed to investigate the relationship between rs1412125 and rs1360485 polymorphisms in HMGB1 and the risk and survival of lung cancer. 850 cases and 733 controls were included. Logistic regression analysis and survival analysis were performed to investigate the association between SNPs and the risk and survival of lung cancer. Crossover analysis was used to analyze the interaction between SNPs and tobacco exposure. Results indicated that rs1412125 polymorphism was associated with lung cancer risk, especially with the risk of lung adenocarcinoma and small cell lung cancer. Carriers with CT and CC genotypes had a decreased risk of lung cancer (CT + CC vs.TT: adjusted OR = 0.736, p = 0.004). Similar results were obtained in the stratification analysis for non-smokers and female population. For rs1360485 polymorphism, AG and GG genotypes could decrease the risk of lung adenocarcinoma and female lung cancer by 0.771-fold and 0.789-fold. However, no significant interaction between polymorphisms and tobacco exposure or association between SNPs and the survival of lung cancer was observed. This study indicated polymorphisms in HMGB1 may be a novel biomarker for female lung adenocarcinoma risk.
Department of Epidemiology, School of Public Health, China Medical University, Shenyang 110122, China. mij9620@163.com.Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Province Department of Education, Shenyang 110122, China. mij9620@163.com.
Department of Epidemiology, School of Public Health, China Medical University, Shenyang 110122, China. xlli@mail.cmu.edu.cn.Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Province Department of Education, Shenyang 110122, China. xlli@mail.cmu.edu.cn.
Department of Epidemiology, School of Public Health, China Medical University, Shenyang 110122, China. quanxiaowei126@126.com.Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Province Department of Education, Shenyang 110122, China. quanxiaowei126@126.com.
Department of Epidemiology, School of Public Health, China Medical University, Shenyang 110122, China. xyingl0608@163.com.Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Province Department of Education, Shenyang 110122, China. xyingl0608@163.com.
Department of Epidemiology, School of Public Health, China Medical University, Shenyang 110122, China. bszhou@cmu.edu.cn.Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Province Department of Education, Shenyang 110122, China. bszhou@cmu.edu.cn.
Single Nucleotide Polymorphisms in HMGB1 Correlate with Lung Cancer Risk in the Northeast Chinese Han Population.

To assess preadolescents' emotional reactions and intended use of refusal responses to tobacco and ecstasy.A total of 333 students from two junior schools in Baise City were recruited with cluster-sampling method, filled the questionnaire to assess a respondent's emotional reactions and refusal skills in response to an offer of tobacco and MDMA from Feb to Jul 2014.88. 89%-93. 39% of preadolescents would more likely to use say no and tell them you don't want it . A series of 2( type of drug) × 2( offerer) × 2( sex) ANOVAs showed there were main effects for sex in explicit refusal scale ( F = 8. 391, P = 0. 004), excuse scale ( F =156. 560, P < 0. 001), implicit refusal scale ( F = 84. 498, P < 0. 001), aggression scale ( F = 31. 911, P < 0. 001). For the excuse scale, there were main effects for drug( F = 12. 009, P = 0. 001). A series of χ~2-tests showed that participants were more curious to MDMA offers than tobacco offers from close friends and acquaintances( χ~2=13. 76, P = 0. 0003; χ~2= 10. 24, P = 0. 002). For the close friends offers, participants were more pleasure to tobacco offers than MDMA offers( χ~2= 8. 33, P = 0. 006).There were significant effects of sex and offers in refusal style for drug offers. Preadolescents would show different emotional reaction to type of drug supplier or provider.
School of Public Health and Management, Youjiang Medical University for Nationalities, Baise 533000, China.
Wei sheng yan jiu = Journal of hygiene research
[Preadolescents' refusal skills and responses emotional reactions to the offer of tobacco and ecstasy in Youjiang District in Baise City in 2014].

1 Program Design and Evaluation Services, Oregon Public Health Division, Oregon Health Authority, Portland, OR, USA.
2 Health Promotion and Chronic Disease Prevention Section, Oregon Public Health Division, Oregon Health Authority, Portland, OR, USA.
Public health reports (Washington, D.C. : 1974)
Including a Novel Tobacco Product in Oregon's Indoor Clean Air Act: Lessons Learned for Clean Air Policy, 2015-2016.

To measure the area of central scotoma obtained with semi-automated kinetic perimetry (SKP) in patients suffering from tobacco-alcohol toxic neuropathy (TATN).Twelve eyes of six patients with TATN were examined with SKP. Area of central scotoma was measured in square degrees (deg2). Additionally, static automated perimetry (SAP) within 60° was performed in each patient.Area of central scotoma was 41.8 deg2 for III4e isopter, 22.9 deg2 for I4e isopter and 16.1 deg2 for I2e isopter in TATN patients. SAP revealed central scotoma in all patients. There was 100% of accordance between two methods.SKP is comparable with SAP in assessing central scotoma. SKP offers advantage of measuring central scotoma and assessing remaining peripheral visual field in TATN, even with low incidence and prevalence of this clinical entity.
a Department of General Ophthalmology , Medical University , Lublin , Poland.
b Human Anatomy Department , Medical University , Lublin , Poland.
c Department of Ophthalmology , University Eye Hospital , Rostock , Germany.
a Department of General Ophthalmology , Medical University , Lublin , Poland.d Department of Experimental Pharmacology , Medical Research Centre, Polish Academy of Sciences , Warsaw , Poland.
Central scotoma in tobacco-alcohol toxic optic neuropathy measured with semi-automated kinetic perimetry.

National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD.
Paediatr Perinat Epidemiol. 2018-09;32(5):439-441.
Childhood hearing loss and established risk factors: What is the contribution of tobacco exposure prenatally or after birth?

Prenatal drug exposure, including cocaine, alcohol, marijuana, and tobacco, is associated with deficits in behavioral regulation and attention. Using fMRI, the objective of this study was to characterize the association between prenatal cocaine exposure (PCE) and the underlying neural substrates associated with behavioral outcomes of attention. Forty-seven young adults were recruited for this study from the ongoing Maternal Health Practices and Child Development (MHPCD) Project, a longitudinal study of the effects of PCE on growth, behavior, and cognitive function. Three groups were compared: 1) prenatal exposure to cocaine, alcohol, marijuana, and tobacco (CAMT, n = 15), 2) prenatal exposure to alcohol, marijuana, and tobacco (AMT, n = 17), and 3) no prenatal exposure to drugs (Controls, n = 15). Subjects were frequency matched on gender, race, handedness, and 15-year IQ. This study used the theoretical model proposed by Posner and Peterson (1990), which posits three dissociable components of attention: alerting, orienting, and executive attention. Subjects completed a functional MRI (fMRI) scan while performing the Attention Network Task, a validated neuroimaging measure of the 3-network model of attention. Behavioral and fMRI data revealed no associations between PCE and task accuracy, speed of processing, or activation in key brain regions associated with each of the attention networks. The results of this study show that any subtle differences in brain function associated with PCE are not detectable using the ANT task and fMRI. These results should be interpreted in the context of other studies that have found associations between PCE and arousal with emotionally arousing stimuli, compared to this study that found no associations using emotionally neutral stimuli.
Copyright © 2018 Elsevier Inc. All rights reserved.
Department of Psychology, Slippery Rock University, 1 Morrow Way, Slippery Rock, PA 16057, United States of America. Electronic address: jennifer.willford@sru.edu.
Department of Mathematics, Slippery Rock University, 1 Morrow Way, Slippery Rock, PA 16057, United States of America. Electronic address: dil.singhabahu@sru.edu.
Department of Physics, Slippery Rock University, 1 Morrow Way, Slippery Rock, PA 16057, United States of America. Electronic address: athula.herat@sru.edu.
Department of Psychiatry, University of Pittsburgh School of Medicine, 3811 O'Hara Street, Pittsburgh, PA 15213, United States of America. Electronic address: gar@pitt.edu.
An examination of the association between prenatal cocaine exposure and brain activation measures of arousal and attention in young adults: An fMRI study using the Attention Network Task.

Lung adenocarcinoma (LADC) is the leading cause of cancer death worldwide. Nevertheless, syngeneic mouse models of the disease are sparse, and cell lines suitable for transplantable and immunocompetent mouse models of LADC remain unmet needs. We established multiple mouse LADC cell lines by repeatedly exposing two mouse strains (FVB, Balb/c) to the tobacco carcinogens urethane or diethylnitrosamine and by culturing out the resulting lung tumours for prolonged periods of time. Characterization of the resulting cell lines (n = 7) showed that they were immortal and phenotypically stable in vitro, and oncogenic, metastatic and lethal in vivo. The primary tumours that gave rise to the cell lines, as well as secondary tumours generated by transplantation of the cell lines, displayed typical LADC features, such as glandular architecture and mucin and thyroid transcription factor 1 expression. Moreover, these cells exhibited marked molecular similarity with human smokers' LADC, including carcinogen-specific Kras point mutations (KrasQ61R in urethane- and KrasQ61H in diethylnitrosamine-triggered cell lines) and Trp53 deletions and displayed stemness features. Interestingly, all cell lines overexpressed proliferin, a murine prolactin orthologue, which functioned as a lung tumour promoter. Furthermore, prolactin was overexpressed and portended poor prognosis in human LADC. In conclusion, we report the first LADC cell lines derived from mice exposed to tobacco carcinogens. These cells closely resemble human LADC and provide a valuable tool for the functional investigation of the pathobiology of the disease.
© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Laboratory for Molecular Respiratory Carcinogenesis, Department of Physiology, Faculty of Medicine, University of Patras, Rio, Achaia, Greece.
Lung Carcinogenesis Group, Comprehensive Pneumology Center (CPC) and Institute for Lung Biology and Disease (iLBD), Ludwig-Maximilian University and Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Munich, Bavaria, Germany.
Stem Cell Biology Laboratory, Department of Physiology, Faculty of Medicine, Greece.
Department of Anatomy, Faculty of Medicine, University of Patras, Rio, Achaia, Greece.
Laboratory for Molecular Respiratory Carcinogenesis, Department of Physiology, Faculty of Medicine, University of Patras, Rio, Achaia, Greece.Lung Carcinogenesis Group, Comprehensive Pneumology Center (CPC) and Institute for Lung Biology and Disease (iLBD), Ludwig-Maximilian University and Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Munich, Bavaria, Germany.
Tobacco chemical-induced mouse lung adenocarcinoma cell lines pin the prolactin orthologue proliferin as a lung tumour promoter.

Tobacco kills 6 million people annually and its global health costs are continuously rising. The main addictive component of every tobacco product is nicotine. Among the mechanisms by which nicotine, and its major metabolite, cotinine, contribute to heart disease is the renin-angiotensin-aldosterone system (RAAS) activation. This increases aldosterone production from the adrenals and circulating aldosterone levels. Aldosterone is a mineralocorticoid hormone with various direct harmful effects on the myocardium, including increased reactive oxygen species (ROS) generation, which contributes significantly to cardiac mitochondrial dysfunction and cardiac aging. Aldosterone is produced in the adrenocortical zona glomerulosa (AZG) cells in response to angiotensin II (AngII), activating its type 1 receptor (AT1R). The AT1R is a G protein-coupled receptor (GPCR) that leads to aldosterone biosynthesis and secretion, via signaling from both Gq/11 proteins and the GPCR adapter protein βarrestin1, in AZG cells. Adrenal βarrestin1 is essential for AngII-dependent adrenal aldosterone production, which aggravates heart disease. Since adrenal βarrestin1 is essential for raising circulating aldosterone in the body and tobacco compounds are also known to elevate aldosterone levels in smokers, accelerating heart disease progression, our central hypothesis is that nicotine and cotinine increase aldosterone levels to induce cardiac injury by stimulating adrenal βarrestin1. In the present review, we provide an overview of the current literature of the physiology and pharmacology of adrenal aldosterone production regulation, of the effects of tobacco on this process and, finally, of the effects of tobacco and aldosterone on cardiac structure and function, with a particular focus on cardiac mitochondrial function. We conclude our literature account with a brief experimental outline, as well as with some therapeutic perspectives of our pharmacological hypothesis, that is that adrenal βarrestin1 is a novel molecular target for preventing tobacco-induced hyperaldosteronism, thereby also ameliorating tobacco-related heart disease development.
Department of Basic Sciences New York University New York New York.
Laboratory for the Study of Neurohormonal Control of the Circulation, Department of Pharmaceutical Sciences Nova Southeastern University College of Pharmacy Fort Lauderdale, Florida.
Pharmacol Res Perspect. 2019-08;7(4):e00497.
Adrenal βarrestin1 targeting for tobacco-associated cardiac dysfunction treatment: Aldosterone production as the mechanistic link.

The research evaluated point-of-care drug interaction resources for scope, completeness, and consistency in drug-ethanol and drug-tobacco content.In a cross-sectional analysis, 2 independent reviewers extracted data for 108 clinically relevant interactions using 7 drug information resources (Clinical Pharmacology Drug Interaction Report, Facts & Comparisons eAnswers, Lexicomp Interactions, Micromedex Drug Interactions, Drug Interactions Analysis and Management, Drug Interaction Facts, and Stockley's Drug Interactions). Scope (presence of an entry), completeness (content describing mechanism, clinical effects, severity, level of certainty, and course of action for each present interaction; up to 1 point per assessed item for a total possible score of 5 points), and consistency (similarity among resources) were evaluated.Fifty-three drug-ethanol and 55 drug-tobacco interactions were analyzed. Drug-ethanol interaction entries were most commonly present in Lexicomp (84.9%), Clinical Pharmacology (83.0%), and Stockley's Drug Interactions (73.6%), compared to other resources (p<0.05). Drug-tobacco interactions were more often covered in Micromedex (56.4%), Stockley's Drug Interactions (56.4%), Drug Interaction Facts (43.6%), and Clinical Pharmacology (41.8%) (p<0.001). Overall completeness scores were higher for Lexicomp, Micromedex, Drug Interaction Facts, and Facts & Comparisons (median 5/5 points, interquartile range [IQR] 5 to 5, p<0.001) for drug-ethanol and for Micromedex (median 5/5 points, IQR 5 to 5, p<0.05) for drug-tobacco, compared to other resources. Drug Interaction Facts and Micromedex were among the highest scoring resources for both drug-ethanol (73.7%, 68.6%) and drug-tobacco (75.0%, 32.3%) consistency.Scope and completeness were high for drug-ethanol interactions, but low for drug-tobacco interactions. Consistency was highly variable across both interaction types.
Associate Professor of Pharmacy Practice and Director of the Drug Information Center, College of Pharmacy, Natural & Health Sciences, Manchester University, Fort Wayne, IN, rdbeckett@manchester.edu.
Doctor of Pharmacy Student, College of Pharmacy, Natural & Health Sciences, Manchester University, Fort Wayne, IN, cdstump2018@manchester.edu.
Doctor of Pharmacy Student, College of Pharmacy, Natural & Health Sciences, Manchester University, Fort Wayne, IN, madyer2018@manchester.edu.
Journal of the Medical Library Association : JMLA
Evaluation of drug information resources for drug-ethanol and drug-tobacco interactions.

Sorafenib remains the standard care for patients with hepatocellular carcinoma (HCC) even though it has low antitumor efficacy. Protein neddylation is abnormally activated in many types of human cancer. However, whether dysregulation of neddylation is involved in HCC progression and whether targeting neddylation sensitizes HCC cells to sorafenib need to be ascertained. In the present study, it was demonstrated that high expression of neddylation components, neural precursor cell expressed, developmentally downregulated 8 (NEDD8) and NEDD8‑activating enzyme 1 (NAE1), were associated with poor survival of patients with HCC. Inhibition of neddylation by MLN4924, a small‑molecule inhibitor of NAE1, significantly inhibited HCC growth, reduced clonogenic survival, increased apoptosis, and decreased migration capacity. Sorafenib alone exhibited minimal anticancer efficacy. However, a combination of sorafenib with MLN4924 at a low concentration significantly enhanced the inhibition of cell proliferation and migration as well as the induction of apoptosis induced by sorafenib. In vivo HCC xenograft mouse models also showed that MLN4924 increased the antitumor efficacy of sorafenib. Mechanistically, MLN4924 enhanced the antitumor activity of sorafenib in HCC cells via upregulation of cullin‑RING E3 ubiquitin ligase (CRL)/Skp1‑Cullin1‑F box (SCF) E3 ubiquitin ligase substrates p21, p27, Deptor and IκBɑ. Taken together, these findings suggest that combination therapy of MLN4924 with sorafenib appears to present an additive effect with a maximal in the treatment of HCC.
Key Laboratory of Hepatobiliary and Pancreatic Surgery, Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Shapingba, Chongqing 400038, P.R. China.
Inhibition of neddylation modification by MLN4924 sensitizes hepatocellular carcinoma cells to sorafenib.

The tetraspanins Tspan8 and CD151 promote metastasis, exosomes (Exo) being suggested to be important in the crosstalk between tumor and host. The contribution of Tspan8 and CD151 to host versus tumor-derived exosome (TEX) activities being not defined, we approached the questions using 3-methylcholanthrene-induced (MCA) tumors from wt, Tspan8ko, CD151ko and Tspan8/CD151 (db)ko mice, implanted into tetraspanin-competent and deficient hosts.Tumor growth and dissemination, hematopoiesis and angiogenesis were surveyed in wild type (wt), Tspan8ko, CD151ko and dbko mice bearing tetraspanin-competent and -deficient MCA tumors. In vitro studies using tumor cells, bone marrow cells (BMC) and endothelial cells (EC) elaborated the mechanism of serum (s)Exo- and TEX-induced target modulation.Tumors grew in autochthonous and syngeneic hosts differing in Tspan8- and/or CD151-competence. However, Tspan8ko- and/or CD151ko-tumor cell dissemination and settlement in metastatic organs was significantly reduced in the autochthonous host, and less severely in the wt-host. Impaired wt-MCA tumor dissemination in the ko-host confirmed a contribution of host- and tumor-Tspan8/-CD151 to tumor cell dissemination, delivery of sExo and TEX being severely impaired by a Tspan8ko/CD151ko. Coculturing tumor cells, BMC and EC with sExo and TEX revealed minor defects in epithelial mesenchymal transition and apoptosis resistance of ko tumors. Strongly reduced migratory and invasive capacity of Tspan8ko/CD151ko-MCA relies on distorted associations with integrins and CAM and missing Tspan8/CD151-promoted recruitment of proteases. The defects, differing between Tspan8ko- and CD151ko-MCA, were rescued by wt-TEX and, less efficiently Tspan8ko- and CD151ko-TEX. Minor defects in hematopoietic progenitor maturation were based on the missing association of hematopoietic growth factors /- receptors with CD151 and, less pronounced, Tspan8. Rescue of impaired angiogenesis in ko mice by wt-sExo and promotion of angiogenesis by TEX depended on the association of Tspan8 and CD151 with GPCR and RTK in EC and tumor cells.Tspan8-/CD151-TEX play central roles in tumor progression. Tspan8-/CD151-sExo and TEX contribute by stimulating angiogenesis. Tspan8 and CD151 fulfill these tasks by associating with function-relevant proteins, the additive impact of Tspan8 and CD151 relying on differences in preferred associations. The distinct Tspan8 and CD151 contributions suggest a blockade of TEX-Tspan8 and -CD151 promising for therapeutic intervention.
Pancreas Section, University Hospital of Surgery, Ruprecht-Karls-University, Heidelberg, Germany.
Pancreas Section, University Hospital of Surgery, Ruprecht-Karls-University, Heidelberg, Germany.Present Address: Department of Oncology, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangdong, China.
Interdisciplinary Neurobehavioral Core, Institute of Pharmacology, Ruprecht-Karls-University, Heidelberg, Germany. claudia.pitzer@pharma.uni-heidelberg.de.
Pancreas Section, University Hospital of Surgery, Ruprecht-Karls-University, Heidelberg, Germany. margot.zoeller@gmx.net.
Journal of experimental & clinical cancer research : CR
Tspan8 and Tspan8/CD151 knockout mice unravel the contribution of tumor and host exosomes to tumor progression.

Manufactured doubt describes the efforts used by organizations or individuals to obscure the harmful effects of their products or actions by manipulating science. Although approaches to do so are widely used, relevant stakeholders are often unaware of these tactics. Here, we examine the strategies used in five cases of manufactured doubt: tobacco and adverse health; coal and black lung; Syngenta and the herbicide atrazine; the sugar industry and cardiovascular disease; and the Marshall Institute and climate change. By describing the tactics used in these cases, effective methods for identifying and countering instances of manufactured doubt can be generated.
Graduate program in Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA, USA.
Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts - Amherst, 171C Goessmann, 686 N. Pleasant Street, Amherst, MA 01003, USA.
Distract, delay, disrupt: examples of manufactured doubt from five industries.

To evaluate the hyaluronic acid (HA) inflammatory reaction, fibroblasts, fibrosis and duration of effect in the dorsal region of tobacco-exposed rats.Ten Wistar rats were divided into two groups: tobacco-exposed-group (TEG;n=5) and air-control-group (CG;n=5). The TEG animals were tobacco-exposed twice a day, 30-minutes/session, during 60 days. After this period, all animals received 0.1 mL HA subcutaneous injection in the dorsal area. The volume of HA was measured immediately after HA injection and weekly using a hand-caliper in nine weeks. After this period, all the animals were euthanized, and a specimen of was collected to evaluate inflammatory cells, fibroblasts, and fibrosis by HE.This study showed a higher inflammatory reaction in TEG than CG: inflammatory cell-count (CG: 1.07±0.9; TEG: 8.61±0.36, p<0.001); fibroblast count (CG: 2.92±0.17; TEG: 19.14±0.62, p<0.001), and fibrosis quantification (CG: 2.0; TEG: 3.75, p<0.001). The analysis of the HA volume in nine weeks in the dorsal region did not show a difference between groups (p=0.39).This study suggested that the HA injection in the TEG caused an increase in inflammatory cell count, fibroblast, and fibrosis quantification when compared to the CG. There was no difference in the duration of effect of HA between the groups.
MD, Division of Plastic Surgery, Hospital das Clínicas, Laboratory of Microsurgery and Plastic Surgery (LIM-04), Medical School, Universidade de São Paulo (USP), Brazil. Intellectual and scientific content of the study, interpretation of data, statistics analysis, manuscript writing, critical revision.
Graduate student, Laboratory of Microsurgery and Plastic Surgery (LIM-04), Medical School, USP, Sao Paulo-SP, Brazil. Acquisition, analysis and interpretation of data; technical procedures.
Daniel Imbassahy de Sá Bittencourt Camara E
PhD, Division of Plastic Surgery, Hospital das Clínicas, Laboratory of Microsurgery and Plastic Surgery (LIM-04), Medical School, USP, Sao Paulo-SP, Brazil. Intellectual and scientific content of the study, interpretation of data, critical revision.
Hyaluronic acid in tobacco-exposed rats. Inflammatory reaction, and duration of effect1.

Individuals with bipolar disorder (BD) have higher than average rates of coffee, tobacco and alcohol use. These substances may have deleterious effects on sleep quality and quantity, which may destabilize sleep/wake cycles and negatively impact the clinical course and prognosis of BD. The use of these substances may also be perceived as a self-medication attempt, for example, to induce sleep or to increase vigilance during the day. The objective of the current study was to investigate associations between the self-reported daily use of coffee, tobacco, and alcohol, and objective measures of sleep and activity patterns in adult individuals with BD. A sample of 147 euthymic individuals with BD were assessed for daily coffee, tobacco and alcohol consumption and 21 days of actigraphy monitoring. Actigraphic measures of sleep quantity and daytime activity were compared between groups classified as coffee+/coffee-, tobacco+/tobacco- and alcohol+/alcohol-, defined according to their current daily use. Then, we examined potential correlations between sleep/wake cycle parameters and the amount of daily consumption of each substance. Multivariable analyses identified associations between the use of coffee, tobacco, and alcohol and several sleep and activity parameters, such as between coffee, alcohol, and the relative amplitude of activity (respectively, p = .003 and p = .005), between alcohol and M10 onset (onset time of the 10 most active hours during the 24-h cycle) (p = .003), and between coffee and sleep duration (p = .047). This study supports the hypothesis that there is a relationship, whose direction would be bidirectional, between the daily use of these substances and the sleep/wake cycle in euthymic individuals with BD. These preliminary results require replications in other retrospective and prospective samples. They may have a clinical impact on psycho-education strategies to be proposed to individuals with BD.
INSERM U1144, Optimisation Thérapeutique en Neuropsychopharmacologie , Paris, France.Pôle de Psychiatrie et Psychologie Clinique, Centre Psychothérapique de Nancy , Laxou, France.Faculté de Médecine, Université de Lorraine , France.
INSERM U1144, Optimisation Thérapeutique en Neuropsychopharmacologie , Paris, France.Département de Psychiatrie et de Médecine Addictologique, Hôpital Fernand Widal, Assistance Publique des Hôpitaux de Paris (APHP) , Paris, France.Université de Paris , Paris, France.
INSERM U1144, Optimisation Thérapeutique en Neuropsychopharmacologie , Paris, France.Université de Lille, CNRS, CHU Lille, UMR 9193 - SCALab - Sciences Cognitives et Sciences Affectives , Lille, France.Université de Lille, CHRU Lille, Clinique de Psychiatrie, Unité CURE , Lille, France.Université de Lille, Hôpital Fontan CHRU , Lille, France.
INSERM U955, Equipe Psychiatrie Translationnelle , Créteil, France.
Pôle sectoriel, Centre Hospitalier Fondation Vallée , Gentilly, France.
INSERM U1144, Optimisation Thérapeutique en Neuropsychopharmacologie , Paris, France.Université de Paris , Paris, France.Département de psychiatrie et de médecine addictologique, Assistance Publique des Hôpitaux de Paris (APHP), Centre Hospitalo-Universitaire Bichat-Claude Bernard , Paris, France.
Pôle de Psychiatrie et Psychologie Clinique, Centre Psychothérapique de Nancy , Laxou, France.Faculté de Médecine, Université de Lorraine , France.Clinique soins-études, Fondation Santé des Etudiants de France , Vitry-le-François, France.Fondation FondaMental , Créteil, France.
INSERM U955, Equipe Psychiatrie Translationnelle , Créteil, France.Fondation FondaMental , Créteil, France.Faculté de Médecine, Université Paris Est Créteil , Créteil, France.AP-HP, Hôpitaux Universitaires Henri Mondor, DHU Pepsy, Pôle de Psychiatrie et d'Addictologie , Créteil, France.
INSERM U1144, Optimisation Thérapeutique en Neuropsychopharmacologie , Paris, France.Département de Psychiatrie et de Médecine Addictologique, Hôpital Fernand Widal, Assistance Publique des Hôpitaux de Paris (APHP) , Paris, France.Université de Paris , Paris, France.Fondation FondaMental , Créteil, France.
Association between coffee, tobacco, and alcohol daily consumption and sleep/wake cycle: an actigraphy study in euthymic patients with bipolar disorders.

Mounting evidence indicates that the cerebral cortex is an important physiological system of emotional activity, and its dysfunction may be the main cause of stress. Glutamate is the primary excitatory neurotransmitter in the central nervous system (CNS), which initiates rapid signal transmission in the synapse before its reuptake into the surrounding glia, specifically astrocytes (ASTs). The astrocytic excitatory amino acid transporters 1 (EAAT1) and 2 (EAAT2) are the major transporters that take up synaptic glutamate to maintain optimal extracellular glutamic levels, thus preventing accumulation in the synaptic cleft and ensuing excitotoxicity. Growing evidence has shown that excitotoxicity is associated with depression. Therefore, we hypothesized that the underlying antidepressant-like mechanism of Xiaoyaosan (XYS), a Chinese herbal formula, may be related to the regulation of astrocytic EAATs. Therefore, we studied the antidepressant mechanism of XYS on the basis of EAAT dysfunction in ASTs.Eighty adult C57BL/6 J mice were randomly divided into 4 groups: a control group, a chronic unpredictable mild stress (CUMS) group, a Xiaoyaosan (XYS) treatment group and a fluoxetine hydrochloride (Flu) treatment group. Except for the control group, mice in the other groups all received chronic unpredictable mild stress for 21 days. Mice in the control and CUMS groups received gavage administration with 0.5 mL of normal saline (NS) for 21 days, and mice in the XYS and Flu treatment groups were administered dosages of 0.25 g/kg/d and 2.6 mg/kg/d by gavage. The effects of XYS on the depressive-like behavioral tests, including the open field test (OFT), forced swimming test (FST) and sucrose preference test (SPT), were examined. The glutamate (Glu) concentrations of the prefrontal cortex (PFC) were detected with colorimetry. The morphology of neurons in the PFC was observed by Nissl staining. The expression of glial fibrillary acidic protein (GFAP), NeuN, EAAT1 and EAAT2 proteins in the PFC of mice was detected by using Western blotting and immunohistochemistry. Quantitative real-time PCR (qPCR) was used to detect the expression of the GFAP, NeuN, EAAT1 and EAAT2 genes in the PFC of mice.The results of behavioral tests showed that CUMS-induced mice exhibited depressive-like behavior, which could be improved in some tests with XYS and Flu treatment. Immunohistochemistry and Western blot analysis showed that the protein levels of GFAP, NeuN, EAAT1 and EAAT2 in the PFC of CUMS mice were significantly lower than those in the control group, and these changes could be reversed by XYS and Flu. The results of qPCR analysis showed that the expression of GFAP, NeuN, EAAT1 and EAAT2 mRNAs in the PFC of CUMS mice was not significantly changed, with the exception of EAAT2, compared with that of the control group, while the expression of the above mRNAs was significantly higher in the XYS and Flu groups than that in the CUMS group.XYS may exert antidepressant-like effects by improving the functions of AST and EAATs and attenuating glutamate-induced neuronal damage in the frontal cortex.
School of Pre-clinical Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, China.School of Pre-clinical Medicine, Henan University of Chinese Medicine, Zhengzhou, 450046, China.
School of Traditional Chinese medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing, 100029, China.
School of Pre-clinical Medicine, Henan University of Chinese Medicine, Zhengzhou, 450046, China.
School of Pre-clinical Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, China.
School of Pre-clinical Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, China.School of Traditional Chinese medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing, 100029, China.
School of Pre-clinical Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, China. chenjiaxu@hotmail.com.Formula-pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China. chenjiaxu@hotmail.com.School of Traditional Chinese medicine, Beijing University of Chinese Medicine, No. 11 North Third Ring Road Chaoyang District, Beijing, 100029, China. chenjiaxu@hotmail.com.
BMC complementary and alternative medicine
BMC Complement Altern Med. 2019-08-14;19(1):215.
Xiaoyaosan exerts antidepressant-like effects by regulating the functions of astrocytes and EAATs in the prefrontal cortex of mice.

Associations of GSTM1, GSTT1 and CYP1A1 gene variants with risk of developing nasopharyngeal cancer were evaluated in this case-control study, in which 130 cases along with 151 population-based healthy controls of Pashtun ethnicity from Khyber Pakhtunkhwa province of Pakistan were recruited. Socio-demographic data were obtained and blood samples were collected with informed consent for analysis. Specific RT-PCR and conventional PCR methods were used to detect CYP1A1 and GSTs, respectively, and results analyzed through SPSS version 20. Study showed that CYP1A1 homozygous (C/C) had an almost 4-fold increased risk for nasopharyngeal cancer; while heterozygous (T/C) had an almost 2 times increased risk. Overall the C allele is significantly associated with nasopharyngeal cancer as compared to T allele. Null genotypes of GSTM1 were having 3-fold increased risk; whereas null genotype of GSTT1 was having 2 times increased risk. Similarly, GSTM/GSTT both null genotype was having more than 5 times increased association. Presence of all three gene variants showed strong and significant association. Findings of the study suggest that presence of GSTM1 and/or GSTT1 null genotypes along with variant alleles of CYP1A1 are significant risk factors for nasopharyngeal cancer susceptibility in Pashtun population.
Department of Pharmacy, University of Peshawar, Peshawar, Pakistan.
Institute of Radiotherapy & Nuclear Medicine, Peshawar, Pakistan.
Department of Biotechnology Quaid-i-Azam University, Islamabad, Pakistan.
Pakistan journal of pharmaceutical sciences
Association of nasopharyngeal cancer risk with genetic polymorphisms of drug-metabolizing enzyme genes GSTM1, GSTT1 and CYP1A1 (rs4646903 variant), in tobacco addicted patients of Pashtun ethnicity of Khyber Pakhtunkhwa Province of Pakistan.

Nicotine, the major alkaloid in tobacco, is a toxic, carcinogenic, and addictive compound. In recent years, nicotine catabolism in prokaryotes, including the catabolic pathways for its degradation and the catabolic genes that encode the enzymes of these pathways, have been systemically investigated. In this review, the three known pathways for nicotine catabolism in bacteria are summarized: the pyridine pathway, the pyrrolidine pathway, and a variation of the pyridine and pyrrolidine pathway (VPP pathway). The three nicotine catabolic pathways appear to have evolved separately in three distantly related lineages of bacteria. However, the general mechanism for the breakdown of the nicotine molecule in all three pathways is conserved and can be divided into six major enzymatic steps or catabolic modules that involve hydroxylation of the pyridine ring, dehydrogenation of the pyrrolidine ring, cleavage of the side chain, cleavage of the pyridine ring, dehydrogenation of the side chain, and deamination of pyridine ring-lysis products. In addition to summarizing our current understanding of nicotine degradation pathways, we identified several potential nicotine-degrading bacteria whose genome sequences are in public databases by comparing the sequences of conserved catabolic enzymes. Finally, several uncharacterized genes that are colocalized with nicotine degradation genes and are likely to be involved in nicotine catabolism, including regulatory genes, methyl-accepting chemotaxis protein genes, transporter genes, and cofactor genes are discussed. This review provides a comprehensive overview of the catabolism of nicotine in prokaryotes and highlights aspects of the process that still require additional research.
Copyright © 2020 Elsevier Inc. All rights reserved.
Department of Microbiology, College of Life Sciences, Key Laboratory of Environmental Microbiology for Agriculture, Ministry of Agriculture, Nanjing Agricultural University, Nanjing, 210095, China; Department of Microbiology and Molecular Genetics, College of Biological Sciences, University of California, Davis, Davis, CA, USA.
College of Life Sciences, Zaozhuang University, Zaozhuang, 277160, China.
Department of Microbiology and Molecular Genetics, College of Biological Sciences, University of California, Davis, Davis, CA, USA.
College of Life Sciences, Zhejiang University, Hangzhou, 310058, China.
Department of Microbiology, College of Life Sciences, Key Laboratory of Environmental Microbiology for Agriculture, Ministry of Agriculture, Nanjing Agricultural University, Nanjing, 210095, China.
Department of Microbiology, College of Life Sciences, Key Laboratory of Environmental Microbiology for Agriculture, Ministry of Agriculture, Nanjing Agricultural University, Nanjing, 210095, China. Electronic address: qiujiguo@njau.edu.cn.
Department of Microbiology, College of Life Sciences, Key Laboratory of Environmental Microbiology for Agriculture, Ministry of Agriculture, Nanjing Agricultural University, Nanjing, 210095, China. Electronic address: jiang_jjd@njau.edu.cn.
Bacterial catabolism of nicotine: Catabolic strains, pathways and modules.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Tobacco use is the main risk factor for HNSCC, and tobacco-associated HNSCCs have poor prognosis and response to available treatments. Recently approved anti-PD-1 immune checkpoint inhibitors showed limited activity (≤20%) in HNSCC, highlighting the need to identify new therapeutic options. For this, mouse models that accurately mimic the complexity of the HNSCC mutational landscape and tumor immune environment are urgently needed. Here, we report a mouse HNSCC model system that recapitulates the human tobacco-related HNSCC mutanome, in which tumors grow when implanted in the tongue of immunocompetent mice. These HNSCC lesions have similar immune infiltration and response rates to anti-PD-1 (≤20%) immunotherapy as human HNSCCs. Remarkably, we find that >70% of HNSCC lesions respond to intratumoral anti-CTLA-4. This syngeneic HNSCC mouse model provides a platform to accelerate the development of immunotherapeutic options for HNSCC.
Moores Cancer Center, University of California San Diego, 3855 Health Sciences Drive, La Jolla, CA, USA.
Moores Cancer Center, University of California San Diego, 3855 Health Sciences Drive, La Jolla, CA, USA.Department of Pharmacology, University of California San Diego, La Jolla, CA, USA.
Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
Cancer Biology and Immunotherapies Group, Sanford Research, Sioux Falls, SD, USA.
National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
International College of Dentistry, Walailak University, Nakhon Si Thammarat, Thailand.
Moores Cancer Center, University of California San Diego, 3855 Health Sciences Drive, La Jolla, CA, USA.Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA.
Moores Cancer Center, University of California San Diego, 3855 Health Sciences Drive, La Jolla, CA, USA.Department of Medicine, Division of Hematology-Oncology, University of California, San Diego, La Jolla, CA, USA.
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Dermatology, Bosch Institute, University of Sydney, Camperdown, NSW, 2050, Australia.Cancer Services, Royal Prince Alfred Hospital, Camperdown, NSW, 2050, Australia.Centenary Institute, Camperdown, NSW, 2050, Australia.
Moores Cancer Center, University of California San Diego, 3855 Health Sciences Drive, La Jolla, CA, USA.Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
Moores Cancer Center, University of California San Diego, 3855 Health Sciences Drive, La Jolla, CA, USA. sgutkind@ucsd.edu.Department of Pharmacology, University of California San Diego, La Jolla, CA, USA. sgutkind@ucsd.edu.
Syngeneic animal models of tobacco-associated oral cancer reveal the activity of in situ anti-CTLA-4.

In this study, the association between students' substance use and suicide attempts in the past 1 year was examined using secondary data from the 13th Korea Risk Behavior Web-based Survey. Participants were 7th- to 12th-grade students and 50.9% were male. A binominal logistic regression analysis was used to investigate the association between past experience of substance use (alcohol, tobacco, and caffeine) and suicide attempts after controlling for sociodemographic and psychological factors. Compared with no use, daily use of alcohol (odds ratio [OR] = 8.00), caffeine (OR = 2.13), and tobacco (OR = 1.41) was associated with increased odds of suicide attempts. These results indicate that school-based suicide prevention programs should cover awareness, surveillance, and treatment referral for these 3 substances. Moreover, mental health professionals should monitor intake of these substances when evaluating risk of suicide attempts in youth.
Ewha Womans University, Seoul, Republic of Korea.
Journal of primary care & community health
J Prim Care Community Health. ;11():2150132720913720.
Use of Alcohol, Tobacco, and Caffeine and Suicide Attempts: Findings From a Nationally Representative Cross-sectional Study.

Our early studies demonstrated an impressive chemopreventive efficacy of dihydromethysticin (DHM), unique in kava, against tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in A/J mice in which DHM was supplemented in the diet. The current work was carried out to validate the efficacy, optimize the dosing schedule, and further elucidate the mechanisms using oral bolus dosing of DHM. The results demonstrated a dose-dependent chemopreventive efficacy of DHM (orally administered 1 h before each of the two NNK intraperitoneal injections, 1 week apart) against NNK-induced lung adenoma formation. Temporally, DHM at 0.8 mg per dose (∼32 mg per kg body weight) exhibited 100% lung adenoma inhibition when given 3 and 8 h before each NNK injection and attained >93% inhibition when dosed at either 1 or 16 h before each NNK injection. The simultaneous treatment (0 h) or 40 h pretreatment (-40 h) decreased lung adenoma burden by 49.8% and 52.1%, respectively. However, post-NNK administration of DHM (1-8 h after each NNK injection) was ineffective against lung tumor formation. In short-term experiments for mechanistic exploration, DHM treatment reduced the formation of NNK-induced O6-methylguanine (O6-mG, a carcinogenic DNA adduct in A/J mice) in the target lung tissue and increased the urinary excretion of NNK detoxification metabolites as judged by the ratio of urinary NNAL-O-gluc to free NNAL, generally in synchrony with the tumor prevention efficacy outcomes in the dose scheduling time-course experiment. Overall, these results suggest DHM as a potential chemopreventive agent against lung tumorigenesis in smokers, with O6-mG and NNAL detoxification as possible surrogate biomarkers.
Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, Florida 32610, United States.
Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, Florida 32610, United States.Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, United States.
Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, United States.
Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, United States.
Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, United States.Department of Veterinary Population Medicine, University of Minnesota, St. Paul, Minnesota 55108, United States.
Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, United States.
Oral Dosing of Dihydromethysticin Ahead of Tobacco Carcinogen NNK Effectively Prevents Lung Tumorigenesis in A/J Mice.

Electronic cigarettes (ECs) are categorized into generations which differ in terms of design, aerosol production, and customizability. Current and former smokers prefer third-generation devices that satisfy tobacco cravings more effectively than older generations. Recent studies indicate that EC aerosols from first- and second-generation devices contain reactive carbonyls and free radicals and can cause in vitro cytotoxicity. Third-generation ECs have not been adequately studied. Further, previous studies have focused on cells from the respiratory tract, whereas those of the oral cavity, which is exposed to high levels of EC aerosols, have been understudied. We quantified the production of reactive carbonyls and free radicals by a third-generation EC and investigated the induction of cytotoxicity and oxidative stress in normal and cancerous human oral cell lines using a panel of eight commercial EC liquids. We found that EC aerosols produced using a new atomizer contained formaldehyde, acetaldehyde, and acrolein, but did not contain detectable levels of free radicals. We found that EC aerosols generated from only one of the eight liquids tested using a new atomizer induced cytotoxicity against two human oral cells in vitro. Treatment of oral cells with the cytotoxic EC aerosol caused a concomitant increase in intracellular oxidative stress. As atomizer age increased with repeated use of the same atomizer, carbonyl production, radical emissions, and cytotoxicity increased. Overall, our results suggest that third-generation ECs may cause adverse effects in the oral cavity and normal EC use, which involves repeated use of the same atomizer to generate aerosol, may enhance the potential toxic effects of third-generation ECs.
Department of Food Science, The Pennsylvania State University, University Park, Pennsylvania 16802, United States.
Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802, United States.
Department of Food Science, The Pennsylvania State University, University Park, Pennsylvania 16802, United States.Center for Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, Pennsylvania 16802, United States.
Impact of Atomizer Age and Flavor on In Vitro Toxicity of Aerosols from a Third-Generation Electronic Cigarette against Human Oral Cells.

Lung cancer coexisting with idiopathic pulmonary fibrosis (IPF) or chronic obstructive pulmonary disease (COPD) can lead to poor prognosis. Telomere-related polymorphisms may be implicated in the pathogenesis of these three lung diseases. As to elucidate the mechanism of lung cancer via IPF or COPD may enable early detection and early treatment of the disease, we firstly examined the association between telomere-related polymorphisms and the risk of IPF and COPD in a case-control study.A total of 572 patients with IPF (n = 155) or COPD (n = 417), who were derived from our on-going cohort study, and controls (n = 379), who were derived from our previous case-control study, were included in this study. Telomerase reverse transcriptase (TERT) rs2736100, telomere RNA component (TERC) rs1881984, and oligonucleotide/oligosaccharide-binding fold containing1 (OBFC1) rs11191865 were genotyped with real-time PCR using TaqMan fluorescent probes. Unconditional logistic regression was used to assess the adjusted odds ratios and 95% confidence intervals.TERT rs2736100 was significantly associated with the risk of IPF; increases in the number of this risk allele increased the risk of IPF (Ptrend = 0.008). Similarly, TERT rs2736100 was associated with the risk of COPD. In regard to the combined action of the three loci, increasing numbers of at-risk genotypes increased the risk of IPF in a dose-dependent manner (P trend=0.003).TERT rs2736100 was associated with the risks of both IPF and COPD in a Japanese population. A combination of the at-risk genotypes might be important to identify the population at risk for IPF more clearly.
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University,Fukuoka,Japan.
Kirigaoka Tsuda Hospital, Fukuoka, Japan.
Division of Respiratory Medicine, National Hospital Organization, Fukuoka Higashi Medical Center, Fukuoka, Japan.
Division of Respiratory Medicine, Kyushu Rosai Hospital, Fukuoka, Japan.
Department of Respiratory Medicine, Fukuoka University Chikushi Hospital, Fukuoka, Japan.
Department of Respiratory Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, Fukuoka, Japan.
Department of Respiratory Medicine, Wakamatsu Hospital of the University of Occupational and Environmental Health, Japan, Fukuoka, Japan.
Division of Respirology, Neurology, and Rheumatology, Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan.
Department of Respiratory Medicine, Fukuoka University School of Medicine, Fukuoka, Japan.
Association between Telomere-Related Polymorphisms and the Risk of IPF and COPD as a Precursor Lesion of Lung Cancer: Findings from the Fukuoka Tobacco-Related Lung Disease (FOLD) Registry.

Oropharyngeal squamous cell carcinoma (OPSCC) incidence is increasing at a nearly epidemic rate, largely driven by the human papillomavirus (HPV). Despite the generally favorable clinical outcomes of patients with HPV driven (HPV+) OPSCC, a significant subset of HPV tumors associated with tobacco exposure have diminished treatment response and worse survival. The tumor immune microenvironment (TIME) has been shown to be a critical driver of treatment response and oncologic outcomes in OPSCC generally and HPV+ OPSCC more specifically. However, the impact of tobacco exposure on the TIME in OPSCC patients remains unclear. We analyzed the relationship between TIME, tobacco exposure and clinical outcomes in OPSCC patients (n = 143) with extensive tobacco exposure (median pack-years = 40). P16 overexpression, a surrogate marker of HPV association, was a strong predictor of relapse-free (RFS) and overall survival (OS) (p < 0.001, p < 0.001 respectively) regardless of tobacco exposure and associated strongly with differential infiltration of the tumor by both CD3 and CD8 lymphocytes measured via immunohistochemistry (p < 001, p < 0.001 respectively). CD3 and CD8 infiltration was a strong predictor of RFS and OS and associated strongly with disease stage (AJCC 8th Edition Staging Manual). Tobacco exposure correlated significantly (p < 0.001) with decreased CD8 infiltration in p16+ OPSCC tumors. Our findings demonstrate that the HPV+ OPSCC clinical outcomes are strongly correlated with the TIME, which is potentially modulated by tobacco exposure. Immunomodulatory strategies targeting this disease in smokers must take into consideration the potential modifying effects of tobacco exposure on treatment effectiveness and clinical outcomes.
Department of Medicine, Section of Hematology Oncology, Baylor College of Medicine, Houston, TX, USA.
Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA.
Bobby R. Alford Department of Otolaryngology- Head and Neck Surgery, Baylor College of Medicine, Houston, TX, USA.
Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Bobby R. Alford Department of Otolaryngology- Head and Neck Surgery, Baylor College of Medicine, Houston, TX, USA.Operative Care Line, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA.
Bobby R. Alford Department of Otolaryngology- Head and Neck Surgery, Baylor College of Medicine, Houston, TX, USA. vlad.sandulache@bcm.edu.Operative Care Line, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA. vlad.sandulache@bcm.edu.
CD8 infiltration is associated with disease control and tobacco exposure in intermediate-risk oropharyngeal cancer.

Diabetes and tobacco use are two of the largest public health challenges of our time. We aim to investigate the association between the two by comparing biochemical profiles of diabetic tobacco users (TUs) and tobacco nonus-ers (TNUs) to provide insight into the joint effect of tobacco and diabetes on body systems. This case-controlled study included 265 subjects, aged 18-60 yr, from the suburban population of Delhi, India. With the help of a questionnaire, participants are interviewed regarding their history of tobacco use. Results show association of tobacco use with elevated body-mass index, blood glucose levels, and insulin resistance in otherwise healthy and diabetic TUs. Even without previous history of coronary heart disease, total cholesterol and triglycerides are significantly further increased in TUs rather than in TNUs, indicative of initiation of lipid metabolism disorders. Tobacco use is also seen as a cause of oxidant/antioxidant imbalance in the body. Low serum albumin coupled with increased markers of inflammation and globulin levels is an indicator of generalized inflammation caused by tobacco's toxic effects. Creatinine levels are significantly higher in diabetic TUs, posing a threat to nephropathy progression. Evidence sufficiently infers that tobacco activates multiple biological pathways, through which the risk of metabolic disease increases. These factors may work in conjunction to increase risk of certain microvascular and macrovascular complications.
Department of Biochemistry, HIMSR & HAHC Hospital, Jamia Hamdard, New Delhi 110062, India.
Department of Medicine, National Heart Institute, New Delhi 110065, India.
Department of Biotechnology, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi 110062, India.
Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer
J Environ Pathol Toxicol Oncol. 2020;39(1):23-37.
Effects of Tobacco on Biochemical Parameters in Healthy and Type 2 Diabetic Subjects.

Background: Betel quid chewing is a deep-rooted practice in India and neighboring countries, which has migrated to other parts of the world. Betel leaf acts as a carrier for areca nut and most often, smokeless tobacco, both of which are carcinogenic, making betel quid a harmful product. Objectives: The first objective was to compare the prevalence of use of betel quid with tobacco from GATS-1 to GATS-2. The second was to study the association of use of betel quid with and without tobacco with different socio-economic groups (wealth quintiles) according to select background characteristics. Methods: This study used data from the Global Adult Tobacco Surveys (GATS), 2009-10 and 2016-17. Logistic regression with adjustment of co-variates (age, gender, residence and education) was used to study association of use of betel quid with different socio-economic groups. Results: Highest reduction (40 percent) was seen in use of betel quid with tobacco among male youth (15-24 years) over the two rounds of GATS. No change was seen in this form of use among females. The odds of use of betel quid with tobacco had a positive gradient with decreasing wealth quintiles. Use of betel quid without tobacco showed highest odds among participants with moderate levels of education. Conclusion: Health promotion interventions around harmful effects of betel quid with and without tobacco are needed for all genders from poorer populations with low education. Stress needs to be laid on universal population-level public health awareness campaigns about the carcinogenic properties of areca nut in betel quid.
Public Health Foundation of India, Gurugram, India.HRIDAY, New Delhi, India.
Public Health Foundation of India, Gurugram, India.
Use of Betel Quid in India from 2009 to 2017: An Epidemiological Analysis of the Global Adult Tobacco Survey (GATS).

Department of Hygiene and Public Health, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan. Electronic address: kawada@nms.ac.jp.
High lithium levels in tobacco, incidences of Parkinson's disease and melanoma: Mechanism of the association.

Numerous groups, such as the tobacco industry, have deliberately altered and misrepresented knowable facts and empirical evidence to promote an agenda, often for monetary benefit, with consequences for environmental and public health. Previous research has explored cases individually, but none have conducted an in-depth comparison between cases. The purpose of this study was to compile a comprehensive list of tactics used by disparate groups and provide a framework for identifying further instances of manufactured doubt.We examined scholarly books, peer-reviewed articles, well-researched journalism pieces, and legal evidence related to five disparate industries and organizations selected for their destructive impacts on environmental and public health (tobacco, coal, and sugar industries, manufacturers of the pesticide Atrazine, and the Marshall Institute, an institute focused on climate change research, and other scientists from the era that associated with those in the Institute). These documents provided evidence for a list of tactics used to generate pro-industry spin and manufacture doubt about conferred harm. We then identified trends among sets of strategies that could explain their differential use or efficacy.We recognized 28 unique tactics used to manufacture doubt. Five of these tactics were used by all five organizations, suggesting that they are key features of manufactured doubt. The intended audience influences the strategy used to misinform, and logical fallacies contribute to their efficacy.This list of tactics can be used by others to build a case that an industry or group is deliberately manipulating information associated with their actions or products. Improved scientific and rhetorical literacy could be used to render them less effective, depending on the audience targeted, and ultimately allow for the protection of both environmental health and public health more generally.
Graduate Program in Epidemiology, School of Public Health and Health Sciences, University of Massachusetts Amherst, Amherst, USA.
Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts Amherst, 171C Goessmann, 686 N. Pleasant Street, Amherst, MA, 01003, USA. lvandenberg@schoolph.umass.edu.
Environmental health : a global access science source
The science of spin: targeted strategies to manufacture doubt with detrimental effects on environmental and public health.

Department of Gynecology and Obstetrics, Paule de Viguier Hospital, CHU Toulouse, INSERM UMR 1048, I2MC, Université de Toulouse, Toulouse, France.
Department of Obstetrics, CHU Lille, University of Lille, ULR 2694-METRICS, Lille, France.
Department of Obstetrics and Gynecology, Poissy-Saint-Germain Hospital, Poissy, France.
Department of Gynecology & Obstetrics, Angers University Hospital (CHU d'Angers), Angers, France.
Department of Obstetrics, Port-Royal Maternity Unit, Paris, Hôpitaux Universitaires Paris Centre, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France.
Département de Pharmacologie, Hôpital Pitié-Salpêtrière, Paris, France; and Centre Universitaire de Médecine Générale et Santé Publique, UNISANTE, Université de Lausanne, Switzerland.
CNGOF and SFT Expert Report and Guidelines Group
Tobacco and Nicotine Cessation During Pregnancy.

This study investigates the effect of smokeless tobacco on the tribological properties of two commercially used dental composite materials: Tetric N-Ceram and Z350 Dentin shade. It is to evaluate the effect of smokeless tobacco on the wear properties of two dental composite materials after some stipulated period. The wear test was conducted on pin-on-disk tribometer in the presence of artificial saliva under different loading conditions of 10, 15 and 20 N. The pins of the dental composite material were immersed in tobacco solution. The tribological behavior was studied after 2 days, 3.5 days, 6 days, 15 days and 1 month which represented the real conditions for the contact of 1 week, 2 weeks, 1 month, 2 months and 5 months, respectively, between the dental material and the tobacco solution. Under different loading conditions, Z350 Dentin material exhibited much less wear than the Tetric N-Ceram material in the presence of synthetic saliva for the specimen with or without tobacco immersion. The microstructure of the pin surface was inspected using scanning electron microscopy.
School of Mechanical Engineering (SMEC), VIT, Vellore, India.
Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine
Tribological behavior of dental restorative composites in chewable tobacco environment.

As early sexual initiation is increasingly common in East Asia, we examined its relations to risky sexual practices in alcohol- and tobacco-using individuals in Taiwan and evaluated whether the associations were mediated through preceding-sex use of illicit drugs.Participants, recruited from alcohol- and tobacco-using adults aged 18 to 50 in Taipei through respondent-driven sampling (N = 1115), completed a computer-assisted self-interview covering questions on substance use and sexual experiences. In a subsample of 916 participants who had had sexual experience (median age 27), we examined the relations of early sexual initiation (< 16 years) to multiple sexual partners, casual sex, group sex, and rare condom use. Causal mediation analyses were conducted to examine whether illicit drug use preceding sex mediated these associations.Around 9.3% reported early sexual initiation and the prevalence of risky sexual practices ranged from 7% (group sex) to 47% (rare condom use). Early initiators had a higher prevalence of regular binge drinking, illicit drug use, and risky sexual practices. In the multivariable analyses, higher odds of multiple sexual partners, casual sex, and group sex were consistently associated with early sexual initiation, gender, and their interaction. Mediation through preceding-sex use of illicit drugs was found between early sexual initiation and the three risky sexual practices, with the proportions mediated ranging from 17 to 19%.Early sexual initiators were more likely to engage in risky sexual practices and preceding-sex use of illicit drugs partially explained this relationship, calling for more attention to this population's sexual health.
Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
School of Big Data Management, Soochow University, Taipei, Taiwan.
Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.Institute of Public Health, National Yang-Ming University, Taipei, Taiwan.Center for Neuropsychiatric Research, National Health Research Institutes, Zhunan, Miaoli County, Taiwan.
Kunming Prevention and Control Center, Taipei City Hospital, Taipei, Taiwan.
Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan. wjchen@ntu.edu.tw.Center for Neuropsychiatric Research, National Health Research Institutes, Zhunan, Miaoli County, Taiwan. wjchen@ntu.edu.tw.Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan. wjchen@ntu.edu.tw.Department of Psychiatry, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan. wjchen@ntu.edu.tw.
Early sexual initiation and risky sexual practices among alcohol- and tobacco-using young adults in Taiwan: mediation analysis of preceding-sex use of illicit drugs.

Department of Public Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea.
Southern Gyeonggi Regional Smoking Cessation Centre, Hallym University, Anyang, Gyeonggi-do, Republic of Korea.
National Tobacco Control Centre, Korea Health Promotion Institute, Seoul, Republic of Korea wwwvince77@gmail.com.
British American Tobacco's 'Glo Sens' promotion with K-pop.

Institute of Public Health & Social Sciences, Khyber Medical University, Peshawar, Pakistan.Office of Research, Innovation & Commercialization, Khyber Medical University, Peshawar, Pakistan.
Department for Health, Tobacco Control Research Group (TCRG), University of Bath, Bath, UK.
Department of Health Sciences, University of York, York, UK.
Tobacco Control Cell, Ministry of National Health Services Regulations and Coordination, Government of Pakistan, Islamabad, Pakistan.
Big Tobacco's Predictable Prebudget Tantrums in Pakistan.

Laboratoire de Parasitologie-Mycologie, Centre Hospitalier Régional Universitaire de Besançon, Besançon, France; Centre National de Référence Echinococcoses, Centre Hospitalier Régional Universitaire de Besançon, Besançon, France; UMR 6249, Chronoenvironnement, Université de Franche-Comté, 25030 Besançon, France; Services d'Hepato-Gastroenterologie et; de Médecine Tropicale et Humanitaire, Hôpitaux Universitaires de Genève, Suisse. Electronic address: sbresson@chu-besancon.fr.
Laboratoire de Parasitologie-Mycologie, Centre Hospitalier Régional Universitaire de Besançon, Besançon, France; Laboratoire de Pharmacologie Clinique, Centre Hospitalier Régional Universitaire de Besançon, Besançon, France.
Laboratoire de Parasitologie-Mycologie, Centre Hospitalier Régional Universitaire de Besançon, Besançon, France; Service d'Hépatologie, Centre Hospitalier Régional Universitaire de Besançon, Besançon, France.
Laboratoire de Parasitologie-Mycologie, Centre Hospitalier Régional Universitaire de Besançon, Besançon, France; Service de Radiologie Viscérale, Centre Hospitalier Régional Universitaire de Besançon, Besançon, France.
Service de Maladies Infectieuses, Centre Hospitalier Chalon sur Saône, France.
Cabinet de Radiologie des Hauts de Chazal, Besançon, France.
Laboratoire de Parasitologie-Mycologie, Centre Hospitalier Régional Universitaire de Besançon, Besançon, France; Service de Médecine Nucléaire, Centre Hospitalier Régional Universitaire de Besançon, Besançon, France.
Laboratoire de Parasitologie-Mycologie, Centre Hospitalier Régional Universitaire de Besançon, Besançon, France; UMR 6249, Chronoenvironnement, Université de Franche-Comté, 25030 Besançon, France; Sérologie Infectieuse, Centre Hospitalier Régional Universitaire de Besançon, Besançon, France.
Centre National de Référence Echinococcoses, Centre Hospitalier Régional Universitaire de Besançon, Besançon, France.
Laboratoire de Parasitologie-Mycologie, Centre Hospitalier Régional Universitaire de Besançon, Besançon, France; Centre National de Référence Echinococcoses, Centre Hospitalier Régional Universitaire de Besançon, Besançon, France; UMR 6249, Chronoenvironnement, Université de Franche-Comté, 25030 Besançon, France.
Tobacco, cannabis, and liquorice: Hidden players altering albendazole metabolism in patients with hepatic alveolar echinococcosis.

Radiotherapy and cisplatin lead to cell killing in head and neck squamous cell carcinoma patients, but adverse events and response to treatment are not the same in patients with similar clinicopathological aspects. The aim of this prospective study was to evaluate the roles of TP53 c.215G > C, FAS c.-671A > G, FAS c.-1378G > A, FASL c.-844 C > T, CASP3 c.-1191A > G, and CASP3 c.-182-247G > T single nucleotide variants in toxicity, response rate, and survival of cisplatin chemoradiation-treated head and neck squamous cell carcinoma patients. Genomic DNA was analyzed by polymerase chain reaction for genotyping. Differences between groups of patients were analyzed by chi-square test or Fisher's exact test, multiple logistic regression analysis, and Cox hazards model. One hundred nine patients with head and neck squamous cell carcinoma were enrolled in study. All patients were smokers and/or alcoholics. Patients with FAS c.-671GG genotype, FAS c.-671AG or GG genotype, and FASL c.-844CC genotype had 5.52 (95% confidence interval (CI): 1.42-21.43), 4.03 (95% CI: 1.51-10.79), and 5.77 (95% CI: 1.23-27.04) more chances of presenting chemoradiation-related anemia of grades 2-4, lymphopenia of grade 3 or 4, and ototoxicity of all grades, respectively, than those with the remaining genotypes. FAS c.-671GG genotype was also seen as an independent predictor of shorter event-free survival (hazard ratio (HR): 2.05; P = 0.007) and overall survival (HR: 1.83; P = 0.02) in our head and neck squamous cell carcinoma patients. These findings present, for the first time, preliminary evidence that inherited abnormalities in apoptosis pathway, related to FAS c.-671A > G and FASL c.-844 C > T single nucleotide variants, can alter toxicity and survival of tobacco- and alcohol-related head and neck squamous cell carcinoma patients homogeneously treated with cisplatin chemoradiation.
Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
Department of Clinical Pathology, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
Department of Ophthalmology and Otorhinolaryngology, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
Department of Pathology, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
Department of Radiology, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
FAS and FASL variations in outcomes of tobacco- and alcohol-related head and neck squamous cell carcinoma patients.

Department of Hepatogastroenterology, Hepatology and Liver Transplant Unit, Saint Eloi Hospital, University of Montpellier, Montpellier, France.
Letter to the Editor: Cancer After Liver Transplant: Don't Forget Tobacco and Tacrolimus.

To establish a nicotine intravenous self-administration rat model, and to examine, with this model, the effects of two flavoring additives, menthol and cineole, on nicotine dependence.Thirty male Sprague-Dawley (SD) rats were included in the study. After jugular venous catheterization was performed, fixed concentration of nicotine was administered in order to train the rats and establish the rat model of intravenous self-administration groups, receiving intraperitoneal injection of menthol, cineole, and dimethyl sulfoxide (DMSO), the vehicle that was used for the control group. The rats were tested with different fixed-ratio (FR) schedules, including FR1 schedule, in which the rat received one nicotine infusion for every active nose poke, FR2 schedule, in which the rat received one nicotine infusion for every two active nose pokes, and FR5 schedule, in which the rat received one nicotine infusion for every five active nose pokes. The number of active and inactive poke responses and the number of nicotine infusion were documented accordingly.After 10 days of training in nicotine self-administration, the 30 rats demonstrated significant increase in the number of active poke responses and the number of nicotine infusion, which were maintained at a stable and relatively high level. The number of active poke responses was significantly higher that of inactive poke responses ( P< 0.001). The rat model of intravenous nicotine self-administration was successfully established. In the testing phase, under the FR2 schedule, the menthol group showed a reduced number of active poke responses ( P=0.020). Under the FR5 schedule, the groups showed obvious interaction between time and the number of active poke responses ( P<0.011), with the menthol group showing reduced number of active poke responses on day three ( P=0.011) and the cineole group showing rising number of active poke responses on day three ( P=0.003). The DMSO control group did not show any significant change.Menthol and cineole are shown to have an effect on nicotine dependence. When there is relative difficulty involved in obtaining nicotine, menthol suppresses nicotine dependence, whereas cineole enhances nicotine dependence.
Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).
Mental Health Center, West China Hospital, Sichuan University, Chengdu 610041, China.
Chongqing Municipal Key Laboratory of Scientific Utilization of Tobacco Resources, Chongqing 400060, China.
Department of Psychiatry, Suzhou Psychiatric Hospital, Suzhou 215137, China.
Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition
Sichuan Da Xue Xue Bao Yi Xue Ban. 2021-07;52(4):649-654.
[Animal Experimental Study of the Role of Menthol and Cineole, Two Tobacco Additives, on Nicotine Dependence].

Osteosarcoma is a challenging bone disease which is commonly associated with critically sized bone defects and cancer recurrence. Here, we designed and developed a multifunctional, hierarchical structured bone scaffold which can meet the demanding requirements for osteosarcoma management. The 3D printed Ti6Al4V scaffold with hydrothermally induced TiO2/TiP coating can offer a unique photothermal conversion property for in vitro bone cancer ablation. The scaffold is also infused with drug-laden gelatin/hydroxyapatite nanocomposite, which provides the ideal porous structure for cell adhesion/bone ingrowth and promotes bone regeneration. The scaffold has been thoroughly characterized by SEM/EDX, TEM, XPS, XRD, TGA, and UV-vis, and its in vitro bone cancer ablation efficiency has been validated using MG-63 cells. The hybrid scaffold showed excellent biocompatibility, and its osteointegration function has been demonstrated using an animal model.
Analytical & Testing Center, Department of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu 610065, China.College of Medical Technology and Engineering, Henan University of Science and Technology, 263 Kaiyuan Avenue, Luoyang 471023, China.
Analytical & Testing Center, Department of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu 610065, China.
Advanced Composite Research Group (ACRG), School of Mechanical and Aerospace Engineering, Queens University Belfast, Belfast BT9 5AH, United Kingdom.
Institute of Metal Research, Chinese Academy of Sciences, 72 Wenhua Road, Shenyang 110016, China.
School of Materials Science and Physics, China University of Mining and Technology, Xuzhou 221116, China.
3D Printed Multifunctional Ti6Al4V-Based Hybrid Scaffold for the Management of Osteosarcoma.

The Tobacco Industry (henceforth TI) yearns to portray itself as being socially responsible and fights for the decision-making positions; that are it used to deter, delay or dilute tobacco control measures. There is little documented evidence of Tobacco Industry Interference (henceforth TII) from India, the scope of their interference and challenges faced by the experts for effective tobacco control. This research study seeks to cover this significant gap in the literature on the TI of India.A cross-sectional qualitative research design, based upon in-depth interviews (N = 26), was used to explore the key stakeholders' opinions regarding TII in India. The interviews used a set of questions to collect information about the participant's roles and responsibilities in tobacco control, the nature of TII faced by the participants, means of influence by TI, barriers and challenges to tobacco control efforts.Most of the respondents were engaged in tobacco control, training, advocacy and awareness generation activities for 5-10 years or more. The respondents defined the TI and its scope as per their experience with the help of the power ranking methodology. Most of them perceived TI as 'manufacturers' while others consider them as 'advertisers', 'public relation companies', 'wholesalers', 'vendors', and 'Government firms with TI stocks. The research team identified six significant domains: influencing the policy and administrative decisions, Interference in the implementation of tobacco control laws and activities, false propaganda and hiding the truth, manipulating front action groups (FAG), rampant tobacco advertising and promotion activities and others under which TII activities were classified. Most respondents believed that TI players were interfering in the policy decisions, implementing the tobacco control laws and activities and manipulating the FAG. A detailed taxonomic classification of the TII strategies that emerged from our analysis was linked to article 5.3 of FCTC.The study documented a significant level of TII in different domains, with stakeholders acting at various hierarchical levels. Thus providing insight into the tactics of the TI in order to enable stakeholders to anticipate and pre-empt the kinds of alliances the TI may attempt to build; stimulating academicians and researchers to undertake in-depth analysis into various strategies and therefore underscoring the need to ensuring transparency in official interaction with the TI and its representatives.
Department of Community Medicine and School of Public Health, Post Graduate Institute of Medical Education and Research, Sector 12, Chandigarh, 160012, India. sonugoel007@yahoo.co.in.Public Health Masters Program at School of Medicine, University of Limerick, Limerick, Ireland. sonugoel007@yahoo.co.in.Faculty of Human and Health Sciences, Swansea University, Swansea, United Kingdom. sonugoel007@yahoo.co.in.
Department of Preventive & Social Medicine, Jawaharlal Institute of Postgraduate Institute of Medical Education & Research, Puducherry, India.
Department of Community and Family Medicine, All India Institute of Medical Sciences Bathinda, Bathinda, Punjab, India.
Community & Family Medicine, All India Institute of Medical Sciences Patna, Patna, India.
Department of English and Cultural Studies, Panjab University, Chandigarh, India.
Evidence on article 5.3 of FCTC (tobacco industry interference in tobacco control activities) in India- a qualitative scoping study.

A desirable tester that elicits greater genetic difference in Striga resistance among test crosses in a breeding program has not been reported. Therefore, this study was conducted to characterize 30 Striga resistant yellow endosperm maize inbred lines and three testers with varying resistance levels to Striga using DArTseq SNP markers and agronomic traits to identify a suitable tester for resistance hybrid breeding. Marker-based and agronomic trait-based genetic distances were estimated for yellow endosperm maize inbred lines and testers with varying resistance levels to Striga. The Marker-based cluster analysis separated the Striga resistant lines and testers into two distinct groups. Although the susceptible tester (T3) was the most distantly related to the 30 Striga resistant inbred lines, it exhibited a narrower range in genetic distance estimates and poor agronomic performance under Striga infestation in crosses with the resistant lines. In contrast, the resistant tester (T2) showed a broader range in genetic distance estimates in pairs with the 30 resistant lines. Also, it formed many high yielding hybrids with desirable traits under parasite pressure. Furthermore, the most significant positive association between agronomic trait-based and marker-based distance estimates (r = 0.389, P = 0.01) was observed when T2 has paired with the Striga resistant maize inbred lines. It thus appears that T2 may be used as a suitable tester to determine the breeding value of lines in hybrid maize resistance breeding programs. T2 was the most suitable tester, with a tolerant tester (T1) as an alternative tester to characterize the combining ability of Striga resistant maize inbred lines. This result can also encourage other breeders to investigate testers relative discriminating ability with varying levels of resistance in hybrid breeding for resistance to diseases, pests, and other parasitic plants.
International Institute of Tropical Agriculture (IITA), Ibadan, Nigeria.Pan Africa University of Life and Earth Sciences Institute, University of Ibadan, Ibadan, Nigeria.Department of Plant Science, College of Agricultural Sciences, Arba Minch University, Arba Minch, Ethiopia.
International Institute of Tropical Agriculture (IITA), Ibadan, Nigeria.
Department of Agronomy, University of Ibadan, Ibadan, Nigeria.
Identifying suitable tester for evaluating Striga resistant lines using DArTseq markers and agronomic traits.

The present work describes the first visible light-assisted, metal-free and organic base 1,1,3,3-tetramethyl guanidine (TMG) mediated synthesis of unsymmetrical methyl aryl/alkyl carbonates from the reaction of alcohols, methanol, and CO2 in high to excellent yields under atmospheric pressure and ambient temperature conditions.
Chemical & Material Sciences Division, CSIR-Indian Institute of Petroleum, Haridwar Road, Mohkampur, Dehradun-248005, India. suman@iip.res.in.Academy of Scientific and Innovative Research, Ghaziabad-201002, India.
Department of Chemical Sciences, Tezpur University, Napaam, Tezpur-784028, Assam, India.
Chemical & Material Sciences Division, CSIR-Indian Institute of Petroleum, Haridwar Road, Mohkampur, Dehradun-248005, India. suman@iip.res.in.
Light-induced synthesis of unsymmetrical organic carbonates from alcohols, methanol and CO2 under ambient conditions.

Treatment for advanced gastric cancer is challenging. Epidermal growth factor receptor (EGFR) contributes to the proliferation and development of gastric cancer (GC), and its overexpression is associated with unfavorable prognosis in GC. Cetuximab, a monoclonal antibody targeting EGFR, failed to improve the overall survival of gastric cancer patients indicated in phase III randomized trials. Glutamine is a vital nutrient for tumor growth and its metabolism contributes to therapeutic resistance, making glutamine uptake an attractive target for cancer treatment. The aim of the present study was to investigate whether intervention of glutamine uptake could improve the effect of cetuximab on GC. The results of MTT assay showed that by glutamine deprivation or inhibition of glutamine uptake, the viability of gastric carcinoma cells was inhibited more severely than that of human immortal gastric mucosa epithelial cells (GES-1). The expression of the key glutamine transporter alanine-serine-cysteine (ASC) transporter 2 (ASCT2; SLC1A5) was significantly higher in gastric carcinoma tissues and various gastric carcinoma cell lines than in normal gastric tissues and cells, as shown by immunohistochemistry and western blotting, while silencing ASCT2 significantly inhibited the viability and proliferation of gastric carcinoma cells. Consistent with previous studies, it was shown herein by MTT and EdU assays that cetuximab had a weak inhibitory effect on the cell viability of gastric carcinoma cells. However, inhibiting glutamine uptake by blockade of ASCT2 with l-γ-glutamyl-p-nitroanilide (GPNA) significantly enhanced the inhibitory effect of cetuximab on suppressing the proliferation of gastric cancer both in vitro and in vivo. Moreover, combining cetuximab and GPNA induced cell apoptosis considerably in gastric carcinoma cells, as shown by flow cytometry, and had a higher depressing effect on gastric cancer proliferation both in vitro and in vivo, as compared to either treatment alone. The present study suggested that inhibition of glutamine uptake may be a promising strategy for improving the inhibitory efficacy of cetuximab on advanced gastric cancer.
Southern Medical University, Guangzhou, P.R. China.
Inhibition of Glutamine Uptake Improves the Efficacy of Cetuximab on Gastric Cancer.

This article describes the origins and purposes of alcohol industry social aspects organizations as portrayed in internal tobacco industry documents.We systematically searched the Truth Tobacco Documents Library for information regarding alcohol industry social aspects organizations. Using content provided by industry actors themselves, we identified a series of episodes in their evolution from the early 1950s to the early 1990s.Hill and Knowlton, a public relations company, developed and managed the tobacco industry's scientific programs from the early 1950s onward. At the same time, the company performed a similar function for the U.S. distilled spirits industry, with research funding central to advancing what were conceived as public relations goals. They sought to persuade the public and policy makers that the cause of alcohol problems was the people who drank distilled spirits, rather than the product itself. Facing the existential threat posed by the developing population-level understanding of alcohol problems in the 1980s, national and international trade associations collaborated with the tobacco industry in various ways. The largest companies sought to bring together the different sectors of the alcohol industry to support a global network of national-level social aspects organizations.Alcohol industry social aspects organizations were developed to advance long-term public relations goals to manage both policy and science.
Department of Health Sciences, University of York, York, United Kingdom.
La Trobe University, Melbourne, Australia.Centre for Social Research on Alcohol and Drugs, Department of Public Health Sciences, Stockholm University, Stockholm, Sweden.
The Origins and Purposes of Alcohol Industry Social Aspects Organizations: Insights From the Tobacco Industry Documents.

Nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a Group 1 human carcinogen, as classified by the International Agency for Research of Cancer (IARC), and plays a significant role in lung carcinogenesis. However, its carcinogenic mechanism has not yet been fully elucidated. In this study, we performed colony formation assays, soft-agar assays, and tumor growth in nude mice to show that 100 mg/L NNK facilitates the malignant transformation of human bronchial epithelial Beas-2B cells. Transcriptome sequencing showed that insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), a post-transcriptional regulator, was differentially expressed in NNK-induced malignant transformed Beas-2B cells (2B-NNK cells). Small interfering RNA (SiRNA) was used to downregulate the expression of the IGF2BP1 gene. The reduction in protein expression, cell proliferation rate, and colony-forming ability and the increase in the apoptosis rate of Beas-2B cells transfected with the SiRNA indicated a role for IGF2BP1 in NNK-induced malignant transformation. IGF2BP1 is an N6-methyladenosine (m6A) regulatory factor, but it is not known whether its association with m6A mediates the malignant transformation of cells. Therefore, we measured the overall levels of m6A in Beas-2B cells. We found that the overall m6A level was lower in 2B-NNK cells, and knocking down IGF2BP1, the overall level of m6A was restored. Hence, we concluded that IGF2BP1 is involved in the NNK-induced malignant transformation of Beas-2B cells, possibly via m6A modification. This study therefore contributes novel insights into the environmental pathogenesis of lung cancer and the gene regulatory mechanisms of chemical carcinogenesis.
Copyright © 2021 Elsevier Inc. All rights reserved.
The Institute for Chemical Carcinogenesis, Guangzhou Medical University, Xinzao, Panyu District, Guangzhou 511436, China.
School of Anesthesiology, Southern Medical University, 1023-1063 Shatai Nan Road, Baiyun District, Guangzhou 510515, China.
The Institute for Chemical Carcinogenesis, Guangzhou Medical University, Xinzao, Panyu District, Guangzhou 511436, China; State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, No. 151 Yanjiang Road, Yuexiu District, Guangzhou 510120, China. Electronic address: qiaoyuan_yang@gzhmu.edu.cn.
Involvement of m6A regulatory factor IGF2BP1 in malignant transformation of human bronchial epithelial Beas-2B cells induced by tobacco carcinogen NNK.

Department of Primary Care and Public Health, Imperial College London, London, UK.
Department for Health, University of Bath, Bath, UK.
Department of Primary Care and Public Health, Imperial College London, London, UK f.filippidis@imperial.ac.uk.
Beware big tobacco bearing gifts: tobacco industry corporate social responsibility activities in Greece.

We examined the prospective association of physical exertion at work with subsequent tobacco, cannabis, alcohol use, and sugar and fat consumption. Volunteers of the French population-based CONSTANCES cohort currently employed were included from 2012 to 2017 for tobacco and cannabis outcomes (n = 100,612), and from 2012 to 2016 for alcohol and sugar and fat outcomes (n = 75,414). High level of physical exertion at work was defined as a score ≥ 12 at the Rating Perceived Exertion Borg scale. Substance use was self-reported and diet rich in sugar and fat was obtained from principal component analysis and analyzed as quartiles. Generalized linear models computed odds of substance use and sugar and fat consumption at follow-up according to baseline physical exertion at work, while adjusting for sociodemographic factors, depressive symptoms and baseline level of consumption. High physical exertion was associated with tobacco use with dose-dependent relationships. It was also associated with increased odds of cannabis use at least once per month compared to no use in the past and with increased odds of diet rich in sugar and fat. Hence, the role of physical exertion at work on tobacco and cannabis use and diet rich in sugar and fat should be tackled for information and prevention strategies.
INSERM, Population-Based Epidemiological Cohorts Unit, UMS 011, 16 Avenue Paul Vaillant Couturier, 94807, Villejuif, France. nadine.hamieh@inserm.fr.
Poison Control Center, Academic Hospital CHU Angers, F-49000, Angers, France.Univ Angers, Centre Hospitalier Universitaire CHU Angers, Université de Rennes, INSERM, École des hautes études en santé publique, Institut de recherche en santé, environnement et travail Irset UMR_S 1085, F-49000, Angers, France.
INSERM, Population-Based Epidemiological Cohorts Unit, UMS 011, 16 Avenue Paul Vaillant Couturier, 94807, Villejuif, France.Université de Paris, Faculty of Health, School of Medicine, Paris, France.
Université de Paris, AP-HP, Hôpital européen Georges-Pompidou, Service de Nutrition, Paris, France.
Université de Paris, AP-HP, Hôpital Corentin-Celton, DMU Psychiatrie et Addictologie, Service de psychiatrie et d'addictologie de l'adulte et du sujet âgé, Issy-les-Moulineaux, INSERM, Institut de Psychiatrie et Neurosciences de Paris (IPNP), UMR_S1266, Paris, France.
INRAE, Centre Maurice Halbwachs (ENS, EHESS, CNRS) UMR 8097, Paris, France.
Poison Control Center, Academic Hospital CHU Angers, F-49000, Angers, France.University of Angers, Centre Hospitalier Universitaire d'Angers, Université de Rennes, Centre de consultations de pathologie professionnelle et santé au travail, F-49000, Angers, France.
Université de Paris, AP-HP, Hôpital Hôtel-Dieu, DMU Psychiatrie et Addictologie, Service de Psychiatrie de l'adulte, INSERM, Institut de Psychiatrie et Neurosciences de Paris (IPNP), UMR_S1266, Paris, France.
INSERM, Population-Based Epidemiological Cohorts Unit, UMS 011, 16 Avenue Paul Vaillant Couturier, 94807, Villejuif, France.
INSERM, Population-Based Epidemiological Cohorts Unit, UMS 011, 16 Avenue Paul Vaillant Couturier, 94807, Villejuif, France.Université de Paris, Faculty of Health, School of Medicine, Paris, France.Université de Paris, AP-HP.Centre-Université de Paris, DMU Psychiatrie et Addictologie, Paris, France.
Physical exertion at work and addictive behaviors: tobacco, cannabis, alcohol, sugar and fat consumption: longitudinal analyses in the CONSTANCES cohort.

A novel visible light-driven catalyst-free oxidation of aldehydes using CO2 both in batch and flow photoreactors to get corresponding acids along with the formation of CO in the effluent gas is described.
Process Engineering Technology Transfer Division, CSIR-Indian Institute of Chemical Technology, Hyderabad-500007, India.
Chemical & Material Sciences Division, CSIR-Indian Institute of Petroleum, Haridwar Road, Mohkampur, Dehradun-248005, India. suman@iip.res.in.Director, CSIR-Indian Institute of Petroleum, Mohkampur, Dehradun-248004, India.
CO2 as oxidant: an unusual light-assisted catalyst free oxidation of aldehydes to acids under mild conditions.

Lacy-Nichols and Williams' examination of the food industry illustrates how it altered its approach from mostly oppositional to regulation to one of appeasement and co-option. This reflection builds upon this by using a commercial determinants of health (CDoH) lens to understand, expose and counter industry co-option, appeasement and partnership strategies that impact public health. Lessons learned from tobacco reveal how tobacco companies maintained public credibility by recruiting scientists to produce industry biased data, co-opting public health groups, gaining access to policy elites and sitting on important government regulatory bodies. Potential counter solutions to food industry appeasement and co-option include (i) understanding corporate actions of health harming industries, (ii) applying mechanisms to minimize industry engagement, (iii) dissecting industry relationship building, and (iv) exposing the negative effects of public private partnerships (PPPs). Such counter-solutions might help to neutralise harmful industry practices, products and policies which currently threaten to undermine healthy food policies.
© 2022 The Author(s); Published by Kerman University of Medical Sciences This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
School of Public Health, University of Nevada Reno, Reno, NV, USA.Ozmen Institute for Global Studies, University of Nevada Reno, Reno, NV, USA.
World Public Health Nutrition Association, London, UK.Department of Health, University of Bath, Bath, UK.
Applying a Commercial Determinants of Health Lens to Understand, Expose and Counter Industry Co-option, Appeasement and Partnership Comment on 'Part of the Solution': Food Corporation Strategies for Regulatory Capture and Legitimacy .

In 2018, South Africa opened public consultations on its newly proposed tobacco control bill, resulting in substantial public debate in which a range of arguments, either in favour of or against the Bill, was advanced. These were accompanied by the recurring discussions about the annual adjustments in tobacco taxation. This study uses the concept of framing to examine the public debate in South African print media on the potential effects of the legislation, as well as tobacco tax regulations, between their proponents and detractors.A systematic search of news articles using multiple data sources identified 132 media articles published between January 2018 and September 2019 that met the inclusion criteria.Seven overarching frames were identified as characterising the media debate, with the three dominant frames being Economic, Harm reduction and vaping, and Health. The leading Economic frame consisted primarily of arguments unsupportive of tobacco control legislation. Economic arguments were promoted by tobacco industry spokespeople, trade unions, organisations of retailers, media celebrities and think tanks-several of which have been identified as front groups or third-party lobbyists for the tobacco industry.The dominance of economic arguments opposing tobacco control legislation risks undermining tobacco control progress. Local and global tobacco control advocates should seek to build relationships with media, as well as collate and disseminate effective counterarguments to those advanced by the industry.
© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Department for Health, University of Bath, Bath, UK zatonski.mateusz@gmail.com.European Observatory of Health Inequalities, Calisia University, Kalisz, Poland.
Alcohol, Tobacco and Other Drug Research Unit, South African Medical Research Council, Pretoria, Gauteng, South Africa.Department of Public Health, Sefako Makgatho Health Sciences University, Pretoria, Gauteng, South Africa.
Department for Health, University of Bath, Bath, UK.Department of Preventive and Social Medicine, University of Otago, Dunedin, New Zealand.
Framing the policy debate over tobacco control legislation and tobacco taxation in South Africa.

The World Health Organization (WHO) Framework Convention on Tobacco Control (FCTC) seeks to realize the right to health through national tobacco control policies. However, few states have met their obligations under Article 14 of the FCTC to develop evidence-based policies to support tobacco cessation. This article examines how human rights obligations could provide a legal and moral basis for states to implement greater support for individuals to overcome their addiction to tobacco.The United Nations (UN) has a well-established legal framework for promoting human rights, looking to the right to health to realize health autonomy. Where addiction undermines autonomy, it is widely acknowledged that addiction presents a significant barrier to cessation for individuals who use tobacco, undermining the right to health. The UN human rights system could, therefore, provide a complementary basis for monitoring state obligations under Article 14 of the FCTC, identifying challenges to FCTC implementation and motivating states to support tobacco cessation.The United Nations' human rights system offers a mechanism that could be used to monitor Framework Convention on Tobacco Control implementation in national policy, facilitating accountability for the progressive realization of cessation support.
© 2022 Society for the Study of Addiction.
Gillings School of Global Public Health, University of North Carolina at Chapel Hill, USA.
School of Global Public Health, New York University, New York, NY, USA.International Centre for Tobacco Cessation, UK.
School of Global Public Health, New York University, New York, NY, USA.
Action on Smoking and Health (ASH), Washington, DC, USA.
Could international human rights obligations motivate countries to implement tobacco cessation support?

For decades, the link between poor oral hygiene and the increased prevalence of oral cancer has been suggested. Most recently, emerging evidence has suggested that chronic inflammatory diseases from the oral cavity (e.g., periodontal disease), to some extent, play a role in the development of oral squamous cell carcinoma (OSCC). The present study aimed to explore the direct impact of biofilm‑induced periodontitis in the carcinogenesis process using a tobacco surrogate animal model for oral cancer. A total of 42 Wistar rats were distributed into four experimental groups: Control group, periodontitis (Perio) group, 4‑nitroquinoline 1‑oxide (4‑NQO) group and 4NQO/Perio group. Periodontitis was stimulated by placing a ligature subgingivally, while oral carcinogenesis was induced by systemic administration of 4NQO in the drinking water for 20 weeks. It was observed that the Perio, 4NQO and 4NQO/Perio groups presented with significantly higher alveolar bone loss compared with that in the control group. Furthermore, all groups receiving 4NQO developed lesions on the dorsal surface of the tongue; however, the 4NQO/Perio group presented larger lesions compared with the 4NQO group. There was also a modest overall increase in the number of epithelial dysplasia and OSCC lesions in the 4NQO/Perio group. Notably, abnormal focal activation of cellular differentiation (cytokeratin 10‑positive cells) that extended near the basal cell layer of the mucosa was observed in rats receiving 4NQO alone, but was absent in rats receiving 4NQO and presenting with periodontal disease. Altogether, the presence of periodontitis combined with 4NQO administration augmented tumor size in the current rat model and tampered with the protective mechanisms of the cellular differentiation of epithelial cells.
Department of Periodontology, Federal University of Rio Grande do Sul, Porto Alegre, RS 90010‑150, Brazil.
Department of Oral Pathology, Federal University of Rio Grande do Sul, Porto Alegre, RS 90010‑150, Brazil.
Department of Periodontics and Oral Medicine, University of Michigan, Ann Arbor, MI 48109‑1078, USA.
Periodontal disease affects oral cancer progression in a surrogate animal model for tobacco exposure.

Tobacco consumption and radon exposure are considered the first and second most common causes of lung cancer, respectively. The aim of this study was to analyze both whether selected genetic polymorphisms in loci that are in DNA repair pathways, are related to non-small-cell lung cancer (NSCLC) and whether they may modulate the association between residential radon exposure and lung cancer in both smokers and never smokers.A multicentre, hospital-based, case-control study with 826 cases and 1201 controls was designed in a radon-prone area. Genotyping was determined in whole blood and residential radon exposure was measured in participants' dwellings.Attending to tobacco exposure, the variant in the gene NBN (rs1805794) was associated with lung cancer in never smokers (OR 2.72; 95%1.44-5.2) and heavy smokers (OR 3.04; 95%CI 1.21-7.69). The polymorphism with the highest lung cancer association was OGG1 (rs125701), showing an OR of 8.04 (95%CI 1.64-58.29) for its homozygous variant genotype in heavy smokers. Attending to indoor radon exposure (>200Bq/m3), rs1452584, for its homozygous variant genotype, showed the highest association (OR 3.04 (95%CI 1.15-8.48).The genes analyzed seem to have no association with the fully adjusted model, but they might modulate lung cancer association when different categories of tobacco consumption are considered (i.e. heavy smokers). This association may similarly be elevated for those individuals having high indoor radon exposures, though at a minor extent.
Copyright © 2021 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.
Service of Preventive Medicine, University Complex of Santiago de Compostela, Spain; Department of Preventive Medicine, Santiago de Compostela University Teaching Hospital Complex, Santiago de Compostela, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública, CIBERESP), Spain.
Department of Preventive Medicine, Santiago de Compostela University Teaching Hospital Complex, Santiago de Compostela, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública, CIBERESP), Spain; Health Research Institute of Santiago de Compostela (Instituto de Investigación Sanitaria de Santiago de Compostela-IDIS), Santiago de Compostela, Spain. Electronic address: alberto.ruano@usc.es.
Department of Preventive Medicine, Santiago de Compostela University Teaching Hospital Complex, Santiago de Compostela, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública, CIBERESP), Spain; Health Research Institute of Santiago de Compostela (Instituto de Investigación Sanitaria de Santiago de Compostela-IDIS), Santiago de Compostela, Spain.
Department of Epidemiology, Brown School of Public Health, Brown University, Providence, Rhode Island, USA.
Department of Preventive Medicine, Santiago de Compostela University Teaching Hospital Complex, Santiago de Compostela, Spain.
Service of Neumology, University Hospital Complex of Vigo, Spain.
Service of Neumology, University Hospital Complex of Ourense, Spain.
Service of Medical Oncology, Puerta del Hierro University Hospital of Madrid, Spain.
Service of Neumology, University Hospital Complex of A Coruña, Spain.
Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública, CIBERESP), Spain.
Radon, Tobacco Exposure and Non-Small Cell Lung Cancer Risk Related to BER and NER Genetic Polymorphisms.

Hopkinton High School, Hopkinton, Massachusetts; Division of Allergy and Immunology, Boston Children's Hospital, Boston, Massachusetts.
Division of Allergy and Immunology, Boston Children's Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts.
University of Minnesota Masonic Cancer Center, Minneapolis, Minnesota.
Harvard Medical School, Boston, Massachusetts; Division of General Pediatrics, Pediatric Environmental Health Center, Boston Children's Hospital, Boston, Massachusetts; Region 1 New England Pediatric Environmental Health Specialty Unit, Boston, Massachusetts. Electronic address: Marissa.hauptman@childrens.harvard.edu.
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology
Cross-sectional study of urinary biomarkers of environmental tobacco and e-cigarette exposure and asthma morbidity.

The Tobacco and Alcohol Questionnaire (TAQ) and the Cannabis Experience Questionnaire (CEQ) are two instruments employed in the evaluation of substance use. The First Episode Psychosis (FEP) study in Athens employed two versions of those questionnaires, as part of a battery of psychometric tools, detecting environmental and genetic factors associated with FEP and addressed specifically to the distinctive characteristics of patients with FEP. The goal of the present study is to present those two versions, regarding their content, their use in international research, their translation in Greek, and their test-retest reliability. The two questionnaires were translated by two independent translators and administered to 32 subjects with FEP twice, in order to be tested for test-retest reliability. Cohen's kappa was used to measure agreement between qualitative variables and ICC between quantitative variables. Significant agreement was found between the two measurements in all items of the TAQ version and almost all items of the CEQ version. Our study is an indication that both translations are reliable, although a more thorough test of their psychometric properties is needed. Both might be used in the Greek research field as part of a broad package of psychometric tools, specifically addressed to patients with FEP.
First Psychiatric Department of National and Kapodistrian University, Eginition Hospital, Athens, Greece.
Tobacco and Alcohol and Cannabis Experience Questionnaires. Greek translation and test-retest reliability.

Institute for Cancer Control, National Cancer Center, Tokyo, Japan tohirano@ncc.go.jp.
Japan Tobacco corporate social responsibility activities misleadingly claim to advance Sustainable Development Goals.

Nicotine lactate, nicotine tartrate, nicotine benzoate, and freebase nicotine (FBN) are four forms of nicotine salt systems that are present in tobacco products. However, few in vivo studies have compared their pharmacological (pK) efficacies, which are important for understanding their roles in the addiction and abuse of tobacco and nicotine products. In this work, the pK of the above nicotine salt systems was studied by subcutaneously injecting their aqueous solutions in rats and obtaining blood samples from the jugular vein. Nicotine levels in the blood were analyzed by LC-MS/MS. The results demonstrated that rapid nicotine absorption occurred in all nicotine systems. Of them, NB had the smallest Tmax , while FBN had the largest Tmax . The nicotine metabolic rate and clearance decreased for FBN, indicating that nicotine retention in the body was higher than for the other three salt-based systems. Compared with nicotine salts, FBN could reach and maintain a higher concentration in the animal model. Additionally, as the benzoic acid ratios increased, the Cmax of the nicotine benzoate (NB) in the plasma decreased. This indicates that the lower the pH, the lower the Cmax . When different concentrations of NB were used, the higher the NB concentration, the greater the Cmax and AUC(0-t) . These results demonstrate that nicotine adsorption by NB in the animal model depended on both pH and concentration. This baseline information could be used to explain different clinical pharmacological observations in humans, though this study only considered the effects of nicotine on pharmacokinetics in vivo.
© 2022 The Authors. Drug Testing and Analysis published by John Wiley & Sons Ltd.
China National Tobacco Quality Supervision and Test Center, Zhengzhou, China.Key Laboratory of Tobacco Biological Effects, Zhengzhou, China.
China National Tobacco Quality Supervision and Test Center, Zhengzhou, China.
Pharmacokinetics of freebase nicotine and nicotine salts following subcutaneous administration in male rats.

Rectal gland volatiles are key mediators of sexual interactions in tephritid fruit flies. We used solid-phase microextraction (SPME) plus gas chromatography-mass spectrometry (GC-MS) and gas chromatography-flame ionization detection (GC-FID) to substantially expand rectal gland chemical characterisation of the Queensland fruit fly (Bactrocera tryoni (Diptera: Tephritidae); Qfly). The SPME GC-MS analysis identified 24 of the 30 compounds previously recorded from Qfly rectal glands, plus another 21 compounds that had not previously been reported. A few amides and fatty acid esters dominated the chromatograms of males and females respectively, but we also found other esters, alcohols and aldehydes and a ketone. The GC-FID analyses also revealed over 150 others, as yet unidentified, volatiles, generally in lesser amounts. The GC-FID analyses also showed 49 and 12 compounds were male- and female-specific, respectively, both in single sex (virgin) and mixed sex (mostly mated) groups. Another ten compounds were male-specific among virgins but undetected in mixed sex groups, and 29 were undetected in virgins but male-specific in mixed sex groups. The corresponding figures for females were four and zero, respectively. Most short retention time peaks (including a ketone and an ester) were male-specific, whereas most female-biased peaks (including five fatty acid esters) had long retention times. Our results indicate previously unsuspected diversity of rectal gland volatiles that might have pheromone functions in males, but far fewer in females.
Land and Water, Commonwealth Scientific and Industrial Research Organisation, Black Mountain, ACT, Australia.Applied BioSciences, Macquarie University, North Ryde, NSW, Australia.Australian Research Council Centre for Fruit Fly Biosecurity Innovation, Macquarie University, North Ryde, NSW, Australia.
Land and Water, Commonwealth Scientific and Industrial Research Organisation, Black Mountain, ACT, Australia.Applied BioSciences, Macquarie University, North Ryde, NSW, Australia.
Land and Water, Commonwealth Scientific and Industrial Research Organisation, Black Mountain, ACT, Australia.Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC, Australia.
National Collections and Marine Infrastructure, Commonwealth Scientific and Industrial Research Organisation, Black Mountain, ACT, Australia.
Applied BioSciences, Macquarie University, North Ryde, NSW, Australia.Australian Research Council Centre for Fruit Fly Biosecurity Innovation, Macquarie University, North Ryde, NSW, Australia.
Diversity and sex differences in rectal gland volatiles of Queensland fruit fly, Bactrocera tryoni (Diptera: Tephritidae).

The first photochemical synthesis of linear carbonates from the reaction of CO2 with alcohols using a silver-doped ceria nanocomposite at room temperature under visible light irradiation is described. DFT calculations suggested the electron transfer from Ag 4d states to Ce 4f states in the composite for the photoreaction.
Chemical & Material Sciences Division, CSIR-Indiam Institute of Petroleum, Haridwar Road, Mohkampur, Dehradun-248005, India. suman@iip.res.in.Academy of Scientific and Innovative Research, Ghaziabad-201002, India.
Chemical & Material Sciences Division, CSIR-Indiam Institute of Petroleum, Haridwar Road, Mohkampur, Dehradun-248005, India. suman@iip.res.in.
Department of Chemistry, Cotton University, Guwahati-781001, Assam, India.
Advanced Materials Group, Materials Sciences & Technology Division, CSIR-NEIST, Jorhat-785006, Assam, India.
Visible-light driven reaction of CO2 with alcohols using a Ag/CeO2 nanocomposite: first photochemical synthesis of linear carbonates under mild conditions.

In a series of previous studies we reported that black raspberry (BRB) powder inhibits dibenzo[a,l]pyrene (DBP)-induced DNA damage, mutagenesis, and oral squamous cell carcinoma (OSCC) development in mice. In the present study, using human oral leukoplakia (MSK-Leuk1) and squamous cell carcinoma (SCC1483) cells, we tested the hypothesis that BRB extract (BRBE) will enhance the synthesis of glutathione (GSH) and in turn increase GSH conjugation of the fjord-region DBP diol epoxide (DBPDE) derived from DBP leading to inhibition of DBP-induced DNA damage. The syntheses of DBPDE-GSH conjugate, DBPDE-dA adduct, and the corresponding isotope-labeled internal standards were performed; LC-MS/MS methods were used for their quantification. BRBE significantly (p < 0.05) increased cellular GSH by 31% and 13% at 6 and 24 h, respectively, in OSCC cells; in MSK-LeuK1 cells, the levels of GSH significantly (p < 0.05) increased by 55% and 22%, at 1 and 6 h. Since BRBE significantly enhanced the synthesis of GSH in both cell types, subsequent experiments were performed in MSK-Leuk1 cells. Western blot analysis was performed to determine the types of proteins involved in the synthesis of GSH. BRBE significantly (p < 0.05) increased the protein expression (2.5-fold) of the glutamate-cysteine ligase catalytic subunit (GCLC) but had no effect on the glutamate-cysteine ligase modifier subunit (GCLM) and glutathione synthetase (GSS). LC-MS/MS analysis showed that pretreatment of cells with BRBE followed by DBPDE significantly (p < 0.05) increased the levels of DBPDE-GSH conjugate (2.5-fold) and decreased DNA damage by 74% measured by assessing levels of DBPDE-dA adduct formation. Collectively, the results of this in vitro study clearly support our hypothesis, and the LC-MS/MS methods developed in the present study will be highly useful in testing the same hypothesis initially in our mouse model and ultimately in smokers.
Black Raspberry Extract Enhances Glutathione Conjugation of the Fjord-Region Diol Epoxide Derived from the Tobacco Carcinogen Dibenzo[def,p]chrysene in Human Oral Cells.

The effects of genetic polymorphisms on muscle structure and function remain elusive. The present study tested for possible associations of 16 polymorphisms (across ten candidate genes) with fittness and skeletal muscle phenotypes in 17- to 37-year-old healthy Caucasian male endurance (n = 86), power/strength (n = 75) and team athletes (n = 60), and non-athletes (n = 218). Skeletal muscle function was measured with eight performance tests covering multiple aspects of muscular fitness. Along with body mass and height, the upper arm and limb girths, and maximal oxygen uptake were measured. Genotyping was conducted on DNA extracted from blood. Of the 16 polymorphisms studied, nine (spanning seven candidate genes and four gene families/signalling pathways) were independently associated with at least one skeletal muscle fitness measure (size or function, or both) measure and explained up to 4.1% of its variation. Five of the studied polymorphisms (activin- and adreno-receptors, as well as myosine light chain kinase 1) in a group of one to three combined with body height, age and/or group explained up to 20.4% of the variation of muscle function. ACVR1B (rs2854464) contributed 2.0-3.6% to explain up to 14.6% of limb proximal girths. The G allele (genotypes AG and GG) of the ACVR1B (rs2854464) polymorphism was significantly overrepresented among team (60.4%) and power (62.0%) athletes compared to controls (52.3%) and endurance athletes (39.2%), and G allele was also most consistently/frequently associated with muscle size and power. Overall, the investigated polymorphisms determined up to 4.1% of the variability of muscular fitness in healthy young humans.
Institute of Sport Science and Innovations, Lithuanian Sports University, Kaunas, Lithuania.
Institute of Sport Science and Innovations, Lithuanian Sports University, Kaunas, Lithuania.Department of Life Sciences, Musculoskeletal Science and Sports Medicine Research Centre, Institute of Sport, Manchester Metropolitan University, Manchester, United Kingdom.
Genetic polymorphisms of muscular fitness in young healthy men.

Exposure to tobacco and cannabis during developmental periods of enhanced vulnerability (e.g., in utero and early childhood) may have long-lasting effects on child health. One potential mechanism underlying these associations is the alteration of inflammatory pathways. Using data from a longitudinal study of mother/child dyads, we examined the adjusted and combined associations of prenatal and postnatal tobacco and cannabis exposure with inflammation in early childhood. Furthermore, we explored the relations between different measures of exposure, partly reflecting differences in timing, dose, and level of fetal exposure (e.g., self-report vs. biomarker), and inflammation. Finally, we explored child sex as a moderator of prenatal and postnatal tobacco and cannabis exposure and inflammation.Women were recruited from a local hospital during their first prenatal appointment. Repeated assessments were conducted at each trimester, at birth, and when children were 2, 9, 16, 24, 36, and 60 months old (N = 215; 112 female children). To evaluate associations with different measurement approaches, prenatal tobacco and cannabis exposure were assessed using: 1) continuous dose-response variables of maternal self-reported tobacco and cannabis use during each trimester to assess associations with timing and severity of exposure, 2) categorization of children into exposure groups based on drugs and metabolites present in infant meconium reflecting later pregnancy fetal exposure, and 3) categorization into exposure groups using a combination of maternal self-report data and biomarker data derived from maternal saliva samples and infant meconium taking advantage of multiple methods of assessment to examine group differences. Postnatal exposure to tobacco (assessed using child salivary cotinine) and cannabis (assessed using maternal self-reported average joints smoked per day) was measured at each infancy/early childhood assessment. Adjusted pre- and postnatal exposure associations with child inflammation were assessed by including both measures as predictor variables in linear regression models predicting child salivary C-reactive protein (CRP) concentrations at 60 months. Interactions between pre- and postnatal exposure variables were then modeled to investigate the combined relations between pre- and postnatal substance exposure with child salivary CRP concentrations at 60 months.Adjusting for postnatal exposure variables, there was a significant interaction between the average daily cigarettes and the average daily cannabis joints smoked during the third trimester predicting salivary CRP concentrations in early childhood. At high tobacco exposure, the effect of cannabis on CRP concentrations was negligible, whereas at low tobacco exposure, the effect of cannabis exposure on CRP concentrations was positive. Adjusting for postnatal tobacco and cannabis exposure, children for whom meconium data indicated co-exposure to tobacco and cannabis showed approximately 43% lower CRP concentrations at age 60 months compared to children with no exposure. However, when mother/child dyads were categorized based on a combination of maternal self-report data and biomarker data from saliva samples and infant meconium, there were no differences in salivary CRP concentrations at age 60 months across the three groups (no prenatal exposure, prenatal tobacco exposure only, prenatal co-exposure to tobacco and cannabis), controlling for postnatal associations. Regardless of the measurement method used to assess prenatal exposures in adjusted analyses, prenatal tobacco exposure alone did not predict CRP concentrations in early childhood, nor did postnatal tobacco exposure. Among boys, postnatal cannabis exposure was associated with higher concentrations of CRP at age 60 months, controlling for prenatal exposure relations. There were no significant combined associations of pre- and postnatal exposure with CRP concentrations.This study expands upon known relations between prenatal and postnatal substance exposure and immunological outcomes in early childhood, underscoring the importance of assessing cannabis exposure during gestation and early life in combination with tobacco exposure.
Copyright © 2022. Published by Elsevier Inc.
Department of Psychological Science, School of Social Ecology, University of California Irvine, Irvine, CA, USA. Electronic address: sgsimon@uci.edu.
Department of Psychology & Consortium for Combating Substance Abuse, The Pennsylvania State University, University Park, PA, USA.
Department of Child and Youth Studies, Brock University, St. Catharines, ON, Canada.
Institute of Emerging Health Professions, Thomas Jefferson University, Philadelphia, PA, USA.
Department of Psychological Science, School of Social Ecology, University of California Irvine, Irvine, CA, USA; Institute for Interdisciplinary Salivary Bioscience Research, University of California at Irvine, Irvine, CA, USA.
Associations between prenatal and postnatal substance exposure and salivary C-reactive protein in early childhood.

Prenatal tobacco exposure (PTE) and prenatal alcohol exposure (PAE) have been associated with an increased risk of delayed neurodevelopment in children as well as differential newborn DNA methylation (DNAm). However, the biological mechanisms connecting PTE and PAE, DNAm, and neurodevelopment are largely unknown. Here we aim to determine whether differential DNAm mediates the association between PTE and PAE and neurodevelopment at 6 (N = 112) and 24 months (N = 184) in children from the South African Drakenstein Child Health Study. PTE and PAE were assessed antenatally using urine cotinine measurements and the ASSIST questionnaire, respectively. Cord blood DNAm was measured using the EPIC and 450 K BeadChips. Neurodevelopment (cognitive, language, motor, adaptive behavior, socioemotional) was measured using the Bayley Scales of Infant and Toddler Development, Third Edition. We constructed methylation risk scores (MRS) for PTE and PAE and conducted causal mediation analysis (CMA) with these MRS as mediators. Next, we conducted a high-dimensional mediation analysis to identify individual CpG sites as potential mediators, followed by a CMA to estimate the average causal mediation effects (ACME) and total effect (TE). PTE and PAE were associated with neurodevelopment at 6 but not at 24 months. PTE MRS reached a prediction accuracy (R2) of 0.23 but did not significantly mediate the association between PTE and neurodevelopment. PAE MRS was not predictive of PAE (R2 = 0.006). For PTE, 31 CpG sites and eight CpG sites were identified as significant mediators (ACME and TE P < 0.05) for the cognitive and motor domains at 6 months, respectively. For PAE, 16 CpG sites and 1 CpG site were significant mediators for the motor and adaptive behavior domains at 6 months, respectively. Several of the associated genes, including MAD1L1, CAMTA1, and ALDH1A2 have been implicated in neurodevelopmental delay, suggesting that differential DNAm may partly explain the biological mechanisms underlying the relationship between PTE and PAE and child neurodevelopment.
Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
Institute of Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.Institute for Medical Information Processing, Biometry, and Epidemiology, Pettenkofer School of Public Health, LMU Munich, Munich, Germany.Division of Metabolic and Nutritional Medicine, Dr. von Hauner Children's Hospital, University of Munich Medical Center, Munich, Germany.
Neuroscience Institute, University of Cape Town, Cape Town, South Africa.South African Medical Research Council (SAMRC) Unit on Risk and Resilience in Mental Disorders, University of Cape Town, Cape Town, South Africa.Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa.
Neuroscience Institute, University of Cape Town, Cape Town, South Africa.Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa.Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, UK.
Neuroscience Institute, University of Cape Town, Cape Town, South Africa.Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa.
South African Medical Research Council (SAMRC) Unit on Risk and Resilience in Mental Disorders, University of Cape Town, Cape Town, South Africa.Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa.
Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA. anke.huels@emory.edu.Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA. anke.huels@emory.edu.
DNA methylation as a potential mediator of the association between prenatal tobacco and alcohol exposure and child neurodevelopment in a South African birth cohort.

Exposure to polycyclic aromatic hydrocarbons (PAH) and tobacco smoke is associated with epithelial damage and reduced lung function. Club cell secretory protein (CC16) is a known biomarker for lung epithelial cells. However, the potential relationships between PAH and tobacco smoke exposure, CC16 levels, and reduced lung function remain unclear.This longitudinal study aimed to explore the potential role of CC16 in the association of tobacco smoke and PAH co-exposure with lung function.We enrolled 313 workers from a coking plant in China in 2014 and followed them up in 2019. The concentrations of PAH and nicotine metabolites in urine were determined using high-performance liquid chromatography (HPLC) with a fluorescence detector and HPLC-tandem mass spectrometry, respectively. The plasma CC16 concentration was determined using an enzyme-linked immunosorbent assay.An analysis of the generalized estimating equation showed that each 1-unit increase in log-transformation of the last tertile of trans-3'-hydroxycotinine (3HC) was associated with a 3.30 ng/ml decrease in CC16. Restricted cubic spline analysis revealed a significant nonlinear dose-effect association between cotinine (COT) and CC16 (Pnonlinear = 0.018). In the low- CC16 subgroup, we found a significant association between total nicotine metabolites and forced vital capacity (FVC%) (β: 1.45, 95% CI: 2.87, -0.03), and the associations of nicotine (NIC), COT, and 3HC with FVC% were all of marginal significance. High levels of total hydroxyl polycyclic aromatic hydrocarbons (ΣOH-PAH) and NIC in the urine had an interactive effect on the decline of CC16 (P < 0.05). Cross-lagged panel analysis indicated that the decrease in CC16 preceded the decrease in FVC%. CC16 mediated the association between elevated nicotine metabolites and decreased FVC% in the low- CC16 subgroup.CC16 plays an essential role in the association of PAH and tobacco smoke exposure with reduced lung function. Coke oven workers with low plasma CC16 levels are more likely to experience decreased lung function after tobacco smoke exposure.
Copyright © 2022 Elsevier GmbH. All rights reserved.
Department of Occupational Health, School of Public Health, Shanxi Medical University, China; NHC Key Laboratory of Pneumoconiosis, China.
Shanxi Provincial Center for Disease Control and Prevention, China.
Center of Occupational Disease Prevention, Xishan Coal Electricity (Group) Co., Ltd, China.
Department of Occupational Health, School of Public Health, Shanxi Medical University, China; NHC Key Laboratory of Pneumoconiosis, China. Electronic address: yang_jin@sxmu.edu.cn.
International journal of hygiene and environmental health
Effect of Club cell secretory proteins on the association of tobacco smoke and PAH co-exposure with lung function decline: A longitudinal observation of Chinese coke oven workers.

There are numerous pharmacologic treatments for opioid use disorder (OUD), but none that directly target the underlying addictive effects of opioids. Oxytocin, a peptide hormone produced in the paraventricular nucleus (PVN) of the hypothalamus, has been investigated as a potential therapeutic for OUD. Promising preclinical and clinical results have been reported, but the brain region(s) and mechanism(s) by which oxytocin impacts reward processes remain undetermined.Here, we assess peripherally administered oxytocin's impacts on cued reinstatement of heroin seeking following forced abstinence and its effects on neuronal activation in the PVN and key projection regions. We also examine how designer receptors exclusively activated by designer drug (DREADD)-mediated activation or inhibition of oxytocinergic PVN neurons alters cued heroin seeking and social interaction.As predicted, peripheral oxytocin administration successfully decreased cued heroin seeking on days 1 and 30 of abstinence. Oxytocin administration also led to increased neuronal activity within the PVN and the central amygdala (CeA). Activation of oxytocinergic PVN neurons with an excitatory (Gq) DREADD did not impact cued reinstatement or social interaction. In contrast, suppression with an inhibitory (Gi) DREADD reduced heroin seeking on abstinence day 30 and decreased time spent interacting with a novel conspecific.These findings reinforce oxytocin's therapeutic potential for OUD, the basis for which may be driven in part by increased PVN-CeA circuit activity. Our results also suggest that oxytocin has distinct signaling and/or other mechanisms of action to produce these effects, as inhibition, but not activation, of oxytocinergic PVN neurons did not recapitulate the suppression in heroin seeking.
© 2023 The Author(s). Published by S. Karger AG, Basel.
Department of Neuroscience, Medical University of South Carolina, Charleston, South Carolina, USA, carterjo@musc.edu.
Department of Neuroscience, Medical University of South Carolina, Charleston, South Carolina, USA.
Paraventricular Nucleus of the Hypothalamus Oxytocin and Incubation of Heroin Seeking.

News media coverage can influence support for and implementation of tobacco control policies. This research aims to analyse and compare newspaper coverage of newly implemented policies: a substantial tobacco tax increase, point-of-sale display ban and plain packaging.We conducted a content analysis of articles covering the three policies from ten national Dutch newspapers. Articles published between November 2017 and November 2019 were coded for type and tone. The policy dystopia model was used to code arguments opposing the policies. Tobacco industry appearances in news articles were also analysed for frequency and type.A total of 134 news articles were analysed, of which the industry appeared in 28%. The majority of coverage was neutral in tone, although among articles that were coded as expressing a positive or negative tone, plain packaging and the point-of-sale ban were portrayed more negatively than positively. Negative coverage was predominantly accounted for by industry presence. Arguments opposing the policies focused on negative economic consequences, challenging the need for policy and adverse consequences for retailers for tax, plain packaging and the point-of-sale display ban, respectively. We identified six specific new arguments that fit within existing domains of the policy dystopia model.The tobacco industry and its allies still appear in a substantial proportion of news articles in relation to tobacco policy. This study identifies contemporary industry arguments against tobacco control policies in Europe which, alongside the policy dystopia model, can be used to predict and counter the tobacco industry's future attempts to oppose policies.
IVO, The Hague, the Netherlands poole@ivo.nl.Department of Health Promotion, Maastricht University Care and Public Health Research Institute, Maastricht, the Netherlands.
Department of Family Medicine, Maastricht University Care and Public Health Research Institute, Maastricht, the Netherlands.
Department of Health Promotion, Maastricht University Care and Public Health Research Institute, Maastricht, the Netherlands.Drug Monitoring and Policy, Trimbos-instituut, Utrecht, the Netherlands.
IVO, The Hague, the Netherlands.Department of Health Promotion, Maastricht University Care and Public Health Research Institute, Maastricht, the Netherlands.
Content analysis of Dutch newspaper coverage of three tobacco control policies, 2017-2019.

The nucleus accumbens core (NAcc) is a sexually differentiated brain region that is modulated by steroid hormones such as 17β-estradiol (estradiol), with consequential impacts on relevant motivated behaviors and disorders such as addiction, anxiety, and depression. NAcc estradiol levels naturally fluctuate, including during the estrous cycle in adult female rats, which is analogous to the menstrual cycle in adult humans. Across the estrous cycle, excitatory synapse properties of medium spiny neurons rapidly change, as indicated by analysis of miniature excitatory postsynaptic currents (mEPSCs). mEPSC frequency decreases during estrous cycle phases associated with high estradiol levels. This decrease in mEPSC frequency is mimicked by acute topical exposure to estradiol. The identity of the estrogen receptor (ER) underlying this estradiol action is unknown. Adult rat NAcc expresses three ERs, all extranuclear: membrane ERα, membrane ERβ, and GPER1.In this brief report, we take a first step toward addressing this challenge by testing whether activation of ERs via acute topical agonist application is sufficient for inducing changes in mEPSC properties recorded via whole-cell patch clamp.An agonist of ERα induced large decreases in mEPSC frequency, while agonists of ERβ and GPER1 did not robustly modulate mEPSC properties.These data provide evidence that activation of ERα is sufficient for inducing changes in mEPSC frequency and is a likely candidate underlying the estradiol-induced changes observed during the estrous cycle. Overall, these findings extend our understanding of the neuroendocrinology of the NAcc and implicate ERα as a primary target for future studies.
Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina, USA.
Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina, USA.Comparative Medicine Institute, North Carolina State University, Raleigh, North Carolina, USA.Center for Human Health and the Environment, North Carolina State University, Raleigh, North Carolina, USA.
ERα Stimulation Rapidly Modulates Excitatory Synapse Properties in Female Rat Nucleus Accumbens Core.

The one-minute sit-to-stand-test (1-min STST) is a quick, space saving test to evaluate functional capacity. Exercise testing plays an important role in the long-term follow-up of pulmonary hypertension (PH) patients and is currently evaluated using the six-minute-walk-test (6MWT). The aim of the study was to assess the convergent validity of the 1-min STST in patients with PH and its association with markers of PH severity.We evaluated 106 PH patients with the 1-min-STST and 6MWT and measured cardiorespiratory parameters (heart rate, blood pressure, oxygen saturation) before and after test conduction. N-terminal pro brain-type natriuretic peptide (NT-proBNP), WHO functional class (WHO-FC) and mean pulmonary artery pressure (mPAP) were defined as markers of PH severity.Strong correlation was found between performances of 1-min STST and 6MWT (r = .711, p < .001), indicating convergent validity. Both tests were inversely associated with NT-proBNP (STST: r = -.405, p < .001; 6MWT: r = -.358, p < .001), WHO-FC (STST: r = -.591, p < .001; 6MWT: r = -.643, p < .001) and mPAP (STST: r = -.280, p < .001; 6MWT: r = -.250, p < .001). Significant changes in cardiorespiratory parameters were observed in both tests (all p < 0.001). Further the post-exercise cardiorespiratory parameters correlated strongly between the 1-min STST and 6MWT (all r ≥ .651, all p < .001).The 1-min STST demonstrated good convergent validity with the 6MWT and was associated with markers of PH severity. Furthermore, both exercise tests caused similar cardiorespiratory responses.
Copyright: © 2023 Kronberger et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Department of Cardiology, Medical University of Vienna, Vienna, Austria.
Department of Cardiology, Clinic Favoriten, Vienna, Austria.
Center for Medical Data Science, Medical University of Vienna, Vienna, Austria.
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
Functional capacity testing in patients with pulmonary hypertension (PH) using the one-minute sit-to-stand test (1-min STST).

Preclinical literature, frequently utilizing rats, suggests females display a more rapid advancement of substance abuse and a greater risk of relapse following drug abstinence. In clinical populations, it is less clear as to what extent biological sex is a defining variable in the acquisition and maintenance of substance use. Even without considering environmental experiences, genetic factors are presumed to critically influence the vulnerability to addiction. Genetically diverse mouse models provide a robust tool to examine the interactions between genetic background and sex differences in substance abuse.We explored mouse strain variability in male versus female behavioral sensitization to cocaine. Locomotor sensitization was observed following 5 consecutive days of subcutaneous cocaine across three genetically different mice strains: C57BL/6J, B6129SF2/J, and Diversity Outbred (DO/J).Sex differences in cocaine locomotor sensitization were dependent on mouse strain. Specifically, we observed opposing sex differences in locomotor sensitization, with male C57BL/6J and female B6129SF2/J mice displaying heightened activity compared to their opposite sex counterparts. Conversely, no sex differences were observed in the DO/J mice. Acute cocaine administration resulted in locomotor differences across strains in male, but not female, mice. The magnitude of sensitization (or lack thereof) also varied by genetic background.While sex differences in drug addiction may be observed, these effects can be mitigated, or even reversed, depending on genetic background. The clinical implications are that in the absence of understanding the genetic variables underlying vulnerability to addiction, sex provides little information regarding the predisposition of an individual to drug abuse.
Department of Neuroscience and Medical Discovery Team on Addiction, University of Minnesota, Minneapolis, Minnesota, USA.
Sex Differences in Cocaine Sensitization Vary by Mouse Strain.

Women are more vulnerable than men in many aspects of opioid use disorder (OUD); a major theory of sex differences in substance use disorders is that these differences are due to ovarian hormones with estradiol enhancing vulnerability in females. However, most of this evidence is for psychostimulants and alcohol; evidence with opioids is sparse. Thus, the goal of this study was to determine the impact of estradiol on vulnerability in females in a rat model of OUD.Following self-administration training, ovariectomized (OVX) females with (E) or without (V) estradiol replacement were given extended (24 h/day), intermittent access (2, 5-min trials/h) to fentanyl for 10 days. Then, the development of three key features of OUD were assessed, including physical dependence, defined by the magnitude and time course of weight loss during withdrawal; an enhanced motivation for fentanyl, assessed using a progressive-ratio schedule; and relapse vulnerability, assessed using an extinction/cue-induced reinstatement procedure. These later two characteristics were examined following 14 days of withdrawal when the phenotypes are known to be highly expressed.OVX+E females self-administered markedly higher levels of fentanyl under extended, intermittent-access conditions and showed a longer time course of physical dependence, a greater increase in motivation for fentanyl, and an enhanced sensitivity to the reinstating effects of fentanyl-associated cues compared to OVX+V rats. Severe health complications were also observed in OVX+E, but not OVX+V females, during withdrawal.These results indicate that, as with findings with psychostimulants and alcohol, estradiol enhances vulnerability in females to developing opioid addiction-like features and serious opioid-related health complications.
Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, Virginia, USA.Medical Scientist Training Program, University of Virginia, Charlottesville, Virginia, USA.
Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, Virginia, USA.
Estradiol Enhances the Development of Addiction-Like Features in a Female Rat Model of Opioid Use Disorder.

Vaccination is considered as the main tool for the Global Control and Eradication Strategy for peste des petits ruminants (PPR), and the efficacity of the PPR-vaccine in conferring long-life immunity has been established. Despite this, previous studies asserted that vaccination can be expensive and consequently, the effectiveness of disease control may not necessarily translate to overall profit for farmers. Also, the consequences of PPR control on socioeconomic indicators like food and nutrition security at a macro-national level have not been explored thoroughly. Therefore, this study seeks to assess ex-ante the impact of PPR control strategies on farm-level profitability and the socioeconomic consequences concerning food and nutrition security at a national level in Senegal. A bi-level system dynamics model, compartmentalised into five modules consisting of integrated production-epidemiological, economics, disease control, marketing, and policy modules, was developed with the STELLA Architect software, validated, and simulated for 30 years at a weekly timestep. The model was parameterised with data from household surveys from pastoral areas in Northern Senegal and relevant existing data. Nine vaccination scenarios were examined considering different vaccination parameters (vaccination coverage, vaccine wastage, and the provision of government subsidies). The findings indicate that compared to a no-vaccination scenario, all the vaccination scenarios for both 26.5% (actual vaccination coverage) and 70% (expected vaccination coverage) resulted in statistically significant differences in the gross margin earnings and the potential per capita consumption for the supply of mutton and goat meat. At the prevailing vaccination coverage (with or without the provision of government subsidies), farm households will earn an average gross margin of $69.43 (annually) more than without vaccination, and the average per capita consumption for mutton and goat meat will increase by 1.13kg/person/year. When the vaccination coverage is increased to the prescribed threshold for PPR eradication (i.e., 70%), with or without the provision of government subsidies, the average gross margin earnings would be $72.23 annually and the per capita consumption will increase by 1.23kg/person/year compared to the baseline (without vaccination). This study's findings offer an empirical justification for a sustainable approach to PPR eradication. The information on the socioeconomic benefits of vaccination can be promoted via sensitization campaigns to stimulate farmers' uptake of the practice. This study can inform investment in PPR control.
Copyright: © 2023 Aboah et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
International Livestock Research Institute, West Africa Regional Office, Dakar, Senegal.Commonwealth Scientific and Industrial Research Organisation, Agriculture & Food Business Unit, Brisbane, Australia.
CIRAD, UMR ASTRE Montpellier, Montpellier, France.
Institute of Virology and Immunology, Mittelhäusern, Switzerland.Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
International Water Management Institute, C/o ILRI 2R87+GPC, Addis Ababa, Ethiopia.
International Livestock Research Institute, West Africa Regional Office, Dakar, Senegal.
Ex-ante impact of pest des petits ruminant control on micro and macro socioeconomic indicators in Senegal: A system dynamics modelling approach.

The renin-angiotensin (RA) system has been implicated in lung tumorigenesis without detailed mechanistic elucidation. Here, we demonstrate that exposure to the representative tobacco-specific carcinogen nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) promotes lung tumorigenesis through deregulation of the pulmonary RA system. Mechanistically, NNK binding to the nicotinic acetylcholine receptor (nAChR) induces Src-mediated signal transducer and activator of transcription 3 (STAT3) activation, resulting in transcriptional upregulation of angiotensinogen (AGT) and subsequent induction of the angiotensin II (AngII) receptor type 1 (AGTR1) signaling pathway. In parallel, NNK concurrently increases insulin-like growth factor 2 (IGF2) production and activation of IGF-1R/insulin receptor (IR) signaling via a two-step pathway involving transcriptional upregulation of IGF2 through STAT3 activation and enhanced secretion from intracellular storage through AngII/AGTR1/PLC-intervened calcium release. NNK-mediated crosstalk between IGF-1R/IR and AGTR1 signaling promoted tumorigenic activity in lung epithelial and stromal cells. Lung tumorigenesis caused by NNK exposure or alveolar type 2 cell-specific Src activation was suppressed by heterozygous Agt knockout or clinically available inhibitors of the nAChR/Src or AngII/AGTR1 pathways. These results demonstrate that NNK-induced stimulation of the lung RA system leads to IGF2-mediated IGF-1R/IR signaling activation in lung epithelial and stromal cells, resulting in lung tumorigenesis in smokers.
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Republic of Korea.Department of Histology, College of Medicine, Jeju National University, Jeju, 63243, Republic of Korea.
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Republic of Korea.
School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju-si, Chungcheongbuk-do, 28116, Republic of Korea.
Soonchunhyang University Bucheon Hospital, Bucheon, Gyeonggi-do, 14584, Republic of Korea.
Vessel-Organ Interaction Research Center (VOICE, MRC), College of Pharmacy, Kyungpook National University, Daegu, 41566, Republic of Korea.
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Republic of Korea. hylee135@snu.ac.kr.
The tobacco-specific carcinogen NNK induces pulmonary tumorigenesis via nAChR/Src/STAT3-mediated activation of the renin-angiotensin system and IGF-1R signaling.

The objective of our study was to assess the effect of rumen-protected niacin supplementation on the transcriptome of liver tissue in growing Angus × Simmental steers and heifers through RNA-seq analysis. Consequently, we wanted to assess the known role of niacin in the physiological processes of vasodilation, detoxification, and immune function in beef hepatic tissue. Normal weaned calves (~8 months old) were provided either a control diet or a diet supplemented with rumen-protected niacin (6 g/hd/d) for a 30-day period, followed by a liver biopsy. We observed a significant list of changes at the transcriptome level due to rumen-protected niacin supplementation. Several metabolic pathways revealed potential positive effects to the animal's liver metabolism due to administration of rumen-protected niacin; for example, a decrease in lipolysis, apoptosis, inflammatory responses, atherosclerosis, oxidative stress, fibrosis, and vasodilation-related pathways. Therefore, results from our study showed that the liver transcriptional machinery switched several metabolic pathways to a condition that could potentially benefit the health status of animals supplemented with rumen-protected niacin. In conclusion, based on the results of our study, we can suggest the utilization of rumen-protected niacin supplementation as a nutritional strategy could improve the health status of growing beef cattle in different beef production stages, such as backgrounding operations or new arrivals to a feedlot.
Copyright: © 2023 Alfaro et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Department of Animal Sciences, Auburn University, Auburn, AL, United States of America.
Department of Agricultural, Environmental and Food Sciences, Università degli Studi del Molise, Campobasso, Italy.
Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, United States of America.
Department of Animal Sciences, University of Tennessee, Knoxville, TN, United States of America.
Department of Animal Sciences, Auburn University, Auburn, AL, United States of America.Cooperative Extension Service, University of Kentucky, Kentucky, Lexington, United States of America.
Department of Poultry Sciences, Auburn University, Auburn, AL, United States of America.
Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, United States of America.HudsonAlpha Institute for Biotechnology, Huntsville, AL, United States of America.
Hepatic transcript profiling in beef cattle: Effects of rumen-protected niacin supplementation.

The habitation and environment are affected by the stable isotopes of caesium (Cs) and strontium (Sr), as well as by their radioactive isotopes. The current work gives insight on Alstonia scholaris' capacity to phytoextract stable caesium (Cs) and strontium (Sr), as well as the plant's ability to protect against the toxicity of both elements. Experiments with Cs [0-5 mM (CsCl)] and Sr [0-3 mM (SrCl2. 6H2O)] dosing in controlled light, temperature, and humidity condition in greenhouse for 21 days were undertaken. Cs and Sr accumulation in different plant parts was quantified with atomic absorption spectroscopy (AAS) and inductively coupled plasma-optical emission spectrometry (ICP-OES) respectively. Hyper-accumulation capacity for Cs and Sr was estimated with indices like transfer factor (TF) and translocation factors (TrF). The uptake pattern of caesium in Alstonia scholaris is 5452.8-24,771.4 mg/kg DW (TF = 85.2-57.6) and in the case of Sr is 1307.4-8705.7 mg/kg DW (TF = 85.3-1.46). The findings demonstrated the plant's ability to transfer Cs and Sr to aboveground biomass on the basis of dry weight, with the majority of the metals being deposited in the shoot rather than the root portion of the plant. For Cs and Sr, with increasing concentration, the plants exhibited the enzymatic expression for defence against metal toxicity by free radicals compared to control. Field emission electron microscopy with energy-dispersive spectroscopy (FESEM with EDS) was employed to assess the spatial distribution of Cs and Sr in plant leaf, indicating the accumulation of Cs, Sr, and their homologous components.
© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
Environment and Sustainability Department, CSIR-IMMT, Bhubaneshwar, 751013, India. bsmanishasingh@gmail.com.Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India. bsmanishasingh@gmail.com.
Environment and Sustainability Department, CSIR-IMMT, Bhubaneshwar, 751013, India.
Safety Research Institute, AERB, Kalpakkam, 603102, India.
Atomic Energy Regulatory Board, Niyamak Bhavan, Anushakti Nagar, Mumbai, 400094, India.
Retaliation of Alstonia scholaris (L.) R.Br. to caesium and strontium in hydroponics: effect on morpho-physiology and induction of enzymatic defence.

Recently, spiropyran-based composites have gained more attention on account of their stimuli-responsive essence, especially of the fascinating and green photo stimulus. However, the great dipole moment change between the ring-opened merocyanine and ring-closed spiropyran requires a large free volume available for isomerization, which significantly restrains the photoisomerization of spiropyran-based nanocomposites. Herein, a fascinating pathway by regulating the states both of spiropyran and the immobilized nanoparticle supports was put forward to facilitate the photoisomerization. The results demonstrated that the spiropyran grafting percentage of 5.18% and immobilized supports with less aggregation, high specific surface area, large pore size, and noncrystalline structure were suitable to fabricate spiropyran-based nanocomposites, which showed a significant improvement for Pb2+ and Cr3+ removal from aqueous solution on account of free photoisomerization of spiropyran on the support's surface. This work will pave the pathway to extend the exploitation of spiropyran-based nanocomposites in various fields such as biotechnology, physiology, and electronics to photonics and environmental-friendly fields.
College of Bioresources Chemical and Materials Engineering, Key Laboratory of Auxiliary Chemistry and Technology for Chemical Industry, Ministry of Education, Shaanxi Collaborative Innovation Center of Industrial Auxiliary Chemistry and Technology, Shaanxi University of Science & Technology, Xi'an, Shaanxi 710021, PR China.Nano Medical Engineering Laboratory, RIKEN Cluster for Pioneering Research, 2-1 Hirosawa, Wako 351-0198, Saitama, Japan.Key Laboratory of Leather Chemistry and Engineering (Sichuan University), Ministry of Education, Chengdu 610065, PR China.
College of Bioresources Chemical and Materials Engineering, Key Laboratory of Auxiliary Chemistry and Technology for Chemical Industry, Ministry of Education, Shaanxi Collaborative Innovation Center of Industrial Auxiliary Chemistry and Technology, Shaanxi University of Science & Technology, Xi'an, Shaanxi 710021, PR China.
Chengdu Decoli Polymer Materials Corporation Limited, Chengdu 610065, PR China.
Fascinating Pathway to Facilitate the Photoisomerization of Spiropyran-Based Nanocomposites.

The distribution pattern of species diversity along various elevation gradients reflects the biological and ecological characteristics of species, distribution status and adaptability to the environment. Altitude, a comprehensive ecological factor, affects the spatial distribution of species diversity in plant communities by causing integrated changes in light, temperature, water and soil factors. In Guiyang City, we studied the species diversity of lithophytic mosses and the relationships between species and environmental factors. The results showed that: (1) There were 52 species of bryophytes in 26 genera and 13 families within the study area. The dominant families were Brachytheciaceae, Hypnaceae and Thuidiaceae. The dominant genera were Brachythecium, Hypnum, Eurhynchium, Thuidium, Anomodon and Plagiomnium; The dominant species were Eurohypnum leptothallum, Brachythecium salebrosum, Brachythecium pendulum etc. The number of family species and dominant family genera increased first and then decreased with the increase of altitude, and their distribution in elevation gradient III (1334-1515m) was the largest, with 8 families, 13 genera and 21 species. The elevation gradient I (970-1151m) was the least species distributed, with 5 families, 10 genera and 14 species. The dominant species with the largest number in each elevational gradient were Eurohypnum leptothallum, Brachythecium pendulum, Brachythecium salebrosum and Entodon prorepens; (2) There were five kinds of life forms in different elevation gradients, including Wefts, Turfs, Mat, Pendants and Tail. Among them, wefts and turfs appeared in all elevations, while a small amount of Pendants appeared in the area of elevational gradient I (970-1151m), and the most abundant life form was found in the range of elevational gradient III (1334-1515m); (3) Patrick richness index and Shannon-Wiener diversity index were highly significantly (p<0.01) positively correlated, both of which increased and then decreased with elevation, reaching a maximum at elevation gradient III (1334-1515m); The Simpson dominance index had a highly significant (p<0.01) negative correlation with the Patrick richness index and the Shannon-Wiener diversity index, which showed a decreasing and then increasing trend with increasing altitude; Pielou evenness index showed no discernible trend; (4) β diversity study revealed that while the similarity coefficient tended to decrease with increasing altitude, the species composition of bryophytes increased. The elevation gradient II (1151-1332m) and elevation gradient I (970-1151m) shared the most similarities, whereas elevation gradient III (1515-1694m) and elevation gradient I shared the least similarities (970-1151m). The findings can enrich the theory of the distribution pattern of lithophytic moss species diversity at distinct elevation gradients in karst regions, and serve a scientific and reasonable reference for restoring rocky desertification and protecting biodiversity there.
Copyright: © 2023 Jin, Wang. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
College of Forestry, Guizhou University, Guiyang, Guizhou, China.
Diversity of lithophytic moss species in karst regions in response to elevation gradients.

Sex and ovarian hormones influence cocaine seeking and relapse vulnerability, but less is known regarding the cellular and synaptic mechanisms contributing to these behavioral sex differences. One factor thought to influence cue-induced seeking behavior following withdrawal is cocaine-induced changes in the spontaneous activity of pyramidal neurons in the basolateral amygdala (BLA). However, the mechanisms underlying these changes, including potential sex or estrous cycle effects, are unknown.Ex vivo whole-cell patch clamp electrophysiology was conducted to investigate the effects of cocaine exposure, sex, and estrous cycle fluctuations on two properties that can influence spontaneous activity of BLA pyramidal neurons: (1) frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) and (2) intrinsic excitability. Recordings of BLA pyramidal neurons were conducted in adult male and female rats and across the estrous cycle following 2-4 weeks of withdrawal from extended-access cocaine self-administration (6 h/day for 10 days) or drug-naïve conditions.In both sexes, cocaine exposure increased the frequency, but not amplitude, of sEPSCs and neuronal intrinsic excitability. Across the estrous cycle, sEPSC frequency and intrinsic excitability were significantly elevated only in cocaine-exposed females in the estrus stage of the cycle, a stage when cocaine-seeking behavior is known to be enhanced.Here, we identify potential mechanisms underlying cocaine-induced alterations in the spontaneous activity of BLA pyramidal neurons in both sexes along with changes in these properties across the estrous cycle.
Graduate School of Biomedical Sciences, Rowan University School of Osteopathic Medicine, Stratford, New Jersey, USA.Department of Cell Biology and Neuroscience, Rowan University School of Osteopathic Medicine, Stratford, New Jersey, USA.
Department of Cell Biology and Neuroscience, Rowan University School of Osteopathic Medicine, Stratford, New Jersey, USA.
Cocaine Exposure Increases Excitatory Synaptic Transmission and Intrinsic Excitability in the Basolateral Amygdala in Male and Female Rats and across the Estrous Cycle.

Circular RNAs (circRNAs) have gained significant attention in recent years. This bibliometric analysis aimed to provide insights into the current state and future trends of global circRNA research. The scientific output on circRNAs from 2010 to 2022 was retrieved from the Web of Science Core Collection with circRNA-related terms as the subjects. Key bibliometric indicators were calculated and evaluated using CiteSpace. A total of 7385 studies on circRNAs were identified. The output and citation number have increased rapidly after 2015. China, the USA, and Germany were top three publishing countries. Currently, circCDR1as, circHIPK3, circPVT1, circSHPRH, and circZNF609 are the most studied circRNAs; and all are related to cancer. The theme of research have shifted from transcript, exon circularization and miRNA sponge topics to the transcriptome, tumor suppressor, and biomarkers, indicating that research interests have evolved from basic to applied research. CircRNAs will continue to be a highly active research area in the near future. From the current understanding of circRNA characterization and regulatory mechanisms as miRNA sponges in cancer, future directions may examine potential diagnostic and therapeutic roles of circRNAs in cancers or the function and mechanism of circRNAs in other diseases.
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Institute of Wound Prevention and Treatment, Shanghai University of Medicine and Health Sciences, Shanghai, China.Department of Human Anatomy and Histology, School of Fundamental Medicine, Shanghai University of Medicine and Health Sciences, Shanghai, China.
Department of Human Anatomy and Histology, School of Fundamental Medicine, Shanghai University of Medicine and Health Sciences, Shanghai, China.Department of Physiology and Biochemistry, School of Fundamental Medicine, Shanghai University of Medicine and Health Sciences, Shanghai, China.
Institute of Wound Prevention and Treatment, Shanghai University of Medicine and Health Sciences, Shanghai, China.
Institute of Wound Prevention and Treatment, Shanghai University of Medicine and Health Sciences, Shanghai, China. zhaojh@sumhs.edu.cn.Department of Human Anatomy and Histology, School of Fundamental Medicine, Shanghai University of Medicine and Health Sciences, Shanghai, China. zhaojh@sumhs.edu.cn.
Bibliometric Analysis of Global Research on Circular RNA: Current Status and Future Directions.

Healthy and active aging and age-friendly society frameworks attempt to address the well-documented challenges and opportunities of population aging. To meet the needs of an increasingly older society, there is a demand for professionals with appropriate age-related knowledge and skills. To this end, a master's in active aging is in development. This study reports on the consultation with prospective students, employers, older people and academics on the knowledge areas to be included in the course. An anonymous online survey gathered data from stakeholders in Ireland, Slovenia, Austria, Portugal, Finland, and Greece. Participants ranked the importance of 14 broad knowledge areas and linked topics. The influence of participant characteristics on decisions was examined using multivariate regression modeling. Across all stakeholder groups (total sample N = 757), health promotion was most often deemed very important (80%), followed by psychology (73%), and social inclusion and engagement (71%). Potential students from healthcare backgrounds were more interested than others in aging physiology, social aspects, and the physical environment. More western-located European countries overall showed more enthusiasm for the topics presented, additional to regional variations between topics. This learning needs analysis provides multi-stakeholder insights into priorities regarding learning in healthy and active aging and age-friendly society.
Centre for Gerontology and Rehabilitation, School of Medicine, University College Cork, Cork, Ireland.
School of Applied Psychology, University College Cork, Cork, Ireland.
Faculty of Social Work, University of Ljubljana, Ljubljana, Slovenia.
Institute for Applied Research on Ageing, Dep. Health and Assistive Technologies, School of Medical Engineering, Carinthia University of Applied Sciences, Klagenfurt, Austria.
Department of Nursing, Laboratory of Prevention, National and Kapodistrian University of Athens, Athens, Greece.
Karelia University of Applied Sciences, Joensuu, Finland.
CIPER, Faculdade de Motricidade Humana, Universidade de Lisboa, Lisbon, Portugal.
School of Public Health, University College Cork, Cork, Ireland.Department of Statistics, School of Mathematical Science, University College Cork, Cork, Ireland.
Learning needs in healthy and active aging according to key stakeholders: A multinational survey.

For adopting recently introduced hypertension phenotypes categorized using office and out of office blood pressure (BP) for the diagnosis of hypertension and antihypertension drug therapy, it is mandatory to define the corresponding out of office BP with the specific target BP recommended by the major guidelines. Such conditions include white-coat hypertension (WCH), masked hypertension (MH), white-coat uncontrolled hypertension (WUCH), and masked uncontrolled hypertension (MUCH). Here, the authors review the relevant literature and discuss the related issue to facilitate the use of corresponding BPs for proper diagnosis of WCH, MH, WUCH, and MUCH in the setting of standard target BP as well as intensive target BP. The methodology of deriving the corresponding BP has evolved from statistical methods such as standard deviation, percentile value, and regression to an outcome-based approach using pooled international cohort study data and comparative analysis in randomized clinical trials for target BPs such as the SPRINT and STEP studies. Corresponding BPs to 140/90 and 130/80 mm Hg in office BP is important for safe and strict achievement of intensive BP targets. The corresponding home, daytime, and 24-h BPs to 130/80 mm Hg in office BP are 130/80, 130/80, and 125/75 mm Hg, respectively. However, researchers have found some discrepancies among the home corresponding BPs. As tentative criterion for de-escalation of antihypertensive therapy as shown in European guidelines was 120 mm Hg in office BP, corresponding home, daytime, and 24-h systolic BPs to 120 mm Hg in office systolic BP are 120, 120, and 115 mm Hg, respectively.
© 2023 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.
Division of Cardiology, Department of Internal Medicine, Hanyang University College of Medicine, Seoul, South Korea.
Department of Cardiovascular Medicine, The Shanghai Institute of Hypertension, Shanghai Key Laboratory of Hypertension, National Research Centre for Translational Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Department of Medical Sciences, School of Healthcare and Medical Sciences, Sunway University, Bandar Sunway, Selangor Darul Ehsan, Malaysia.Department of Primary Care Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical University School of Medicine, Tochigi, Japan.
Department of Medicine, National Yang-Ming Chiao Tung University College of Medicine, Taipei, Taiwan.
Department of Internal Medicine, University of Medicine and Pharmacy, Hue University, ., Vietnam.
Department of Internal Medicine, General Medicine and Cardiology, Hiroshima City Asa Hospital, Hiroshima, Japan.
University of the East Ramon Magsaysay Memorial Medical Center Inc., Quezon City, Philippines.
Division of Cardiology, Cardiovascular Hospital, Yonsei Health System, Seoul, South Korea.
Punjab Medical Center, Lahore, Pakistan.
Section of Cardiology, Department of Medicine, Medical Center Manila, Manila, Philippines.
Department of Cardiology and Vascular Medicine, Faculty of Medicine, University of Indonesia-National Cardiovascular Center, Harapan Kita, Jakarta, Indonesia.
Fortis Hospitals, Chennai, Tamil Nadu, India.College of Medical Sciences, Kathmandu University, Bharatpur, Nepal.
Department of General Medicine, Tan Tock Seng Hospital, Singapore, Singapore.
Division of Nephrology Department of Medicine, Yong Loo Lin School of Medicine, Singapore, Singapore.
JC School of Public Health and Primary Care, JC Institute of Ageing, SH Big Data Decision Analytics Research Centre, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.
Faculty of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, Jakarta, Indonesia.
Indian Society of Hypertension, King George's Medical University, Lucknow, Uttar Pradesh, India.
Department of Internal Medicine, National Taiwan University College of Medicine, Taipei City, Taiwan.
Divisions of Hypertension and Heart Failure, Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Journal of clinical hypertension (Greenwich, Conn.)
The HOPE Asia Network consensus on blood pressure measurements corresponding to office measurements: Automated office, home, and ambulatory blood pressures.

Decision making during aortic arch surgery regarding cannulation strategy and nadir temperature are important in reducing risk, and there is a need to determine the best individualized strategy in a data-driven fashion. Using machine learning (ML), we modeled the risk of death or stroke in elective aortic arch surgery based on patient characteristics and intraoperative decisions.The study cohort comprised 1323 patients from 9 institutions who underwent an elective aortic arch procedure between 2002 and 2021. A total of 69 variables were used in developing a logistic regression and XGBoost ML model trained for binary classification of mortality and stroke. Shapely additive explanations (SHAP) values were studied to determine the importance of intraoperative decisions.During the study period, 3.9% of patients died and 5.4% experienced stroke. XGBoost (area under the curve [AUC], 0.77 for death, 0.87 for stroke) demonstrated better discrimination than logistic regression (AUC, 0.65 for death, 0.75 for stroke). From SHAP analysis, intraoperative decisions are 3 of the top 20 predictors of death and 6 of the top 20 predictors of stroke. Predictor weights are patient-specific and reflect the patient's preoperative characteristics and other intraoperative decisions. Patient-level simulation also demonstrates the variable contribution of each decision in the context of the other choices that are made.Using ML, we can more accurately identify patients at risk of death and stroke, as well as the strategy that better reduces the risk of adverse events compared to traditional prediction models. Operative decisions made may be tailored based on a patient's specific characteristics, allowing for maximized, personalized benefit.
Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.
Peter Munk Cardiac Center, Toronto General Hospital, Toronto, Ontario, Canada.
Department of Cardiac Surgery, London Health Sciences Center, London, Ontario, Canada.
Peter Munk Cardiac Center, Toronto General Hospital, Toronto, Ontario, Canada. Electronic address: maral.ouzounian@uhn.ca.
The Journal of thoracic and cardiovascular surgery
Machine learning and decision making in aortic arch repair.

The high level of oxidative stress induced by angiotensin II (AngII) is the main pathophysiological process that promotes the proliferation and migration of vascular smooth muscle cells (VSMCs) and induces vascular remodeling. LncRNA metastasis-related lung adenocarcinoma transcript 1 (MALAT1) has been determined to play an important role in the modulation of oxidative stress and the development of cardiovascular diseases. Nevertheless, the function and underlying mechanism of MALAT1 in restenosis induced by hypertensive angioplasty remain unclear. AngII increased the expression of MALAT1 in VSMCs. We found that antisense oligonucleotide lncRNA MALAT1 (ASO-MALAT1) could inhibit AngII-induced reactive oxygen species production and VSMCs proliferation and migration by inducing the expression of glutathione peroxidase 4 (GPX4), which can be reversed by siRNA-GPX4. GPX4 overexpression can inhibit the proliferation and migration of VSMCs induced by AngII. In addition, we found that the process by which MALAT1 knockdown induces GPX4 expression involves nuclear factor erythrocyte 2-related factor 2 (Nrf2). Overexpression of Nrf2 can increase the expression of GPX4, and downregulation of GPX4 by ML385 (Nrf2 inhibitor) blocked the protective effect of ASO-MALAT1 on AngII-induced proliferation and migration of VSMCs. Ferrostatin-1 (Fer-1, ip 5 mg/kg per day for 2 weeks), a GPX4 agonist, significantly inhibited neointimal formation in spontaneously hypertensive rat by the inhibition of oxidative stress. In conclusion, these data imply that ASO-MALAT1 suppresses the AngII-induced oxidative stress, proliferation, and migration of VSMCs by activating Nrf2/GPX4 antioxidant signaling. GPX4 may be a potential target for the therapeutic intervention of hypertensive vascular restenosis.
Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.
Department of Cardiology, Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital, Ganzhou, Jiangxi, China.Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China.
Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China.
Department of Cardiology, Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital, Ganzhou, Jiangxi, China.
Department of Critical Care Medicine, Department of Emergency Medicine, the Fifth Affiliated Hospital of Zunyi Medical University, Zhuhai, China; and.
Department of Pharmacy, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China.
LncRNA MALAT1-Targeting Antisense Oligonucleotide Ameliorates the AngII-Induced Vascular Smooth Muscle Cell Proliferation and Migration Through Nrf2/GPX4 Antioxidant Pathway.

Acta Biochim Biophys Sin (Shanghai). 2023-12-20;56(12):1896.
Corrigendum to: C-reactive protein is associated with the development of tongue squamous cell carcinoma.

Von Willebrand disease (VWD) is an inherited haemostatic disorder with a wide range of bleeding phenotypes based on von Willebrand factor (VWF) levels. Multiple assays including VWF gene analysis are employed to correctly diagnose VWD and its subtypes. However, data on VWF mutations among Southeast Asian populations are lacking. We, therefore, aimed to explore genetic variations in Thai patients with type 2 and type 3 VWD by whole exome sequencing (WES).In this multicentre study, Thai patients with type 2 and type 3 VWD, according to the definitions and VWF levels recommended by the international guidelines, were recruited. WES was performed using DNA extracted from peripheral blood in all cases. The novel variants were verified by Sanger sequencing.Fifteen patients (73% females; median age at diagnosis 3.0 years) with type 2 (n=12) and type 3 VWD (n=3) from 14 families were enrolled. All patients harboured at least one VWF variant. Six missense (p.Arg1374Cys, p.Arg1374His, p.Arg1399Cys, p.Arg1597Trp, p.Ser1613Pro, p.Pro1648Arg) and one splice-site (c.3379+1G>A) variants in the VWF gene were formerly described. Notably, six VWF variants, including three missense (p.Met814Ile, p.Trp856Cys, p.Pro2032Leu), one deletion (c.2251delG) and two splice-site (c.7729+4A>C, c.8115+2delT) mutations were novelly identified. Compound heterozygosity contributed to type 2 and type 3 VWD phenotypes in two and one patients, respectively.Type 2 and type 3 VWD in Thailand demonstrate the mutational variations among VWF exons/introns with several unique variants. The WES-based approach potentially provides helpful information to verify VWD diagnosis and facilitate genetic counselling in clinical practice.
© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.
Department of Pediatrics, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand.Integrative and Innovative Hematology/Oncology Research Unit, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand.Center of Excellence in Translational Hematology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
Center of Excellence for Medical Genomics, Medical Genomics Cluster, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.Excellence Center for Genomics and Precision Medicine, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.
Department of Pediatrics, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand.
Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Department of Pediatrics, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand dsosothikul@hotmail.com.Integrative and Innovative Hematology/Oncology Research Unit, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Genetic variations of type 2 and type 3 von Willebrand diseases in Thailand.

Two-dimensional transition metal carbide nitrides (MXenes) have been extensively explored in diverse areas, such as electrochemical energy storage and flexible electronics. Although the solution-processed MXene-based device has made significant achievements, it is still a challenge to develop large-scale and high-resolution printing methods for flexible printed electronics. In this work, we reported a novel strategy of a porous interlocking structure to obtain flexible MXene/laser-induced graphene (LMX) composite electrodes with enhanced adhesion and high printing resolution. In comparison to traditional printed MXene electrodes, the LMX electrode with an interlocking interface possesses enhanced mechanical properties (adhesive strength of 2.17 MPa) and comparable electrical properties (0.68 S/mm). Furthermore, owing to the outstanding stability and flexibility, the LMX-based triboelectric nanogenerator (TENG) can be used as a self-powered sensor to monitor finger-bending movement. A support vector machine (SVM)-assisted self-powered motion sensor can distinguish the bending angle with high recognition accuracy and can effectively identify different angles. The successful experience of directly printing flexible electrodes with excellent mechanical and electrical properties can be promoted to other solution-processed two-dimensional materials. Our strategy opens up a promising perspective to develop flexible and printed electronics.
Institute of Semiconductors, Chinese Academy of Sciences, Beijing 100083, People's Republic of China.Beijing Key Laboratory of Inorganic Stretchable and Flexible Information Technology, Beijing 100083, People's Republic of China.
Fujian Key Laboratory of Functional Marine Sensing Materials, College of Materials and Chemical Engineering, Minjiang University, Fuzhou, Fujian 350108, People's Republic of China.
Institute of Semiconductors, Chinese Academy of Sciences, Beijing 100083, People's Republic of China.Fujian Key Laboratory of Functional Marine Sensing Materials, College of Materials and Chemical Engineering, Minjiang University, Fuzhou, Fujian 350108, People's Republic of China.
Printed High-Adhesion Flexible Electrodes Based on an Interlocking Structure for Self-Powered Intelligent Movement Monitoring.

Type A aortic dissection (TAAD) is a life-threatening disease with high mortality and poor prognosis, usually treated by surgery. There are many complications in its perioperative period, one of which is oxygenation impairment (OI). As a common complication of TAAD, OI usually occurs throughout the perioperative period of TAAD and requires prolonged mechanical ventilation (MV) and other supportive measures. The purpose of this article is to review the risk factors, mechanisms, and treatments of type A aortic dissection-related oxygenation impairment (TAAD-OI) so as to improve clinicians' knowledge about it. Among risk factors, elevated body mass index (BMI), prolonged extracorporeal circulation (ECC) duration, higher inflammatory cells and stored blood transfusion stand out. A reduced occurrence of TAAD-OI can be achieved by controlling these risk factors such as suppressing inflammatory response by drugs. As for its mechanism, it is currently believed that inflammatory signaling pathways play a major role in this process, including the HMGB1/RAGE signaling pathway, gut-lung axis and macrophage, which have been gradually explored and are expected to provide evidences revealing the specific mechanism of TAAD-OI. Numerous treatments have been investigated for TAAD-OI, such as nitric oxide (NO), continuous pulmonary perfusion/inflation, ulinastatin and sivelestat sodium, immunomodulation intervention and mechanical support. However, these measures are all aimed at postoperative TAAD-OI, and not all of the therapies have shown satisfactory effects. Treatments for preoperative TAAD-OI are not currently available because it is difficult to correct OI without correcting the dissection. Therefore, the best solution for preoperative TAAD-OI is to operate as soon as possible. At present, there is no specific method for clinical application, and it relies more on the experience of clinicians or learns from treatments of other diseases related to oxygenation disorders. More efforts should be made to understand its pathogenesis to better improve its treatments in the future.
Department of Cardiopulmonary Bypass, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Extracorporeal Circulation and Mechanical Circulation Assistants, Center for Cardiac Intensive Care, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
Perioperative oxygenation impairment related to type a aortic dissection.

Acute respiratory failure (ARF) strikes an estimated two million people in the United States each year, with care exceeding US$50 billion. The hallmark of ARF is a heterogeneous injury, with normal tissue intermingled with a large volume of low compliance and collapsed tissue. Mechanical ventilation is necessary to oxygenate and ventilate patients with ARF, but if set inappropriately, it can cause an unintended ventilator-induced lung injury (VILI). The mechanism of VILI is believed to be overdistension of the remaining normal tissue known as the 'baby' lung, causing volutrauma, repetitive collapse and reopening of lung tissue with each breath, causing atelectrauma, and inflammation secondary to this mechanical damage, causing biotrauma. To avoid VILI, extracorporeal membrane oxygenation (ECMO) can temporally replace the pulmonary function of gas exchange without requiring high tidal volumes (VT) or airway pressures. In theory, the lower VT and airway pressure will minimize all three VILI mechanisms, allowing the lung to 'rest' and heal in the collapsed state. The optimal method of mechanical ventilation for the patient on ECMO is unknown. The ARDSNetwork Acute Respiratory Management Approach (ARMA) is a Rest Lung Approach (RLA) that attempts to reduce the excessive stress and strain on the remaining normal lung tissue and buys time for the lung to heal in the collapsed state. Theoretically, excessive tissue stress and strain can also be avoided if the lung is fully open, as long as the alveolar re-collapse is prevented during expiration, an approach known as the Open Lung Approach (OLA). A third lung-protective strategy is the Stabilize Lung Approach (SLA), in which the lung is initially stabilized and gradually reopened over time. This review will analyze the physiologic efficacy and pathophysiologic potential of the above lung-protective approaches.
SUNY Upstate Medical University, Syracuse, NY, USA.
Alexandria Faculty of Medicine, Alexandria, Egypt.
Critical Care Department, Faculty of Medicine Cairo University, Cairo, Egypt.
Aswan Heart Centre, Magdi Yacoub Foundation, Aswan, Egypt.
Weill Cornell Medicine, New York, NY, USA.
The use of protective mechanical ventilation during extracorporeal membrane oxygenation for the treatment of acute respiratory failure.

Handpumps are used by millions of people as their main source of water. Although handpumps represent only a basic form of water provision, there have been continuous efforts to improve the performance of these systems as they are likely to remain in use for many years to come. The introduction of a professional maintenance service in southern Kenya has shown an order of magnitude improvement in operational performance over community-based management, with 90% of handpump faults repaired within 3 days of being reported. One driver behind these efforts is the assumption that a more reliable water supply will lead to a reduction in water-related disease. However, it is not clear if operational improvements lead to health gains. Despite limited empirical evidence, some modeling studies suggest that even short periods of drinking contaminated water can lead to disproportionate negative health impacts.The aim of this study was to assess whether the improvements in operational performance from the rapid professional maintenance of rural handpumps lead to improved household health outcomes.From a sample of households using handpumps as their primary water source in Kwale County, Kenya, we measured the 2-week prevalence of World Health Organization-defined diarrhea in children, reported by the adult respondent for each household. We compared the rates before and after a period during which the households' handpumps were being professionally maintained. We then conducted a cross-sectional analysis, fitting logistic regression models with reported diarrhea as the dependent variable and speed of repair as the independent exposure of interest, adjusting for household socioeconomic characteristics; dwelling construction; and Water, Sanitation, and Hygiene (WASH)-related factors. We fitted an additional model to examine select interactions between covariates.Reported diarrhea in children was lower in households whose pumps had been repaired within 24 hours (adjusted odds ratio 0.35, 95% CI 0.24-0.51). This effect was robust to the inclusion of multiple categories of covariates. No reduction was seen in households whose pump repairs took more than 24 hours. Analysis of interaction terms showed that certain interventions associated with improved WASH outcomes were only associated with reductions in diarrhea in conjunction with socioeconomic improvements.Only pump repairs consistently made within 24 hours of failure led to a reduction in diarrhea in the children of families using handpumps. While the efficacy of reduction in diarrhea is substantial, the operational challenges of guaranteeing same-day repairs limits the effectiveness of even best-in-class pump maintenance. Maintenance regimes that cannot bring handpump downtimes close to zero will struggle to generate health benefits. Other factors that reduce diarrhea prevalence have limited effect in isolation, suggesting that WASH interventions will be more effective when undertaken as part of more holistic poverty-reduction efforts.
©Patrick Thomson, Justin Stoler, Michelle Byford, David J Bradley. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 16.01.2024.
School of Geography and the Environment, University of Oxford, Oxford, United Kingdom.Department of Engineering Science, University of Oxford, Oxford, United Kingdom.
Department of Geography and Sustainable Development, University of Miami, Coral Gables, FL, United States.Department of Public Health Sciences, University of Miami, Miami, FL, United States.
Barts Health NHS Trust, London, United Kingdom.
School of Geography and the Environment, University of Oxford, Oxford, United Kingdom.London School of Hygiene & Tropical Medicine, London, United Kingdom.
JMIR Public Health Surveill. 2024-01-16;10():e42462.
The Impact of Rapid Handpump Repairs on Diarrhea Morbidity in Children: Cross-Sectional Study in Kwale County, Kenya.

Military trainees are at increased risk for infectious disease outbreaks because of the unique circumstances of the training environment (e.g., close proximity areas and physiologic/psychologic stress). Standard medical countermeasures in military training settings include routine immunization (e.g., influenza and adenovirus) as well as chemoprophylaxis [e.g., benzathine penicillin G (Bicillin) for the prevention of group A streptococcal disease] for pathogens associated with outbreaks in these settings. In a population of U.S. Army Infantry trainees, we evaluated changes in the oral microbiome during a 14-week military training cycle.Trainees were enrolled in an observational cohort study in 2015-2016. In 2015, Bicillin was administered to trainees to ameliorate the risk of group A Streptococcus outbreaks, whereas in 2016, trainees did not receive a Bicillin inoculation. Oropharyngeal swabs were collected from participants at days 0, 7, 14, 28, 56, and 90 of training. Swabs were collected, flash frozen, and stored. DNA was extracted from swabs, and amplicon sequencing of the 16s rRNA gene was performed. Microbiome dynamics were evaluated using the QIIME 2 workflow along with DADA2, SINA with SILVA, and an additional processing in R.We observed that microbiome samples from the baseline (day 0) visit were distinct from one another, whereas samples collected on day 14 exhibited significant microbiome convergence. Day 14 convergence was coincident with an increase in DNA sequences associated with Streptococcus, though there was not a significant difference between Streptococcus abundance over time between 2015 and 2016 (P = .07), suggesting that Bicillin prophylaxis did not significantly impact overall Streptococcus abundance.The temporary convergence of microbiomes is coincident with a rise in communicable infections in this population. The dynamic response of microbiomes during initial military training supports similar observations in the literature of transient convergence of the human microbiome under cohabitation in the time frame including in this experiment. This population and the associated longitudinal studies allow for controlled studies of human microbiome under diverse conditions.
© The Association of Military Surgeons of the United States 2024. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Research and Exploratory Development Department, Johns Hopkins University Applied Physics Laboratory, Laurel, MD 20723, USA.
Asymmetric Operations Sector, Johns Hopkins University Applied Physics Laboratory, Laurel, MD 20723, USA.
Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA.
Division of Infectious Diseases, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA.
Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Multidrug-Resistant Organism Repository and Surveillance Network, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Dynamics of the Oral Microbiome During Initial Military Training at Fort Benning, Georgia.

Transcription factors (TFs) fulfill a critical role in the formation and maintenance of different cell types during the developmental process as well as disease. It is believed that cancer-associated fibroblasts (CAFs) are activation status of tissue-resident fibroblasts or derived from form other cell types via transdifferentiation or dedifferentiation. Despite a subgroup of CAFs exhibit anti-cancer effects, most of them are reported to exert effects on tumor progression, further indicating their heterogeneous origin.This review aimed to summarize and review the roles of TFs in the reciprocal crosstalk between CAFs and tumor cells, discuss the emerging mechanisms, and their roles in cell-fate decision, cellular reprogramming and advancing our understanding of the gene regulatory networks over the period of cancer initiation and progression.This manuscript delves into the key contributory factors of TFs that are involved in activating CAFs and maintaining their unique states. Additionally, it explores how TFs play a pivotal and multifaceted role in the reciprocal crosstalk between CAFs and tumor cells. This includes their involvement in processes such as epithelial-mesenchymal transition (EMT), proliferation, invasion, and metastasis, as well as metabolic reprogramming. TFs also have a role in constructing an immunosuppressive microenvironment, inducing resistance to radiation and chemotherapy, facilitating angiogenesis, and even 'educating' CAFs to support the malignancies of tumor cells. Furthermore, this manuscript delves into the current status of TF-targeted therapy and considers the future directions of TFs in conjunction with anti-CAFs therapies to address the challenges in clinical cancer treatment.
Copyright © 2024. Published by Elsevier B.V.
Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Institute of Pathology, Fudan University, Shanghai 200032, China.
Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Institute of Pathology, Fudan University, Shanghai 200032, China. Electronic address: shengweiqi2006@163.com.
Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Institute of Pathology, Fudan University, Shanghai 200032, China. Electronic address: xumd27202003@sina.com.
The role of transcription factors in the crosstalk between cancer-associated fibroblasts and tumor cells.

The US heart allocation system prioritizes medically urgent candidates with a high risk of dying without transplant. The current therapy-based 6-status system is susceptible to manipulation and has limited rank ordering ability.To develop and validate a candidate risk score that incorporates current clinical, laboratory, and hemodynamic data.A registry-based observational study of adult heart transplant candidates (aged ≥18 years) from the US heart allocation system listed between January 1, 2019, and December 31, 2022, split by center into training (70%) and test (30%) datasets. Adult candidates were listed between January 1, 2019, and December 31, 2022.A US candidate risk score (US-CRS) model was developed by adding a predefined set of predictors to the current French Candidate Risk Score (French-CRS) model. Sensitivity analyses were performed, which included intra-aortic balloon pumps (IABP) and percutaneous ventricular assist devices (VAD) in the definition of short-term mechanical circulatory support (MCS) for the US-CRS. Performance of the US-CRS model, French-CRS model, and 6-status model in the test dataset was evaluated by time-dependent area under the receiver operating characteristic curve (AUC) for death without transplant within 6 weeks and overall survival concordance (c-index) with integrated AUC.A total of 16 905 adult heart transplant candidates were listed (mean [SD] age, 53 [13] years; 73% male; 58% White); 796 patients (4.7%) died without a transplant. The final US-CRS contained time-varying short-term MCS (ventricular assist-extracorporeal membrane oxygenation or temporary surgical VAD), the log of bilirubin, estimated glomerular filtration rate, the log of B-type natriuretic peptide, albumin, sodium, and durable left ventricular assist device. In the test dataset, the AUC for death within 6 weeks of listing for the US-CRS model was 0.79 (95% CI, 0.75-0.83), for the French-CRS model was 0.72 (95% CI, 0.67-0.76), and 6-status model was 0.68 (95% CI, 0.62-0.73). Overall c-index for the US-CRS model was 0.76 (95% CI, 0.73-0.80), for the French-CRS model was 0.69 (95% CI, 0.65-0.73), and 6-status model was 0.67 (95% CI, 0.63-0.71). Classifying IABP and percutaneous VAD as short-term MCS reduced the effect size by 54%.In this registry-based study of US heart transplant candidates, a continuous multivariable allocation score outperformed the 6-status system in rank ordering heart transplant candidates by medical urgency and may be useful for the medical urgency component of heart allocation.
Department of Medicine, University of Chicago, Chicago, Illinois.
Advocate Heart Institute, Advocate Christ Medical Center, Oak Lawn, Illinois.Department of Medicine, University of Illinois-Chicago.
Agence de la Biomédecine, Direction Prélèvement Greffe Organes-Tissus, Saint-Denis La Plaine, France.
Pritzker School of Medicine, University of Chicago, Chicago, Illinois.
Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison.
Department of Medicine, University of Wisconsin, Madison.
Division of Cardiovascular Medicine, Department of Medicine, Stanford University, Stanford, California.
Department of Medicine, University of Chicago, Chicago, Illinois.Department of Public Health Sciences, University of Chicago, Chicago, Illinois.MacLean Center for Clinical Medical Ethics, University of Chicago, Chicago, Illinois.
Development and Validation of a Risk Score Predicting Death Without Transplant in Adult Heart Transplant Candidates.

Nitrogen dioxide (NO2) has been frequently linked to a range of diseases and associated with high rates of mortality and morbidity worldwide. However, there is limited evidence regarding the risk of NO2 on a spectrum of causes of mortality. Moreover, adjustment for potential confounders in NO2 analysis has been insufficient, and the spatial resolution of exposure assessment has been limited.This study aimed to quantitatively assess the relationship between short-term NO2 exposure and death from a range of causes by adjusting for potential confounders in Guangzhou, China, and determine the modifying effect of gender and age.A time series study was conducted on 413,703 deaths that occurred in Guangzhou during the period of 2010 to 2018. The causes of death were classified into 10 categories and 26 subcategories. We utilized a generalized additive model with quasi-Poisson regression analysis using a natural cubic splines function with lag structure of 0 to 4 days to estimate the potential lag effect of NO2 on cause-specific mortality. We estimated the percentage change in cause-specific mortality rates per 10 μg/m3 increase in NO2 levels. We stratified meteorological factors such as temperature, humidity, wind speed, and air pressure into high and low levels with the median as the critical value and analyzed the effects of NO2 on various death-causing diseases at those high and low levels. To further identify potentially vulnerable subpopulations, we analyzed groups stratified by gender and age.A significant association existed between NO2 exposure and deaths from multiple causes. Each 10 μg/m3 increment in NO2 density at a lag of 0 to 4 days increased the risks of all-cause mortality by 1.73% (95% CI 1.36%-2.09%) and mortality due to nonaccidental causes, cardiovascular disease, respiratory disease, endocrine disease, and neoplasms by 1.75% (95% CI 1.38%-2.12%), 2.06% (95% CI 1.54%-2.59%), 2.32% (95% CI 1.51%-3.13%), 2.40% (95% CI 0.84%-3.98%), and 1.18% (95% CI 0.59%-1.78%), respectively. Among the 26 subcategories, mortality risk was associated with 16, including intentional self-harm, hypertensive disease, and ischemic stroke disease. Relatively higher effect estimates of NO2 on mortality existed for low levels of temperature, relative humidity, wind speed, and air pressure than with high levels, except a relatively higher effect estimate was present for endocrine disease at a high air pressure level. Most of the differences between subgroups were not statistically significant. The effect estimates for NO2 were similar by gender. There were significant differences between the age groups for mortality due to all causes, nonaccidental causes, and cardiovascular disease.Short-term NO2 exposure may increase the risk of mortality due to a spectrum of causes, especially in potentially vulnerable populations. These findings may be important for predicting and modifying guidelines for NO2 exposure in China.
©Jie Zeng, Guozhen Lin, Hang Dong, Mengmeng Li, Honglian Ruan, Jun Yang. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 05.02.2024.
Department of Internet Medical Center, Guangdong Second Provincial General Hospital, Guangzhou, China.
Guangzhou Center for Disease Control and Prevention, Guangzhou, China.Institute of Public Health, Guangzhou Medical University and Guangzhou Center for Disease Control and Prevention, Guangzhou, China.
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
School of Public Health, Guangzhou Medical University, Guangzhou, China.
JMIR Public Health Surveill. 2024-02-05;10():e44648.
Association Between Nitrogen Dioxide Pollution and Cause-Specific Mortality in China: Cross-Sectional Time Series Study.

Glaucoma is an eye disease that is the most common cause of irreversible blindness worldwide. It has been suggested that gut microbiota can produce reactive oxygen species and pro-inflammatory cytokines that may travel from the gastric mucosa to distal sites, for example, the optic nerve head or trabecular meshwork. There is evidence for a gut-eye axis, as microbial dysbiosis has been associated with retinal diseases. We investigated the microbial composition in patients with glaucoma and healthy controls. Moreover, we analyzed the association of the gut microbiome with intraocular pressure (IOP; risk factor of glaucoma) and vertical cup-to-disc ratio (VCDR; quantifying glaucoma severity).The discovery analyses included participants of the Rotterdam Study and the Erasmus Glaucoma Cohort. A total of 225 patients with glaucoma and 1247 age- and sex-matched participants without glaucoma were included in our analyses. Stool samples were used to generate 16S rRNA gene profiles. We assessed associations with 233 genera and species. We used data from the TwinsUK and the Study of Health in Pomerania (SHIP) to replicate our findings.Several butyrate-producing taxa (e.g. Butyrivibrio, Caproiciproducens, Clostridium sensu stricto 1, Coprococcus 1, Ruminococcaceae UCG 007, and Shuttleworthia) were less abundant in people with glaucoma compared to healthy controls. The same taxa were also associated with lower IOP and smaller VCDR. The replication analyses confirmed the findings from the discovery analyses.Large human studies exploring the link between the gut microbiome and glaucoma are lacking. Our results suggest that microbial dysbiosis plays a role in the pathophysiology of glaucoma.
Department of Ophthalmology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Department of Ophthalmology, King's College London, London, United Kingdom.Department of Twins Research and Genetic Epidemiology, King's College London, London, United Kingdom.
Interfaculty Institute of Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.Department of Medicine A, University Medicine Greifswald, Greifswald, Germany.
Department of Medicine A, University Medicine Greifswald, Greifswald, Germany.
Department of Ophthalmology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Department of Ophthalmology, University Medicine Greifswald, Greifswald, Germany.
Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
Department of Ophthalmology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.Department of Ophthalmology, Radboud University Medical Center, Nijmegen, The Netherlands.Institute of Molecular and Clinical Ophthalmology, University of Basel, Basel, Switzerland.
Investigative ophthalmology & visual science
Invest Ophthalmol Vis Sci. 2024-02-01;65(2):7.
Glaucoma Patients Have a Lower Abundance of Butyrate-Producing Taxa in the Gut.

Drug abuse is considered a global health problem with serious social impact. In recent decades, changes in drug consumption patterns have shown a clear rising trend in the use of multiple drugs. Although the buccal micronucleus cytome (BMCyt) assay has evaluated cytotoxicity in drug abuse, there has not been an approach that takes into account this pattern of multiple drug use. Therefore, in this study, we evaluate for the first time the cytogenotoxic effects in multidrug users, and its correlation with the amount consumed and years of abuse. This study was conducted on 166 individuals by the BMCyt assay. A total of 83 individuals with a history of multiple licit (alcohol and tobacco) and at least one illicit drug abuse (marijuana, methamphetamines, cocaine, and/or inhalants), and 83 healthy individuals, non-drug abusers were analyzed. The results showed that drug abusers had higher frequencies of nuclear abnormalities nuclear buds, binucleated cells, pyknotic nuclei (PNs), karyorrhexis (KX), and abnormally condensed chromatin when compared with healthy controls. Moreover, results suggests that the use of licit and illicit drugs is related to cytogenotoxic damage, as was shown by an upward trend in the frequency of nuclear abnormalities identified in groups 1 (alcohol + tobacco + at least one illicit drug) and 2 (tobacco + at least one illicit drug). Furthermore, a positive correlation was found in the different groups, between the years and the amount of consumption of some drugs (alcohol, methamphetamine, and tobacco) with cytotoxicity markers such as KL, KX, and PNs.
© 2024 Environmental Mutagenesis and Genomics Society.
Departamento de Ciencias Biomédicas, División de Ciencias de la Salud, Centro Universitario de Tonalá, Universidad de Guadalajara, Tonalá, Jalisco, Mexico.
Departamento de Ciencias de la Salud-Enfermedad como Proceso Individual, Centro Universitario de Tonalá, Universidad de Guadalajara, Tonalá, Jalisco, Mexico.Unidad de intervención de Medicina Crítica, Hospital General de Occidente, Secretaría de Salud Jalisco, Zapopan, Jalisco, Mexico.
Laboratorio de Mutagénesis, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, Mexico.
Instituto de Genética Humana Dr. Enrique Corona Rivera, Departamento de Biología Molecular y Genómica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico.
Cytogenotoxicity effects in addicts with multidrug consumption.

In Italy, it has been difficult to accurately quantify hospital admissions of patients with a COVID-19 diagnosis using the Hospital Information System (HIS), mainly due to the heterogeneity of codes used in the hospital discharge records during different waves of the COVID-19 pandemic.The objective of this study was to define a specific combination of codes to identify the COVID-19 hospitalizations within the HIS and to investigate the risk factors associated with mortality due to COVID-19 among patients admitted to Italian hospitals in 2020.A retrospective study was conducted using the hospital discharge records, provided by more than 1300 public and private Italian hospitals. Inpatient hospitalizations were detected by implementing an algorithm based on specific International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code combinations. Hospitalizations were analyzed by different clinical presentations associated with COVID-19 diagnoses. In addition, 2 multivariable Cox regression models were performed among patients hospitalized due to COVID-19 from January 1 to December 31, 2020, to investigate potential risk factors associated with 30-day death and the temporal changes over the course of the pandemic; in particular, the 30-day death rates during the first and the second waves were analyzed across 3 main geographical areas (North, Center, and South and Islands) and by discharge wards (ordinary and intensive care).We identified a total of 325,810 hospitalizations with COVID-19-related diagnosis codes. Among these, 73.4% (n=239,114) were classified as due to COVID-19, 14.5% (n=47,416) as SARS-CoV-2 positive, but not due to COVID-19, and 12.1% (n=39,280) as suspected COVID-19 hospitalizations. The cohort of patients hospitalized due to COVID-19 included 205,048 patients, with a median age of 72 years and a higher prevalence of male patients (n=124,181, 60.6%). The overall 30-day death rate among hospitalized patients due to COVID-19 was 9.9 per 1000 person-days. Mortality was lower for women (hazard ratio [HR]=0.83; P<.001) and for patients coming from high migration pressure countries, especially Northern Africans (HR=0.65; P<.001) and Central and Eastern Europeans (HR=0.66; P<.001), compared to patients coming from Italy and high-income countries. In the southern regions and the Islands, mortality was higher compared to the northern regions (HR=1.17; P<.001), especially during the second wave of COVID-19 among patients with a transfer to intensive care units (HR=2.52; P<.001).To our knowledge, the algorithm is the first attempt to define, at a national level, selection criteria for identifying COVID-19 hospitalizations within the HIS. The implemented algorithm will be used to monitor the pandemic over time, and the patients selected in 2020 will be followed up in the next years to assess the long-term effects of COVID-19.
©Barbara Giordani, Alessandra Burgio, Francesco Grippo, Alessandra Barone, Erica Eugeni, Giovanni Baglio. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 23.02.2024.
Research, National Outcomes Evaluation Programme (PNE) and International Relations Unit, Italian National Agency for Regional Healthcare Services, Rome, Italy.
Italian National Institute of Statistics, Rome, Italy.
JMIR Public Health Surveill. 2024-02-23;10():e44062.
The Use of ICD-9-CM Coding to Identify COVID-19 Diagnoses and Determine Risk Factors for 30-Day Death Rate in Hospitalized Patients in Italy: Retrospective Study.

Health care authorities often use text messages to enhance compliance with medical recommendations. The effectiveness of different message framings has been studied extensively over the past 3 decades. Recently, health care providers have begun using digital media platforms to disseminate health-related messages.This study aimed to examine the effectiveness of some of the most widely used message framings on the uptake rates of medical checkups.This study used a large-scale digital outreach campaign conducted by Maccabi Healthcare Services (MHS) during 2020-2021, involving a total of 113,048 participants. MHS members aged 50-74 years were invited to take their recommended medical actions from the following list: human papillomavirus (HPV), mammography, abdominal aortic aneurysm, fecal occult blood test (FOBT), and pneumococcal vaccination. Each member was randomly assigned to receive 1 of 6 message framings: control (neutrally framed; n=20,959, 18.5%), gains (benefits of compliance; n=20,393, 18%), losses (negative consequences of noncompliance; n=15,165, 13.4%), recommendation (a recommendation by an authoritative figure, in this context by a physician; n=20,584, 18.2%), implementation intentions (linking potential outcomes to future reactions; n=20,701, 18.3%), and empowerment (emphasizing personal responsibility for maintaining good health; n=15,246, 13.5%). The time frames for measuring a successful intervention were 14 days for scheduling screenings (ie, HPV, mammography, or abdominal aortic aneurysm), 30 days for performing the FOBT, and 60 days for receiving pneumococcal vaccination. We also examined the effectiveness of media channels (text message or email) on uptake rates and whether the subject-line length is correlated with message-opening rates.No significant effect of message framing on uptake rates of medical checkups was observed. The rates of appointments for screening ranged from 12.9% to 14.1% across treatments. Based on a chi-square test, there was no evidence to reject the null hypothesis that these compliance rates are independent of the treatments (P=.35). The uptake rates for the FOBT and pneumococcal vaccination ranged from 23.3% to 23.8% across treatments, and we could not reject the hypothesis that they are independent of the treatments (P=.88). We also found that emails are more effective than text messages (P<.001) and that the subject-line length is negatively correlated with message-opening rates.No evidence was found for an effect of the 5 message framings on uptake rates of medical checkups. To enhance compliance rates, public health officials may consider alternative framings. Furthermore, media channels and the subject-line length should be given careful consideration in the planning stages of health care campaigns.AEA RCT Registry AEARCTR-0006317; https://www.socialscienceregistry.org/trials/6317/history/201365.
©Amnon Maltz, Stella Rashkovich, Adi Sarid, Yafit Cohen, Tamar Landau, Elina Saifer, Neta Amorai Belkin, Tamar Alcalay. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 06.03.2024.
Department of Economics, University of Haifa, Haifa, Israel.
Nursing Division, Maccabi Healthcare Services, Tel Aviv, Israel.
Marketing Automation Department, Maccbi Healthcare Services, Tel Aviv, Israel.
AI & Big Data Department, Maccabi Healthcare Services, Tel Aviv, Israel.
JMIR Public Health Surveill. 2024-03-06;10():e45379.
The Framing Effect of Digital Textual Messages on Uptake Rates of Medical Checkups: Field Study.

The management of neuropsychiatric systemic lupus erythematosus (NPSLE) poses considerable challenges due to limited clinical trials. Therapeutic decisions are customized based on suspected pathogenic mechanisms and symptoms severity. This study aimed to investigate therapeutic strategies and disease outcome for patients with NPSLE experiencing their first neuropsychiatric (NP) manifestation.This retrospective cohort study defined NP events according to the American College of Rheumatology case definition, categorizing them into three clusters: central/diffuse, central/focal and peripheral. Clinical judgment and a validated attribution algorithm were used for NP event attribution. Data included demographic variables, SLE disease activity index, cumulative organ damage, and NP manifestation treatments. The clinical outcome of all NP events was determined by a physician seven-point Likert scale. Predictors of clinical improvement/resolution were investigated in a multivariable logistic regression analysis.The analysis included 350 events. Immunosuppressants and corticosteroids were more frequently initiated/escalated for SLE-attributed central diffuse or focal NP manifestations. At 12 months of follow-up, 64% of patients showed a clinical improvement in NP manifestations. Focal central events and SLE-attributed manifestations correlated with higher rates of clinical improvement. Patients with NP manifestations attributed to SLE according to clinical judgment and treated with immunosuppressants had a significantly higher probability of achieving clinical response (OR 2.55, 95%CI 1.06-6.41, P = 0.04). Age at diagnosis and focal central events emerged as additional response predictors.NP manifestations attributed to SLE by clinical judgment and treated with immunosuppressants demonstrated improved 12-month outcomes. This underscores the importance of accurate attribution and timely diagnosis of NPSLE.
© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Section of Rheumatology, Department of Medical Sciences University of Ferrara and Azienda Ospedaliera-Universitaria di Ferrara, Cona, Italy.
Rheumatology and Clinical Immunology Unit, 4th Department of Internal Medicine, Attikon University Hospital, National and Kapodistrian University of Athens Medical School, Athens, Greece.
Rheumatology Unit, Department of Orthopedics, Rheumatology and Traumatology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil.
Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Epidemiology Unit, Italian Society of Rheumatology, Milan, Italy.
Rheumatology Unit, University Clinic, AOU Cagliari, Cagliari, Italy.Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
Dipartimento di Scienze Cliniche, Internistiche, Anestesiologiche e Cardiovascolari (SCIAC), Sapienza University, Rome, Italy.
Rheumatology Unit, University of Udine, Department of Medicine, University Hospital Santa Maria della Misericordia, Udine, Italy.
Rheumatology Unit, Department of Medicine-DIMED, University of Padova, Padova, Italy.
Rheumatology and Clinical Immunology Unit and Clinical and Experimental Science Department ASST Spedali Civili and University of Brescia, Brescia, Italy.
Division of Rheumatology, Departments of Medicine and Pathology, Dalhousie University and Queen Elizabeth II Health Sciences Center, Halifax, NS, Canada.
Division of Rheumatology, Departments of Medicine, Dalhousie University and Queen Elizabeth II Health Sciences Center, Halifax, NS, Canada.
Epidemiology Unit, Italian Society of Rheumatology, Milan, Italy.School of Medicine, University of Milano Bicocca, Milan, Italy.
Internal Medicine Department, Rheumatology Unit, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), Trieste, Italy.
Department of Rheumatology, Clinical Immunology, University of Crete Medical School and University Hospital of Heraklion, Heraklion, Greece.Laboratory of Rheumatology, Autoimmunity and Inflammation, Infections & Immunity Division, Institute of Molecular Biology and Biotechnology (FORTH), Heraklion, Greece.
Therapeutic strategies and outcomes in neuropsychiatric systemic lupus erythematosus: an international multicentre retrospective study.

In patients with advanced soft tissue sarcoma (STS), surgery had been reported to be associated with superior overall survival (OS). Chemotherapy details for such patients were less reported, and whether multimodal treatment with surgery and chemotherapy provides extra survival benefit remains unclear.We retrospectively reviewed patients with newly diagnosed advanced STS treated at National Taiwan University Hospital from January 1, 2011, to December 31, 2017. OS was calculated from the day of diagnosis of advanced STS to the day of death or last follow-up. Baseline patient characteristics and details regarding surgery and chemotherapy were recorded.A total of 545 patients were diagnosed with STS from 2011 to 2017, of which 226 patients had advanced STS. The median age was 54.7 years, and 54% of patients were women. Approximately 38% of patients with advanced STS underwent surgery and exhibited a trend of longer OS compared with who did not (median = 18.6 vs. 11.9 months, p = 0.083). In the chemotherapy subgroup, the benefit of surgery was more prominent (median = 21.9 vs. 16.5 months, p = 0.037). Patients who received chemotherapy prior to surgery exhibited numerically longer OS than those who underwent surgery first (median = 33.9 vs. 18.3 months, p = 0.155). After adjusting other clinical factors, chemotherapy remained an independent factor associated with favourable OS.Surgery may be more beneficial for the patients who receive chemotherapy. Our results support evaluation of sequential multimodal treatments strategy including surgery and chemotherapy in patients with advanced STS.
Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.
Department of Oncology, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan, ROC; Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan, ROC; Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan, ROC. Electronic address: robarroyce@gmail.com.
Department of Oncology, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan, ROC; Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan, ROC; Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan, ROC. Electronic address: hsingwuc@gmail.com.
Department of Orthopedic Surgery, National Taiwan University Hospital, Taipei, Taiwan, ROC. Electronic address: ethanlin@ntuh.gov.tw.
Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan, ROC. Electronic address: phuang3@ntuh.gov.tw.
Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan, ROC. Electronic address: mwlin@ntu.edu.tw.
Department of Surgery, National Taiwan University Hospital, and National Taiwan University College of Medicine, Taipei, Taiwan, ROC. Electronic address: cyang@ntuh.gov.tw.
Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan, ROC; Department of Radiation Oncology, National Taiwan University Cancer Center, Taipei, Taiwan, ROC. Electronic address: codiwa@ntuh.gov.tw.
Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan, ROC; Department of Radiation Oncology, National Taiwan University Cancer Center, Taipei, Taiwan, ROC. Electronic address: chiachun@ntuh.gov.tw.
Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan, ROC. Electronic address: leejenchieh@ntuh.gov.tw.
Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan, ROC. Electronic address: koping@ntuh.gov.tw.
Department of Urology, National Taiwan University Hospital, Taipei, Taiwan, ROC. Electronic address: khhuang@ntuh.gov.tw.
Health Data Research Center, National Taiwan University, Taipei, Taiwan, ROC. Electronic address: homin.chen@gmail.com.
Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan, ROC; Department of Medical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan, ROC; Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan, ROC. Electronic address: tomwchen@ntuh.gov.tw.
Department of Orthopedic Surgery, National Taiwan University Hospital, Taipei, Taiwan, ROC. Electronic address: rsyang@ntuh.gov.tw.
Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan, ROC; Department of Medical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan, ROC. Electronic address: rlhong@ntuh.gov.tw.
Journal of the Formosan Medical Association = Taiwan yi zhi
Sequential multimodal treatments with chemotherapy and surgery for advanced soft tissue sarcoma may be associated with better survival than chemotherapy.

Wireless emergency alerts (WEAs), which deliver disaster information directly to individuals' mobile phones, have been widely used to provide information related to COVID-19 and to encourage compliance with social distancing guidelines during the COVID-19 pandemic. The floating population refers to the number of people temporarily staying in a specific area, and this demographic data can be a useful indicator to understand the level of social distancing people are complying with during the COVID-19 pandemic.This study aimed to empirically analyze the impact of WEAs on the floating population where WEAs were transmitted in the early stages of the COVID-19 pandemic. As most WEA messages focus on compliance with the government's social distancing guidelines, one of the goals of transmitting WEAs during the COVID-19 pandemic is to control the floating population at an appropriate level.We investigated the empirical impact of WEAs on the floating population across 25 districts in Seoul by estimating a panel regression model at the district-hour level with a series of fixed effects. The main independent variables were the number of instant WEAs, the daily cumulative number of WEAs, the total cumulative number of WEAs, and information extracted from WEAs by natural language processing at the district-hour level. The data set provided a highly informative empirical setting as WEAs were sent by different local governments with various identifiable district-hour-level data.The estimates of the impact of WEAs on the floating population were significantly negative (-0.013, P=.02 to -0.014, P=.01) across all specifications, implying that an additional WEA issuance reduced the floating population by 1.3% (=100(1-e-0.013)) to 1.4% (=100(1-e-0.014)). Although the coefficients of DCN (the daily cumulative number of WEAs) were also negative (-0.0034, P=.34 to -0.0052, P=.15) across all models, they were not significant. The impact of WEAs on the floating population doubled (-0.025, P=.02 to -0.033, P=.005) when the first 82 days of observations were used as subsamples to reduce the possibility of people blocking WEAs.Our results suggest that issuing WEAs and distributing information related to COVID-19 to a specific district was associated with a decrease in the floating population of that district. Furthermore, among the various types of information in the WEAs, location information was the only significant type of information that was related to a decrease in the floating population. This study makes important contributions. First, this study measured the impact of WEAs in a highly informative empirical setting. Second, this study adds to the existing literature on the mechanisms by which WEAs can affect public response. Lastly, this study has important implications for making optimal WEAs and suggests that location information should be included.
©Sungwook Yoon, Hyungsoo Lim, Sungho Park. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 25.03.2024.
Korea Information Society Development Institute, Jincheon, Republic of Korea.
Department of Information Systems, Business Statistics, and Operations Management, School of Business and Management, Hong Kong University of Science and Technology, Clear Water Bay, China (Hong Kong).
Business School, Seoul National University, Seoul, Republic of Korea.
JMIR Public Health Surveill. 2024-03-25;10():e43554.
The Impact of Wireless Emergency Alerts on a Floating Population in Seoul, South Korea: Panel Data Analysis.

In May 2020, the World Health Organization (WHO) declared Latin America and the Caribbean (LAC) the epicenter of the COVID-19 pandemic, with over 40% of worldwide COVID-19-related deaths at the time. This high disease burden was a result of the unique circumstances in LAC.This study aimed to (1) measure whether the pandemic was expanding or contracting in LAC when the WHO declared the end of COVID-19 as a public health emergency of international concern on May 5, 2023; (2) use dynamic and genomic surveillance methods to describe the history of the pandemic in the region and situate the window of the WHO declaration within the broader history; and (3) provide, with a focus on prevention policies, a historical context for the course of the pandemic in the region.In addition to updates of traditional surveillance data and dynamic panel estimates from the original study, we used data on sequenced SARS-CoV-2 variants from the Global Initiative on Sharing All Influenza Data (GISAID) to identify the appearance and duration of variants of concern (VOCs). We used Nextclade nomenclature to collect clade designations from sequences and Pangolin nomenclature for lineage designations of SARS-CoV-2. Additionally, we conducted a 1-sided t test for whether the regional weekly speed (rate of novel COVID-19 transmission) was greater than an outbreak threshold of 10. We ran the test iteratively with 6 months of data across the period from August 2020 to May 2023.The speed of pandemic spread for the region had remained below the outbreak threshold for 6 months by the time of the WHO declaration. Acceleration and jerk were also low and stable. Although the 1- and 7-day persistence coefficients remained statistically significant for the 120-day period ending on the week of May 5, 2023, the coefficients were relatively modest in magnitude (0.457 and 0.491, respectively). Furthermore, the shift parameters for either of the 2 most recent weeks around May 5, 2023, did not indicate any change in this clustering effect of cases on future cases. From December 2021 onward, Omicron was the predominant VOC in sequenced viral samples. The rolling t test of speed=10 became entirely insignificant from January 2023 onward.Although COVID-19 continues to circulate in LAC, surveillance data suggest COVID-19 is endemic in the region and no longer reaches the threshold of the pandemic definition. However, the region experienced a high COVID-19 burden in the early stages of the pandemic, and prevention policies should be an immediate focus in future pandemics. Ahead of vaccination development, these policies can include widespread testing of individuals and an epidemiological task force with a contact-tracing system.
©Lori Ann Post, Scott A Wu, Alan G Soetikno, Egon A Ozer, Yingxuan Liu, Sarah B Welch, Claudia Hawkins, Charles B Moss, Robert L Murphy, Maryann Mason, Robert J Havey, Alexander L Lundberg. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 17.05.2024.
Buehler Center for Health Policy and Economics, Robert J Havey, MD Institute for Global Health, Northwestern University, Chicago, IL, United States.Department of Emergency Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.
Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.
Department of Medicine, Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.Center for Pathogen Genomics and Microbial Evolution, Robert J Havey, MD Institute for Global Health, Northwestern University, Chicago, IL, United States.
Department of Medicine, Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.Center for Global Communicable and Emerging Infectious Diseases, Robert J Havey, MD Institute for Global Health, Northwestern University, Chicago, IL, United States.
Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL, United States.
Department of Medicine, Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.Robert J Havey, MD Institute for Global Health, Northwestern University, Chicago, IL, United States.
Robert J Havey, MD Institute for Global Health, Northwestern University, Chicago, IL, United States.Department of Medicine, General Internal Medicine and Geriatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.
JMIR Public Health Surveill. 2024-05-17;10():e44398.
Updated Surveillance Metrics and History of the COVID-19 Pandemic (2020-2023) in Latin America and the Caribbean: Longitudinal Trend Analysis.

The author reflects on a decade of antipsychotic treatment, providing an intimate glimpse into living with schizophrenia. Their narrative unravels the balance of vulnerability and strength, coercion, and dialogue inherent in the acceptance of medication. Their journey from defiance to adherence showcases the profound complexities patients face and the ethical dilemmas confronting caregivers. Interactions with loved ones and mentors underscore the importance of a shared decision-making approach. The author emphasizes not just the significance of medication but the broader, holistic perspective of aligning treatment with one's life goals and values. Their story champions the power of lived experiences, aiming to inspire a more empathetic and collaborative approach to antipsychotic treatment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Deprescribing is a long-overdue concept for psychiatrists and therapists, presenting potentially more sophisticated approaches to psychiatric care. This approach is fueled by both scientific pursuits and contemporary social ideologies that underscore the pivotal role of a patient's values and their freedom of choice. Indeed, deprescribing is well woven with modern liberal and progressive values. Yet, amidst the emphasis on these aspects, it is crucial not to lose sight of the conservative perspective within this discourse-one that emphasizes the potential consequences of failure. While constantly addressing relapse as a looming cloud may not yield benefits for patients, overlooking these potential pitfalls could tip the balance too far, resulting in unintended harm rather than good. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
Navigating the straits of deprescribing: Psychiatrist's personal account of fears and hopes.

In recent years, there has been a notable surge of interest in hybrid materials within the biomedical field, particularly for applications in bone repair and regeneration. Ceramic-polymeric hybrid scaffolds have shown promising outcomes. This study aimed to synthesize bioactive glass (BG-58S) for integration into a bioresorbable polymeric matrix based on PDLLA, aiming to create a bioactive scaffold featuring stable pH levels. The synthesis involved a thermally induced phase separation process followed by lyophilization to ensure an appropriate porous structure. BG-58S characterization revealed vitreous, bioactive, and mesoporous structural properties. The scaffolds were analyzed for morphology, interconnectivity, chemical groups, porosity and pore size distribution, zeta potential, pH, in vitro degradation, as well as cell viability tests, total protein content and mineralization nodule production. The PDLLA scaffold displayed a homogeneous morphology with interconnected macropores, while the hybrid scaffold exhibited a heterogeneous morphology with smaller diameter pores due to BG-58S filling. The hybrid scaffold also demonstrated a pH buffering effect on the polymer surface. In addition to structural characteristics, degradation tests indicated that by incorporating BG-58S modified the acidic degradation of the polymer, allowing for increased total protein production and the formation of mineralization nodules, indicating a positive influence on cell culture.
Characterization and Processing Laboratory of Advanced Materials, Institute for Research and Development, University of Vale do Paraíba, São Paulo, Brazil.
Selaz - Industry and Commercialization of Biomechanical Devices, São Paulo, Brazil.
Characterization and Processing Laboratory of Advanced Materials, Institute for Research and Development, University of Vale do Paraíba, São Paulo, Brazil.Selaz - Industry and Commercialization of Biomechanical Devices, São Paulo, Brazil.
Laboratório de Plasma e Processos, Instituto Tecnológico de Aeronáutica. Laboratório, São José dos Campos. Praça Marechal Eduardo Gomes, CEP, Brasil.
Institute of Science and Technology, Paulista State University, Francisco José Longo, São José dos Campos, SP, CEP, Brazil.
Journal of biomaterials science. Polymer edition
Development and characterization of ceramic-polymeric hybrid scaffolds for bone regeneration: incorporating of bioactive glass BG-58S into PDLLA matrix.

High blood pressure (BP) remains a major health problem globally, with a proportion of hypertension-mediated organ damage (HMOD) increasing worldwide including in Asia region. Cardiovascular (CV), cerebral and kidney diseases related to hypertension were reported to be closely associated with morning surge and nocturnal hypertension-a subset of BP variability-which can be detected by out-of-office BP measurement. Ambulatory BP monitoring (ABPM) and Home BP monitoring (HBPM) have been recommended by major guidelines to be used in the evaluation of BP variability and outcomes' prediction of hypertension patients. However, an interesting profile of ABPM in Asia has been reported and hypothesized to correlate with different outcomes. This review will focus on the current recommendation of ABPM use by the guidelines, the major different profiles of ABPM in Asia as compared to Western countries according to clinical indications, and the challenges in implementing optimal use of ABPM in Asian countries based on available evidence.
© 2024 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.
Department of Cardiology and Vascular Medicine, Faculty of Medicine Universitas Indonesia - National Cardiovascular Center Harapan Kita, Jakarta, Indonesia.
Department of Preventive and Community Medicine, University of the East Ramon Magsaysay Memorial Medical Center Research Institute for Health Sciences, Manila, Philippines.
Cardiovascular Division, Department of Medicine, Faculty of Medicine Chiang Mai University, Chiang Mai, Thailand.
Ambulatory blood pressure monitoring profiles in Asia.

Explore a lived experience perspective on using antipsychotic medicine and call to action for psychiatric rehabilitation practitioners to get involved in preparing people diagnosed with serious mental illness (SMI) to have a voice and choice in antipsychotic medication treatment.A first-person account of awakening on an antipsychotic medication for the first time is used to understand the lived experience and challenges of using it. Lessons learned are amplified through de-identified queries of the CommonGround database capturing concerns about antipsychotic medication of people diagnosed with SMI in public sector mental health clinics in the United States.Lived experience of me-on-medicine included embodied and perceptual changes to self when taking antipsychotic medications. Discordance between the team's goal and personal goals for medication treatment interfered with recovery. Analysis of more than 100,000 concerns about antipsychotic medications expressed by 57,370 CommonGround users showed the most frequent concerns are that medication is perceived as unhelpful (21%), side effects (13%), impact on health (12%), and concerns about feeling unmotivated to use medication (8%). Among CommonGround users below age 30, low motivation to take antipsychotics was the third most prevalent concern. Among CommonGround users over age 30, concerns about the impact on health were the third most dominant.Psychiatric rehabilitation practitioners can support people diagnosed with SMI getting prepared to participate in decision making about antipsychotic medications with psychiatric care providers by identifying concerns and building skills and strategies to negotiate the new me-on-medicine. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
Department of Social and Behavioral Sciences, College of Public Health, Temple University.
Awakening on antipsychotic medication: A call to action.

Neurology, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Spain luciamaure.lm@gmail.com.
Neurology, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Spain.
Internal Medicine Department, Hospital FREMAP Majadahonda, Madrid, Spain.
Neurophysiology Department, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain.
Internal Medicine Department, Hospital Universitario Doce de Octubre, Madrid, Comunidad de Madrid, Spain.
Rehabilitation Centre, Hospital FREMAP Majadahona, Madrid, Spain.
Acute proximal weakness and paraesthesiae.

Packaging plays an important role in protecting foodstuffs against physicochemical damage and microbial activity, as well as extending shelf life. In recent years, petrochemical compounds that cause environmental pollution and contamination due to their non-biodegradability have been replaced by biocompatible polymer-based films in the food packaging industry. Due to aromatic essential oils (EO), various biological activities, and their potential to replace chemical preservatives in the field of food preservation, Star Anise essential oil, which has properties, such as free radical scavenger, antibacterial, antifungal and antiviral, was used as an additive in this study. Biodegradable and biocompatible polyvinyl alcohol (PVA) polymer was used as the matrix and polymer-based films were produced in 3 different concentrations. Spectral analysis, structural, chemical, and thermal characterizations, and surface morphologies of the produced films by the direct incorporation method were examined. In addition, the antibacterial activities of the films on Staphylococcus epidermidis ATCC 12228, Escherichia coli ATCC 25922, and Acinetobacter baumannii ATCC BAA 747 bacteria were investigated. As a result of the examinations, it was determined that an interfacial interaction occurred between the matrix and the filler, and the produced films were thermally resistant and showed antibacterial activity against Gram (+)/Gram (-) bacteria. Consequently, it can be concluded that PVA films containing Star Anise essential oil present a prospective substitute in a variety of industrial packaging systems, including those for food, medicine, and cosmetics.
Department of Medical Services and Techniques, Vocational School of Health Sciences, Istanbul Gelisim University, Istanbul, Turkey.
Department of Physics, Faculty of Science, Firat University, Elazig, Turkey.
Production and characterization of polyvinyl alcohol films containing essential oil.

The interaction between the integrin and collagen is important in cell adhesion and signaling. Collagen, as the main component of extracellular matrix, is a base material for tissue engineering constructs. In tissue engineering, the collagen structure and molecule state may be altered to varying degrees in the process of processing and utilizing, thereby affecting its biological properties. In this work, the impact of changes in collagen structure and molecular state on the binding properties of collagen to integrin α2β1 and integrin specific cell adhesion were explored. The results showed that the molecular structure of collagen is destroyed under the influence of heating, freeze-grinding and irradiation, the triple helix integrity is reduced and molecular breaking degree is increased. The binding ability of collagen to integrin α2β1 is increased with the increase of triple helix integrity and decays exponentially with the increase of molecular breaking degree. The collagen molecular state can also influences the binding ability of collagen to cellular receptor. The collagen fibrils binding to integrin α2β1 and HT1080 cells is stronger than to collagen monomolecule. Meanwhile, the hybrid fibril exhibits a different cellular receptor binding performance from corresponding single species collagen fibril. These findings provide ideas for the design and development of new collagen-based biomaterials and tissue engineering research.
School of Chemical and Environmental Engineering, Wuhan Polytechnic University, Wuhan, China.
College of Life Science and Technology, Hubei Key Laboratory of Quality Control of Characteristic Fruits and Vegetables, Hubei Engineering University, Xiaogan, China.
Impact of changes in collagen construction and molecular state on integrin - binding properties.

Infected bone defect (IBD) is a great challenge in orthopedics, which involves in bone loss and infection. Here, a self-assembling hydrogel scaffold (named AMP-RAD/EXO), integrating antimicrobial peptides(AMPs), RADA16 and BMSCs exosomes with an innovative strategy, is developed and applied in IBD treatment for sustained antimicrobial ability, accelerating osteoblasts proliferation and promoting bone regeneration. AMPs present an excellent ability to inhibit infection, RADA16 is a self-assembling peptide hydrogel for AMPs delivery, and BMSCs exosomes can promote the bone regeneration. The prepared AMP-RAD/EXO exhibited a polyporous 3D structure for imbibition of BMSCs exosomes and migration of osteoblasts. In vitro studies indicate AMP-RAD/EXO can inhibit the growth of Staphylococcus aureus, accelerate the proliferation and migration of BMSCs. More importantly, in vivo results also prove that AMP-RAD/EXO exhibit an excellent effect on IBD treatment. Thus, the prepared AMP-RAD/EXO provides a multifunctional scaffold concept for bone tissue engineering technology.
Orthopaedics, Wuhan Fourth Hospital, Wuhan, Hubei Province, P.R. China.
Nursing Department, Wuhan Fourth Hospital, Wuhan, Hubei Province, P.R. China.
Self-assembling peptide hydrogel scaffold integrating stem cell-derived exosomes for infected bone defects.

Biological sex influences the risk of depression and cognitive impairment, but its role in relation to postoperative delirium is unclear. This analysis investigates sex differences in delirium risk after coronary artery bypass graft (CABG) surgery and sex-related differences in relation to affective and cognitive symptoms.This is a secondary analysis of the Neuropsychiatric Outcomes After Heart Surgery (NOAHS) study, a single-site, observational study of a CABG surgery cohort (n = 149). Preoperative characteristics are stratified by sex, and baseline variables that differ by sex are evaluated to understand whether sex modifies their relationships with delirium. We also evaluate sex differences in one-month depression and cognition.Female sex is associated with several delirium risk factors, including higher risk of preoperative depression and middle cerebral artery (MCA) stenosis. MCA stenosis was statistically associated with delirium only among women (OR 15.6, 95% CI 1.5, 164.4); mild cognitive impairment (MCI) was associated with delirium only in men (OR 4.6, 95% CI 1.2, 17.9). Other sex-based differences failed to reach statistical significance. Depression remained commoner among women 1 month post-CABG.Women in this CABG cohort were more likely to have depression at baseline and 1 month postoperatively, as well as MCA stenosis and postoperative delirium. Sex might modify the relationship between post-CABG delirium and its risk factors including MCA stenosis and MCI. Cerebrovascular disease deserves study as a potential explanation linking female sex and a range of poor outcomes among women with coronary heart disease.
Department of Psychiatry University of Rochester Medical Center, Rochester, NY, USA.
College of Arts and Sciences, Cornell University, Ithaca, NY, USA.
Journal of geriatric psychiatry and neurology
J Geriatr Psychiatry Neurol. 2024-11;37(6):473-481.
Sex Differences in Delirium after Coronary Artery Bypass Graft Surgery and Perioperative Neuropsychiatric Conditions: A Secondary Analysis of a Cohort Study.

Malignant cerebral edema (MCE) is a life-threatening complication of ischemic stroke. Few studies have evaluated MCE in patients with acute basilar artery occlusion (BAO) receiving endovascular treatment (EVT). Therefore, the authors investigated the incidence, predictors, and functional outcomes of MCE in BAO patients undergoing EVT.This was a post hoc analysis of the Endovascular Treatment for Acute Basilar Artery Occlusion (ATTENTION) trial, a prospective, randomized, multicenter clinical trial that compared endovascular treatment with conventional care of patients with BAO at 36 centers in China. Brain edema was retrospectively assessed using the Jauss score for all available follow-up scans, and patients with a Jauss score ≥ 4 were classified as having MCE. Clinical functional independence was defined as a modified Rankin Scale (mRS) score of 0-2, and a good outcome was defined as an mRS score of 0-3 at the 90-day follow-up. Univariate and multivariate analyses were used to explore the predictors of MCE and the impact of MCE on prognosis.A total of 189 patients were analyzed, and 13.2% of patients developed MCE. Multivariate analysis showed that the baseline Glasgow Coma Scale (GCS) score (OR 0.722, 95% CI 0.548-0.950; p = 0.020) and the number of procedures (OR 1.594, 95% CI 1.051-2.419; p = 0.028) were significantly associated with MCE. After adjusting for confounding factors, the presence of MCE was significantly associated with a lower rate of functional independence (OR 0.115, 95% CI 0.023-0.563; p = 0.008), a lower rate of good outcome (OR 0.092, 95% CI 0.023-0.360; p = 0.001), and a higher rate of mortality (OR 5.373, 95% CI 2.055-14.052; p = 0.001) at the 90-day follow-up.MCE is not uncommon in BAO patients undergoing EVT and is associated with poor outcomes. Baseline GCS score and the number of procedures were predictors of MCE. In clinical practice, it is crucial that physicians identifying MCE after EVT in patients with BAO and identification of MCE will help in the selection of an appropriate pharmacological treatment strategy and close monitoring.
1Department of Neurology, Yijishan Hospital, Wannan Medical College, Wuhu, Anhui, China.
2Department of Neurology, Linyi People's Hospital, Linyi, Shandong, China.
3Stroke Center & Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China; and.
4Department of Neurology, Huangshan City People's Hospital, Huangshan, Anhui, China.
Incidence, predictors, and outcomes of malignant cerebral edema in acute basilar artery occlusion after endovascular treatment: a secondary analysis of the ATTENTION trial.

Castration-resistant prostate cancer remains a significant clinical challenge, wherein patients display no response to existing hormone therapies. The standard of care often includes aggressive treatment options using chemotherapy, radiation therapy and various drugs to curb the growth of additional metastases. As such, there is a dire need for the development of innovative technologies for both its diagnosis and its management. Traditionally, scientific exploration of prostate cancer and its treatment options has been heavily reliant on animal models and two-dimensional (2D) in vitro technologies. However, both laboratory tools often fail to recapitulate the dynamic tumor microenvironment, which can lead to discrepancies in drug efficacy and side effects in a clinical setting. In light of the limitations of traditional animal models and 2D in vitro technologies, the emergence of microfluidics as a tool for prostate cancer research shows tremendous promise. Namely, microfluidics-based technologies have emerged as powerful tools for assessing prostate cancer cells, isolating circulating tumor cells, and examining their behaviour using tumor-on-a-chip models. As such, this review aims to highlight recent advancements in microfluidics-based technologies for the assessment of castration-resistant prostate cancer and its potential to advance current understanding and to improve therapeutic outcomes.
Institute of Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada.
Institute of Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada.Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada.Department of Mechanical and Materials Engineering, Queen's University, Kingston, ON K7L 2V9, Canada.
Microfluidics-Based Technologies for the Assessment of Castration-Resistant Prostate Cancer.

Blood cells in Drosophila serve primarily innate immune responses. Various stressors influence blood cell homeostasis regarding both numbers and the proportion of blood cell types. The principle molecular mechanisms governing hematopoiesis are conserved amongst species and involve major signaling pathways like Notch, Toll, JNK, JAK/Stat or RTK. Albeit signaling pathways generally rely on the activity of protein kinases, their specific contribution to hematopoiesis remains understudied. Here, we assess the role of Serine/Threonine kinases with the potential to phosphorylate the transcription factor Su(H) in crystal cell homeostasis. Su(H) is central to Notch signal transduction, and its inhibition by phosphorylation impedes crystal cell formation. Overall, nearly twenty percent of all Drosophila Serine/Threonine kinases were studied in two assays, global and hemocyte-specific overexpression and downregulation, respectively. Unexpectedly, the majority of kinases influenced crystal cell numbers, albeit only a few were related to hematopoiesis so far. Four kinases appeared essential for crystal cell formation, whereas most kinases restrained crystal cell development. This group comprises all kinase classes, indicative of the complex regulatory network underlying blood cell homeostasis. The rather indiscriminative response we observed opens the possibility that blood cells measure their overall phospho-status as a proxy for stress-signals, and activate an adaptive immune response accordingly.
Department of Molecular Genetics, Institute of Biology, University of Hohenheim, 70599 Stuttgart, Germany.
Institute of Biology, University of Hohenheim, 70599 Stuttgart, Germany.
Numerous Serine/Threonine Kinases Affect Blood Cell Homeostasis in Drosophila melanogaster.

Ductular reaction (DR) is a complex cellular response that occurs in the liver during chronic injuries. DR mainly consists of hyper-proliferative or reactive cholangiocytes and, to a lesser extent, de-differentiated hepatocytes and liver progenitors presenting a close spatial interaction with periportal mesenchyme and immune cells. The underlying pathology of DRs leads to extensive tissue remodeling in chronic liver diseases. DR initiates as a tissue-regeneration mechanism in the liver; however, its close association with progressive fibrosis and inflammation in many chronic liver diseases makes it a more complicated pathological response than a simple regenerative process. An in-depth understanding of the cellular physiology of DRs and their contribution to tissue repair, inflammation, and progressive fibrosis can help scientists develop cell-type specific targeted therapies to manage liver fibrosis and chronic liver diseases effectively.
Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.Division of Applied Cell Biology and Physiology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Ductular Reactions in Liver Injury, Regeneration, and Disease Progression-An Overview.

Hereditary spastic paraplegias (HSPs) are a heterogeneous group of mono-genetic inherited neurological disorders, whose primary manifestation is the disruption of the pyramidal system, observed as a progressive impaired gait and leg spasticity in patients. Despite the large list of genes linked to this group, which exceeds 80 loci, the number of cellular functions which the gene products engage is relatively limited, among which endoplasmic reticulum (ER) morphogenesis appears central. Mutations in genes encoding ER-shaping proteins are the most common cause of HSP, highlighting the importance of correct ER organisation for long motor neuron survival. However, a major bottleneck in the study of ER morphology is the current lack of quantitative methods, with most studies to date reporting, instead, on qualitative changes. Here, we describe and apply a quantitative image-based screen to identify genetic modifiers of ER organisation using a mammalian cell culture system. An analysis reveals significant quantitative changes in tubular ER and dense sheet ER organisation caused by the siRNA-mediated knockdown of HSP-causing genes ATL1 and RTN2. This screen constitutes the first attempt to examine ER distribution in cells in an automated and high-content manner and to detect genes which impact ER organisation.
UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, 4 Dublin, Ireland.
Cell Screening Laboratory, UCD School of Biology and Environmental Science, University College Dublin, 4 Dublin, Ireland.
An Automated Imaging-Based Screen for Genetic Modulators of ER Organisation in Cultured Human Cells.

Duchenne muscular dystrophy (DMD) is a genetic progressive muscle-wasting disorder that leads to rapid loss of mobility and premature death. The absence of functional dystrophin in DMD patients reduces sarcolemma stiffness and increases contraction damage, triggering a cascade of events leading to muscle cell degeneration, chronic inflammation, and deposition of fibrotic and adipose tissue. Efforts in the last decade have led to the clinical approval of novel drugs for DMD that aim to restore dystrophin function. However, combination therapies able to restore dystrophin expression and target the myriad of cellular events found impaired in dystrophic muscle are desirable. Muscles are higher energy consumers susceptible to mitochondrial defects. Mitochondria generate a significant source of reactive oxygen species (ROS), and they are, in turn, sensitive to proper redox balance. In both DMD patients and animal models there is compelling evidence that mitochondrial impairments have a key role in the failure of energy homeostasis. Here, we highlighted the main aspects of mitochondrial dysfunction and oxidative stress in DMD and discussed the recent findings linked to mitochondria/ROS-targeted molecules as a therapeutic approach. In this respect, dual targeting of both mitochondria and redox homeostasis emerges as a potential clinical option in DMD.
Department of Medical Biotechnology and Translational Medicine (BioMeTra), Università degli Studi di Milano, via Fratelli Cervi 93, 20054 Segrate, Italy.
Department for Innovation in Biological, Agro-Food and Forest Systems (DIBAF), Università degli Studi della Tuscia, Largo dell'Università snc, 01100 Viterbo, Italy.
Department of Biomedical and Clinical Sciences (DIBIC), Università degli Studi di Milano, via G.B. Grassi 74, 20157 Milano, Italy.
Mitochondria and Reactive Oxygen Species: The Therapeutic Balance of Powers for Duchenne Muscular Dystrophy.

Spinal cord injury (SCI) leads to significant functional impairments below the level of the injury, and astrocytes play a crucial role in the pathophysiology of SCI. Astrocytes undergo changes and form a glial scar after SCI, which has traditionally been viewed as a barrier to axonal regeneration and functional recovery. Astrocytes activate intracellular signaling pathways, including nuclear factor κB (NF-κB) and Janus kinase-signal transducers and activators of transcription (JAK/STAT), in response to external stimuli. NF-κB and STAT3 are transcription factors that play a pivotal role in initiating gene expression related to astrogliosis. The JAK/STAT signaling pathway is essential for managing secondary damage and facilitating recovery processes post-SCI: inflammation, glial scar formation, and astrocyte survival. NF-κB activation in astrocytes leads to the production of pro-inflammatory factors by astrocytes. NF-κB and STAT3 signaling pathways are interconnected: NF-κB activation in astrocytes leads to the release of interleukin-6 (IL-6), which interacts with the IL-6 receptor and initiates STAT3 activation. By modulating astrocyte responses, these pathways offer promising avenues for enhancing recovery outcomes, illustrating the crucial need for further investigation into their mechanisms and therapeutic applications in SCI treatment.
OpenLab Gene and Cell Technology, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia.
OpenLab Gene and Cell Technology, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia.Division of Medical and Biological Sciences, Tatarstan Academy of Sciences, 420111 Kazan, Russia.
OpenLab Gene and Cell Technology, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia.Department of Histology, Cytology and Embryology, Kazan State Medical University, 420012 Kazan, Russia.
NF-κB and JAK/STAT Signaling Pathways as Crucial Regulators of Neuroinflammation and Astrocyte Modulation in Spinal Cord Injury.

Previous research indicates that carcinogenesis involves disrupting the functions of numerous genes, including factors involved in the regulation of transcription and cell proliferation. For these reasons, in endometrial carcinogenesis, we decided to investigate the expression of TSG101 (a suppressor of tumor transformation) and LSF (a transcription factor involved in numerous cellular processes, such as cell cycle regulation, cell growth, development, and apoptosis). LSF may be involved in the regulation of TSG101 expression. The research material consisted of endometrial cancer samples from 60 patients. The control group consisted of normal endometrium samples donated by 60 women undergoing surgery for benign diseases of the female reproductive organs. The samples were subjected to immunohistochemical staining with antibodies specific to TSG101 and LSF. Specific antibodies were used to identify TSG101 and LSF in the examined histopathological preparations. An approximately 14-fold lower risk of endometrial cancer development was observed in patients with TSG expression in more than 75% of the assessed cells (4% vs. 36%; OR = 0.07; p = 0.0182). There was a four-fold lower risk of endometrial cancer development in patients with LSF expression in more than 50% of the assessed cells (32% vs. 64%; OR = 0.26; p = 0.0262). A more than three-fold lower risk of endometrial cancer development was observed in patients with LSF expression in more than 75% of the assessed cells (24% vs. 52%; OR = 0.29; p = 0.0454). Endometrial cancer was diagnosed in those with a lower level of TSG101 expression than in those with a cancer-free endometrium. Decreased expression of TSG101 may be a marker of endometrial cancer, and increased expression of LSF when diagnosed with endometrial cancer may indicate greater advancement of the disease. These markers might be used as diagnostic and prognostic markers-however, there is a lack of a correlation between them.
Department of Obstetrics and Pathology of Pregnancy, Medical University of Lublin, 20-059 Lublin, Poland.
Department of Molecular Virology, Institute of Experimental Biology, Adam Mickiewicz University in Poznan, 61-712 Poznań, Poland.
Department of Pathomorphology and Forensic Medicine, School of Medicine, Collegium Medicum, University of Warmia and Mazury, 11-082 Olsztyn, Poland.
Department of Gynecology Oncology and Gynecology, Medical University of Lublin, 20-059 Lublin, Poland.
Analysis of the Expression of LSF Transcription Factor in the Regulation of Transcription and TSG101 during the Neoplastic Transformation of Endometrial Cells.

Recombination among different phages sometimes facilitates their ability to grow on new hosts. Protocols to direct the evolution of phage host range, as might be used in the application of phage therapy, would then benefit from including steps to enable recombination. Applying mathematical and computational models, in addition to experiments using phages T3 and T7, we consider ways that a protocol may influence recombination levels. We first address coinfection, which is the first step to enabling recombination. The multiplicity of infection (MOI, the ratio of phage to cell concentration) is insufficient for predicting (co)infection levels. The force of infection (the rate at which cells are infected) is also critical but is more challenging to measure. Using both a high force of infection and high MOI (>1) for the different phages ensures high levels of coinfection. We also apply a four-genetic-locus model to study protocol effects on recombinant levels. Recombinants accumulate over multiple generations of phage growth, less so if one phage outgrows the other. Supplementing the phage pool with the low-fitness phage recovers some of this 'lost' recombination. Overall, fine tuning of phage recombination rates will not be practical with wild phages, but qualitative enhancement can be attained with some basic procedures.
Department of Biological Sciences, University of Idaho, Moscow, ID 83844, USA.Institute for Modeling Collaboration and Innovation, University of Idaho, Moscow, ID 83844, USA.
Institute for Modeling Collaboration and Innovation, University of Idaho, Moscow, ID 83844, USA.Department of Mathematics and Statistical Science, University of Idaho, Moscow, ID 83844, USA.
Institute for Cell and Molecular Biology, Department of Molecular Biosciences, LaMontagne Center for Infectious Diseases, The University of Texas, Austin, TX 78712, USA.
Controlling Recombination to Evolve Bacteriophages.

The pro-protein convertase FURIN (PCSK3) is implicated in a wide range of normal and pathological biological processes such as infectious diseases, cancer and cardiovascular diseases. Previously, we performed a systemic inhibition of FURIN in a mouse model of atherosclerosis and demonstrated significant plaque reduction and alterations in macrophage function. To understand the cellular mechanisms affected by FURIN inhibition in myeloid cells, we optimized a CRISPR-mediated gene deletion protocol for successfully deriving hemizygous (HZ) and nullizygous (NZ) FURIN knockout clones in U937 monocytic cells using lipotransfection-based procedures and a dual guide RNA delivery strategy. We observed differences in monocyte and macrophage functions involving phagocytosis, lipid accumulation, cell migration, inflammatory gene expression, cytokine release patterns, secreted proteomics (cytokines) and whole-genome transcriptomics between wild-type, HZ and NZ FURIN clones. These studies provide a mechanistic basis on the possible roles of myeloid cell FURIN in cardiovascular disorders.
Program in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, Singapore 169857, Singapore.
Centre for Computational Biology, Duke-NUS Medical School, Singapore 169857, Singapore.
Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore.
Program in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, Singapore 169857, Singapore.Centre for Computational Biology, Duke-NUS Medical School, Singapore 169857, Singapore.Laboratory of Computational Biology, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
Functional and Multi-Omics Effects of an Optimized CRISPR-Mediated FURIN Depletion in U937 Monocytes.

Cockayne syndrome (CS) is a rare hereditary autosomal recessive disorder primarily caused by mutations in Cockayne syndrome protein A (CSA) or B (CSB). While many of the functions of CSB have been at least partially elucidated, little is known about the actual developmental dysregulation in this devasting disorder. Of particular interest is the regulation of cerebral development as the most debilitating symptoms are of neurological nature. We generated neurospheres and cerebral organoids utilizing Cockayne syndrome B protein (CSB)-deficient induced pluripotent stem cells derived from two patients with distinct severity levels of CS and healthy controls. The transcriptome of both developmental timepoints was explored using RNA-Seq and bioinformatic analysis to identify dysregulated biological processes common to both patients with CS in comparison to the control. CSB-deficient neurospheres displayed upregulation of the VEGFA-VEGFR2 signalling pathway, vesicle-mediated transport and head development. CSB-deficient cerebral organoids exhibited downregulation of brain development, neuron projection development and synaptic signalling. We further identified the upregulation of steroid biosynthesis as common to both timepoints, in particular the upregulation of the cholesterol biosynthesis branch. Our results provide insights into the neurodevelopmental dysregulation in patients with CS and strengthen the theory that CS is not only a neurodegenerative but also a neurodevelopmental disorder.
Institute for Stem Cell Research and Regenerative Medicine, University Hospital Düsseldorf, Moorenstrasse 5, D-40225 Duesseldorf, Germany.IUF-Leibniz Research Institute for Environmental Medicine, Auf'm Hennekamp 50, D-40225 Duesseldorf, Germany.
Institute for Stem Cell Research and Regenerative Medicine, University Hospital Düsseldorf, Moorenstrasse 5, D-40225 Duesseldorf, Germany.
IUF-Leibniz Research Institute for Environmental Medicine, Auf'm Hennekamp 50, D-40225 Duesseldorf, Germany.
Institute for Stem Cell Research and Regenerative Medicine, University Hospital Düsseldorf, Moorenstrasse 5, D-40225 Duesseldorf, Germany.Zayed Centre for Research into Rare Diseases in Children (ZCR), University College London (UCL)-EGA Institute for Women's Health, 20 Guilford Street, London WC1N 1DZ, UK.
Cockayne Syndrome Patient iPSC-Derived Brain Organoids and Neurospheres Show Early Transcriptional Dysregulation of Biological Processes Associated with Brain Development and Metabolism.

Reelin, a large extracellular glycoprotein, plays critical roles in neuronal development and synaptic plasticity in the central nervous system (CNS). Recent studies have revealed non-neuronal functions of plasma Reelin in inflammation by promoting endothelial-leukocyte adhesion through its canonical pathway in endothelial cells (via ApoER2 acting on NF-κB), as well as in vascular tone regulation and thrombosis. In this study, we have investigated the safety and efficacy of selectively depleting plasma Reelin as a potential therapeutic strategy for chronic inflammatory diseases. We found that Reelin expression remains stable throughout adulthood and that peripheral anti-Reelin antibody treatment with CR-50 efficiently depletes plasma Reelin without affecting its levels or functionality within the CNS. Notably, this approach preserves essential neuronal functions and synaptic plasticity. Furthermore, in mice induced with experimental autoimmune encephalomyelitis (EAE), selective modulation of endothelial responses by anti-Reelin antibodies reduces pathological leukocyte infiltration without completely abolishing diapedesis. Finally, long-term Reelin depletion under metabolic stress induced by a Western diet did not negatively impact the heart, kidney, or liver, suggesting a favorable safety profile. These findings underscore the promising role of peripheral anti-Reelin therapeutic strategies for autoimmune diseases and conditions where endothelial function is compromised, offering a novel approach that may avoid the immunosuppressive side effects associated with conventional anti-inflammatory therapies.
Department of Molecular Genetics, University of Texas (UT) Southwestern Medical Center, Dallas, TX 75390, USA.Center for Translational Neurodegeneration Research, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Reelin Therapeutics Inc., La Jolla, CA 92130, USA.
Department of Molecular Genetics, University of Texas (UT) Southwestern Medical Center, Dallas, TX 75390, USA.Center for Translational Neurodegeneration Research, UT Southwestern Medical Center, Dallas, TX 75390, USA.Department of Neuroscience, UT Southwestern Medical Center, Dallas, TX 75390, USA.Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Safety of Anti-Reelin Therapeutic Approaches for Chronic Inflammatory Diseases.

Proteolysis-targeting chimeras (PROTACs) describe compounds that bind to and induce degradation of a target by simultaneously binding to a ubiquitin ligase. More generally referred to as bifunctional degraders, PROTACs have led the way in the field of targeted protein degradation (TPD), with several compounds currently undergoing clinical testing. Alongside bifunctional degraders, single-moiety compounds, or molecular glue degraders (MGDs), are increasingly being considered as a viable approach for development of therapeutics, driven by advances in rational discovery approaches. This review focuses on drug discovery with respect to bifunctional and molecular glue degraders within the ubiquitin proteasome system, including analysis of mechanistic concepts and discovery approaches, with an overview of current clinical and pre-clinical degrader status in oncology, neurodegenerative and inflammatory disease.
Laboratoire de Chimie de Coordination LCC-UPR 8241-CNRS, 31077 Toulouse, France.
Sygnature Discovery, Bio City, Pennyfoot St., Nottingham NG1 1GR, UK.
Departamento de Ingeniería Celular y Biocatálisis, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca 62209, Morelos, Mexico.
Laboratoire de Chimie de Coordination LCC-UPR 8241-CNRS, 31077 Toulouse, France.Pharmadev, UMR 152, Université de Toulouse, IRD, UT3, 31400 Toulouse, France.B Molecular, Centre Pierre Potier, Canceropôle, 31106 Toulouse, France.
Breaking Bad Proteins-Discovery Approaches and the Road to Clinic for Degraders.

Human adipose-derived stromal cells (ADSCs) are an important resource for cell-based therapies. However, the dynamics of ADSCs after transplantation and their mechanisms of action in recipients remain unclear. Herein, we generated genetically engineered mouse ADSCs to clarify their biodistribution and post-transplantation status and to analyze their role in recipient mesenchymal tissue modeling. Immortalized ADSCs (iADSCs) retained ADSC characteristics such as stromal marker gene expression and differentiation potential. iADSCs expressing a fluorescent reporter gene were seeded into biocompatible nonwoven fabric sheets and transplanted into the dorsal subcutaneous region of neonatal mice. Transplanted donor ADSCs were distributed as CD90-positive stromal cells on the sheets and survived 1 month after transplantation. Although accumulation of T lymphocytes or macrophages inside the sheet was not observed with or without donor cells, earlier migration and accumulation of recipient blood vascular endothelial cells (ECs) inside the sheet was observed in the presence of donor cells. Thus, our mouse model can help in studying the interplay between donor ADSCs and recipient cells over a 1-month period. This system may be of value for assessing and screening bioengineered ADSCs in vivo for optimal cell-based therapies.
Department of Plastic and Reconstructive Surgery, University of the Ryukyus Hospital, 207 Uehara, Nishihara 903-0215, Japan.
Institute for Animal Research, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara 903-0215, Japan.
Department of Plastic and Reconstructive Surgery, University of the Ryukyus Hospital, 207 Uehara, Nishihara 903-0215, Japan.Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara 903-0215, Japan.
Development of a Mouse Experimental System for the In Vivo Characterization of Bioengineered Adipose-Derived Stromal Cells.

The oral mucosa represents a defensive barrier between the external environment and the rest of the body. Oral mucosal cells are constantly bathed in hypotonic saliva (normally one-third tonicity compared to plasma) and are repeatedly exposed to environmental stresses of tonicity, temperature, and pH by the drinks we imbibe (e.g., hypotonic: water, tea, and coffee; hypertonic: assorted fruit juices, and red wines). In the mouth, the broad-spectrum antiviral mediator MxA (a dynamin-family large GTPase) is constitutively expressed in healthy periodontal tissues and induced by Type III interferons (e.g., IFN-λ1/IL-29). Endogenously induced human MxA and exogenously expressed human GFP-MxA formed membraneless biomolecular condensates in the cytoplasm of oral carcinoma cells (OECM1 cell line). These condensates likely represent storage granules in equilibrium with antivirally active dispersed MxA. Remarkably, cytoplasmic MxA condensates were exquisitely sensitive sensors of hypotonicity-the condensates in oral epithelium disassembled within 1-2 min of exposure of cells to saliva-like one-third hypotonicity, and spontaneously reassembled in the next 4-7 min. Water, tea, and coffee enhanced this disassembly. Fluorescence changes in OECM1 cells preloaded with calcein-AM (a reporter of cytosolic macromolecular crowding ) confirmed that this process involved macromolecular uncrowding and subsequent recrowding secondary to changes in cell volume. However, hypertonicity had little effect on MxA condensates. The spontaneous reassembly of GFP-MxA condensates in oral epithelial cells, even under continuous saliva-like hypotonicity, was slowed by the protein-phosphatase-inhibitor cyclosporin A (CsA) and by the K-channel-blocker tetraethylammonium chloride (TEA); this is suggestive of the involvement of the volume-sensitive WNK kinase-protein phosphatase (PTP)-K-Cl cotransporter (KCC) pathway in the regulated volume decrease (RVD) during condensate reassembly in oral cells. The present study identifies a novel subcellular consequence of hypotonic stress in oral epithelial cells, in terms of the rapid and dynamic changes in the structure of one class of phase-separated biomolecular condensates in the cytoplasm-the antiviral MxA condensates. More generally, the data raise the possibility that hypotonicity-driven stresses likely affect other intracellular functions involving liquid-liquid phase separation (LLPS) in cells of the oral mucosa.
Department of Cell Biology and Anatomy, New York Medical College, Valhalla, NY 10595, USA.Department of Medicine, New York Medical College, Valhalla, NY 10595, USA.
Department of Cell Biology and Anatomy, New York Medical College, Valhalla, NY 10595, USA.
Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA.
Touro College of Dental Medicine at New York Medical College, Hawthorne, NY 10532, USA.
Oral Antiviral Defense: Saliva- and Beverage-like Hypotonicity Dynamically Regulate Formation of Membraneless Biomolecular Condensates of Antiviral Human MxA in Oral Epithelial Cells.

Achieving successful hematopoietic stem cell transplantation (HSCT) relies on two fundamental pillars: effective mobilization and efficient collection through apheresis to attain the optimal graft dose. These cornerstones pave the way for enhanced patient outcomes. The primary challenges encountered by the clinical unit and collection facility within a transplant program encompass augmenting mobilization efficiency to optimize the harvest of target cell populations, implementing robust monitoring and predictive strategies for mobilization, streamlining the apheresis procedure to minimize collection duration while ensuring adequate yield, prioritizing patient comfort by reducing the overall collection time, guaranteeing the quality and purity of stem cell products to optimize graft function and transplant success, and facilitating seamless coordination between diverse entities involved in the HSCT process. In this review, we aim to address key questions and provide insights into the critical aspects of mobilizing and collecting hematopoietic stem cells for transplantation purposes.
Operative Research Unit of Transfusion Medicine and Cellular Therapy, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Roma, Italy.
Operative Research Unit of Hematology and Stem Cell Transplantation, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Roma, Italy.Program in Immunology, Molecular Medicine and Applied Biotechnologies, Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy.
Operative Research Unit of Hematology and Stem Cell Transplantation, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Roma, Italy.
Stem Cells Collection and Mobilization in Adult Autologous/Allogeneic Transplantation: Critical Points and Future Challenges.

Coevolution of hosts and their parasites has shaped heterogeneity of effector hemocyte types, providing immune defense reactions with variable effectiveness. In this work, we characterize hemocytes of Drosophila willistoni, a species that has evolved a cellular immune system with extensive variation and a high degree of plasticity. Monoclonal antibodies were raised and used in indirect immunofluorescence experiments to characterize hemocyte subpopulations, follow their functional features and differentiation. Pagocytosis and parasitization assays were used to determine the functional characteristics of hemocyte types. Samples were visualized using confocal and epifluorescence microscopy. We identified a new multinucleated giant hemocyte (MGH) type, which differentiates in the course of the cellular immune response to parasitoids. These cells differentiate in the circulation through nuclear division and cell fusion, and can also be derived from the central hematopoietic organ, the lymph gland. They have a binary function as they take up bacteria by phagocytosis and are involved in the encapsulation and elimination of the parasitoid. Here, we show that, in response to large foreign particles, such as parasitoids, MGHs differentiate, have a binary function and contribute to a highly effective cellular immune response, similar to the foreign body giant cells of vertebrates.
Innate Immunity Group, Institute of Genetics, HUN-REN Biological Research Centre, 6726 Szeged, Hungary.
Innate Immunity Group, Institute of Genetics, HUN-REN Biological Research Centre, 6726 Szeged, Hungary.Doctoral School of Biology, University of Szeged, 6720 Szeged, Hungary.
MTA SZBK Lendület Laboratory of Cell Cycle Regulation, Institute of Biochemistry, HUN-REN Biological Research Centre, 6726 Szeged, Hungary.National Laboratory for Biotechnology, Institute of Genetics, HUN-REN Biological Research Centre, 6726 Szeged, Hungary.
Department of Molecular Biology, Umea University, 901 87 Umea, Sweden.
Cellular Immunity of Drosophila willistoni Reveals Novel Complexity in Insect Anti-Parasitoid Defense.

Cutaneous T cell lymphomas (CTCLs), encompassing mycosis fungoides (MF) and Sézary syndrome (SS), present a complex landscape influenced by cytokines and cellular responses. In this work, the intricate relationship between these inflammatory proteins and disease pathogenesis is examined, focusing on what is known at the clinical and therapeutic levels regarding the most well-known inflammatory mediators. An in-depth look is given to their possible alterations caused by novel immunomodulatory drugs and how they may alter disease progression. From this narrative review of the actual scientific landscape, Interferon-gamma (IFN-γ) emerges as a central player, demonstrating a dual role in both promoting and inhibiting cancer immunity, but the work navigates through all the major interleukins known in inflammatory environments. Immunotherapeutic perspectives are elucidated, highlighting the crucial role of the cutaneous microenvironment in shaping dysfunctional cell trafficking, antitumor immunity, and angiogenesis in MF, showcasing advancements in understanding and targeting the immune phenotype in CTCL. In summary, this manuscript aims to comprehensively explore the multifaceted aspects of CTCL, from the immunopathogenesis and cytokine dynamics centred around TNF-α and IFN-γ to evolving therapeutic modalities. Including all the major known and studied cytokines in this analysis broadens our understanding of the intricate interplay influencing CTCL, paving the way for improved management of this complex lymphoma.
Institute of Dermatology, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy.Dipartimento di Scienze Mediche e Chirurgiche, University of Bologna, 40138 Bologna, Italy.
Dipartimento di Scienze Mediche e Chirurgiche, University of Bologna, 40138 Bologna, Italy.Dermatology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy.
Dipartimento di Scienze Mediche e Chirurgiche, University of Bologna, 40138 Bologna, Italy.Haematopathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy.
The Role of Cytokines in Cutaneous T Cell Lymphoma: A Focus on the State of the Art and Possible Therapeutic Targets.

The transmembrane glycoprotein OX40 receptor (OX40) and its ligand, OX40L, are instrumental modulators of the adaptive immune response in humans. OX40 functions as a costimulatory molecule that promotes T cell activation, differentiation, and survival through ligation with OX40L. T cells play an integral role in the pathogenesis of several inflammatory skin conditions, including atopic dermatitis (AD). In particular, T helper 2 (TH2) cells strongly contribute to AD pathogenesis via the production of cytokines associated with type 2 inflammation (e.g., IL-4, IL-5, IL-13, and IL-31) that lead to skin barrier dysfunction and pruritus. The OX40-OX40L interaction also promotes the activation and proliferation of other T helper cell populations (e.g., TH1, TH22, and TH17), and AD patients have demonstrated higher levels of OX40 expression on peripheral blood mononuclear cells than healthy controls. As such, the OX40-OX40L pathway is a potential target for AD treatment. Novel therapies targeting the OX40 pathway are currently in development, several of which have demonstrated promising safety and efficacy results in patients with moderate-to-severe AD. Herein, we review the function of OX40 and the OX40-OX40L signaling pathway, their role in AD pathogenesis, and emerging therapies targeting OX40-OX40L that may offer insights into the future of AD management.
Division of Dermatology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
An OX-Tra'Ordinary Tale: The Role of OX40 and OX40L in Atopic Dermatitis.

Absorption spectra of red blood cell (RBC) suspensions are investigated in an osmolarity range in the medium from 200 mOsm to 900 mOsm. Three spectral parameters are used to characterize the process of swelling or shrinkage of RBC-the absorbance at 700 nm, the Soret peak height relative to the spectrum background, and the Soret peak wavelength. We show that with an increase in the osmolarity, the absorbance at 700 nm increases and the Soret peak relative height decreases. These changes are related to the changes in the RBC volume and the resulting increase in the hemoglobin intracellular concentration and index of refraction. Confocal microscopy and flow cytometry measurements supported these conclusions. The maximum wavelength of the Soret peak increases with increasing osmolarity due to changes in the oxygenation state of hemoglobin. Using these spectrum parameters, the process of osmosis in RBCs can be followed in real time, but it can also be applied to various processes, leading to changes in the volume and shape of RBCs. Therefore, we conclude that UV-Vis absorption spectrophotometry offers a convenient, easily accessible, and cost-effective method to monitor changes in RBC, which can find applications in the field of drug discovery and diagnostics of RBC and hemoglobin disorders.
Department of Physics and Biophysics, Faculty of Medicine, Trakia University, 11 Armeiska, 6000 Stara Zagora, Bulgaria.
Department of Physics and Biophysics, Faculty of Medicine, Trakia University, 11 Armeiska, 6000 Stara Zagora, Bulgaria.Institute of Transfusion Medicine, Charite-Universitatsrnedizin Berlin, Chariteplatz 1, 10117 Berlin, Germany.
Change in Osmotic Pressure Influences the Absorption Spectrum of Hemoglobin inside Red Blood Cells.

Preclinical research has provided compelling evidence indicating that exposure to hypobaric hypoxia (HH) results in a deterioration of spermatogenesis. This adverse effect extends to the underlying molecular mechanisms, progressively leading to impairments in the seminiferous epithelium and germ cells and alterations in semen parameters. Indeed, several studies have demonstrated that animals exposed to HH, whether in natural high-altitude environments or under simulated hypoxic conditions, exhibit damage to the self-renewal and differentiation of spermatogenesis, an increase in germline cell apoptosis, and structural alterations in the seminiferous tubules. One of the primary mechanisms associated with the inhibition of differentiation and an increase in apoptosis among germ cells is an elevated level of oxidative stress, which has been closely associated with HH exposure. Human studies have shown that individuals exposed to HH, such as mountaineers and alpinists, exhibit decreased sperm count, reduced motility, diminished viability, and increased sperm with abnormal morphology in their semen. This evidence strongly suggests that exposure to HH may be considered a significant risk factor that could elevate the prevalence of male infertility. This literature review aims to provide a comprehensive description and propose potential mechanisms that could elucidate the infertility processes induced by HH. By doing so, it contributes to expanding our understanding of the challenges posed by extreme environments on human physiology, opening new avenues for research in this field.
Exercise Applied Physiology Laboratory, Centro de Investigación en Fisiología y Medicina de Altura (FIMEDALT), Departamento Biomédico, Facultad de Ciencias de la Salud, Universidad de Antofagasta, Antofagasta 1271155, Chile.
Laboratorio de Biología de la Reproducción, Departamento Biomédico, Facultad de Ciencias de la Salud, Universidad de Antofagasta, Antofagasta 1271155, Chile.
Consequences of Exposure to Hypobaric Hypoxia Associated with High Altitude on Spermatogenesis and Seminal Parameters: A Literature Review.

Research into the neonatal Fc receptor (FcRn) has increased dramatically ever since Simister and Mostov first purified a rat version of the receptor. Over the years, FcRn has been shown to function not only as a receptor that transfers immunity from mother to fetus but also performs an array of different functions that include transport and recycling of immunoglobulins and albumin in the adult. Due to its important cellular roles, several clinical trials have been designed to either inhibit/enhance FcRn function or develop of non-invasive therapeutic delivery system such as fusion of drugs to IgG Fc or albumin to enhance delivery inside the cells. Here, we report the accidental identification of several FcRn alternatively spliced variants in both mouse and human cells. The four new mouse splice variants are capable of binding immunoglobulins' Fc and Fab portions. In addition, we have identified FcRn-specific vesicles in which immunoglobulins and albumin can be stored and that are involved in the endosomal-lysosomal system. The complexity of FcRn functions offers significant potential to design and develop novel and targeted therapeutics.
Division of Renal Disease and Hypertension, Department of Medicine, School of Medicine, University of Colorado, Aurora, CO 80045, USA.
Identification of Four Mouse FcRn Splice Variants and FcRn-Specific Vesicles.

The aim of this article is to describe sustained myopic eye growth's effect on astrocyte cellular distribution and its association with inner retinal layer thicknesses. Astrocyte density and distribution, retinal nerve fiber layer (RNFL), ganglion cell layer, and inner plexiform layer (IPL) thicknesses were assessed using immunochemistry and spectral-domain optical coherence tomography on seventeen common marmoset retinas (Callithrix jacchus): six induced with myopia from 2 to 6 months of age (6-month-old myopes), three induced with myopia from 2 to 12 months of age (12-month-old myopes), five age-matched 6-month-old controls, and three age-matched 12-month-old controls. Untreated marmoset eyes grew normally, and both RNFL and IPL thicknesses did not change with age, with astrocyte numbers correlating to RNFL and IPL thicknesses in both control age groups. Myopic marmosets did not follow this trend and, instead, exhibited decreased astrocyte density, increased GFAP+ spatial coverage, and thinner RNFL and IPL, all of which worsened over time. Myopic changes in astrocyte density, GFAP+ spatial coverage and inner retinal layer thicknesses suggest astrocyte template reorganization during myopia development and progression which increased over time. Whether or not these changes are constructive or destructive to the retina still remains to be assessed.
Department of Biological Sciences, State University of New York College of Optometry, New York, NY 10036, USA.
Sustained Retinal Defocus Increases the Effect of Induced Myopia on the Retinal Astrocyte Template.

Cell therapies derived from induced pluripotent stem cells (iPSCs) offer a promising avenue in the field of regenerative medicine due to iPSCs' expandability, immune compatibility, and pluripotent potential. An increasing number of preclinical and clinical trials have been carried out, exploring the application of iPSC-based therapies for challenging diseases, such as muscular dystrophies. The unique syncytial nature of skeletal muscle allows stem/progenitor cells to integrate, forming new myonuclei and restoring the expression of genes affected by myopathies. This characteristic makes genome-editing techniques especially attractive in these therapies. With genetic modification and iPSC lineage specification methodologies, immune-compatible healthy iPSC-derived muscle cells can be manufactured to reverse the progression of muscle diseases or facilitate tissue regeneration. Despite this exciting advancement, much of the development of iPSC-based therapies for muscle diseases and tissue regeneration is limited to academic settings, with no successful clinical translation reported. The unknown differentiation process in vivo, potential tumorigenicity, and epigenetic abnormality of transplanted cells are preventing their clinical application. In this review, we give an overview on preclinical development of iPSC-derived myogenic cell transplantation therapies including processes related to iPSC-derived myogenic cells such as differentiation, scaling-up, delivery, and cGMP compliance. And we discuss the potential challenges of each step of clinical translation. Additionally, preclinical model systems for testing myogenic cells intended for clinical applications are described.
Vita Therapeutics, Baltimore, MD 21043, USA.
Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA.
Challenges and Considerations of Preclinical Development for iPSC-Based Myogenic Cell Therapy.

Glioblastoma is the most frequent and aggressive brain tumor in adults. This study aims to evaluate the expression and prognostic impact of CD99, a membrane glycoprotein involved in cellular migration and invasion. In a cohort of patients with glioblastoma treated with surgery, radiotherapy and temozolomide, we retrospectively analyzed tumor expression of CD99 by immunohistochemistry (IHC) and by quantitative real-time polymerase chain reaction (qRT-PCR) for both the wild type (CD99wt) and the truncated (CD99sh) isoforms. The impact on overall survival (OS) was assessed with the Kaplan-Meier method and log-rank test and by multivariable Cox regression. Forty-six patients with glioblastoma entered this study. Immunohistochemical expression of CD99 was present in 83%. Only the CD99wt isoform was detected by qRT-PCR and was significantly correlated with CD99 expression evaluated by IHC (rho = 0.309, p = 0.037). CD99 expression was not associated with OS, regardless of the assessment methodology used (p = 0.61 for qRT-PCR and p = 0.73 for IHC). In an exploratory analysis of The Cancer Genome Atlas, casuistry of glioblastomas CD99 expression was not associated with OS nor with progression-free survival. This study confirms a high expression of CD99 in glioblastoma but does not show any significant impact on survival. Further preclinical studies are needed to define its role as a therapeutic target in glioblastoma.
Department of Medical, Surgical and Health Sciences, University of Trieste, 34147 Trieste, Italy.
Cancer Epidemiology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy.
Neurosurgery, ASST Cremona, Viale Concordia 1, 26100 Cremona, Italy.Division of Biology and Genetics, Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.
Breast and Brain Unit, ASST Cremona, Viale Concordia 1, 26100 Cremona, Italy.
Translational Genomics and Targeted Therapies in Solid Tumors Group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), C. Villaroel 170, 08036 Barcelona, Spain.Medical Oncology Department, Hospital Clínic of Barcelona, 08036 Barcelona, Spain.Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, 08036 Barcelona, Spain.
Medical Oncology Department, Hospital Clínic of Barcelona, 08036 Barcelona, Spain.Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, 08036 Barcelona, Spain.
Neurosurgery, ASST Cremona, Viale Concordia 1, 26100 Cremona, Italy.
Pathology Unit, ASST Cremona, Viale Concordia 1, 26100 Cremona, Italy.
Radiotherapy Unit, ASST Cremona, Viale Concordia 1, 26100 Cremona, Italy.
Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy.
Department of Medical, Surgical and Health Sciences, University of Trieste, 34147 Trieste, Italy.Breast and Brain Unit, ASST Cremona, Viale Concordia 1, 26100 Cremona, Italy.
CD99 Expression and Prognostic Impact in Glioblastoma: A Single-Center Cohort Study.

Zika virus (ZIKV) infection and pathogenesis are linked to the disruption of neurogenesis, congenital Zika syndrome and microcephaly by affecting neural progenitor cells. Nonstructural protein 5 (NS5) is the largest product encoded by ZIKV-RNA and is important for replication and immune evasion. Here, we studied the potential effects of NS5 on microtubules (MTs) and autophagy flux, together with the interplay of NS5 with histone deacetylase 6 (HDAC6). Fluorescence microscopy, biochemical cell-fractionation combined with the use of HDAC6 mutants, chemical inhibitors and RNA interference indicated that NS5 accumulates in nuclear structures and strongly promotes the acetylation of MTs that aberrantly reorganize in nested structures. Similarly, NS5 accumulates the p62 protein, an autophagic-flux marker. Therefore, NS5 alters events that are under the control of the autophagic tubulin-deacetylase HDAC6. HDAC6 appears to degrade NS5 by autophagy in a deacetylase- and BUZ domain-dependent manner and to control the cytoplasmic expression of NS5. Moreover, NS5 inhibits RNA-mediated RIG-I interferon (IFN) production, resulting in greater activity when autophagy is inhibited (i.e., effect correlated with NS5 stability). Therefore, it is conceivable that NS5 contributes to cell toxicity and pathogenesis, evading the IFN-immune response by overcoming HDAC6 functions. HDAC6 has emerged as an anti-ZIKV factor by targeting NS5.
Laboratorio de Inmunología Celular y Viral, Unidad de Farmacología, Sección de Medicina, Facultad de Ciencias de la Salud, Universidad de La Laguna, 38200 La Laguna, Spain.
Department of Análisis Matemático, Facultad de Ciencias, Universidad de La Laguna, 38296 La Laguna, Spain.
The ZIKV NS5 Protein Aberrantly Alters the Tubulin Cytoskeleton, Induces the Accumulation of Autophagic p62 and Affects IFN Production: HDAC6 Has Emerged as an Anti-NS5/ZIKV Factor.

Cells must change their properties in order to adapt to a constantly changing environment. Most of the cellular sensing and regulatory mechanisms described so far are based on proteins that serve as sensors, signal transducers, and effectors of signalling pathways, resulting in altered cell physiology. In recent years, however, remarkable examples of the critical role of non-coding RNAs in some of these regulatory pathways have been described in various organisms. In this review, we focus on all classes of non-coding RNAs that play regulatory roles during stress response, starvation, and ageing in different yeast species as well as in structured yeast populations. Such regulation can occur, for example, by modulating the amount and functional state of tRNAs, rRNAs, or snRNAs that are directly involved in the processes of translation and splicing. In addition, long non-coding RNAs and microRNA-like molecules are bona fide regulators of the expression of their target genes. Non-coding RNAs thus represent an additional level of cellular regulation that is gradually being uncovered.
Department of Genetics and Microbiology, Faculty of Science, Charles University, BIOCEV, 128 00 Prague, Czech Republic.
Non-Coding RNAs: Regulators of Stress, Ageing, and Developmental Decisions in Yeast?

Precision medicine is rapidly gaining recognition in the field of (ultra)rare conditions, where only a few individuals in the world are affected. Clinical trial design for a small number of patients is extremely challenging, and for this reason, the development of N-of-1 strategies is explored to accelerate customized therapy design for rare cases. A strong candidate for this approach is Stargardt disease (STGD1), an autosomal recessive macular degeneration characterized by high genetic and phenotypic heterogeneity. STGD1 is caused by pathogenic variants in ABCA4, and amongst them, several deep-intronic variants alter the pre-mRNA splicing process, generally resulting in the insertion of pseudoexons (PEs) into the final transcript. In this study, we describe a 10-year-old girl harboring the unique deep-intronic ABCA4 variant c.6817-713A>G. Clinically, she presents with typical early-onset STGD1 with a high disease symmetry between her two eyes. Molecularly, we designed antisense oligonucleotides (AONs) to block the produced PE insertion. Splicing rescue was assessed in three different in vitro models: HEK293T cells, fibroblasts, and photoreceptor precursor cells, the last two being derived from the patient. Overall, our research is intended to serve as the basis for a personalized N-of-1 AON-based treatment to stop early vision loss in this patient.
Department of Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
Department of Ophthalmology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
Department of Ophthalmology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.Dutch Center for RNA Therapeutics, 2311 EZ Leiden, The Netherlands.
Department of Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.Dutch Center for RNA Therapeutics, 2311 EZ Leiden, The Netherlands.Department of Pediatrics, Amalia Children's Hospital, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
Department of Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.Dutch Center for RNA Therapeutics, 2311 EZ Leiden, The Netherlands.
Preclinical Development of Antisense Oligonucleotides to Rescue Aberrant Splicing Caused by an Ultrarare ABCA4 Variant in a Child with Early-Onset Stargardt Disease.

Mycoplasmopsis bovis is a causative agent of crucial diseases in both dairy and beef cattle leading to substantial economic losses. However, limited control measures for M. bovis-related diseases exist due to a lack of understanding about the virulence factors of this pathogen, a common challenge in mycoplasma research. Consequently, this study aimed to characterize a novel nucleomodulin as a virulence-related factor of M. bovis. Employing bioinformatic tools, we initially predicted MbovP467 to be a secreted protein with a nuclear localization signal based on SignalP scores and the cNLS (Nuclear Localization Signal) Mapper, respectively. Subsequently, the MbovP467 gene was synthesized and cloned into a pEGFP plasmid with EGFP labeling to obtain a recombinant plasmid (rpEGFP-MbovP467) and then was also cloned in pET-30a with a consideration for an Escherichia coli codon bias and expressed and purified for the production of polyclonal antibodies against the recombinant MbovP467 protein. Confocal microscopy and a Western blotting assay confirmed the nuclear location of MbovP467 in bovine macrophages (BoMacs). RNA-seq data revealed 220 up-regulated and 20 down-regulated genes in the rpEGFP-MbovP467-treated BoMac group compared to the control group (pEGFP). A GO- and KEGG-enrichment analysis identified associations with inflammatory responses, G protein-coupled receptor signaling pathways, nuclear receptor activity, sequence-specific DNA binding, the regulation of cell proliferation, IL-8, apoptotic processes, cell growth and death, the TNF signaling pathway, the NF-κB signaling pathway, pathways in cancer, and protein families of signaling and cellular processes among the differentially expressed up-regulated mRNAs. Further experiments, investigating cell viability and the inflammatory response, demonstrated that MbovP467 reduces BoMac cell viability and induces the mRNA expression of IL-1β, IL-6, IL-8, TNF-α, and apoptosis in BoMac cells. Further, MbovP467 increased the promoter activity of TNF-α. In conclusion, this study identified a new nucleomodulin, MbovP467, for M. bovis, which might have an important role in M. bovis pathogenesis.
National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China.Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan 430070, China.College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.Hubei International Scientific and Technological Cooperation Base of Veterinary Epidemiology, Huazhong Agricultural University, Wuhan 430070, China.International Research Center for Animal Disease, Ministry of Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.
Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China, School of Life Sciences, Ningxia University, Yinchuan 750021, China.
The Identification of a Novel Nucleomodulin MbovP467 of Mycoplasmopsis bovis and Its Potential Contribution in Pathogenesis.

Understanding the structure and function of intermediate filaments (IFs) is necessary in order to explain why more than 70 related IF genes have evolved in vertebrates while maintaining such dramatically tissue-specific expression. Desmin is a member of the large multigene family of IF proteins and is specifically expressed in myocytes. In an effort to elucidate its muscle-specific behavior, we have used a yeast two-hybrid system in order to identify desmin's head binding partners. We described a mitochondrial and a lysosomal protein, NADH ubiquinone oxidoreductase core subunit S2 (NDUFS2), and saposin D, respectively, as direct desmin binding partners. In silico analysis indicated that both interactions at the atomic level occur in a very similar way, by the formation of a three-helix bundle with hydrophobic interactions in the interdomain space and hydrogen bonds at R16 and S32 of the desmin head domain. The interactions, confirmed also by GST pull-down assays, indicating the necessity of the desmin head domain and, furthermore, point out its role in function of mitochondria and lysosomes, organelles which are disrupted in myopathies due to desmin head domain mutations.
Biotechnology Department, Agricultural University of Athens, 11855 Athens, Greece.
Center of Basic Research, Biomedical Research Foundation, Academy of Athens, 4 Soranou Ephesiou, 11527 Athens, Greece.Biochemistry & Biotechnology Department, University of Thessaly, 41500 Larisa, Greece.
Center of Basic Research, Biomedical Research Foundation, Academy of Athens, 4 Soranou Ephesiou, 11527 Athens, Greece.
IMGT, The International ImMunoGeneTics Information System, National Center for Scientific Research (CNRS), Institute of Human Genetics (IGH), University of Montpellier (UM), 34090 Montpellier, France.
Unraveling Desmin's Head Domain Structure and Function.

In vitro and preclinical in vivo research in the last 35 years has clearly highlighted the crucial physiopathological role of glial cells, namely astrocytes/microglia/oligodendrocytes and satellite glial cells/Schwann cells in the central and peripheral nervous system, respectively. Several possible pharmacological targets to various neurodegenerative disorders and painful conditions have therefore been successfully identified, including receptors and enzymes, and mediators of neuroinflammation. However, the translation of these promising data to a clinical setting is often hampered by both technical and biological difficulties, making it necessary to perform experiments on human cells and models of the various diseases. In this review we will, therefore, summarize the most relevant data on the contribution of glial cells to human pathologies and on their possible pharmacological modulation based on data obtained in post-mortem tissues and in iPSC-derived human brain cells and organoids. The possibility of an in vivo visualization of glia reaction to neuroinflammation in patients will be also discussed.
Laboratory of Pain Therapy and Neuroimmunology, Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, via Balzaretti, 9, 20133 Milan, Italy.
Human Glial Cells as Innovative Targets for the Therapy of Central Nervous System Pathologies.

Among patients on peritoneal dialysis (PD), 50-80% will develop peritoneal fibrosis, and 0.5-4.4% will develop life-threatening encapsulating peritoneal sclerosis (EPS). Here, we investigated the role of extracellular vesicles (EVs) on the TGF-β- and PDGF-B-driven processes of peritoneal fibrosis. EVs were isolated from the peritoneal dialysis effluent (PDE) of children receiving continuous ambulatory PD. The impact of PDE-EVs on the epithelial-mesenchymal transition (EMT) and collagen production of the peritoneal mesothelial cells and fibroblasts were investigated in vitro and in vivo in the chlorhexidine digluconate (CG)-induced mice model of peritoneal fibrosis. PDE-EVs showed spherical morphology in the 100 nm size range, and their spectral features, CD63, and annexin positivity were characteristic of EVs. PDE-EVs penetrated into the peritoneal mesothelial cells and fibroblasts and reduced their PDE- or PDGF-B-induced proliferation. Furthermore, PDE-EVs inhibited the PDE- or TGF-β-induced EMT and collagen production of the investigated cell types. PDE-EVs contributed to the mesothelial layer integrity and decreased the submesothelial thickening of CG-treated mice. We demonstrated that PDE-EVs significantly inhibit the PDGF-B- or TGF-β-induced fibrotic processes in vitro and in vivo, suggesting that EVs may contribute to new therapeutic strategies to treat peritoneal fibrosis and other fibroproliferative diseases.
Pediatric Center, MTA Center of Excellence, Semmelweis University, 1083 Budapest, Hungary.HUN-REN-SU Pediatrics and Nephrology Research Group, 1052 Budapest, Hungary.
Pediatric Center, MTA Center of Excellence, Semmelweis University, 1083 Budapest, Hungary.
TTK Biological Nanochemistry Research Group, Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, 1117 Budapest, Hungary.
Department of Genetics, Cell- and Immunobiology, Semmelweis University, 1089 Budapest, Hungary.
Extracellular Vesicles of Patients on Peritoneal Dialysis Inhibit the TGF-β- and PDGF-B-Mediated Fibrotic Processes.

Transcription factors (TFs) regulate gene expression by recognizing specific target enhancers in the genome. The DNA-binding and regulatory activity of TFs depend on the presence of additional protein partners, leading to the formation of versatile and dynamic multimeric protein complexes. Visualizing these protein-protein interactions (PPIs) in the nucleus is key for decrypting the molecular cues underlying TF specificity in vivo. Over the last few years, Bimolecular Fluorescence Complementation (BiFC) has been developed in several model systems and applied in the analysis of different types of PPIs. In particular, BiFC has been applied when analyzing PPIs with hundreds of TFs in the nucleus of live Drosophila embryos. However, the visualization of PPIs at the level of specific target enhancers or genomic regions of interest awaits the advent of DNA-labelling methods that can be coupled with BiFC. Here, we present a novel experimental strategy that we have called BiFOR and that is based on the coupling of BiFC with the bacterial ANCHOR DNA-labelling system. We demonstrate that BiFOR enables the precise quantification of the enrichment of specific dimeric protein complexes on target enhancers in Drosophila salivary gland nuclei. Given its versatility and sensitivity, BiFOR could be applied more widely to other tissues during Drosophila development. Our work sets up the experimental basis for future applications of this strategy.
Institut de Génomique Fonctionnelle de Lyon (IGFL), UMR5242, Ecole Normale Supérieure de Lyon (ENSL), CNRS, Université de Lyon, 69007 Lyon, France.
Visualization of the Association of Dimeric Protein Complexes on Specific Enhancers in the Salivary Gland Nuclei of Drosophila Larva.

Pancreatic cancer is a highly lethal disease with a 5-year survival rate of around 11-12%. Surgery, being the treatment of choice, is only possible in 20% of symptomatic patients. The main reason is that when it becomes symptomatic, IT IS the tumor is usually locally advanced and/or has metastasized to distant organs; thus, early diagnosis is infrequent. The lack of specific early symptoms is an important cause of late diagnosis. Unfortunately, diagnostic tumor markers become positive at a late stage, and there is a lack of early-stage markers. Surgical and non-surgical cases are treated with neoadjuvant and/or adjuvant chemotherapy, and the results are usually poor. However, personalized targeted therapy directed against tumor drivers may improve this situation. Until recently, many pancreatic tumor driver genes/proteins were considered untargetable. Chemical and physical characteristics of mutated KRAS are a formidable challenge to overcome. This situation is slowly changing. For the first time, there are candidate drugs that can target the main driver gene of pancreatic cancer: KRAS. Indeed, KRAS inhibition has been clinically achieved in lung cancer and, at the pre-clinical level, in pancreatic cancer as well. This will probably change the very poor outlook for this disease. This paper reviews the genetic characteristics of sporadic and hereditary predisposition to pancreatic cancer and the possibilities of a personalized treatment according to the genetic signature.
Department of Biosciences, Biotechnologies and Environment, University of Bari Aldo Moro , 70125 Bari, Italy.
Oncomed, Via Pier Capponi 6, 50132 Florence, Italy.
Genetic Signature of Human Pancreatic Cancer and Personalized Targeting.

Membrane nanotubes (NTs) are dynamic communication channels connecting spatially separated cells even over long distances and promoting the transport of different cellular cargos. NTs are also involved in the intercellular spread of different pathogens and the deterioration of some neurological disorders. Transport processes via NTs may be controlled by cytoskeletal elements. NTs are frequently observed membrane projections in numerous mammalian cell lines, including various immune cells, but their functional significance in the 'antibody factory' B cells is poorly elucidated. Here, we report that as active channels, NTs of B-lymphoma cells can mediate bidirectional mitochondrial transport, promoted by the cooperation of two different cytoskeletal motor proteins, kinesin along microtubules and myosin VI along actin, and bidirectional transport processes are also supported by the heterogeneous arrangement of the main cytoskeletal filament systems of the NTs. We revealed that despite NTs and axons being different cell extensions, the mitochondrial transport they mediate may exhibit significant similarities. Furthermore, we found that microtubules may improve the stability and lifespan of B-lymphoma-cell NTs, while F-actin strengthens NTs by providing a structural framework for them. Our results may contribute to a better understanding of the regulation of the major cells of humoral immune response to infections.
Department of Biophysics, Medical School, University of Pécs, H-7624 Pécs, Hungary.
Department of Immunology, Faculty of Science, Eötvös Loránd University, H-1117 Budapest, Hungary.
Cooperation of Various Cytoskeletal Components Orchestrates Intercellular Spread of Mitochondria between B-Lymphoma Cells through Tunnelling Nanotubes.

Cohesin is a highly conserved ring-shaped complex involved in topologically embracing chromatids, gene expression regulation, genome compartmentalization, and genome stability maintenance. Genomic analyses have detected mutations in the cohesin complex in a wide array of human tumors. These findings have led to increased interest in cohesin as a potential target in cancer therapy. Synthetic lethality has been suggested as an approach to exploit genetic differences in cancer cells to influence their selective killing. In this study, we show that mutations in ESCO1, NIPBL, PDS5B, RAD21, SMC1A, SMC3, STAG2, and WAPL genes are synthetically lethal with stimulation of WNT signaling obtained following LY2090314 treatment, a GSK3 inhibitor, in several cancer cell lines. Moreover, treatment led to the stabilization of β-catenin and affected the expression of c-MYC, probably due to the occupancy decrease in cohesin at the c-MYC promoter. Finally, LY2090314 caused gene expression dysregulation mainly involving pathways related to transcription regulation, cell proliferation, and chromatin remodeling. For the first time, our work provides the underlying molecular basis for synthetic lethality due to cohesin mutations and suggests that targeting the WNT may be a promising therapeutic approach for tumors carrying mutated cohesin.
Institute for Biomedical Technologies (ITB), National Research Council (CNR), 56124 Pisa, Italy.
Synthetic Lethality between Cohesin and WNT Signaling Pathways in Diverse Cancer Contexts.

Autosomal dominant polycystic kidney disease (ADPKD) occurs when the proteins Polycystin-1 (PC1, PKD1) and Polycystin-2 (PC2, PKD2) contain mutations. PC1 is a large membrane receptor that can interact and form a complex with the calcium-permeable cation channel PC2. This complex localizes to the plasma membrane, primary cilia and ER. Dysregulated calcium signalling and consequential alterations in downstream signalling pathways in ADPKD are linked to cyst formation and expansion; however, it is not completely understood how PC1 and PC2 regulate calcium signalling. We have studied Polycystin-2 mediated calcium signalling in the model organism Dictyostelium discoideum by overexpressing and knocking down the expression of the endogenous Polycystin-2 homologue, Polycystin-2. Chemoattractant-stimulated cytosolic calcium response magnitudes increased and decreased in overexpression and knockdown strains, respectively, and analysis of the response kinetics indicates that Polycystin-2 is a significant contributor to the control of Ca2+ responses. Furthermore, basal cytosolic calcium levels were reduced in Polycystin-2 knockdown transformants. These alterations in Ca2+ signalling also impacted other downstream Ca2+-sensitive processes including growth rates, endocytosis, stalk cell differentiation and spore viability, indicating that Dictyostelium is a useful model to study Polycystin-2 mediated calcium signalling.
Department of Microbiology, Anatomy, Physiology and Pharmacology, La Trobe University, Bundoora, Melbourne, VIC 3086, Australia.
Polycystin-2 Mediated Calcium Signalling in the Dictyostelium Model for Autosomal Dominant Polycystic Kidney Disease.

The management of chronic myelogenous leukemia (CML) has seen significant progress with the introduction of tyrosine kinase inhibitors (TKIs), particularly Imatinib. However, a notable proportion of CML patients develop resistance to Imatinib, often due to the persistence of leukemia stem cells and resistance mechanisms independent of BCR::ABL1 This study investigates the roles of IL6R, IL7R, and MYC in Imatinib resistance by employing CRISPR/Cas9 for gene editing and the Non-Invasive Apoptosis Detection Sensor version 2 (NIADS v2) for apoptosis assessment. The results indicate that Imatinib-resistant K562 cells (K562-IR) predominantly express IL6R, IL7R, and MYC, with IL6R and MYC playing crucial roles in cell survival and sensitivity to Imatinib. Conversely, IL7R does not significantly impact cytotoxicity, either alone or in combination with Imatinib. Further genetic editing experiments confirm the protective functions of IL6R and MYC in K562-IR cells, suggesting their potential as therapeutic targets for overcoming Imatinib resistance in CML. This study contributes to understanding the mechanisms of Imatinib resistance in CML, proposing IL6R and MYC as pivotal targets for therapeutic strategies. Moreover, the utilization of NIADS v2 enhances our capability to analyze apoptosis and drug responses, contributing to a deeper understanding of CML pathogenesis and treatment options.
School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, New Taipei City 23561, Taiwan.Ph.D. Program in Medicine Biotechnology, College of Medical Science and Technology, Taipei Medical University, New Taipei City 23561, Taiwan.TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei 11031, Taiwan.Center for Intelligent Drug Systems and Smart Bio-Devices (IDS2B), National Yang Ming Chiao Tung University, Hsinchu 30068, Taiwan.
Research Center for Cancer Biology, China Medical University, Taichung City 40402, Taiwan.Institute of Translational Medicine and New Drug Development, China Medical University, Taichung City 40402, Taiwan.Program for Cancer Biology and Drug Discovery, Drug Development Center, China Medical University, Taichung City 40402, Taiwan.
Division of Hematology and Oncology, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan.Division of Hematology and Oncology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
Department of Physiology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.Chinese Academy of Medical Science Oxford Institute, University of Oxford, Oxford OX3 7BN, UK.
Center for Intelligent Drug Systems and Smart Bio-Devices (IDS2B), National Yang Ming Chiao Tung University, Hsinchu 30068, Taiwan.Institute of Bioinformatics and Systems Biology, National Yang Ming Chiao Tung University, Hsinchu 30068, Taiwan.School of Dentistry, Kaohsiung Medical University, Kaohsiung 807378, Taiwan.
Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.Department of Pediatrics, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan.
Unveiling IL6R and MYC as Targeting Biomarkers in Imatinib-Resistant Chronic Myeloid Leukemia through Advanced Non-Invasive Apoptosis Detection Sensor Version 2 Detection.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) featuring numerous neuropathologies, including optic neuritis (ON) in some patients. However, the molecular mechanisms of ON remain unknown. Galectins, β-galactoside-binding lectins, are involved in various pathophysiological processes. We previously showed that galectin-3 (gal-3) is associated with the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. In the current study, we investigated the expression of gal-3 in the visual pathway in EAE mice to clarify its role in the pathogenesis of ON. Immunohistochemical analysis revealed upregulation of gal-3 in the visual pathway of the EAE mice during the peak stage of the disease, compared with naïve and EAE mice during the chronic stage. Gal-3 was detected mainly in microglia/macrophages and astrocytes in the visual pathway in EAE mice. In addition, gal-3+/Iba-1+ cells, identified as phagocytic by immunostaining for cathepsin D, accumulated in demyelinating lesions in the visual pathway during the peak disease stage of EAE. Moreover, NLRP3 expression was detected in most gal-3+/Iba-1+ cells. These results strongly suggest that gal-3 regulates NLRP3 signaling in microglia/macrophages and neuroinflammatory demyelination in ON. In astrocytes, gal-3 was expressed from the peak to the chronic disease stages. Taken together, our findings suggest a critical role of gal-3 in the pathogenesis of ON. Thus, gal-3 in glial cells may serve as a potential therapeutic target for ON.
Department of Anatomy, Akita University Graduate School of Medicine, Akita 010-8543, Japan.
Department of Functional Glycobiology in Infectious Diseases, National Research Center for the Control and Prevention of Infectious Diseases, Nagasaki University, Nagasaki 852-8523, Japan.
Galectin-3 Plays a Role in Neuroinflammation in the Visual Pathway in Experimental Optic Neuritis.

The uterine cervix is one of the key factors involved in ensuring a proper track of gestation and labor. At the end of the gestational period, the cervix undergoes extensive changes, which can be summarized as a transformation from a non-favorable cervix to one that is soft and prone to dilation. During a process called cervical ripening, fundamental remodeling of the cervical extracellular matrix (ECM) occurs. The cervical ripening process is a derivative of many interlocking and mutually driving biochemical and molecular pathways under the strict control of mediators such as inflammatory cytokines, nitric oxide, prostaglandins, and reactive oxygen species. A thorough understanding of all these pathways and learning about possible triggering factors will allow us to develop new, better treatment algorithms and therapeutic goals that could protect women from both dysfunctional childbirth and premature birth. This review aims to present the possible role of the NLRP3 inflammasome in the cervical ripening process, emphasizing possible mechanisms of action and regulatory factors.
Department of Perinatology, Gynecology and Gynecologic Oncology, Faculty of Health Sciences, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Łukasiewicza 1, 85-821 Bydgoszcz, Poland.Department of Obstetrics and Gynecology, St. Adalbert's Hospital in Gdańsk, Copernicus Healthcare Entity, Jana Pawła II 50, 80-462 Gdańsk, Poland.
The Role of the NLRP3 Inflammasome in the Molecular and Biochemical Mechanisms of Cervical Ripening: A Comprehensive Review.

Epithelial ovarian cancer (EOC) is the deadliest gynecological malignancy worldwide. Despite the latest advances, a major clinical issue in EOC is the disappointing prognosis related to chemoresistance in almost one-third of cases. Drug resistance relies on heterogeneous cancer stem cells (CSCs), endowed with tumor-initiating potential, leading to relapse. No biomarkers of chemoresistance have been validated yet. Recently, major signaling pathways, micro ribonucleic acids (miRNAs), and circulating tumor cells (CTCs) have been advocated as putative biomarkers and potential therapeutic targets for drug resistance. However, further investigation is mandatory before their routine implementation. In accordance with the increasing rate of therapeutic efforts in EOC, the need for biomarker-driven personalized therapies is growing. This review aims to discuss the emerging hallmarks of drug resistance with an in-depth insight into the underlying molecular mechanisms lacking so far. Finally, a glimpse of novel therapeutic avenues and future challenges will be provided.
Unit of Medical Oncology 3, Veneto Institute of Oncology IOV-IRCCS, 35128 Padova, Italy.
Spotlight on New Hallmarks of Drug-Resistance towards Personalized Care for Epithelial Ovarian Cancer.

Extracellular vesicles are pivotal mediators in intercellular communication, facilitating the exchange of biological information among healthy, pathological and tumor cells. Between the diverse subtypes of extracellular vesicles, exosomes have unique properties and clinical and therapeutical applications. Breast cancer ranks as one of the most prevalent malignancies across the globe. Both the tumor core and its surrounding microenvironment engage in a complex, orchestrated interaction that facilitates cancer's growth and spread.The most significant PubMed literature about extracellular vesicles and Adipose-Derived Stem Cell Exosomes and breast cancer was selected in order to report their biological properties and potential applications, in particular in treating triple-negative breast cancer.Adipose-Derived Stem Cell Exosomes represent a potential tool in targeting triple-negative breast cancer cells at three main levels: the tumor core, the tumor microenvironment and surrounding tissues, including metastases.The possibility of impacting triple-negative breast cancer cells with engineered Adipose-Derived Stem Cell Exosomes is real. The opportunity to translate our current in vitro analyses into a future in vivo scenario is even more challenging.
Department of Plastic, Hand and Reconstructive Surgery, University Hospital Regensburg, Franz-Josef-Strauß Allee 11, 93053 Regensburg, Germany.
Department of Plastic, Hand and Reconstructive Surgery, BG Klinik Ludwigshafen, University of Heidelberg, Ludwig-Guttmann-Straße 13, 67071 Ludwigshafen, Germany.
The Triple Adipose-Derived Stem Cell Exosome Technology as a Potential Tool for Treating Triple-Negative Breast Cancer.

Cancer stem cells (CSCs) are closely associated with tumor initiation, metastasis, chemoresistance, and recurrence, which represent some of the primary obstacles to cancer treatment. Targeting CSCs has become an important therapeutic approach to cancer care. Secoemestrin C (Sec C) is a natural compound with strong anti-tumor activity and low toxicity. Here, we report that Sec C effectively inhibited colorectal CSCs and non-CSCs concurrently, mainly by inhibiting proliferation, self-renewal, metastasis, and drug resistance. Mechanistically, RNA-seq analysis showed that the pro-inflammation pathway of the IL17 axis was enriched, and its effector S100A8 was dramatically decreased in Sec C-treated cells, whose roles in the stemness of CSCs have not been fully clarified. We found that the overexpression of S100A8 hindered the anti-CSCs effect of Sec C, and S100A8 deficiency attenuated the stemness traits of CSCs to enhance the Sec C killing activity on them. Meanwhile, the p38 signal pathway, belonging to the IL17 downstream axis, can also mediate CSCs and counter with Sec C. Notably, we found that S100A8 upregulation increased the p38 protein level, and p38, in turn, promoted S100A8 expression. This indicated that p38 may have a mutual feedback loop with S100A8. Our study discovered that Sec C was a powerful anti-colorectal CSC agent, and that the positive feedback loop of p38-S100A8 mediated Sec C activity. This showed that Sec C could act as a promising clinical candidate in colorectal cancer treatment, and S100A8 could be a prospective drug target.
State Key Laboratory of Respiratory Health and Multimorbidity, Key Laboratory of Antibiotic Bioengineering, Ministry of Health, Laboratory of Oncology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
NHC Key Laboratory of Biotechnology of Antibiotics, National Center for New Microbial Drug Screening, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Tiantan Xili, Beijing 100050, China.
The Natural Product Secoemestrin C Inhibits Colorectal Cancer Stem Cells via p38-S100A8 Feed-Forward Regulatory Loop.

Cardiolipin (CL) is a mitochondria-exclusive phospholipid synthesized in the inner mitochondrial membrane. CL plays a key role in mitochondrial membranes, impacting a plethora of functions this organelle performs. Consequently, it is conceivable that abnormalities in the CL content, composition, and level of oxidation may negatively impact mitochondrial function and dynamics, with important implications in a variety of diseases. This review concentrates on papers published in recent years, combined with basic and underexplored research in CL. We capture new findings on its biological functions in the mitochondria, as well as its association with neurodegenerative diseases such as Alzheimer's disease or Parkinson's disease. Lastly, we explore the potential applications of CL as a biomarker and pharmacological target to mitigate mitochondrial dysfunction.
Departamento de Bioquímica y Biología Molecular y Genética, Facultad de Enfermería y Terapia Ocupacional, Universidad de Extremadura, 10003 Cáceres, Spain.Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, Instituto de Salud Carlos III (CIBER-CIBERNED-ISCIII), 28029 Madrid, Spain.Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), 10003 Cáceres, Spain.
Departmentof Neurology, Columbia University, New York, NY 10032, USA.
The Role of Cardiolipin in Mitochondrial Function and Neurodegenerative Diseases.

During pregnancy, uterine vasculature undergoes significant circumferential growth to increase uterine blood flow, vital for the growing feto-placental unit. However, this process is often compromised in conditions like maternal high blood pressure, particularly in preeclampsia (PE), leading to fetal growth impairment. Currently, there is no cure for PE, partly due to the adverse effects of anti-hypertensive drugs on maternal and fetal health. This study aimed to investigate the vasodilator effect of extra virgin olive oil (EVOO) phenols on the reproductive vasculature, potentially benefiting both mother and fetus. Isolated uterine arteries (UAs) from pregnant rats were tested with EVOO phenols in a pressurized myograph. To elucidate the underlying mechanisms, additional experiments were conducted with specific inhibitors: L-NAME/L-NNA (10-4 M) for nitric oxide synthases, ODQ (10-5 M) for guanylate cyclase, Verapamil (10-5 M) for the L-type calcium channel, Ryanodine (10-5 M) + 2-APB (3 × 10-5 M) for ryanodine and the inositol triphosphate receptors, respectively, and Paxilline (10-5 M) for the large-conductance calcium-activated potassium channel. The results indicated that EVOO-phenols activate Ca2+ signaling pathways, generating nitric oxide, inducing vasodilation via cGMP and BKCa2+ signals in smooth muscle cells. This study suggests the potential use of EVOO phenols to prevent utero-placental blood flow restriction, offering a promising avenue for managing PE.
Department of Biology, Ecology & Earth Science, University of Calabria, 87036 Arcavacata di Rende, CS, Italy.
Department of Obstetrics, Gynecology and Reproductive Sciences, University of Vermont, Larner College of Medicine, Burlington, VT 05405, USA.Department of Neurological Sciences, University of Vermont, Larner College of Medicine, Burlington, VT 05405, USA.
Department of Neurological Sciences, University of Vermont, Larner College of Medicine, Burlington, VT 05405, USA.
Department of Biology, Ecology & Earth Science, University of Calabria, 87036 Arcavacata di Rende, CS, Italy.Department of Obstetrics, Gynecology and Reproductive Sciences, University of Vermont, Larner College of Medicine, Burlington, VT 05405, USA.
Dilation of Pregnant Rat Uterine Arteries with Phenols from Extra Virgin Olive Oil Is Endothelium-Dependent and Involves Calcium and Potassium Channels.

Glioblastoma is the most aggressive, malignant, and lethal brain tumor of the central nervous system. Its poor prognosis lies in its inefficient response to currently available treatments that consist of surgical resection, radiotherapy, and chemotherapy. Recently, the use of mesenchymal stem cells (MSCs) as a possible kind of cell therapy against glioblastoma is gaining great interest due to their immunomodulatory properties, tumor tropism, and differentiation into other cell types. However, MSCs seem to present both antitumor and pro-tumor properties depending on the tissue from which they come. In this work, the possibility of using MSCs to deliver therapeutic genes, oncolytic viruses, and miRNA is presented, as well as strategies that can improve their therapeutic efficacy against glioblastoma, such as CAR-T cells, nanoparticles, and exosomes.
Department of Biochemistry and Genetics, University of Navarra School of Sciences, 31008 Pamplona, Spain.
Interdisciplinary Brain Research Centre, Faculty of Medicine, Aligarh Muslim University, Aligarh 202002, India.
Mesenchymal-Stem-Cell-Based Therapy against Gliomas.

Alterations in olfactory functions are proposed as possible early biomarkers of neurodegenerative diseases. Parkinson's and Alzheimer's diseases manifest olfactory dysfunction as a symptom, which is worth mentioning. The alterations do not occur in all patients, but they can serve to rule out neurodegenerative pathologies that are not associated with small deficits. Several prevalent neurodegenerative conditions, including impaired smell, arise in the early stages of Parkinson's and Alzheimer's diseases, presenting an attractive prospect as a snitch for early diagnosis. This review covers the current knowledge on the link between olfactory deficits and Parkinson's and Alzheimer's diseases. The review also covers the emergence of olfactory receptors as actors in the pathophysiology of these diseases. Olfactory receptors are not exclusively expressed in olfactory sensory neurons. Olfactory receptors are widespread in the human body; they are expressed, among others, in the testicles, lungs, intestines, kidneys, skin, heart, and blood cells. Although information on these ectopically expressed olfactory receptors is limited, they appear to be involved in cell recognition, migration, proliferation, wound healing, apoptosis, and exocytosis. Regarding expression in non-chemosensory regions of the central nervous system (CNS), future research should address the role, in both the glia and neurons, of olfactory receptors. Here, we review the limited but relevant information on the altered expression of olfactory receptor genes in Parkinson's and Alzheimer's diseases. By unraveling how olfactory receptor activation is involved in neurodegeneration and identifying links between olfactory structures and neuronal death, valuable information could be gained for early diagnosis and intervention strategies in neurodegenerative diseases.
Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, University of Barcelona, 08028 Barcelona, Spain.CiberNed, Network Center for Neurodegenerative Diseases, National Spanish Health Institute Carlos III, 28029 Madrid, Spain.School of Chemistry, University of Barcelona, 08028 Barcelona, Spain.
Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, University of Barcelona, 08028 Barcelona, Spain.
Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, University of Barcelona, 08028 Barcelona, Spain.CiberNed, Network Center for Neurodegenerative Diseases, National Spanish Health Institute Carlos III, 28029 Madrid, Spain.
The Olfactory Trail of Neurodegenerative Diseases.

Rheumatoid arthritis (RA) is one of the most common autoimmune diseases. Inflammation of the synovial fluid propagates the pathological process of angiogenesis. Semaphorins play a crucial role in the context of endothelial cell function, and their pleiotropic nature has various effects on the further development of RA. This narrative review summarises the various roles of semaphorins in the pathology of RA and whether they could play a role in developing novel RA treatment options.
Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland.
The Role of Semaphorins in the Pathogenesis of Rheumatoid Arthritis.

The lacrimal gland is crucial for maintaining ocular health by producing the aqueous component of the tear film, which hydrates and nourishes the ocular surface. Decreased production of this component results in dry eye disease, a condition affecting over 250 million people worldwide. However, the scarcity of primary human material for studying its underlying mechanisms and the absence of a cell model for human lacrimal gland epithelial cells present significant challenges. Here, we describe the generation of immortalized human lacrimal gland cell lines through the introduction of an SV40 antigen. We successfully isolated and characterized three cell clones from a female lacrimal gland donor, confirming their epithelial identity through genomic and protein analyses, including PCR, RNAseq, immunofluorescence and cultivation in a 3D spheroid model. Our findings represent a significant advancement, providing improved accessibility to investigate the molecular pathogenesis mechanisms of dry eye disease and potential therapeutic interventions. We identified the expression of typical epithelial cell marker genes and demonstrated the cells' capability to form 2D cell sheets and 3D spheroids. This establishment of immortalized human lacrimal gland cells with epithelial characteristics holds promise for future comprehensive studies, contributing to a deeper understanding of dry eye disease and its cellular mechanisms.
Institute of Functional and Clinical Anatomy, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.
Institute of Functional and Clinical Anatomy, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.Hariram Motumal Nasta & Renu Hariram Nasta Ophthalmic Plastic Surgery Services, LV Prasad Eye Institute, Hyderabad 500034, India.
Department of Molecular Neurology, University Hospital Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.
Department of Medicine 1, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.
CEITEC-Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic.
Department of Otorhinolaryngology, Merciful Brothers Hospital St. Elisabeth, 94315 Straubing, Germany.Department of Otolaryngology, Head & Neck Surgery, Comprehensive Cancer Center Erlangen, University Hospital Erlangen, 91054 Erlangen, Germany.
Department of Otolaryngology, Head & Neck Surgery, Comprehensive Cancer Center Erlangen, University Hospital Erlangen, 91054 Erlangen, Germany.
Institute of Anatomy and Cell Biology, Paracelsus Medical University, Nuremberg Prof. Ernst Nathan Str. 1, 90419 Nuremberg, Germany.
Department of Medicine 1, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.Deutsches Zentrum Immuntherapie (DZI), University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.
A New Immortalized Human Lacrimal Gland Cell Line.

Limbal epithelial progenitor cells (LEPC) rely on their niche environment for proper functionality and self-renewal. While extracellular vesicles (EV), specifically small EVs (sEV), have been proposed to support LEPC homeostasis, data on sEV derived from limbal niche cells like limbal mesenchymal stromal cells (LMSC) remain limited, and there are no studies on sEVs from limbal melanocytes (LM). In this study, we isolated sEV from conditioned media of LMSC and LM using a combination of tangential flow filtration and size exclusion chromatography and characterized them by nanoparticle tracking analysis, transmission electron microscopy, Western blot, multiplex bead arrays, and quantitative mass spectrometry. The internalization of sEV by LEPC was studied using flow cytometry and confocal microscopy. The isolated sEVs exhibited typical EV characteristics, including cell-specific markers such as CD90 for LMSC-sEV and Melan-A for LM-sEV. Bioinformatics analysis of the proteomic data suggested a significant role of sEVs in extracellular matrix deposition, with LMSC-derived sEV containing proteins involved in collagen remodeling and cell matrix adhesion, whereas LM-sEV proteins were implicated in other cellular bioprocesses such as cellular pigmentation and development. Moreover, fluorescently labeled LMSC-sEV and LM-sEV were taken up by LEPC and localized to their perinuclear compartment. These findings provide valuable insights into the complex role of sEV from niche cells in regulating the human limbal stem cell niche.
Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Killianstrasse 5, 79106 Freiburg, Germany.
Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Killianstrasse 5, 79106 Freiburg, Germany.Faculty of Biology, University of Freiburg, Schaenzlestrasse 1, D-79104 Freiburg, Germany.
Institute of Surgical Pathology, Faculty of Medicine, Freiburg, Medical Center, University of Freiburg, 79085 Freiburg im Breisgau, Germany.
Department of Ophthalmology, University Hospital Erlangen, Friedrich-Alexander-University of Erlan-gen-Nürnberg, Schwabachanlage 6, 91054 Erlangen, Germany.
Institute for Infection Prevention and Hospital Epidemiology, Faculty of Medicine, Medical Center, University of Freiburg, 79106 Freiburg, Germany.
Enrichment, Characterization, and Proteomic Profiling of Small Extracellular Vesicles Derived from Human Limbal Mesenchymal Stromal Cells and Melanocytes.

Embryonic neurogenesis can be defined as a period of prenatal development during which divisions of neural stem and progenitor cells give rise to neurons. In the central nervous system of most mammals, including humans, the majority of neocortical neurogenesis occurs before birth. It is a highly spatiotemporally organized process whose perturbations lead to cortical malformations and dysfunctions underlying neurological and psychiatric pathologies, and in which oxygen availability plays a critical role. In case of deprived oxygen conditions, known as hypoxia, the hypoxia-inducible factor (HIF) signaling pathway is activated, resulting in the selective expression of a group of genes that regulate homeostatic adaptations, including cell differentiation and survival, metabolism and angiogenesis. While a physiological degree of hypoxia is essential for proper brain development, imbalanced oxygen levels can adversely affect this process, as observed in common obstetrical pathologies such as prematurity. This review comprehensively explores and discusses the current body of knowledge regarding the role of hypoxia and the HIF pathway in embryonic neurogenesis of the mammalian cortex. Additionally, it highlights existing gaps in our understanding, presents unanswered questions, and provides avenues for future research.
Institute of Clinical Chemistry and Laboratory Medicine, Technische Universität Dresden, 01307 Dresden, Germany.
Institute of Clinical Chemistry and Laboratory Medicine, Technische Universität Dresden, 01307 Dresden, Germany.Experimental Centre, Faculty of Medicine, Technische Universität Dresden, 01307 Dresden, Germany.
From Vessels to Neurons-The Role of Hypoxia Pathway Proteins in Embryonic Neurogenesis.

The global fall in male fertility is a complicated process driven by a variety of factors, including environmental exposure, lifestyle, obesity, stress, and aging. The availability of assisted reproductive technology (ART) has allowed older couples to conceive, increasing the average paternal age at first childbirth. Advanced paternal age (APA), most often considered male age ≥40, has been described to impact several aspects of male reproductive physiology. In this prospective cohort study including 200 normozoospermic patients, 105 of whom were ≤35 years (non-APA), and 95 of whom were ≥42 years (APA), we assessed the impact of paternal age on different endpoints representative of sperm quality and cryopreservation tolerance. Non-APA patients had superior fresh semen quality; DNA fragmentation was notably increased in APA as compared to non-APA individuals (21.7% vs. 15.4%). Cryopreservation further increased the DNA fragmentation index in APA (26.7%) but not in non-APA patients. Additionally, APA was associated with increased mtDNAcn in both fresh and frozen/thawed sperm, which is indicative of poorer mitochondrial quality. Cryopreservation negatively impacted acrosome integrity in both age groups, as indicated by reduced incidences of unreacted acrosome in relation to fresh counterparts in non-APA (from 71.5% to 57.7%) and APA patients (from 75% to 63%). Finally, cryopreservation significantly reduced the phosphorylation status of proteins containing tyrosine residues in sperm from young males. Therefore, the present findings shed light on the effects of paternal age and cryopreservation on sperm quality and serve as valuable new parameters to improve our understanding of the mechanisms underlying sperm developmental competence that are under threat in current ART practice.
Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy.
Biogenesi Reproductive Medicine Center, Istituti Clinici Zucchi, 20900 Monza, Italy.
Paternal Age Amplifies Cryopreservation-Induced Stress in Human Spermatozoa.

(1) Background: Our previous data indicated that disturbance of the Transforming Growth Factor beta (TGFB) signaling pathway via its Type-2 Receptor (TGFBR2) can cause a Corneal Ectasia (CE)-like phenotype. The purpose of this study is to elucidate whether the SMAD4-dependent signaling pathway is involved in the TGFBR2-related CE-like pathogenesis. (2) Methods: Smad4 was designed to be conditionally knocked out from keratocytes. Novel triple transgenic mice, KerartTA; Tet-O-Cre; Smad4flox/flox (Smad4kera-cko), were administered with doxycycline (Dox). Optical Coherence Tomography (OCT) was performed to examine Central Corneal Thickness (CCT), Corneal Radius, Anterior Chamber and CE-like phenotype and compared to the littermate Control group (Smad4Ctrl). (3) Results: The OCT revealed normal cornea in the Smad4Ctrl and a CE-like phenotype in the Smad4kera-cko cornea, in which the overall CCT in Smad4kera-cko was thinner than that of Smad4Ctrl at P42 (n = 6, p < 0.0001) and showed no significant difference when compared to that in Tgfbr2kera-cko. Furthermore, the measurements of the Anterior Chamber and Corneal Radius indicated a substantial ectatic cornea in the Smad4kera-cko compared to Smad4Ctrl. The H&E staining of Smad4kera-cko mimics the finding in the Tgfbr2kera-cko. The positive immunostaining of cornea-specific marker K12 indicating the cell fate of cornea epithelium remained unchanged in Smad4kera-cko and the Proliferating Cell Nuclear Antigen (PCNA) immunostaining further indicated an enhanced proliferation in the Smad4kera-cko. Both immunostainings recapitulated the finding in Tgfbr2kera-cko. The Masson's Trichrome staining revealed decreased collagen formation in the corneal stroma from both Smad4kera-cko and Tgfbr2kera-cko. The collagen type 1 (Col1a1) immunostaining further confirmed the reduction in collagen type 1 formation in Smad4kera-cko. (4) Conclusions: The aforementioned phenotypes in the Smad4kera-cko strain indicated that the SMAD4-dependent signaling pathway is involved in the pathogenesis of the CE-like phenotype observed in Tgfbr2kera-cko.
Edith Crawley Vision Research Center, Department of Ophthalmology, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA.Department of Anesthesia, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA.School of Optometry, Indiana University, Bloomington, IN 47405, USA.
School of Optometry, Indiana University, Bloomington, IN 47405, USA.
Edith Crawley Vision Research Center, Department of Ophthalmology, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA.School of Optometry, Indiana University, Bloomington, IN 47405, USA.
SMAD4-Dependent Signaling Pathway Involves in the Pathogenesis of TGFBR2-Related CE-like Phenotype.

Wound healing is a dynamic and complex process, characterized by the coordinated activities of multiple cell types, each with distinct roles in the stages of hemostasis, inflammation, proliferation, and remodeling. The cells of the immune system not only act as sentinels to monitor the skin and promote homeostasis, but they also play an important role in the process of skin wound repair. Skin-resident and recruited immune cells release cytokines and growth factors that promote the amplification of the inflammatory process. They also work with non-immune cells to remove invading pathogens and debris, as well as guide the regeneration of damaged host tissues. Dysregulation of the immune system at any stage of the process may lead to a prolongation of the inflammatory phase and the development of a pathological condition, such as a chronic wound. The present review aims to summarize the roles of different immune cells, with special emphasis on the different stages of the wound healing process.
National Institute for Health, Migration and Poverty INMP/NIHMP, Via di S.Gallicano, 25, 00153 Rome, Italy.
Role of the Skin Immune System in Wound Healing.

The strategy for treating bladder cancer (BC) depends on whether there is muscle invasion or not, with the latter mostly treated with intravesical therapy, such as with bacillus Calmette-Guérin (BCG). However, BCG treatment is unsuccessful in 70% of patients, who are then subjected to radical cystectomy. Although immune-checkpoint inhibitors have been approved as a second-line therapy for a subset of BC patients, these have failed to meet primary endpoints in clinical trials. Thus, it is crucial to find a new treatment. The mitochondrial gatekeeper protein, the voltage-dependent anion channel 1 (VDAC1), mediates metabolic crosstalk between the mitochondria and cytosol and is involved in apoptosis. It is overexpressed in many cancer types, as shown here for BC, pointing to its significance in high-energy-demanding cancer cells. The BC cell lines UM-UC3 and HTB-5 express high VDAC1 levels compared to other cancer cell lines. VDAC1 silencing in these cells using siRNA that recognizes both human and mouse VDAC1 (si-m/hVDAC1-B) reduces cell viability, mitochondria membrane potential, and cellular ATP levels. Here, we used two BC mouse models: subcutaneous UM-UC3 cells and chemically induced BC using the carcinogen N-Butyl-N-(4-hydroxybutyl) nitrosamine (BBN). Subcutaneous UM-UC3-derived tumors treated with si-m/hVDAC1 showed inhibited tumor growth and reprogrammed metabolism, as reflected in the reduced expression of metabolism-related proteins, including Glut1, hexokinase, citrate synthase, complex-IV, and ATP synthase, suggesting reduced metabolic activity. Furthermore, si-m/hVDAC1-B reduced the expression levels of cancer-stem-cell-related proteins (cytokeratin-14, ALDH1a), modifying the tumor microenvironment, including decreased angiogenesis, extracellular matrix, tumor-associated macrophages, and inhibited epithelial-mesenchymal transition. The BBN-induced BC mouse model showed a clear carcinoma, with damaged bladder morphology and muscle-invasive tumors. Treatment with si-m/hVDAC1-B encapsulated in PLGA-PEI nanoparticles that were administered intravesically directly to the bladder showed a decreased tumor area and less bladder morphology destruction and muscle invasion. Overall, the obtained results point to the potential of si-m/hVDAC1-B as a possible therapeutic tool for treating bladder cancer.
Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
Silencing the Mitochondrial Gatekeeper VDAC1 as a Potential Treatment for Bladder Cancer.

Lysophosphatidic acid (LPA) is a phospholipid that displays potent signalling activities that are regulated in both an autocrine and paracrine manner. It can be found both extra- and intracellularly, where it interacts with different receptors to activate signalling pathways that regulate a plethora of cellular processes, including mitosis, proliferation and migration. LPA metabolism is complex, and its biosynthesis and catabolism are under tight control to ensure proper LPA levels in the body. In cancer patient specimens, LPA levels are frequently higher compared to those of healthy individuals and often correlate with poor responses and more aggressive disease. Accordingly, LPA, through promoting cancer cell migration and invasion, enhances the metastasis and dissemination of tumour cells. In this review, we summarise the role of LPA in the regulation of critical aspects of tumour biology and further discuss the available pre-clinical and clinical evidence regarding the feasibility and efficacy of targeting LPA metabolism for effective anticancer therapy.
Signalling and Cancer Metabolism Laboratory, Division of Cancer Biology, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.
The Emerging Role of LPA as an Oncometabolite.

Current Influenza A virus (IAV) vaccines, which primarily aim to generate neutralizing antibodies against the major surface proteins of specific IAV strains predicted to circulate during the annual 'flu' season, are suboptimal and are characterized by relatively low annual vaccine efficacy. One approach to improve protection is for vaccines to also target the priming of virus-specific T cells that can protect against IAV even in the absence of preexisting neutralizing antibodies. CD4 T cells represent a particularly attractive target as they help to promote responses by other innate and adaptive lymphocyte populations and can also directly mediate potent effector functions. Studies in murine models of IAV infection have been instrumental in moving this goal forward. Here, we will review these findings, focusing on distinct subsets of CD4 T cell effectors that have been shown to impact outcomes. This body of work suggests that a major challenge for next-generation vaccines will be to prime a CD4 T cell population with the same spectrum of functional diversity generated by IAV infection. This goal is encapsulated well by the motto 'ex pluribus unum': that an optimal CD4 T cell response comprises many individual specialized subsets responding together.
Immunity and Pathogenesis Division, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USA.
Ex Pluribus Unum: The CD4 T Cell Response against Influenza A Virus.

Despite being immune cells of the central nervous system (CNS), microglia contribute to CNS development, maturation, and homeostasis, and microglia dysfunction has been implicated in several neurological disorders. Recent advancements in single-cell studies have uncovered unique microglia-specific gene expression. However, there is a need for a simple yet elegant multiplexed approach to quantifying microglia gene expression. To address this, we have designed a NanoString nCounter technology-based murine microglia-specific custom codeset comprising 178 genes. We analyzed RNA extracted from ex vivo adult mouse microglia, primary mouse microglia, the BV2 microglia cell line, and mouse bone marrow monocytes using our custom panel. Our findings reveal a pattern where homeostatic genes exhibit heightened expression in adult microglia, followed by primary cells, and are absent in BV2 cells, while reactive markers are elevated in primary microglia and BV2 cells. Analysis of publicly available data sets for the genes present in the panel revealed that the panel could reliably reflect the changes in microglia gene expression in response to various factors. These findings highlight that the microglia panel used offers a swift and cost-effective means to assess microglial cells and can be used to study them in varying contexts, ranging from normal homeostasis to disease models.
Bielefeld University, Medical School OWL, Anatomy and Cell Biology, 33615 Bielefeld, Germany.
Gerhard-Domagk-Institute of Pathology, Münster University Hospital, 48149 Münster, Germany.
A Custom Panel for Profiling Microglia Gene Expression.

The field cancerization theory is an important paradigm in head and neck carcinoma as its oncological repercussions affect treatment outcomes in diverse ways. The aim of this study is to assess the possible interconnection between peritumor mucosa and the process of tumor neoangiogenesis. Sixty patients with advanced laryngeal carcinoma were enrolled in this study. The majority of patients express a canonical HIF-upregulated proangiogenic signature with almost complete predominancy of HIF-1α overexpression and normal expression levels of the HIF-2α isoform. Remarkably, more than 60% of the whole cohort also exhibited an HIF-upregulated proangiogenic signature in the peritumoral benign mucosa. Additionally, the latter subgroup had a distinctly shifted phenotype towards HIF-2α upregulation compared to the one in tumor tissue, i.e., a tendency towards an HIF switch is observed in contrast to the dominated by HIF-1α tumor phenotype. ETS-1 displays stable and identical significant overexpression in both the proangiogenic phenotypes present in tumor and peritumoral mucosa. In the current study, we report for the first time the existence of an abnormal proangiogenic expression profile present in the peritumoral mucosa in advanced laryngeal carcinoma when compared to paired distant laryngeal mucosa. Moreover, we describe a specific phenotype of this proangiogenic signature that is significantly different from the one present in tumor tissue as we delineate both phenotypes, quantitively and qualitatively. This finding is cancer heterogeneity, per se, which extends beyond the classical borders of the malignancy, and it is proof of a strong interconnection between field cancerization and one of the classical hallmarks of cancer-the process of tumor neoangiogenesis.
Molecular Medicine Center, Medical University-Sofia, 1463 Sofia, Bulgaria.
Department of ENT, Medical University-Sofia, 1463 Sofia, Bulgaria.
Peritumor Mucosa in Advanced Laryngeal Carcinoma Exhibits an Aberrant Proangiogenic Signature Distinctive from the Expression Pattern in Adjacent Tumor Tissue.

Neonatal hypoxia-ischemia (HI) affects 2-3 per 1000 live births in developed countries and up to 26 per 1000 live births in developing countries. It is estimated that of the 750,000 infants experiencing a hypoxic-ischemic event during birth per year, more than 400,000 will be severely affected. As treatment options are limited, rapidly identifying new therapeutic avenues is critical, and repurposing drugs already in clinical use offers a fast-track route to clinic. One emerging avenue for therapeutic intervention in neonatal HI is to target mitochondrial dysfunction, which occurs early in the development of brain injury. Mitochondrial dynamics are particularly affected, with mitochondrial fragmentation occurring at the expense of the pro-fusion protein Optic Atrophy (OPA)1. OPA1, together with mitofusins (MFN)1/2, are required for membrane fusion, and therefore, protecting their function may also safeguard mitochondrial dynamics. Leflunomide, an FDA-approved immunosuppressant, was recently identified as an activator of MFN2 with partial effects on OPA1 expression. We, therefore, treated C17.2 cells with Leflunomide before or after oxygen-glucose deprivation, an in vitro mimic of HI, to determine its efficacy as a neuroprotection and inhibitor of mitochondrial dysfunction. Leflunomide increased baseline OPA1 but not MFN2 expression in C17.2 cells. However, Leflunomide was unable to promote cell survival following OGD. Equally, there was no obvious effect on mitochondrial morphology or bioenergetics. These data align with studies suggesting that the tissue and mitochondrial protein profile of the target cell/tissue are critical for taking advantage of the therapeutic actions of Leflunomide.
Department of Comparative Biomedical Sciences, Royal Veterinary College, London NW1 0TU, UK.
School of Natural Sciences, Institute of Structural and Molecular Biology, Birkbeck, University of London, London WC1E 7HX, UK.
Leflunomide Treatment Does Not Protect Neural Cells following Oxygen-Glucose Deprivation (OGD) In Vitro.

Adjuvant treatment for Glioblastoma Grade 4 with Temozolomide (TMZ) inevitably fails due to therapeutic resistance, necessitating new approaches. Apoptosis induction in GB cells is inefficient, due to an excess of anti-apoptotic XPO1/Bcl-2-family proteins. We assessed TMZ, Methotrexate (MTX), and Cytarabine (Ara-C) (apoptosis inducers) combined with XPO1/Bcl-2/Mcl-1-inhibitors (apoptosis rescue) in GB cell lines and primary GB stem-like cells (GSCs). Using CellTiter-Glo® and Caspase-3 activity assays, we generated dose-response curves and analyzed the gene and protein regulation of anti-apoptotic proteins via PCR and Western blots. Optimal drug combinations were examined for their impact on the cell cycle and apoptosis induction via FACS analysis, paralleled by the assessment of potential toxicity in healthy mouse brain slices. Ara-C and MTX proved to be 150- to 10,000-fold more potent in inducing apoptosis than TMZ. In response to inhibitors Eltanexor (XPO1; E), Venetoclax (Bcl-2; V), and A1210477 (Mcl-1; A), genes encoding for the corresponding proteins were upregulated in a compensatory manner. TMZ, MTX, and Ara-C combined with E, V, and A evidenced highly lethal effects when combined. As no significant cell death induction in mouse brain slices was observed, we conclude that this drug combination is effective in vitro and expected to have low side effects in vivo.
Department of Neurosurgery, Philipps University Marburg, Baldingerstraße 1, 35043 Marburg, Germany.Department of Hematology, Oncology & Immunology, Philipps University Marburg, Baldingerstraße 1, 35043 Marburg, Germany.
FACS Core Facility, Philipps University Marburg, Hans-Meerwein-Straße 3, 35043 Marburg, Germany.
Department of Neuropathology, Philipps University Marburg, Baldingerstraße 1, 35043 Marburg, Germany.
Department of Neuropathology, Philipps University Marburg, Baldingerstraße 1, 35043 Marburg, Germany.University Cancer Center (UCT) Frankfurt-Marburg, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
University Cancer Center (UCT) Frankfurt-Marburg, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.Dr. Senckenberg Institute of Neurooncology, Goethe-University of Frankfurt, Schleusenweg 2-16, 60528 Frankfurt am Main, Germany.
Medical Mass Spectrometry Core Facility, Philipps University Marburg, Baldingerstraße 1, 35043 Marburg, Germany.
Department of Hematology, Oncology & Immunology, Philipps University Marburg, Baldingerstraße 1, 35043 Marburg, Germany.University Cancer Center (UCT) Frankfurt-Marburg, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
Department of Neurosurgery, Philipps University Marburg, Baldingerstraße 1, 35043 Marburg, Germany.University Cancer Center (UCT) Frankfurt-Marburg, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
A Novel Approach for Glioblastoma Treatment by Combining Apoptosis Inducers (TMZ, MTX, and Cytarabine) with E.V.A. (Eltanexor, Venetoclax, and A1210477) Inhibiting XPO1, Bcl-2, and Mcl-1.

In vitro-generated blastocyst-like structures are of great importance since they recapitulate specific features or processes of early embryogenesis, thus avoiding ethical concerns as well as increasing scalability and accessibility compared to the use of natural embryos. Here, we combine cell reprogramming and mechanical stimuli to create 3D spherical aggregates that are phenotypically similar to those of natural embryos. Specifically, dermal fibroblasts are reprogrammed, exploiting the miR-200 family property to induce a high plasticity state in somatic cells. Subsequently, miR-200-reprogrammed cells are either driven towards the trophectoderm (TR) lineage using an ad hoc induction protocol or encapsulated into polytetrafluoroethylene micro-bioreactors to maintain and promote pluripotency, generating inner cell mass (ICM)-like spheroids. The obtained TR-like cells and ICM-like spheroids are then co-cultured in the same micro-bioreactor and, subsequently, transferred to microwells to encourage blastoid formation. Notably, the above protocol was applied to fibroblasts obtained from young as well as aged donors, with results that highlighted miR-200's ability to successfully reprogram young and aged cells with comparable blastoid rates, regardless of the donor's cell age. Overall, the approach here described represents a novel strategy for the creation of artificial blastoids to be used in the field of assisted reproduction technologies for the study of peri- and early post-implantation mechanisms.
Laboratory of Biomedical Embryology and Tissue Engineering, Department of Health, Animal Science and Food Safety and Center for Stem Cell Research, Università degli Studi di Milano, 20133 Milan, Italy.
Department of Agricultural and Environmental Sciences-Production, Landscape, Agroenergy, Università degli Studi di Milano, 20133 Milan, Italy.
Generation of Artificial Blastoids Combining miR-200-Mediated Reprogramming and Mechanical Cues.

Nanometer zinc oxide (ZnONPs) offers strong antibacterial, wound healing, hemostatic benefits, and UV protection. Additionally, poly(hexamethylene biguanide)hydrochloride (PHMB) is an environmentally friendly polymer with strong bactericidal properties. However, the synergistic effect of the combination of ZnONPs and PHMB has not been previously explored. The purpose of this study is to explore the synergies of ZnONPs and PHMB and the healing efficacy of ZnO NPs-PHMB-hydrogel on skin wounds in mice infected with Staphylococcus aureus. Therefore, the mice were subjected to skin trauma to create a wound model and were subsequently infected with S. aureus, and then divided into various experimental groups. The repair effect was evaluated by assessing the healing rate, as well as measuring the levels of TNF-α, IL-2, EGF, and TGF-β1 contents in the tissue. On the 4th and 9th days post-modeling, the Z-P group exhibited notably higher healing rates compared to the control group. However, on the 15th day, both the Z-P and AC groups achieved healing rates exceeding 99%. ZnO NPs-PHMB-hydrogel promoted the formation of a fully restored epithelium, increased new hair follicles and sebaceous glands beneath the epidermis, and markedly reduced inflammatory cell infiltration, which was markedly distinct from the control group. On the 7th day, the Z-P group exhibited significantly higher levels of EGF and TGF-β1, along with a considerable reduction in the TNF-α levels as compared with the control group. These results affirmed that ZnO NPs-PHMB-hydrogel effectively inhibits S. aureus infection and accelerates skin wound healing.
College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.
Department of Basic Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.
Center for Veterinary Sciences, Zhejiang University, Hangzhou, China.
Therapeutic effect of ZnO NPs-polyhexanide-hydrogel on Staphylococcus aureus-induced skin wound infection in mice.

Glioblastoma is a highly aggressive disease with poor survival outcomes. An emerging body of literature links the role of the renin-angiotensin system (RAS), well-known for its function in the cardiovascular system, to the progression of cancers. We studied the expression of RAS-related genes (ATP6AP2, AGTR1, AGTR2, ACE, AGT, and REN) in The Cancer Genome Atlas (TCGA) glioblastoma cohort, their relationship to patient survival, and association with tumour microenvironment pathways. The expression of RAS genes was then examined in 12 patient-derived glioblastoma cell lines treated with chemoradiation. In cases of glioblastoma within the TCGA, ATP6AP2, AGTR1, ACE, and AGT had consistent expressions across samples, while AGTR2 and REN were lowly expressed. High expression of AGTR1 was independently associated with lower progression-free survival (PFS) (p = 0.01) and had a non-significant trend for overall survival (OS) after multivariate analysis (p = 0.095). The combined expression of RAS receptors (ATP6AP2, AGTR1, and AGTR2) was positively associated with gene pathways involved in hypoxia, microvasculature, stem cell plasticity, and the molecular characterisation of glioblastoma subtypes. In patient-derived glioblastoma cell lines, ATP6AP2 and AGTR1 were upregulated after chemoradiotherapy and correlated with an increase in HIF1A expression. This data suggests the RAS is correlated with changes in the tumour microenvironment and associated with glioblastoma survival outcomes.
School of Medicine and Public Health, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, Australia.Mark Hughes Foundation Centre for Brain Cancer Research, University of Newcastle, Callaghan, NSW 2308, Australia.Drug Repurposing and Medicines Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia.
School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, Australia.Mothers and Babies Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia.
School of Medicine and Public Health, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, Australia.Drug Repurposing and Medicines Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia.
School of Medicine and Public Health, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, Australia.Mark Hughes Foundation Centre for Brain Cancer Research, University of Newcastle, Callaghan, NSW 2308, Australia.Drug Repurposing and Medicines Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia.GenesisCare, Gateshead, NSW 2290, Australia.
Mark Hughes Foundation Centre for Brain Cancer Research, University of Newcastle, Callaghan, NSW 2308, Australia.Drug Repurposing and Medicines Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia.School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, Australia.
Upregulation of the Renin-Angiotensin System Is Associated with Patient Survival and the Tumour Microenvironment in Glioblastoma.

GDF15, also known as MIC1, is a member of the TGF-beta superfamily. Previous studies reported elevated serum levels of GDF15 in patients with kidney disorder, and its association with kidney disease progression, while other studies identified GDF15 to have protective effects. To investigate the potential protective role of GDF15 on podocytes, we first performed in vitro studies using a Gdf15-deficient podocyte cell line. The lack of GDF15 intensified puromycin aminonucleoside (PAN)-triggered endoplasmic reticulum stress and induced cell death in cultivated podocytes. This was evidenced by elevated expressions of Xbp1 and ER-associated chaperones, alongside AnnexinV/PI staining and LDH release. Additionally, we subjected mice to nephrotoxic PAN treatment. Our observations revealed a noteworthy increase in both GDF15 expression and secretion subsequent to PAN administration. Gdf15 knockout mice displayed a moderate loss of WT1+ cells (podocytes) in the glomeruli compared to wild-type controls. However, this finding could not be substantiated through digital evaluation. The parameters of kidney function, including serum BUN, creatinine, and albumin-creatinine ratio (ACR), were increased in Gdf15 knockout mice as compared to wild-type mice upon PAN treatment. This was associated with an increase in the number of glomerular macrophages, neutrophils, inflammatory cytokines, and chemokines in Gdf15-deficient mice. In summary, our findings unveil a novel renoprotective effect of GDF15 during kidney injury and inflammation by promoting podocyte survival and regulating endoplasmic reticulum stress in podocytes, and, subsequently, the infiltration of inflammatory cells via paracrine effects on surrounding glomerular cells.
Department of Medicine IV, Renal Division, Ludwig-Maximilians-University Hospital, Ludwig-Maximilians-University Munich, 80336 Munich, Germany.
Department of Medicine IV, Renal Division, Ludwig-Maximilians-University Hospital, Ludwig-Maximilians-University Munich, 80336 Munich, Germany.Klinikum Rechts der Isar, Department of Nephrology, Technical University Munich, 81675 Munich, Germany.
Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology of Jagiellonian University, 30-387 Krakow, Poland.
Klinikum Rechts der Isar, Department of Nephrology, Technical University Munich, 81675 Munich, Germany.
III Department of Medicine, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
GDF-15 Suppresses Puromycin Aminonucleoside-Induced Podocyte Injury by Reducing Endoplasmic Reticulum Stress and Glomerular Inflammation.

Poor prognosis in high-grade gliomas is mainly due to fatal relapse after surgical resection in the absence of efficient chemotherapy, which is severely hampered by the blood-brain barrier. However, the leaky blood-brain-tumour barrier forms upon tumour growth and vascularization, allowing targeted nanocarrier-mediated drug delivery. The homotypic targeting ability of cell-membrane fragments obtained from cancer cells means that these fragments can be exploited to this aim. In this experimental work, injectable nanoemulsions, which have a long history of safe clinic usage, have been wrapped in glioma-cell membrane fragments via co-extrusion to give targeted, homogeneously sized, sterile formulations. These systems were then loaded with three different chemotherapeutics, in the form of hydrophobic ion pairs that can be released into the target site thanks to interactions with physiological components. The numerous assays performed in two-dimensional (2D) and three-dimensional (3D) cell models demonstrate that the proposed approach is a versatile drug-delivery platform with chemo-tactic properties towards glioma cells, with adhesive interactions between the target cell and the cell membrane fragments most likely being responsible for the effect. This approach's promising translational perspectives towards personalized nanomedicine mean that further in vivo studies are foreseen for the future.
Department of Drug Science and Technology, University of Turin, via Pietro Giuria 9, 10124 Turin, Italy.
Department of Clinical and Biological Sciences, University of Turin, Corso Raffaello 30, 10124 Turin, Italy.
Department of Chemistry, University of Turin, Via Quarello 15/a, 10135 Turin, Italy.Nanostructured Interfaces and Surfaces (NIS) Interdepartmental Centre, University of Turin, 10124 Turin, Italy.
Department of Drug Science and Technology, University of Turin, via Pietro Giuria 9, 10124 Turin, Italy.Nanostructured Interfaces and Surfaces (NIS) Interdepartmental Centre, University of Turin, 10124 Turin, Italy.
Cell Membrane Fragment-Wrapped Parenteral Nanoemulsions: A New Drug Delivery Tool to Target Gliomas.

Insulin-producing pancreatic β cells play a crucial role in the regulation of glucose homeostasis, and their failure is a key event for diabetes development. Prolonged exposure to palmitate in the presence of elevated glucose levels, termed gluco-lipotoxicity, is known to induce β cell apoptosis. Autophagy has been proposed to be regulated by gluco-lipotoxicity in order to favor β cell survival. However, the role of palmitate metabolism in gluco-lipotoxcity-induced autophagy is presently unknown. We therefore treated INS-1 cells for 6 and 24 h with palmitate in the presence of low and high glucose concentrations and then monitored autophagy. Gluco-lipotoxicity induces accumulation of LC3-II levels in INS-1 at 6 h which returns to basal levels at 24 h. Using the RFP-GFP-LC3 probe, gluco-lipotoxicity increased both autophagosomes and autolysosmes structures, reflecting early stimulation of an autophagy flux. Triacsin C, a potent inhibitor of the long fatty acid acetyl-coA synthase, completely prevents LC3-II formation and recruitment to autophagosomes, suggesting that autophagic response requires palmitate metabolism. In contrast, etomoxir and bromo-palmitate, inhibitors of fatty acid mitochondrial β-oxidation, are unable to prevent gluco-lipotoxicity-induced LC3-II accumulation and recruitment to autophagosomes. Moreover, bromo-palmitate and etomoxir potentiate palmitate autophagic response. Even if gluco-lipotoxicity raised ceramide levels in INS-1 cells, ceramide synthase 4 overexpression does not potentiate LC3-II accumulation. Gluco-lipotoxicity also still stimulates an autophagic flux in the presence of an ER stress repressor. Finally, selective inhibition of sphingosine kinase 1 (SphK1) activity precludes gluco-lipotoxicity to induce LC3-II accumulation. Moreover, SphK1 overexpression potentiates autophagic flux induced by gluco-lipotxicity. Altogether, our results indicate that early activation of autophagy by gluco-lipotoxicity is mediated by SphK1, which plays a protective role in β cells.
Unité BFA, Université Paris Cité, CNRS UMR 8251, 75006 Paris, France.Department of Pathology and Stony Brook Cancer Center, Stony Brook University Renaissance School of Medicine, Stony Brook, NY 11794, USA.
Unité BFA, Université Paris Cité, CNRS UMR 8251, 75006 Paris, France.
Inserm, UMR-S 872, Centre de Recherche des Cordeliers, 75006 Paris, France.
INRA, UMR1347 Agroécologie, ERL CNRS 6300, Plateforme DImaCell, Centre de Microscopie INRA/Université de Bourgogne, 21065 Dijon, France.
INSERM U1151-CNRS UMR 8253, Institut Necker Enfants-Malades, University Paris Descartes, 75006 Paris, France.
Unité BFA, Université Paris Cité, CNRS UMR 8251, 75006 Paris, France.CNRS UMR 9197, Institut des Neurosciences Paris-Saclay, Saclay, University Paris, 91400 Saclay, France.
Role of Sphingosine Kinase 1 in Glucolipotoxicity-Induced Early Activation of Autophagy in INS-1 Pancreatic β Cells.

Increased activation of ovarian primordial follicles in Erβ knockout (ErβKO) rats becomes evident as early as postnatal day 8.5. To identify the ERβ-regulated genes that may control ovarian primordial follicle activation, we analyzed the transcriptome profiles of ErβKO rat ovaries collected on postnatal days 4.5, 6.5, and 8.5. Compared to wildtype ovaries, ErβKO ovaries displayed dramatic downregulation of Indian hedgehog (Ihh) expression. IHH-regulated genes, including Hhip, Gli1, and Ptch1, were also downregulated in ErβKO ovaries. This was associated with a downregulation of steroidogenic enzymes Cyp11a1, Cyp19a1, and Hsd17b1. The expression of Ihh remained very low in ErβKO ovaries despite the high levels of Gdf9 and Bmp15, which are known upregulators of Ihh expression in the granulosa cells of activated ovarian follicles. Strikingly, the downregulation of the Ihh gene in ErβKO ovaries began to disappear on postnatal day 16.5 and recovered on postnatal day 21.5. In rat ovaries, the first wave of primordial follicles is rapidly activated after their formation, whereas the second wave of primordial follicles remains dormant in the ovarian cortex and slowly starts activating after postnatal day 12.5. We localized the expression of Ihh mRNA in postnatal day 8.5 wildtype rat ovaries but not in the age-matched ErβKO ovaries. In postnatal day 21.5 ErβKO rat ovaries, we detected Ihh mRNA mainly in the activated follicles in the ovaries' peripheral regions. Our findings indicate that the expression of Ihh in the granulosa cells of the activated first wave of ovarian follicles depends on ERβ.
Department of Pathology and Laboratory Medicine, University of Kansas Medical Center (KUMC), Kansas City, KS 66160, USA.
Obstetrics and Gynecology, University of Kansas Medical Center (KUMC), Kansas City, KS 66160, USA.
ERβ Regulation of Indian Hedgehog Expression in the First Wave of Ovarian Follicles.

Despite world-class sophisticated technologies, robotics, artificial intelligence, and machine learning approaches, cancer-associated mortalities and morbidities have shown continuous increments posing a healthcare burden. Drug-based interventions were associated with systemic toxicities and several limitations. Natural bioactive compounds derived nanoformulations, especially nanoquercetin (nQ), are alternative options to overcome drug-associated limitations. Moreover, the EVs-based cargo targeted delivery of nQ can have enormous potential in treating hepatocellular carcinoma (HCC). EVs-based nQ delivery synergistically regulates and dysregulates several pathways, including NF-κB, p53, JAK/STAT, MAPK, Wnt/β-catenin, and PI3K/AKT, along with PBX3/ERK1/2/CDK2, and miRNAs intonation. Furthermore, discoveries on possible checkpoints of anticancer signaling pathways were studied, which might lead to the development of modified EVs infused with nQ for the development of innovative treatments for HCC. In this work, we abridged the control of such signaling systems using a synergetic strategy with EVs and nQ. The governing roles of extracellular vesicles controlling the expression of miRNAs were investigated, particularly in relation to HCC.
Department of Anatomy and Cell Biology, College of Medicine, Gachon University, 155 Getbeol-ro, Yeonsu-gu, Incheon 21999, Republic of Korea.
Nanoquercetin and Extracellular Vesicles as Potential Anticancer Therapeutics in Hepatocellular Carcinoma.

The COVID-19 pandemic and related control measures affected the mental health of all populations. Particular subgroups are underrepresented in mainstream surveys because they are hard to reach, and study measurements are not adapted to their skills. These subgroups include people with lower cognitive and literacy skills, such as people with mild intellectual disability (MID), who were considered vulnerable during the COVID-19 pandemic given their low socioeconomic status, small social networks, increased risks of health problems, and difficulties understanding health-related information.This study examines the impact of the COVID-19 pandemic on mental health among people with MID or low literacy skills compared with those predominantly represented in national surveys.A repeated cross-sectional study of people with MID or low literacy skills and a general population sample was conducted in the Netherlands. An easy-read web-based survey was co-designed with, and tested among, people with MID or low literacy skills and conducted in 3 rounds within 1 year of the COVID-19 pandemic (T1: November to December 2020, T2: March to April 2021, and T3: September to October 2021). The survey contained questions about demographics and 6 aspects of mental health: feeling happy, feeling energized, feeling stressed, worry, feeling lonely, and sleeping problems.Our adapted survey and recruitment procedure enabled 1059 persons with MID or low literacy skills to participate (T1: n=412, 38.9%; T2: n=351, 33.1%; and T3: n=296, 28%). They were significantly younger, had a lower level of education, and more often than not were born outside the Netherlands compared to the general population sample (P<.001). Approximately half of them (604/1059, 57.03%) received professional care. They displayed poorer mental health scores than the general population sample. The percentages of people with MID or low literacy skills who reported more negative feelings in T1 ranged from 20.6% (85/412) reporting feeling lonely often or almost always to 57.8% (238/412) reporting feeling happy almost never or sometimes. The general population sample's percentages were 5.4% (160/2930) and 32.2% (941/2918), respectively. Although scores improved over time in both populations, the disproportional effects remained.General COVID-19-related restrictions for the entire Dutch population affected people with MID or low literacy skills more negatively than the general population. Our study underscores the relevance of including these subpopulations in public health research because they are often overlooked in regular health data. An accessible web-based survey particularly targeted at this population enabled us to do so, and we reached a group of respondents significantly different from regular survey participants. This survey's results provided insights into the health of people with MID or low literacy skills and gained knowledge to be used by care organizations and policy makers to reduce health disparities during a pandemic and in general.
©Monique CJ Koks-Leensen, Anouk Menko, Fieke Raaijmakers, Gerdine AJ Fransen-Kuppens, Kirsten E Bevelander. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 30.05.2024.
Department of Primary and Community Care, Radboud university medical center, Nijmegen, Netherlands.Academic Collaborative Intellectual Disability and Health - Sterker op Eigen Benen (SOEB), Nijmegen, Netherlands.
Department of Primary and Community Care, Radboud university medical center, Nijmegen, Netherlands.Academic Collaborative AMPHI - Integrated Health Policy, Nijmegen, Netherlands.
Department of Primary and Community Care, Radboud university medical center, Nijmegen, Netherlands.Academic Collaborative AMPHI - Integrated Health Policy, Nijmegen, Netherlands.Safety and Health Region Gelderland-Midden, Arnhem, Netherlands.
Department of Primary and Community Care, Radboud university medical center, Nijmegen, Netherlands.Academic Collaborative AMPHI - Integrated Health Policy, Nijmegen, Netherlands.Municipal Health Service Gelderland Zuid, Nijmegen, Netherlands.
Department of Primary and Community Care, Radboud university medical center, Nijmegen, Netherlands.Academic Collaborative Intellectual Disability and Health - Sterker op Eigen Benen (SOEB), Nijmegen, Netherlands.Academic Collaborative AMPHI - Integrated Health Policy, Nijmegen, Netherlands.
JMIR Public Health Surveill. 2024-05-30;10():e44827.
An Accessible Web-Based Survey to Monitor the Mental Health of People With Mild Intellectual Disability or Low Literacy Skills During the COVID-19 Pandemic: Comparative Data Analysis.

This research aims to develop and assess the anti-arthritic properties of a topically herbal gel including leaf extracts from Cardiospermum halicacabum and Ricinus communis L. in rats. Utilizing gelling agents carbopol 940 (2.5, 5, 7.5 g), nine herbal gel compositions were created. Prepared formulations were then assessed for physical appearance, spreadability, viscosity, net content, pH, extrudability, in vitro diffusion profile, and main skin irritant tests. According to the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) recommendations, the stability research for the topical herbal gel composition was completed, and Freund's Complete Adjuvant (FCA) induced arthritis technique was used to assess the anti-arthritic efficacy. Additional procedures included measuring the body weight, paw volume, biochemical and hematological variables, histological analysis, and in vitro serum biomarker detection. The prepared gels followed the instructions and were uniform and stable. F5 performed better than the other compositions in terms of release kinetics (97.20%). The gel proved safe and non-toxic since no erythema or edema was seen during the skin irritation test. Comparing the herbal gel F5 comprising carbopol 940 to rats with arthritis, the topical treatment showed considerable (p < .001) anti-arthritic effect. The anti-arthritic action of the gel formulations was confirmed by decreased paw volume, absence of agglutination in reacting protein and rheumatic factor, a decline in TNFα level, restoration to baseline biochemical and hematological characteristics, decrease in thymus and spleen weight, and histopathological study.
Department of Pharmaceutics, ShriRam College of Pharmacy, Banmore, India.
Department of Pharmacognosy, ShriRam College of Pharmacy, Banmore, India.
Design, optimization, and evaluation of topical gel of Cardiospermum halicacabum and Ricinus communis L. leaves extract for the treatment of rheumatoid arthritis.

Tight junctions are a barrier-forming cell-cell adhesion complex and have been proposed to regulate cell proliferation. However, the underlying mechanisms are not well understood. Here, we used cells deficient in the junction scaffold ZO-1 alone or together with its paralog ZO-2, which disrupts the junctional barrier. We found that ZO-1 knockout increased cell proliferation, induced loss of cell density-dependent proliferation control, and promoted apoptosis and necrosis. These phenotypes were enhanced by double ZO-1/ZO-2 knockout. Increased proliferation was dependent on two transcriptional regulators: YAP and ZONAB. ZO-1 knockout stimulated YAP nuclear translocation and activity without changes in Hippo-dependent phosphorylation. Knockout promoted TANK-binding kinase 1 (TBK1) activation and increased expression of the RhoA activator GEF-H1. Knockdown of ZO-3, another paralog interacting with ZO1, was sufficient to induce GEF-H1 expression and YAP activity. GEF-H1, TBK1, and mechanotransduction at focal adhesions were found to cooperate to activate YAP/TEAD in ZO-1-deficient cells. Thus, ZO-1 controled cell proliferation and Hippo-independent YAP activity by activating a GEF-H1- and TBK1-regulated mechanosensitive signalling network.
UCL Institute of Ophthalmology, University College London, London EC1V 9EL, UK.
ZO-1 Regulates Hippo-Independent YAP Activity and Cell Proliferation via a GEF-H1- and TBK1-Regulated Signalling Network.

The human respiratory system is susceptible to a variety of diseases, ranging from chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis to acute respiratory distress syndrome (ARDS). Today, lung diseases represent one of the major challenges to the health care sector and represent one of the leading causes of death worldwide. Current treatment options often focus on managing symptoms rather than addressing the underlying cause of the disease. The limitations of conventional therapies highlight the urgent clinical need for innovative solutions capable of repairing damaged lung tissue at a fundamental level. Pluripotent stem cell technologies have now reached clinical maturity and hold immense potential to revolutionize the landscape of lung repair and regenerative medicine. Meanwhile, human embryonic (HESCs) and human-induced pluripotent stem cells (hiPSCs) can be coaxed to differentiate into lung-specific cell types such as bronchial and alveolar epithelial cells, or pulmonary endothelial cells. This holds the promise of regenerating damaged lung tissue and restoring normal respiratory function. While methods for targeted genetic engineering of hPSCs and lung cell differentiation have substantially advanced, the required GMP-grade clinical-scale production technologies as well as the development of suitable preclinical animal models and cell application strategies are less advanced. This review provides an overview of current perspectives on PSC-based therapies for lung repair, explores key advances, and envisions future directions in this dynamic field.
Leibniz Research Laboratories for Biotechnology and Artificial Organs, Lower Saxony Center for Biomedical Engineering, Implant Research and Development /Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.REBIRTH-Research Center for Translational and Regenerative Medicine, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.Biomedical Research in End-stage and Obstructive Lung Disease (BREATH), Member of the German Center for Lung Research (DZL), Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
Unlocking the Future: Pluripotent Stem Cell-Based Lung Repair.

Giant ichthyosaurs with body length estimates exceeding 20 m were present in the latest Triassic of the UK. Here we report on the discovery of a second surangular from the lower jaw of a giant ichthyosaur from Somerset, UK. The new find is comparable in size and morphology to a specimen from Lilstock, Somerset, described in 2018, but it is more complete and better preserved. Both finds are from the uppermost Triassic Westbury Mudstone Formation (Rhaetian), but the new specimen comes from Blue Anchor, approximately 10 km west along the coast from Lilstock. The more complete surangular would have been >2 m long, from an individual with a body length estimated at ~25 m. The identification of two specimens with the same unique morphology and from the same geologic age and geographic location warrants the erection of a new genus and species, Ichthyotitan severnensis gen. et sp. nov. Thin sections of the new specimen revealed the same histological features already observed in similar giant ichthyosaurian specimens. Our data also supports the previous suggestion of an atypical osteogenesis in the lower jaws of giant ichthyosaurs. The geological age and giant size of the specimens suggest shastasaurid affinities, but the material is too incomplete for a definitive referral. Ichthyotitan severnensis gen. et sp. nov., is the first-named giant ichthyosaur from the Rhaetian and probably represents the largest marine reptile formally described.
Copyright: © 2024 Lomax et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Palaeobiology Research Group, School of Earth Sciences, University of Bristol, Bristol, United Kingdom.Department of Earth and Environmental Sciences, The University of Manchester, Manchester, United Kingdom.
The Etches Collection - Museum of Jurassic Marine Life, Dorset, United Kingdom.
Paleontology division, Institute of Geosciences, University of Bonn, Bonn, Germany.
Dinosaurs Will Always Be Awesome, DWABA Museum, Orlando, Florida, United States of America.
The last giants: New evidence for giant Late Triassic (Rhaetian) ichthyosaurs from the UK.

In recent years, mouse nerve growth factor (mNGF) has emerged as an important biological regulator to repair peripheral nerve injury, but its systemic application is restricted by low efficiency and large dosage requirement. These limitations prompted us to search for biomaterials that can be locally loaded. Oxidized sodium alginate hydrogel (OSA) exhibits good biocompatibility and physicochemical properties, and can be loaded with drugs to construct a sustained-release system that can act locally on nerve injury. Here, we constructed a sustained-release system of OSA-mouse nerve growth factor (mNGF), and investigated the loading and release of the drug through Fourier transform infrared spectroscopy and drug release curves. In vitro and in vivo experiments showed that OSA-mNGF significantly promoted the biological activities of RSC-96 cells and facilitated the recovery from sciatic nerve crush injury in rats. This observation may be attributed to the additive effect of OSA on promoting Schwann cell biological activities or its synergistic effect of cross-activating phosphoinositide 3-kinase (PI3K) through extracellular signal regulated kinase (ERK) signaling. Although the specific mechanism of OSA action needs to be explored in the future, the current results provide a valuable preliminary research basis for the clinical application of the OSA-mNGF sustained-release system for nerve repair.
Medical College, First Affiliated Hospital of Harbin Medical University, Harbin, China.
School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
Oxidized sodium alginate hydrogel-mouse nerve growth factor sustained release system promotes repair of peripheral nerve injury.

Southeast Asia Tobacco Control Alliance, Bangkok, Thailand mary.assunta@cancer.org.au.Advocacy at Global Center for Good Governance in Tobacco Control, Bangkok, Thailand.
Tobacco Control Research Group at the University of Bath, Bath, UK.
Ensuring a safe, tobacco free future for the young: protecting children from tobacco industry interference.

Cerebral palsy (CP) affects body posture and movement coordination and is the most common cause of severe disability in the pediatric population. The diagnosis of CP is not a description of a person's functioning or interaction with their environment. Therefore, the diagnosis should be complemented with a description of functioning, using tools based on the biopsychosocial model proposed by the World Health Organization's International Classification of Functioning, Disability and Health (ICF). This report describes the preliminary data from a multicenter study conducted in Argentina with the aim of standardizing the description of the profiles of functioning of children and adolescents with CP. These data showed that the participants had some skills in sleep functions, mental functions of language, seeing functions, and in some environmental factors. They showed significant difficulties in categories such as maintaining body position, walking, and toileting.
Institute for Research in Health Sciences (Instituto de Investigaciones en Ciencias de la Salud, INICSA)-National Scientific and Technical Research Council (Consejo Nacional de Investigaciones Científicas y Técnicas, CONICET), School of Medical Sciences, Universidad Nacional de Córdoba, Córdoba, Argentina.
Division of Medical Sciences, University of Victoria, British Columbia, Canada.
La parálisis cerebral (PC) afecta la postura y la coordinación del movimiento, y es la causa más común de discapacidad grave en la población pediátrica. El diagnóstico de PC no describe el funcionamiento ni la interacción de la persona con el contexto en el cual se desarrolla. Por lo tanto, el diagnóstico se debe complementar con una descripción del funcionamiento, utilizando herramientas basadas en el modelo biopsicosocial de la Clasificación del Funcionamiento (CIF) de la Organización Mundial de la Salud (OMS). En esta comunicación, describimos los datos preliminares de un estudio multicéntrico en Argentina destinado a estandarizar la descripción del perfil de funcionamiento en niños y adolescentes con PC. Estos datos mostraron que los participantes tienen algunas habilidades en las funciones del sueño, las funciones mentales del lenguaje y las visuales, así como en algunas relacionadas con el contexto. Presentan dificultades importantes en categorías tales como mantener la posición del cuerpo, el andar y la higiene.
Profiles of functioning of a group of children with cerebral palsy in Argentina: Preliminary data from the first national study.

Titanium (Ti) implants are widely used in orthopedic and dental applications due to their excellent biocompatibility and mechanical properties. However, bacterial adhesion and subsequent biofilm formation on implant surfaces pose a significant risk of postoperative infections and complications. Conventional surface modifications often lack long-lasting antibacterial efficacy, necessitating the development of novel coatings with enhanced antimicrobial properties. This study aims to develop a novel Ag-TiO2-OTS (Silver-Titanium dioxide-Octadecyltrichlorosilane, ATO) nanocomposite coating, through a chemical plating method. By employing a 'resist-killing-disintegrate' approach, the coating is designed to inhibit bacterial adhesion effectively, and facilitate pollutant removal with lasting effects. Characterization of the coatings was performed using spectroscopy, electron microscopy, and contact angle analysis. Antibacterial efficacy, quantitatively evaluated against E. coli and S. aureus over 168 h, showed a significant reduction in bacterial adhesion by 76.6% and 66.5% respectively, and bacterial removal rates were up to 83.8% and 73.3% in comparison to uncoated Ti-base material. Additionally, antibacterial assays indicated that the ratio of the Lifshitz-van der Waals apolar component to electron donor surface energy components significantly influences bacterial adhesion and removal, underscoring a tunable parameter for optimizing antibacterial surfaces. Biocompatibility assessments with the L929 cell line revealed that the ATO coatings exhibited excellent biocompatibility, with minimal cytotoxicity and no significant impact on cell proliferation or apoptosis. The ATO coatings provided a multi-functionality surface that not only resists bacterial colonization but also possesses self-cleaning capabilities, thereby marking a substantial advancement in the development of antibacterial coatings for medical implants.
Department of Chemical Biology, School of Pharmaceutical Science, Capital Medical University, Beijing, China.
Department of Beijing Anding Hospital, Capital Medical University, Beijing, China.
NMPA Key Laboratory for Quality Monitoring of Narcotic Drugs and Psychotropic Substances, Chongqing Institute for Food and Drug Control, Chongqing, China.
Chongqing Zhengbo Biotech Ltd, Chongqing, China.
Chongqing Nankai Secondary School, Chongqing, China.
Department of Chemical Biology, School of Pharmaceutical Science, Capital Medical University, Beijing, China.Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, China.
Enhancing antibacterial properties of titanium implants through a novel Ag-TiO2-OTS nanocomposite coating: a comprehensive study on resist-killing-disintegrate approach.

Determining the underlying etiology of acute vertebrobasilar artery occlusion (VBAO) is crucial for selecting an appropriate treatment approach. The authors aimed to investigate the distribution of etiology and the association with functional outcomes in patients with acute VBAO who underwent endovascular treatment in which atherosclerosis, small-vessel disease, cardiac pathology, other causes, and dissection (ASCOD) phenotyping was used.A retrospective study was conducted at 21 centers in China, involving patients with VBAO who received endovascular treatment within 24 hours of the estimated occlusion time. In the ASCOD phenotyping, each phenotype is graded based on the following categories: 1, likely to be causal; 2, uncertain if causal; and 3, unlikely to be causal. The authors defined a single possible cause as a cause graded 1 in a single domain, and multiple possible causes were graded 1 or 2 regardless of overlap. The primary outcome was unfavorable outcome (modified Rankin Scale [mRS] score of 3-6) at 90 days. The secondary outcomes included shift of mRS score at 90 days, 90-day mortality, successful reperfusion, and National Institutes of Health Stroke Scale score at 24 hours. Multivariable regression analysis was used to assess the association between etiological subtypes and functional outcomes. Multivariate competing-risk regression analysis was performed to analyze the association between etiological subtypes and the risk of recurrent stroke.A total of 577 patients were included in this study. Of these, 521 (90%) had a single possible cause. The most common etiology was A1 (382 cases, 73%), followed by C1 (111 cases, 21%) and O1 (28 cases, 5%-in this study the other causes and dissection subtypes were categorized under the umbrella term of O causes). Similar patterns were observed in the multiple possible causes. In the baseline characteristics of the cohort, as rescue therapy, stenting was more frequently used in patients in the A1 group than in the C1 group (53.2% vs 41.7%; p < 0.01). The proportion of atherosclerosis-type etiology increased when the occlusion was located more proximally (p < 0.01). Compared to the A1 group, patients in the C1 group had a lower incidence of unfavorable outcome (OR 0.42, 95% CI 0.24-0.73), which was less likely to shift to a worse mRS score (OR 0.60, 95% CI 0.39-0.91). The O1 subtype was not associated with unfavorable outcome (OR 1.35, 95% CI 0.46-4.01), whereas patients with the O1 subtype were more likely to shift to worse mRS score (OR 2.39, 95% CI 1.09-5.25) and to have a higher 90-day mortality rate (OR 2.60, 95% CI 1.07-6.31). Furthermore, there was no significant association between single etiological subtypes and stroke recurrence within 1 year.The most common etiology in patients with VBAO was atherosclerosis, followed by cardiac pathology and other. Compared to the A1 subgroup, the C1 subgroup showed better functional outcomes, whereas the O1 subgroup showed worse outcomes. Additionally, there was no statistically significant difference in the recurrence risk.
1Graduate School of Bengbu Medical University, Bengbu, Anhui, China.
2Department of Neurology, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of the University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
3Department of Neurology, The Second Hospital of Weinan, Shanxi, China.
4Department of Neurology, Lu'an Fourth People's Hospital, Anhui, China.
5Department of Neurology, Hospital of Traditional Chinese Medicine of Feidong, Hefei, Anhui, China.
6Department of Neurology, The Affiliated Ganzhou Hospital of Nanchang University, Ganzhou, Jiangxi, China.
7Department of Neurology, The Second People's Hospital of Huoqiu County, Lu' an, Anhui, China; and.
8Department of Neurology, The First Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
1Graduate School of Bengbu Medical University, Bengbu, Anhui, China.2Department of Neurology, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of the University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
ASCOD phenotyping of acute vertebrobasilar artery occlusion treated by mechanical thrombectomy: insight from the PERSIST registry.

The aim of this study was to compare the outcomes of early (≤ 90 days) and delayed (> 90 days) cranioplasty following decompressive craniectomy (DC) in patients with traumatic brain injury (TBI).The authors analyzed participants enrolled in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) and the Neurotraumatology Quality Registry (Net-QuRe) studies who were diagnosed with TBI and underwent DC and subsequent cranioplasty. These prospective, multicenter, observational cohort studies included 5091 patients enrolled from 2014 to 2020. The effect of cranioplasty timing on functional outcome was evaluated with multivariable ordinal regression and with propensity score matching (PSM) in a sensitivity analysis of functional outcome (Glasgow Outcome Scale-Extended [GOSE] score) and quality of life (Quality of Life After Brain Injury [QOLIBRI] instrument) at 12 months following DC.Among 173 eligible patients, 73 (42%) underwent early cranioplasty and 100 (58%) underwent delayed cranioplasty. In the ordinal logistic regression and PSM, similar 12-month GOSE scores were found between the two groups (adjusted odds ratio [aOR] 0.87, 95% CI 0.61-1.21 and 0.88, 95% CI 0.48-1.65, respectively). In the ordinal logistic regression, early cranioplasty was associated with a higher risk for hydrocephalus than that with delayed cranioplasty (aOR 4.0, 95% CI 1.2-16). Postdischarge seizure rates (early cranioplasty: aOR 1.73, 95% CI 0.7-4.7) and QOLIBRI scores (β -1.9, 95% CI -9.1 to 9.6) were similar between the two groups.Functional outcome and quality of life were similar between early and delayed cranioplasty in patients who had undergone DC for TBI. Neurosurgeons may consider performing cranioplasty during the index admission (early) to simplify the patient's chain of care and prevent readmission for cranioplasty but should be vigilant for an increased possibility of hydrocephalus. Clinical trial registration nos.: CENTER-TBI, NCT02210221 (clinicaltrials.gov); Net-QuRe, NTR6003 (trialsearch.who.int) and NL5761 (onderzoekmetmensen.nl).
1University Neurosurgical Center Holland, Leiden University Medical Center, Haaglanden Medical Center and Haga Teaching Hospital, Leiden and The Hague, The Netherlands.
2Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge and Addenbrooke's Hospital, Cambridge, United Kingdom.3Neurocenter, Department of Neurosurgery and Research Unit of Clinical Neuroscience, Neurosurgery, Oulu University Hospital and University of Oulu, Finland.
4Department of Neurosurgery, University of California, San Francisco, California.
2Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge and Addenbrooke's Hospital, Cambridge, United Kingdom.
5Department of Neurosurgery, University Hospital Leuven, Belgium.
6Department of Neurosurgery, University Hospital Heidelberg, Germany.
7Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands.
8Department of Neurosurgery, Antwerp University Hospital, Edegem, Belgium.9Department of Translational Neuroscience, Faculty of Medicine and Health Sciences, University of Antwerp, Belgium.
10Neurocenter, Department of Neurosurgery and Turku Brain Injury Center, Turku University Hospital and University of Turku, Finland; and.
1University Neurosurgical Center Holland, Leiden University Medical Center, Haaglanden Medical Center and Haga Teaching Hospital, Leiden and The Hague, The Netherlands.11Department of Surgery, Division of Neurosurgey, QEII Health Sciences Center and Dalhousie University, Halifax, Nova Scotia, Canada.
for the CENTER-TBI Participants and Investigators
Early versus delayed cranioplasty after decompressive craniectomy in traumatic brain injury: a multicenter observational study within CENTER-TBI and Net-QuRe.

Curcuma longa L. and Plumbago zeylanica L. are renowned for their antioxidant, anti-inflammatory, and wound-healing properties, primarily attributed to their polyphenolic compounds. However, the limited water solubility of these compounds poses challenges to their effective utilization. Encapsulation within phytosomes offers a solution by enhancing bioavailability and permeability. This study aimed to formulate a phytosome-based polyherbal gel incorporating methanolic extracts of P. zeylanica and C. longa to explore its potential in wound healing. Methanolic extracts of P. zeylanica roots and C. longa rhizomes were encapsulated in phytosomes using the lipid film hydration technique. Various phytosome formulations were developed and characterized for encapsulation efficiency, particle size, polydispersity index and zeta potential. The optimized phytosomal dispersion (F7) was integrated into a carbopol-based hydrogel matrix. In vitro release studies demonstrated prolonged release compared to conventional forms. Stability testing confirmed the robustness of the phytosomal gel at 4 °C/60 ± 5% RH. Wound healing activity was assessed using an excision wound model. The phytosomal gel exhibited enhanced wound contraction and reduced epithelization time compared to conventional gel and control groups, signifying its potent wound-healing effect. In conclusion, the polyherbal phytosomal gel, incorporating P. zeylanica and C. longa, holds promise in promoting wound healing, presenting a novel and effective approach in the realm of topical formulations for wound care.
Faculty of Pharmacy, Integral University, Lucknow, India.Harsha Institute of Pharmacy, Lucknow, India.
Faculty of Pharmacy, Integral University, Lucknow, India.
Lovely Professional University, Phagwara, Panjab, India.
Hygia Institute of Pharmaceutical Education and Research, Lucknow, India.
Development and efficacy assessment of polyherbal phytosomal gel for accelerated wound healing.
The purpose of this study is to establish a deep learning automatic assistance diagnosis system for benign and malignant classification of mediastinal lesions in endobronchial ultrasound (EBUS) images. EBUS images are in the form of video and contain multiple imaging modes. Different imaging modes and different frames can reflect the different characteristics of lesions. Compared with previous studies, the proposed model can efficiently extract and integrate the spatiotemporal relationships between different modes and does not require manual selection of representative frames. In recent years, Vision Transformer has received much attention in the field of computer vision. Combined with convolutional neural networks, hybrid transformers can also perform well on small datasets. This study designed a novel deep learning architecture based on hybrid transformer called TransEBUS. By adding learnable parameters in the temporal dimension, TransEBUS was able to extract spatiotemporal features from insufficient data. In addition, we designed a two-stream module to integrate information from three different imaging modes of EBUS. Furthermore, we applied contrastive learning when training TransEBUS, enabling it to learn discriminative representation of benign and malignant mediastinal lesions. The results show that TransEBUS achieved a diagnostic accuracy of 82% and an area under the curve of 0.8812 in the test dataset, outperforming other methods. It also shows that several models can improve performance by incorporating two-stream module. Our proposed system has shown its potential to help physicians distinguishing benign and malignant mediastinal lesions, thereby ensuring the accuracy of EBUS examination.
Department of Medicine, National Taiwan University Cancer Center, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Department of Department of Mechanical Engineering, College of Engineering, National Yang Ming Chiao Tung University, Hsin-Chu, Taiwan.
Department of Department of Mechanical Engineering, College of Engineering, National Yang Ming Chiao Tung University, Hsin-Chu, Taiwan. Electronic address: stanley021039@gmail.com.
Department of Department of Mechanical Engineering, College of Engineering, National Yang Ming Chiao Tung University, Hsin-Chu, Taiwan.
Department of Medicine, National Taiwan University Cancer Center, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Biomedical Park Hospital, Hsin-Chu County, 302, Taiwan.
Department of Department of Mechanical Engineering, College of Engineering, National Yang Ming Chiao Tung University, Hsin-Chu, Taiwan. Electronic address: yccheng@nycu.edu.tw.
TransEBUS: The interpretation of endobronchial ultrasound image using hybrid transformer for differentiating malignant and benign mediastinal lesions.
Alopecia areata (AA) is a chronic autoimmune disease characterized by bald patches in certain areas of the body, especially the scalp. Minoxidil (MNX), as a first-line treatment of AA, effectively induces hair growth. However, oral and topical administration pose problems, including low bioavailability, risk of uncontrolled hair growth, and local side effects such as burning hair loss, and scalp irritation. In the latest research, MNX was delivered to the skin via microneedle (MN) transdermally. The MNX concentration was distributed throughout the needle so that drug penetration was reduced and had the potential to irritate. In this study, we formulated MNX into three-layer dissolving microneedles (TDMN) to increase drug penetration and avoid irritation. Physicochemical evaluation, parafilm, was used to evaluate the mechanical strength of TDMN and showed that TDMN could penetrate the stratum corneum. The ex-vivo permeation test showed that the highest average permeation result was obtained for TDMN2, namely 165.28 ± 31.87 ug/cm2, while for Minoxidil cream it was 46.03 ± 8.5 ug/cm2. The results of ex vivo and in vivo dermatokinetic tests showed that the amount of drug concentration remaining in the skin from the TDMN2 formula was higher compared to the cream preparation. The formula developed has no potential for irritation and toxicity based on the HET-CAM test and hemolysis test. TDMN is a promising alternative to administering MNX to overcome MNX problems and increase the effectiveness of AA therapy.
Faculty of Pharmacy, Hasanuddin University, Makassar, Indonesia.
Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.
Trilayer dissolving microneedle for transdermal delivery of minoxidil: a proof-of-concept study.
This study was conducted to investigate the impact of antiplatelet administration in the periprocedural period on the occurrence of thromboembolic complications (TECs) in patients undergoing treatment using the Woven EndoBridge (WEB) device for intracranial wide-necked bifurcation aneurysms. The primary objective was to assess whether the use of antiplatelets in the pre- and postprocedural phases reduces the likelihood of developing TECs, considering various covariates.A retrospective multicenter observational study was conducted within the WorldWideWEB Consortium and comprised 38 academic centers with endovascular treatment capabilities. Univariable and multivariable logistic regression analyses were performed to determine the association between antiplatelet use and TECs, adjusting for covariates. Missing predictor data were addressed using multiple imputation.The study comprised two cohorts: one addressing general thromboembolic events and consisting of 1412 patients, among whom 103 experienced TECs, and another focusing on symptomatic thromboembolic events and comprising 1395 patients, of whom 50 experienced symptomatic TECs. Preprocedural antiplatelet use was associated with a reduced likelihood of overall TECs (OR 0.32, 95% CI 0.19-0.53, p < 0.001) and symptomatic TECs (OR 0.49, 95% CI 0.25-0.95, p = 0.036), whereas postprocedural antiplatelet use showed no significant association with TECs. The study also revealed additional predictors of TECs, including stent use (overall: OR 4.96, 95% CI 2.38-10.3, p < 0.001; symptomatic: OR 3.24, 95% CI 1.26-8.36, p = 0.015), WEB single-layer sphere (SLS) type (overall: OR 0.18, 95% CI 0.04-0.74, p = 0.017), and posterior circulation aneurysm location (symptomatic: OR 18.43, 95% CI 1.48-230, p = 0.024).The findings of this study suggest that the preprocedural administration of antiplatelets is associated with a reduced likelihood of TECs in patients undergoing treatment with the WEB device for wide-necked bifurcation aneurysms. However, postprocedural antiplatelet use did not show a significant impact on TEC occurrence.
1Division of Diagnostic and Therapeutic Neuroradiology, Department of Radiology, St. Michael's Hospital, University of Toronto, Ontario, Canada.
2Department of Neurosurgery and Interventional Neuroradiology, Louisiana State University, Shreveport, Louisiana.
3Neuroendovascular Program, Massachusetts General Hospital and Brigham and Women's Hospital, Harvard University, Boston, Massachusetts.
4Ankara University, Medical Faculty, Department of Radiology, Ankara, Turkey.
6Service de Neuroradiologie Diagnostique et Thérapeutique, Centre Hospitalier de Toulouse, Hôpital Purpan, Toulouse, France.
7Service de Neuroradiologie Interventionnelle, Hôpital Universitaire Erasme, Bruxelles, Belgique.
8Interventistica Neurovascolare, Ospedale Careggi di Firenze, Florence, Italy.
9Neurosurgery & Interventional Neuroradiology, NewYork-Presbyterian Hospital, Weill Cornell School of Medicine, New York, New York.
10Service de radiodiagnostic et radiologie interventionnelle, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
11Department of Neurosurgery, Thomas Jefferson University, Philadelphia, Pennsylvania.
12Département de Neuroradiologie, Hôpital Pitié-Salpêtrière, Université Sorbonne, Paris, France.
13Sektion Vaskuläre und Interventionelle Neuroradiologie, Universitätsklinikum Heidelberg, Germany.
14Department of Neurosurgery, Christian Doppler University Hospital and Institute of Neurointervention, Paracelsus Medical University, Salzburg, Austria.
Departments of15Radiology and.39Neurosurgery, NYU Langone Health Center, New York, New York.
16Department of Neurosurgery, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania.
17Equipo de Neurocirugía Endovascular y Radiología Intervencionista, Clínica La Sagrada Familia, Buenos Aires, Argentina.
18Department of Neurosurgery, Orlando Health Neuroscience and Rehabilitation Institute, Orlando, Florida.
Departments of19Radiology and.40Neurosurgery, Cooper University Health Care, Cooper Medical School of Rowan University, Camden, New Jersey.
20Department of Radiology, Subdivision of Interventional Neuroradiology, Clinical Hospital Center Sisters of Mercy, Zagreb, Croatia.
21Department of Neurosurgery, UTMB and Baylor School of Medicine, Houston, Texas.
22Department of Neurosurgery, Barrow Neurological Institute, Phoenix, Arizona.
23Department of Neurosurgery, State University of New York at Buffalo, New York.
Departments of5Radiology and.38Neurosurgery, Mayo Clinic, Rochester, Minnesota.
37Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital of the Ministry of Health, Ankara, Turkey.
24Department of Radiology, Interventional Radiology and Neurointerventional Services, Austin Health, Melbourne, Victoria, Australia.
Departments of25Neurosurgery and.41Radiology, Geisinger Hospital, Danville, Pennsylvania.
26Interventistica Neurovascolare, Ospedale Niguarda Cà Granda, Milano, Italy.
27Department of Neurointerventional Radiology, UMass Memorial Hospital, Worcester, Massachusetts.
28Interventistica Neurovascolare, Ospedale San Raffaele, Milano, Italy.
29Deparment of Neurosurgery, University of Miami, Florida.
30Department of Neuroscience, Valley Baptist Neuroscience Institute, Harlingen, Texas.
Departments of31Neurosurgery and.42Radiology, University of Alabama at Birmingham, Alabama.
32Department of Neuroradiology, University Hospital of Basel, Switzerland.
33Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Departments of34Radiology and.43Neurosurgery, Mayo Clinic, Jacksonville, Florida.
Departments of35Radiology.44Neurology, and.45Neurosurgery, University of Texas Health Science Center at Houston, Texas.
36Department of Neurological Surgery and Montefiore-Einstein Cerebrovascular Research Lab, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York; and.
Association of preprocedural antiplatelet use with decreased thromboembolic complications for intracranial aneurysms undergoing intrasaccular flow disruption.
The aim of this study was to develop and validate a predictive nomogram model for long-term rebleeding events in patients with hemorrhagic moyamoya disease (HMMD).In total, 554 patients with HMMD from the Fifth Medical Center of the Chinese PLA General Hospital (5-PLAGH cohort) were included and randomly divided into training (390 patients) and internal validation (164 patients) sets. An independent cohort from the First Medical Center and Eighth Medical Center of Chinese PLA General Hospital (the 1-PLAGH and 8-PLAGH cohort) was used for external validation (133 patients). Univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression algorithm were used to identify significant factors associated with rebleeding, which were used to develop a nomogram for predicting 5- and 10-year rebleeding.Intraventricular hemorrhage was the most common type of cerebral hemorrhage (39.0% of patients in the 5-PLAGH cohort and 42.9% of the 1-PLAGH and 8-PLAGH cohort). During the mean ± SD follow-up period of 10.4 ± 2.9 years, 91 (16.4%) patients had rebleeding events in the 5-PLAGH cohort. The rebleeding rates were 12.3% (68 patients) at 5 years and 14.8% (82 patients) at 10 years. Rebleeding events were observed in 72 patients (14.3%) in the encephaloduroarteriosynangiosis (EDAS) surgery group, whereas 19 patients (37.3%) experienced rebleeding events in the conservative treatment group. This difference was statistically significant (p < 0.001). We selected 4 predictors (age at onset, number of episodes of bleeding, posterior circulation involvement, and EDAS surgery) for nomogram development. The concordance index (C-index) values of the nomograms of the training cohort, internal validation cohort, and the external validation cohort were 0.767 (95% CI 0.704-0.830), 0.814 (95% CI 0.694-0.934), and 0.718 (95% CI 0.661-0.775), respectively. The nomogram at 5 years exhibited a sensitivity of 48.1% and specificity of 87.5%. The positive and negative predictive values were 38.2% and 91.3%, respectively. The nomogram at 10 years exhibited a sensitivity of 47.1% and specificity of 89.1%. The positive and negative predictive values were 48.5% and 88.5%, respectively.EDAS may prevent rebleeding events and improve long-term clinical outcomes in patients with HMMD. The nomogram accurately predicted rebleeding events and assisted clinicians in identifying high-risk patients and devising individual treatments. Simultaneously, comprehensive and ongoing monitoring should be implemented for specific patients with HMMD throughout their entire lifespan.
1Medical School of Chinese PLA, Beijing.2Department of Neurosurgery, The First Medical Centre, Chinese PLA General Hospital, Beijing.
3Department of Neurosurgery, The Eighth Medical Centre, Chinese PLA General Hospital, Beijing.
1Medical School of Chinese PLA, Beijing.
1Medical School of Chinese PLA, Beijing.4Department of Neurology, The First Medical Centre, Chinese PLA General Hospital, Beijing; and.
2Department of Neurosurgery, The First Medical Centre, Chinese PLA General Hospital, Beijing.5Department of Neurosurgery, The Fifth Medical Centre, Chinese PLA General Hospital, Beijing, China.
2Department of Neurosurgery, The First Medical Centre, Chinese PLA General Hospital, Beijing.
Development and validation of a novel nomogram for predicting long-term rebleeding risk among patients with hemorrhagic moyamoya disease: a 10-year multicenter retrospective cohort study.
Rheumatoid arthritis (RA) is an idiopathic and chronic autoimmune disease for which there are currently no effective treatments. Oxypeucedanin hydrate (OXH) is a natural coumarin known for its potent anti-inflammatory properties. However, further investigations are needed to determine its therapeutic efficacy in treating RA. In this study, we evaluate the anti-inflammatory activity of OXH by treating LPS-induced RAW264.7 macrophages. Our results show that OXH treatment reverses the changes in iNOS, COX-2, IL-1β, IL-6, and TNF-α levels. Additionally, OXH reduces ROS production. Further analysis reveals that OXH suppresses the activation of the NF-κB/MAPK pathway. CETSA results show that OXH competes with LPS for binding to the TLR4/MD2 complex. MST experiments demonstrate the specific affinity of OXH for the TLR4/MD2 complex, with a Kd value of 33.7 μM. Molecular docking analysis suggests that OXH binds to the pocket of the TLR4/MD2 complex and interacts with specific amino acids, such as GLY-343, LYS-388, and PHE-345. Molecular dynamics simulations further confirm this conclusion. Finally, we investigate the potential of OXH in treating RA using a collagen-induced arthritis (CIA) model in rats. OXH effectively ameliorates the symptoms of CIA, including improving body weight, reducing swelling and redness, increasing talus volume, and decreasing bone erosion. OXH also decreases the mRNA levels of pro-inflammatory factors in synovial tissue. Transcriptome enrichment analysis and western blot analysis confirm that OXH suppresses the NF-κB/MAPK pathway, which is consistent with our in vitro findings.
State Key Laboratory of Southwestern Chinese Medicine Resource, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
State Key Laboratory of Southwestern Chinese Medicine Resource, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.School of Basic Medical Science, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
School of Medicine, Tsinghua University, Beijing 100084, China.
Syngenta Jealott's Hill International Research Centre, Berkshire RG426EY, UK.
Oxypeucedanin hydrate alleviates rheumatoid arthritis by inhibiting the TLR4-MD2/NF-κB/MAPK signaling axis.
To determine whether professional self-perception of nurses in Mongolia improves following an educational intervention and to identify differences in scores among participant subgroups.A prospective observational pre-post design.Using a convenience sample of 67 nurses in Mongolia in 2019, the Nursing Professional Values Scale-3 instrument was used pre- and post-intervention. Independent and paired sample t-tests were conducted. Data were analysed using IBM SPSS 28.0.1.1 and Stata/SE 16.1. This study complied with the STROBE checklist.Of the 67 nurses, 92.0% were female, mean age was 32.15 years (SD 8.96), 70.0% held a bachelor's degree, 58.0% had 5 or more years' nursing experience and 51.0% were members of a professional nursing organization. After participating in the educational training, nurses reported higher overall professional self-perception as well as across subscales: activism, professionalism and caring.Considering the nursing shortage in lower-middle-income countries, it is important to recognise the influence of nurses' professional self-perception on nursing retention. This study highlights the significant role continuing educational opportunities play in increasing nurses' professional self-perception. It is imperative to explore ways of improving this perception and focusing on subgroups of nurses to help guide the use of limited resources. Further research is necessary to include nurses in other areas of Mongolia.Accurately assessing nursing professional self-perception and providing educational opportunities could improve nursing professional self-perception, nursing satisfaction, patient safety and nursing retention in lower-middle-income countries.What problem did the study address? This study meets the need for current study on the nursing professional self-perception of nursing from the perspective of nurses in Mongolia. It addresses the dangerous nursing shortage in Mongolia by determining if an educational intervention could improve nursing professional self-perception and thus improve nursing job satisfaction and retention. What were the main findings? Mongolian nurses in this study scored in the top quartile of the NPVS-3, indicating a baseline high NPSP. Educational intervention (including translated oral education and written clinical pathways) significantly improved the nurses' professional self-perception. Nurses were eager for training in other clinical and leadership topics. Where and on whom will the research have an impact? This research can be impactful for nurses, nurse leaders and policy makers in low- and lower-middle-income countries. Specifically for nurses in Mongolia, with increasing technologies and services such as cardiac catheterization laboratories becoming available, more education in these nursing specialty areas is imperative. Professional Nursing Organizations are poised to foster more educational offerings to their members and to increase membership. Nursing education provided by international volunteer nurses with Non-Governmental Organizations can improve NPSP in nurses in LMICs.This study complied with the STROBE checklist.No patient or public contribution.
Byrdine F. Lewis College of Nursing, Georgia State University, Atlanta, Georgia, USA.Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, Georgia, USA.
Shepherd Center V. Crawford Research Institute, Atlanta, Georgia, USA.Department of Sociology, Georgia State University, Atlanta, Georgia, USA.
Educational training and nursing professional self-perception in Mongolia: A prospective observational pre-post design study.
Biopolymers have the utmost significance in biomedical applications and blending synthetic polymers has shown favorable characteristics versus individual counterparts. The utilization of the blends can be restricted through the use of toxic chemical agents such as initiators or crosslinkers. In this regard, a chemical agent-free ionizing irradiation is a beneficial alternative for preparing the hydrogels for biomedical applications. In this study, carboxymethyl chitosan (CM-CS), guar gum (GG), and poly(vinylpyrrolidone) (PVP) based ternary blends (TB) were crosslinked using various doses of ionizing irradiation to fabricate hydrogels. The prepared hydrogels were characterized for physicochemical properties, swelling analysis, biological assays, and drug delivery applications. Swelling analysis in distilled water revealed that the hydrogels exhibit excellent swelling characteristics. An in vitro cytocompatibility assay showed that the hydrogels have greater than 90% cell viability for the human epithelial cell line and a decreasing cell viability trend for the human alveolar adenocarcinoma cell line. In addition, the prepared hydrogels possessed excellent antibacterial characteristics against gram-positive Staphylococcus aureus (S. aureus) and gram-negative Escherichia coli (E. coli). Finally, the release studies of anti-inflammatory Quercus acutissima (QA) loaded hydrogels exhibited more than 80% release in phosphate-buffered saline (pH = 7.4). These findings suggest that TB hydrogels can be used as suitable carrier media for different release systems and biomedical applications.
Advanced Radiation Technology Institute (ARTI), Korea Atomic Energy Research Institute, Jeongeup, Republic of Korea.Radiation Science and Technology, University of Science and Technology, Daejeon, Republic of Korea.School of Chemical Engineering, Yeungnam University, Gyeongsan, Republic of Korea.
Advanced Radiation Technology Institute (ARTI), Korea Atomic Energy Research Institute, Jeongeup, Republic of Korea.Department of Nuclear Engineering, Hanyang University, Seoul, Republic of Korea.
Inhalation Toxicology Centre for Airborne Risk Factor, Korea Institute of Toxicology, Jeongeup, Republic of Korea.
School of Chemical Engineering, Yeungnam University, Gyeongsan, Republic of Korea.Research Institute of Cell Culture, Yeungnam University, Gyeongsan, Republic of Korea.
Advanced Radiation Technology Institute (ARTI), Korea Atomic Energy Research Institute, Jeongeup, Republic of Korea.Radiation Science and Technology, University of Science and Technology, Daejeon, Republic of Korea.
Synthesis of carboxymethyl chitosan-guar gum-poly(vinylpyrrolidone) ternary blended hydrogels with antibacterial/anticancer efficacy and drug delivery applications.
A new doubly carboxylato-bridged Co(II) dinuclear complex, [Co(bdtbpza)(NCS)]2 (1), was obtained in a satisfactory yield by employing a 'scorpionate'-type precursor, bdtbpza {bis-(3,5-di-tert-butylpyrazol-1-yl)acetate}, and was then structurally characterized. Single-crystal X-ray diffraction analysis revealed that, in 1, each Co(II) is penta-coordinated, leading to a distorted trigonal-bipyramidal geometry within the coordination environment of N3O2. Weak antiferromagnetic coupling within the Co(II) ions in 1 was found based on the isotropic spin Hamiltonian H = -J(S1·S2) for the Si = 3/2 system. For evaluating the spin density distribution and the mechanism for the magnetic exchange coupling, DFT analysis was performed, with the calculated result agreeing the experimental magnetic data. A study into electrochemical H2 evolution, involving cyclic voltammetry (CV), controlled potential electrolysis (CPE), and gas chromatographic (GC) analyses of the graphite electrode modified with the cobalt complex in a neutral aqueous solution revealed the high catalytic activity of the complex with a low overpotential toward H2O reduction. The faradaic efficiency of the catalyst was found to be 83.7% and the di-cobalt catalyst-modified electrode displayed quite an interesting H2-evolution activity compared with that of bare electrodes. These results are encouraging for the future potential application of 1 in water splitting.
Department of Chemistry, University of Calcutta, 92 A.P.C. Road, Kolkata - 700009, India.Institute of Chemistry, Academia Sinica, Nankang - 115, Taipei, Taiwan. amitd_ju@yahoo.co.in.
Department of Chemistry, Bahir Dar University, P.O. Box 79, Bahir Dar, Ethiopia.Institute of Chemistry, Academia Sinica, Nankang - 115, Taipei, Taiwan. amitd_ju@yahoo.co.in.
Dipartimento di Scienze Chimiche, della Vita e della Sostenibilità Ambientale, Università degli Studi di Parma, Viale delle Scienze 17/A, 43124 Parma, Italy.
Dipartimento di Medicina, Chirurgia e Farmacia, Università di Sassari, Viale San Pietro, I-07100 Sassari, Italy.
Departament de Química Inorgànica i Orgànica, Secció Inorgànica and Institut de Nanociència i Nanotecnologia, Universitat de Barcelona, Martí i Franquès, 1-11, 08028-Barcelona, Spain.
Departament de Química, Universitat de les Illes Balears, Crta de Valldemossa km 7.5, 07122 Palma de Mallorca, Baleares, Spain.
Institute of Chemistry, Academia Sinica, Nankang - 115, Taipei, Taiwan. amitd_ju@yahoo.co.in.
Institute of Chemistry, Academia Sinica, Nankang - 115, Taipei, Taiwan. amitd_ju@yahoo.co.in.Department of Chemistry, National Changhua University of Education, Changhua - 50058, Taiwan.
Magnetic study and DFT analysis of a doubly carboxylato-bridged Co(II) derivative anchored with a 'scorpionate' precursor as a potential electrocatalyst for heterogeneous H2 evolution.
To assess efficacy of Chinese medicine (CM) on insomnia considering characteristics of treatment based on syndrome differentiation.A total of 116 participants aged 18 to 65 years with moderate and severe primary insomnia were randomized to the placebo (n=20) or the CM group (n=96) for a 4-week treatment and a 4-week follow-up. Three CM clinicians independently prescribed treatments for each patient based on syndromes differentiation. The primary outcome was change in total sleep time (TST) from baseline. Secondary endpoints included sleep onset latency (SOL), wake time after sleep onset (WASO), sleep efficiency, Pittsburgh Sleep Quality Index (PSQI) and CM symptoms.The CM group had an average 0.6 h more (95% confidence interval (CI): 0.3-0.9, P<0.001) TST and 34.1% (10.3%-58.0%, P=0.005) more patients beyond 0.5 h TST increment than that of the placebo group. PSQI was changed -3.3 (-3.8 to -2.7) in the CM group, a -2.0 (-3.2 to -0.8, P<0.001) difference from the placebo group. The CM symptom score in the CM group decreased -2.0 (-3.3 to -0.7, P=0.003) more than the placebo group. SOL and WASO changes were not significantly different between groups. The analysis of prescriptions by these clinicians revealed blood deficiency and Liver stagnation as the most common syndromes. Prescriptions for these clinicians displayed relative stability, while the herbs varied. All adverse events were mild and were not related to study treatment.CM treatment based on syndrome differentiation can increase TST and improve sleep quality of primary insomnia. It is effective and safe for primary insomnia. In future studies, the long-term efficacy validation and the exploratory of eutherapeutic clinicians' fixed herb formulas should be addressed (Registration No. NCT01613183).
© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.
International Acupuncture and Moxibustion Innovation Institute, School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, 100029, China.
Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China.
School of Computer and Information Technology, Beijing Jiaotong University, Beijing, 100044, China.
Beijing Xicheng District Community Healthcare Center, Beijing, 100120, China.
International Acupuncture and Moxibustion Innovation Institute, School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, 100029, China. yanshiyan@bucm.edu.cn.Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, China. yanshiyan@bucm.edu.cn.
China Academy of Chinese Medical Sciences, Beijing, 100700, China. liuby5505@139.com.
Efficacy of Chinese Medicine Treatment Based on Syndrome Differentiation for Primary Insomnia: A Randomized Placebo Controlled Triple-Blinded Trial.
The objective of this study is to create a nanoemulgel formulation of Ribociclib (RIBO), a highly selective inhibitor of CDK4/6 through the utilization of spontaneous emulsification method. An experimental investigation was conducted to construct pseudo-ternary phase diagram for the most favourable formulation utilizing rice bran oil, which is known for its diverse anticancer properties. The formulation consisted of varying combination of the surfactant and as the co-surfactant (Tween 80 and Transcutol, respectively) referred to as Smix and the trials were optimized to get the desired outcome. The nanoemulsion (NE) formulations that were developed exhibited a droplet size of 179.39 nm, accompanied with a PDI of 0.211. According to the data released by Opt-RIBO-NE, it can be inferred that the Higuchi model had the most favourable fit among many kinetics models considered. The results indicate that the use of nanogel preparations for the topical delivery of RIBO in breast cancer therapy, specifically RIBO-NE-G, is viable. This is supported by the extended release of the RIBO, and the appropriate level of drug permeation observed in Opt-RIBO-NE-G. Due to RIBO and Rice Bran oil, RIBO-NE-G had greater antioxidant activity, indicating its effectiveness as antioxidants. The stability of the RIBO-NE-G was observed over a period of three months, indicating a favourable shelf life. Therefore, this study proposes the utilization of an optimized formulation of RIBO-NE-G may enhance the efficacy of anticancer treatment and mitigate the occurrence of systemic side effects in breast cancer patients, as compared to the use of suspension preparation of RIBO.
Pharmacy Practice Research Unit, Department of Clinical Pharmacy, College of Pharmacy, Jazan University, Jazan, Saudi Arabia.
Department of Pharmaceutical Chemistry and Pharmacognosy, College of Pharmacy, Jazan University, Jazan, Saudi Arabia.
Fabrication and characterization of transdermal delivery of ribociclib nanoemulgel in breast cancer treatment.
Accurately predicting response during neoadjuvant chemoimmunotherapy for resectable non-small cell lung cancer remains clinically challenging. In this study, we investigated the effectiveness of blood-based tumor mutational burden (bTMB) and a deep learning (DL) model in predicting major pathologic response (MPR) and survival from a phase 2 trial.Blood samples were prospectively collected from 45 patients with stage IIIA (N2) non-small cell lung cancer undergoing neoadjuvant chemoimmunotherapy. An integrated model, combining the computed tomography-based DL score, bTMB, and clinical factors, was developed to predict tumor response to neoadjuvant chemoimmunotherapy.At baseline, bTMB were detected in 77.8% (35 of 45) of patients. Baseline bTMB ≥11 mutations/megabase was associated with significantly greater MPR rates (77.8% vs 38.5%, P = .042), and longer disease-free survival (P = .043), but not overall survival (P = .131), compared with bTMB <11 mutations/megabase in 35 patients with bTMB available. The developed DL model achieved an area under the curve of 0.703 in all patients. Importantly, the predictive performance of the integrated model improved to an area under the curve of 0.820 when combining the DL score with bTMB and clinical factors. Baseline circulating tumor DNA (ctDNA) status was not associated with pathologic response and survival. Compared with ctDNA residual, ctDNA clearance before surgery was associated with significantly greater MPR rates (88.2% vs 11.1%, P < .001) and improved disease-free survival (P = .010).The integrated model shows promise as a predictor of tumor response to neoadjuvant chemoimmunotherapy. Serial ctDNA dynamics provide a reliable tool for monitoring tumor response.
Copyright © 2024 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Pathology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
Department of Medicine, Amoy Diagnostics Co, Ltd, Xiamen, China.
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China. Electronic address: dpzhao@tongji.edu.cn.
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China. Electronic address: chenthoracic@163.com.
Predicting therapeutic response to neoadjuvant immunotherapy based on an integration model in resectable stage IIIA (N2) non-small cell lung cancer.
This study aims to evaluate the utility of F-18 FDG PET/CT in the non-invasive diagnosis of autoimmune pancreatitis (AIP) and differentiating it from pancreatic cancer (CaP) based on the amount and pattern of FDG uptake, as well as involvement of extra-pancreatic sites.A systematic search was conducted using PubMed, Scopus, Cochrane Library and Google Scholar. Only those studies that compared the findings of F-18 FDG PET/CT in terms of SUVmax, pattern of FDG uptake and presence of FDG-avid extra-pancreatic sites in both AIP and CaP were included. Studies were qualitatively assessed for risk of bias and publication bias. The diagnostic performance of parameters on PET/CT was examined through pooled sensitivity, specificity, diagnostic odd's ratio (DOR) and summary receiver operator characteristic (SROC) curve analysis.Six studies were included with a total of 580 patients. 178 patients had AIP (Age 18-90 years, male, M: female, F ratio-8.4:1) and 402 patients had CaP (Age 22-88 years, M:F ratio-1.5:1). Type of AIP was reported in only 3 studies, with the included cases predominantly being type 1 AIP. All studies were retrospective with heterogeneity and a risk on patient selection and index test. The FDG uptake, expressed as SUVmax, was lower in AIP with a weighted mean difference of -3.11 (95% confidence interval, CI: -5.28 to -0.94). To diagnose AIP, the pooled sensitivity, specificity and DOR of diffuse pattern of FDG uptake were 0.59 (95% CI: 0.51-0.66), 0.89 (95% CI: 0.86-0.92) and 21.07 (95% CI: 5.07-88.32), respectively, with an area under curve (AUC) of 0.717 on SROC analysis. The pooled sensitivity, specificity and DOR of FDG-avid extra pancreatic sites were 0.55 (95% CI: 0.45-0.65), 0.58 (95% CI: 0.52-0.64) and 2.33 (95% CI: 1.40-3.89), respectively, with an AUC of 0.632.On F-18 FDG PET/CT, a pancreatic lesion of AIP has a lower SUVmax value than CaP. A diffuse pattern of FDG uptake and presence of an extra-pancreatic FDG-avid site are nearly 21 times and twice more likely in AIP than CaP, respectively.
© 2024. The Author(s), under exclusive licence to The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.
Department of Nuclear Medicine, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India.
Department of Surgical Gastroenterology, All India Institute of Medical Sciences, Basni Industrial Area Phase 2, Jodhpur, Rajasthan, 342005, India. selvasriram87@gmail.com.
Department of Community and Family Medicine, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India.
Freelance Editor-Biological Sciences Journal, New Delhi, India.
Department of Surgical Gastroenterology, All India Institute of Medical Sciences, Basni Industrial Area Phase 2, Jodhpur, Rajasthan, 342005, India.
Diagnostic performance of F-18 FDG PET/CT in differentiating autoimmune pancreatitis from pancreatic cancer: a systemic review and meta-analysis.
Reproducible laboratory research relies on correctly identified reagents. We have previously described gene research papers with wrongly identified nucleotide sequence(s), including papers studying miR-145. Manually verifying reagent identities in 36 recent miR-145 papers found that 56% and 17% of papers described misidentified nucleotide sequences and cell lines, respectively. We also found 5 cell line identifiers in miR-145 papers with misidentified nucleotide sequences and cell lines, and 18 cell line identifiers published elsewhere, that did not represent indexed human cell lines. These 23 identifiers were described as non-verifiable (NV), as their identities were unclear. Studying 420 papers that mentioned 8 NV identifier(s) found 235 papers (56%) that referred to 7 identifiers (BGC-803, BSG-803, BSG-823, GSE-1, HGC-7901, HGC-803, and MGC-823) as independent cell lines. We could not find any publications describing how these cell lines were established. Six cell lines were sourced from cell line repositories with externally accessible online catalogs, but these cell lines were not indexed as claimed. Some papers also stated that short tandem repeat (STR) profiles had been generated for three cell lines, yet no STR profiles could be identified. In summary, as NV cell lines represent new challenges to research integrity and reproducibility, further investigations are required to clarify their status and identities.
© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.Sydney School of Veterinary Science, Faculty of Science, The University of Sydney, Sydney, New South Wales, Australia.
School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
Department of Chemical and Biological Engineering, Northwestern University, Evanston, Illinois, USA.
School of Chemistry, Faculty of Science, The University of Sydney, Sydney, New South Wales, Australia.
IRIT UMR 5505 CNRS, University of Toulouse, Toulouse, France.Institut Universitaire de France (IUF), Paris, France.
CNRS, Grenoble INP, Laboratoire d'Informatique de Grenoble, Université Grenoble Alpes, Grenoble, France.
CellBank Australia, Children's Medical Research Institute, The University of Sydney, Sydney, New South Wales, Australia.
Feinberg School of Medicine in the Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois, USA.The Potocsnak Longevity Institute, Northwestern University, Chicago, Illinois, USA.Simpson Querrey Lung Institute for Translational Science, Chicago, Illinois, USA.
School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.NSW Health Statewide Biobank, NSW Health Pathology, Sydney, New South Wales, Australia.
Misspellings or miscellings -Non-verifiable and unknown cell lines in cancer research publications.
Periodontitis is a common chronic inflammatory disease primarily caused by the prevalence of bacterial overgrowth resulting in the development of an inflammatory condition that destroys the tooth's supporting tissues and eventual tooth loss. Comparatively, to other treatment methods, it is difficult for topical antibacterial drugs to effectively permeate the biofilm's physical barrier, making conventional therapy for periodontitis more challenging. This novel study combines thermosensitive in situ hydrogel with microparticles (MPs) to enhance the targeted delivery of metronidazole (MET) to the periodontal pocket. Polycaprolactone (PCL) polymer was utilized to produce bacteria-sensitive MPs. Additionally, the study assessed the attributes of MPs and demonstrated an enhancement in the in vitro antibacterial efficacy of MPs towards Staphylococcus aureus (SA) and Escherichia coli (EC). Subsequently, we incorporated MET-MPs into thermosensitive in situ hydrogel formulations using chitosan. The optimized formulations exhibited stability, appropriate gelation temperature, mucoadhesive strength, and viscosity. In vitro permeation tests showed selective and prolonged drug release against SA and EC. Ex vivo experiments demonstrated no significant differences between in situ hydrogel containing pure MET and MET-MPs in biofilm quantity, bacterial counts, and metabolic activity in biofilms. According to in vitro tests and the effectiveness of the antibacterial activity, this study has exhibited a novel methodology for more efficacious therapies for periodontitis. This study aims to utilize MET in MPs to improve its effectiveness, enhance its antibacterial activity, and improve patient treatment outcomes. In further research, the efficacy of the treatment should be investigated in vivo using an appropriate animal model.
Department of Pharmacy, Faculty of Medicine and Health Sciences, Alauddin Islamic State University, Samata Gowa, Indonesia.
Department of Orthodontic, Faculty of Dentistry, Hasanuddin University, Makassar, Indonesia.
Department of Oral and Maxillofacial Radiology, Faculty of Dentistry, Hasanuddin University, Makassar, Indonesia.
Department of Oral Biology, Faculty of Dentistry, Hasanuddin University, Makassar, Indonesia.
Department of Periodontology, Faculty of Dentistry, Hasanuddin University, Makassar, Indonesia.
Veterinary Paramedic Study Program, Faculty of Vocational Study, Hasanuddin University, Makassar, Indonesia.
Department of Clinical Pharmacy and Therapeutics, Applied Science Private University, Amman, Jordan.
Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, Thailand.
Specific delivery of metronidazole using microparticles and thermosensitive in situ hydrogel for intrapocket administration as an alternative in periodontitis treatment.
Docetaxel (Doc), as a first-line chemotherapy drug for prostate cancer (PC), often loses its therapeutic efficacy due to acquired resistance and lack of targeting specificity. Therefore, there is a need to develop a novel drug that can overcome Doc resistance and enhance its targeting ability to inhibit PC progression. In this study, we prepared Au/Doc/Quer@PDA/A10-3.2 nanoparticles (NPs) composite drug by encapsulating Doc and quercetin (Quer) within polydopamine (PDA)-coated Au NPs and further modifying them with RNA oligonucleotide aptamer A10-3.2. A10-3.2 was used for specific targeting of prostate-specific membrane antigen (PSMA)-positive PC cells (LNCaP). Quer was employed to reverse the resistance of Doc-resistant cell line (LNCaP/R) to Doc. Physical characterization using ultraviolet-visible spectroscopy (UV-vis), transmission electron microscopy (TEM), dynamic light scattering (DLS), X-ray photoelectron spectroscopy (XPS), and Fourier-transform infrared spectroscopy (FTIR) confirmed the successful preparation of Au/Doc/Quer@PDA/A10-3.2 NPs. Fluorescence imaging and flow cytometry experiments demonstrated the targeting ability of Au/Doc/Quer@PDA/A10-3.2 NPs towards PSMA-positive LNCaP/R cells. Cell proliferation, apoptosis, invasion, and migration experiments revealed that Quer reversed the resistance of LNCaP/R cells to Doc. Immunoblotting experiments further confirmed the mechanism behind sensitization of chemotherapy by Quer. Finally, we evaluated the therapeutic efficacy of Au/Doc/Quer@PDA/A10-3.2 NPs in a mouse model of PC. In conclusion, this study synthesized and validated a novel nano-composite drug (Au/Doc/Quer@PDA/A10-3.2 NPs) for combating Doc-resistant PC, which could potentially be applied in clinical treatment of PC.
Urology Department, Lishui City People's Hospital; Postgraduate training base Alliance of Wenzhou Medical University (Lishui City People's Hospital), Lishui City, Zhejiang Province, China.
Au/Doc/Quer@PDA/A10-3.2 Nanoparticles for targeted treatment of docetaxel-resistant prostate cancer.
This study aims to develop a digital twin (DT) framework to enhance adaptive proton stereotactic body radiation therapy (SBRT) for prostate cancer. Prostate SBRT has emerged as a leading option for external beam radiotherapy due to its effectiveness and reduced treatment duration. However, interfractional anatomy variations can impact treatment outcomes. This study seeks to address these uncertainties using DT concept, with the goal of improving treatment quality, potentially revolutionizing prostate radiotherapy to offer personalized treatment solutions. Our study presented a pioneering approach that leverages DT technology to enhance adaptive proton SBRT. The framework improves treatment plans by utilizing patient-specific CTV setup uncertainty, which is usually smaller than conventional clinical setups. This research contributes to the ongoing efforts to enhance the efficiency and efficacy of prostate radiotherapy, with ultimate goals of improving patient outcomes and life quality.
Adaptive Proton Therapy Using CBCT-Guided Digital Twins.
Nanoparticles capped with natural products can be a cost-effective alternative to treat drug-resistant nosocomial infections. Therefore, silibinin-loaded chitosan-capped silver nanoparticles (S-C@AgNPs) were synthesized to evaluate their antimicrobial and anti-inflammatory potential. The S-C@AgNPs plasmon peak was found at 430 nm and had a particle size distribution of about 130 nm with an average hydrodynamic diameter of 101.37 nm. The Scanning Electron Microscopy images showed the presence of sphere-shaped homogeneous nanoparticles. The Fourier Transform Infrared Spectroscopy analysis confirmed the loading of silibinin and chitosan on the AgNPs surface. The minimum inhibitory concentration of the S-C@AgNPs was reported between 3.12 μg/ml to 12.5 μg/ml and a minimum bactericidal concentration between 6.25 μg/ml to 25 μg/ml against drug-resistant nosocomial pathogens. Moreover, concentration-dependent significant inhibition of the biofilm formation was reported against P. aeruginosa (70.21%) and K. pneumoniae (71.02%) at 30 μg/ml, and the highest destruction of preformed biofilm was observed at 100 μg/ml against P. aeruginosa (89.74%) and K. pneumoniae (77.65%) as compared to individual bacterial control. Additionally, the fluorescence live/dead assay for bacterial biofilm confirmed that 100 µg/ml effectively inhibits the biofilm formed by these pathogens. S-C@AgNPs also showed anti-inflammatory activity, which is evident by the significant decrease in the proinflammatory cytokines and chemokines level in THP1 cells treated with LPS. This study concluded that S-C@AgNPs have potent antimicrobial, antibiofilm, and anti-inflammatory properties and could be a potential option for treating drug resistant nosocomial infections.
Department of Microbiology, School of Basic Sciences, Central University of Punjab, Bathinda, Punjab, India.
Silibinin-loaded chitosan-capped silver nanoparticles exhibit potent antimicrobial, antibiofilm, and anti-inflammatory activity against drug-resistant nosocomial pathogens.
In this study, a novel drug delivery system (MSN-PEG-Hypericin) was successfully fabricated using tetraethyl orthosilicate and 3-aminopropyltriethoxysilane as raw materials, and the PEGylation of the prepared aminated mesoporous silica and grafting of hypericin onto the carrier were further conducted to obtain MSN-PEG-Hypericin. The successful preparation of MSN-PEG-Hypericin was characterized by several physical-chemical techniques. Furthermore, the MSN-PEG-Hypericin system increased the ability of hypericin to generate reactive oxygen species (ROS) in vitro. The cytotoxicity assay and hemolysis analysis showed that MSN-PEG-Hypericin had good biocompatibility. For antibacterial studies, the irradiation time and incubation time of photodynamic therapy (PDT) for S. aureus and E. coli were respectively 8 min and 8 h, and the concentrations of hypericin were 2.5 and 5 μg/mL. The result of triphenyl tetrazolium chloride assay indicated that MSN-PEG-Hypericin had stronger photodynamic antibacterial activity than free hypericin, and S. aureus was more sensitive to PDT than E. coli, which was related to their cell structural differences. The antibacterial mechanism study indicated that the generated ROS could destroy the bacterial structures and cause bacterial death due to the leakage of the contents. The MSN-PEG-Hypericin system prepared in this study had potential application prospects in the antibacterial field.
Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), National 111 Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Key Laboratory of Industrial Microbiology, Hubei University of Technology, Wuhan, China.
Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), National 111 Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Key Laboratory of Industrial Microbiology, Hubei University of Technology, Wuhan, China.Hubei Key Lab of Quality and Safety of Traditional Chinese Medicine & Health Food, Jing Brand Chizhengtang Pharmaceutical Co., Ltd, Huangshi, China.
Photodynamic antibacterial research on hypericin-loaded PEGylated mesoporous silica delivery system.
In the current study, we aimed to design an individual hybrid silibinin nano-delivery system consisting of ZnO and BSA components to study its antioxidant activity and apoptotic potential on human pancreatic, breast, lung, and colon cancer cell lines. The folate-linked ZnO-decorated bovine serum albumin/silibinin nanoparticles (FZBS-NP) were synthesized and characterized by FTIR, FESEM, DLS, and zeta potential analysis. The FZBS-NP's cytotoxicity was evaluated by measuring the cancer cells' (MCF-7, A549, HT-29, and Panc) viability. Moreover, the apoptotic potential of the nanoparticles was studied by conducting several analyses including AO/PI and DAPI cell staining analysis, apoptotic gene expression profile (BAX, BCL2, and Caspase-8) preparation, and FITC Annexin V/PI flow cytometry. Finally, both antioxidant assays (ABTS and DPPH) were utilized to analyze the FZBS-NPs' antioxidant activities. The 152-nm FZBS-NP significantly induced the selective apoptotic death on the MCF-7, A549, HT-29, Panc, and Huvec cancer cells by increasing the SubG1 cell population following the increased treatment concentrations of FZBS-NP. Moreover, the FZBS-NPs exhibited powerful antioxidant activity. The BSA component of the FZBS-NPs delivery system improves the ability of the nanoparticles to gradually release silibinin and ZnO near the cancer cells. On the other hand, considering the powerful antioxidant activity of FZBS-NP, they have the potential to selectively induce apoptosis in human colon and breast cancer cells and protect normal types, which makes it an efficient safe anticancer compound. However, to verify the FZBS-NP anti-cancer efficiency further cancer and normal cell lines are required to measure several types of apoptotic gene expression.
Department of Biochemistry, Neyshabur Branch, Islamic Azad University, Neyshabur, Iran.
Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran.
Department of Biochemistry, Faculty of Medicine, Mashhad Medical Sciences, Islamic Azad University, Mashhad, Iran.
Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
The anticancer impact of folate-linked ZnO-decorated bovine serum albumin/silibinin nanoparticles on human pancreatic, breast, lung, and colon cancers.
The utilization of polymethyl methacrylate (PMMA) bone cement is employed for the purpose of stabilizing fractured vertebral bodies. The existence of a mechanical imbalance in hard polymethylmethacrylate (PMMA) bone cement has the potential to increase the likelihood of a fracture occurring in the neighbouring vertebral body. In order to reduce potential difficulties, the primary goal of this study is to investigate the potential benefits of increasing PMMA bone cement's bioactivity and lowering its elastic modulus. The incorporation of a 10% volume fraction of hyaluronic acid (HyA) and polyethylene glycol (PEG) into the bone cement led to an improvement in the bioactivity and decreasing of elastic modulus of polymethylmethacrylate (PMMA). The integration of HyPE gel phase presents several advantages over pure PMMA bone cement, including enhanced setting parameters, improved degradability, and increased biocompatibility. The gel phase is additionally accountable for a reduction in the elastic modulus of polymethylmethacrylate (PMMA) bone cement. In addition, the existence of a porous structure that arises from the degradation of the HyPE gel phase delivers a significant amount of room, thereby enhancing the process of bone regeneration when implanted in the femur of rabbits. The utilization of HyPE in PMMA has been shown through comprehensive µ-CT analysis to enhance bone formation, thereby promoting osteointegration at the implantation site. Furthermore, the histological analysis demonstrated the existence of osteogenic activity in the PMMA polyethylene glycol supplemented with 10% HyA and 10% PEG after a 2-month period subsequent to implantation.
Department of Regenerative Medicine, College of Medicine, Soonchunhyang University, Cheonan, South Korea.
Department of Regenerative Medicine, College of Medicine, Soonchunhyang University, Cheonan, South Korea.Institute of Tissue Regeneration, College of Medicine, Soonchunhyang University, Cheonan, South Korea.
In vivo evaluation of hyaluronic acid-polyethylene glycol amended PMMA bone cement for orthopaedic application.
Fibroblast growth factor (FGF) isoform 13, a distinct type of FGF, boasts significant potential for therapeutic intervention in cardiovascular dysfunctions. However, its impact on regulating fibrosis remains unexplored. This study aims to elucidate the role and mechanism of FGF13 on cardiac fibrosis. Here, we show that following transverse aortic constriction (TAC) surgery, interstitial fibrosis and collagen content increase in mice, along with reduced ejection fraction and fractional shortening, augmented heart mass. However, following Fgf13 deletion, interstitial fibrosis is decreased, ejection fraction and fractional shortening are increased, and heart mass is decreased, compared with those in the TAC group. Mechanistically, incubation of cardiac fibroblasts with transforming growth factor β (TGFβ) increases the expressions of types I and III collagen proteins, as well as α-smooth muscle actin (α-SMA) proteins, and enhances fibroblast proliferation and migration. In the absence of Fgf13, the expressions of these proteins are decreased, and fibroblast proliferation and migration are suppressed, compared with those in the TGFβ-stimulated group. Overexpression of FGF13, but not FGF13 mutants defective in microtubule binding and stabilization, rescues the decrease in collagen and α-SMA protein and weakens the proliferation and migration function of the Fgf13 knockdown group. Furthermore, Fgf13 knockdown decreases ROCK protein expression via microtubule disruption. Collectively, cardiac Fgf13 knockdown protects the heart from fibrosis in response to haemodynamic stress by modulating microtubule stabilization and ROCK signaling pathway.
Department of Pharmacology, the Key Laboratory of Neural and Vascular Biology, Ministry of Education, the Key Laboratory of New Drug Pharmacology and Toxicology, the Hebei Collaboration Innovation Center for Mechanism, Diagnosis and Treatment of Neurological and Psychiatric Disease, Hebei Medical University, Shijiazhuang 050017, China.
Department of Pharmacology, Hebei International Cooperation Center for Ion Channel Function and Innovative Traditional Chinese Medicine, Hebei Higher Education Institute Applied Technology Research Center on TCM Formula Preparation, Hebei University of Chinese Medicine, Shijiazhuang 050091, China.
Department of Emergency, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China.
Department of Cardiology, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, China.
Department of Vascular Surgery, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, China.
Department of Cardiac Surgery, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, China.
Core Facilities and Centers, Hebei Medical University, Shijiazhuang 050017, China.
College of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, China.
Graduate School, Hebei Medical University, Shijiazhuang 050017, China.
Inducible Fgf13 ablation alleviates cardiac fibrosis via regulation of microtubule stability.
The effects of exogenous ketones on appetite and food intake remain elusive, especially for people with type 2 diabetes (T2D). This study aimed to determine whether acute ingestion of an oral ketone monoester supplement (KME) affected appetite sensations, prospective food consumption and intake in T2D. Results showed that acute KME ingestion did not significantly alter appetite scores. However, there was a tendency for lower energy intake during an ad libitum meal 3 h following ketone ingestion compared to non-energetic placebo. Further research is warranted to understand the long-term effects of exogenous ketones for energy and macronutrient intake in T2D.
School of Health and Exercise Sciences, University of British Columbia, Kelowna, BC, Canada.
Department of Human Nutrition, Foods and Exercise, Virginia Tech, Blacksburg, VA, US.
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme
Acute effect of an exogenous ketone monoester supplement on appetite and food intake in adults with type 2 diabetes.
Baicalin (BAN) has shown promise in alleviating myocardial ischemia/reperfusion (I/R) injury, yet its limited solubility and biocompatibility have hindered its application. Developing drug delivery systems is a promising strategy to enhance the therapeutic potential of BAN in the context of I/R injury. This study aims to prepare a BAN-loaded nanodrug system using polydopamine (PDA)-modified Zeolitic imidazolate framework-8 (ZIF-8) as a carrier, with the goal of improving BAN's mitigating effects on I/R injury. We prepared the BAN nanoparticles (NPs) system, PZB NPs, using ZIF-8 as the carrier. The system was characterized in terms of morphology, particle size, zeta potential, and X-ray diffraction (XRD). We assessed the cytotoxicity of PZB NPs in H9c2 cells, investigated its effects and mechanisms in H/R-induced H9c2 cells, and evaluated its ability to alleviate myocardial I/R injury in rats. PZB NPs exhibited good dispersion, with a BAN loading efficiency of 26.43 ± 1.55%, a hydrated particle size of 102.21 ± 1.19 nm, and a zeta potential of -24.84 ± 0.07 mV. It displayed slow and sustained drug release in an acidic environment (pH 5.5). In vitro studies revealed that PZB NPs was non-cytotoxic and significantly enhanced the recovery of H/R injury H9c2 cell viability. PZB NPs suppressed cell apoptosis, activated the Nrf2/HO-1 pathway, and cleared ROS. In vivo study demonstrated that PZB NPs significantly reduced infarct size, ameliorated fibrosis and improved heart function. The PZB NPs markedly enhances BAN's ability to alleviate I/R injury, both in vitro and in vivo, offering a promising drug delivery system for clinical applications.
Department of Cardiology, Taizhou First People's Hospital, Huangyan Hospital of Wenzhou Medical University, Taizhou, Zhejiang, P. R. China.
Baicalin-loaded Polydopamine modified ZIF-8 NPs inhibits myocardial ischemia/reperfusion injury in rats.
Institute for Regenerative Medicine, State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
Department of Biology, Brandeis University, Waltham, MA 02453, USA.
Institute for Regenerative Medicine, State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.National Health Commission Key Laboratory of Birth Defect Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, University of South China, Changsha 410008, China.China Regional Research Centre, International Centre for Genetic Engineering and Biotechnology, Taizhou 212200, China.
A PCR-independent, annealing-free cloning method for the insertion of short DNA fragments.
Docetaxel is one of the most effective and safe chemotherapy drugs according to the World Health Organization, but its clinical use has been discontinued due to its various side effects. To reduce these side effects, the amount of docetaxel drug should be kept at the most effective level, it should be monitored in body fluids. Due to the limitations of traditional analytical methods used for this purpose, such as expensive and low sensitivity, labor-intensive and time-consuming complex preliminary preparation, efficient methods are required for the determination of the docetaxel level in the body. The increasing demand for the development of personalized therapy has recently spurred significant research into biosensors for the detection of drugs and other chemical compounds. In this study, an electrochemical-based portable nanobiosensor system was developed for the rapid, low-cost, and sensitive determination of docetaxel. In this context, mg-p(HEMA)-IMEO nanoparticles to be used as nanobiosensor bioactive layer was synthesized, characterized, and docetaxel determination conditions were optimized. According to the results obtained, the developed nanobiosensor system can detect docetaxel with a sensitivity of 2.22 mg/mL in a wide calibration range of 0.25-10 mg/mL, in only 15 min, in mixed media such as commercially available artificial blood serum and urine. determined. We concluded that the developed nanobiosensor system can be successfully used in routine drug monitoring as a low-cost biomedical device capable of direct, rapid, and specific drug determination within the scope of personalized treatment, providing point-of-care testing.
Buca Municipality Buca Science and Art Center, Izmir, Turkey.Faculty of Science, Department of Biochemistry, Ege University, Izmir, Turkey.
Buca Municipality Buca Science and Art Center, Izmir, Turkey.
Faculty of Science, Department of Biochemistry, Ege University, Izmir, Turkey.Health Science Institute, Department of Medical Biochemistry, Ege University, Izmir, Turkey.
Faculty of Science, Department of Biochemistry, Ege University, Izmir, Turkey.Nanotechnology Research and Application Center, Sabancı University, Istanbul, Turkey.
Therapeutic drug monitoring on-site has the potential to significantly save healthcare expenditures while also improving patient outcomes.Chromatography’s applicability as a routine procedure is restricted by its lack of standardization, expensive equipment, lengthy turnaround times, and labor-intensive sample preparation.Overcoming these drawbacks, nanobiosensors provide an inexpensive, user-friendly, on-site analytical approach to fully explore the possibilities of therapeutic drug monitoring.
Development of nanobiosensor for therapeutic drug monitoring in personalized cancer treatment approach.
Osteoarthritis (OA) is a chronic disease that causes pain, morbidity, and disability. The main strategy for OA treatment focuses on inflammation suppression, inhibition of osteoclastogenesis, and protection of articular cartilage. These functions cannot be performed effectively by monotherapy. Therefore, an effective drug delivery system is required, capable of containing and controlling the efflux of various drugs to alleviate osteoclastogenesis, protect cartilage and subchondral bone, and suppress inflammation. In this work, an encapsulation system is constructed using a self-healing chitosan hydrogel and allocated compound drugs. The self-healing gel is composed of branched-functionalized chitosan, created by simultaneously using polycaprolactone polyethylene glycol azide as a block polymer and the host-guest assembly of β-cyclodextrin and adamantane. Inhibitors of the NFkB pathway are loaded into the cavities of β-cyclodextrin and the spring-like structure of the block polymer, which can be rapidly released upon joint friction (due to the reassembly of β-cyclodextrin and adamantane by shear stress and the stretch of the block polymer). In vitro experiments using BMMs and the ATDC5 cell line confirm that the developed hydrogel can simultaneously suppress osteoclastogenesis and induce chondrogenesis. Additionally, a model of knee arthritis in C57 mice was used to confirm that this double-crosslinked encapsulation system can lubricate the knee joint surface and provide adequate protection on demand through shear-responsive drug release.
Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.Key Laboratory of Musculoskeletal System Degeneration and Regeneration, Translational Research of Zhejiang Province, Hangzhou, China.
Double-crosslinked self-healing hydrogel alleviates osteoarthritis by protecting from wearing and targeting NF-kB signaling.
Prostate-specific membrane antigen radioguided surgery (PSMA-RGS) might identify lymph node invasion (LNI) in prostate cancer (PCa) patients undergoing extended pelvic lymph node dissection (ePLND). The optimal target-to-background (TtB) ratio to define RGS positivity is still unknown.Ad interim analyses which focused on 30 patients with available pathological information were conducted. All patients underwent preoperative PSMA positron emission tomography (PET). 99m-Technetium-PSMA imaging and surgery ([99mTc]Tc-PSMA-I&S) was administered the day before surgery. In vivo measurements were conducted using an intraoperative gamma probe. Performance characteristics and implications associated with different TtB ratios were assessed.Overall, 9 (30%) patients had LNI, with 22 (13%) and 80 (11%) positive regions and lymph nodes, respectively. PSMA-RGS showed uptakes in 12 (40%) vs. 7 (23%) vs. 6 (20%) patients for a TtB ratio ≥ 2 vs. ≥ 3 vs. ≥ 4. At a per-region level, sensitivity, specificity and accuracy for a TtB ratio ≥ 2 vs. ≥ 3 vs. ≥ 4 were 72%, 88% and 87% vs. 54%, 98% and 92% vs. 36%, 99% and 91%. Performing ePLND only in patients with suspicious spots at PSMA PET (n = 7) would have spared 77% ePLNDs at the cost of missing 13% (n = 3) pN1 patients. A TtB ratio ≥ 2 at RGS identified 8 (24%) suspicious areas not detected by PSMA PET, of these 5 (63%) harbored LNI, with one pN1 patient (11%) that would have been missed by PSMA PET. Adoption of a TtB ratio ≥ 2 vs. ≥ 3 vs. ≥ 4, would have allowed to spare 18 (60%) vs. 23 (77%) vs. 24 (80%) ePLNDs missing 2 (11%) vs. 3 (13%) vs. 4 (17%) pN1 patients.PSMA-RGS using a TtB ratio ≥ 2 to identify suspicious nodes, could allow to spare > 50% ePLNDs and would identify additional pN1 patients compared to PSMA PET and higher TtB ratios.
Division of Oncology/Unit of Urology, Gianfranco Soldera Prostate Cancer Lab, Urological Research Institute (URI), IRCCS San Raffaele Scientific Institute, Milan, Italy.
Department of Radiology, IRCCS San Raffaele Scientific Institute, Milan, Italy.Vita-Salute San Raffaele University, Via Olgettina 58, 20132, Milan, Italy.
Department of Nuclear Medicine, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Department of Nuclear Medicine, IRCCS San Raffaele Scientific Institute, Milan, Italy.Vita-Salute San Raffaele University, Via Olgettina 58, 20132, Milan, Italy.
Division of Oncology/Unit of Urology, Gianfranco Soldera Prostate Cancer Lab, Urological Research Institute (URI), IRCCS San Raffaele Scientific Institute, Milan, Italy.Vita-Salute San Raffaele University, Via Olgettina 58, 20132, Milan, Italy.
Division of Oncology/Unit of Urology, Gianfranco Soldera Prostate Cancer Lab, Urological Research Institute (URI), IRCCS San Raffaele Scientific Institute, Milan, Italy. gandaglia.giorgio@hsr.it.Vita-Salute San Raffaele University, Via Olgettina 58, 20132, Milan, Italy. gandaglia.giorgio@hsr.it.
European journal of nuclear medicine and molecular imaging
Defining the optimal target-to-background ratio to identify positive lymph nodes in prostate cancer patients undergoing robot-assisted [99mTc]Tc-PSMA radioguided surgery: updated results and ad interim analyses of a prospective phase II study.
Sympathetic activation is a hallmark of heart failure and the underlying mechanism remains elusive. Butyrate is generated by gut microbiota and influences numerous physiological and pathological processes in the host. The present study aims to investigate whether the intestinal metabolite butyrate reduces sympathetic activation in rats with heart failure (HF) and the underlying mechanisms involved. Sprague-Dawley rats (220‒250 g) are anaesthetized with isoflurane, and the left anterior descending artery is ligated to model HF. Then, the rats are treated with or without butyrate sodium (NaB, a donor of butyrate, 10 g/L in water) for 8 weeks. Blood pressure and renal sympathetic nerve activity (RSNA) are recorded to assess sympathetic outflow. Cardiac function is improved (mean ejection fraction, 22.6%±4.8% vs 38.3%±5.3%; P<0.05), and sympathetic activation is decreased (RSNA, 36.3%±7.9% vs 23.9%±7.6%; P<0.05) in HF rats treated with NaB compared with untreated HF rats. The plasma and cerebrospinal fluid levels of norepinephrine are decreased in HF rats treated with NaB. The infusion of N-methyl-D-aspartic acid (NMDA) into the paraventricular nucleus (PVN) of the hypothalamus of HF model rats increases sympathetic nervous activity by upregulating the NMDA receptor. Microglia polarized to the M2 phenotype and inflammation are markedly attenuated in the PVN of HF model rats after NaB administration. In addition, HF model rats treated with NaB exhibit enhanced intestinal barrier function and increased levels of GPR109A, zona occludens-1 and occludin, but decreased levels of lipopolysaccharide-binding protein and zonulin. In conclusion, butyrate attenuates sympathetic activation and improves cardiac function in rats with HF. The improvements in intestinal barrier function, reductions in microglia-mediated inflammation and decreases in NMDA receptor 1 expression in the PVN are all due to the protective effects of NaB.
Department of Physiology, Hebei Medical University, Shijiazhuang 050017, China.
Department of Reproduction, the Second Hospital of Hebei Medical University, Shijiazhuang 050017, China.
Department of Physiology, Hebei Medical University, Shijiazhuang 050017, China.Hebei Collaborative Innovation Center for Cardio-Cerebrovascular Disease, Shijiazhuang 050017, China.The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang 050017, China.Hebei Key Laboratory of Cardiovascular Homeostasis and Aging, Shijiazhuang 050017, China.
Department of Physiology, Hebei Medical University, Shijiazhuang 050017, China.Experimental Center for Teaching, Hebei Medical University, Shijiazhuang 050017, China.Hebei Key Laboratory of Cardiovascular Homeostasis and Aging, Shijiazhuang 050017, China.
Butyrate attenuates sympathetic activation in rats with chronic heart failure by inhibiting microglial inflammation in the paraventricular nucleus.
The temperamental trait behavioral inhibition (BI) is related to the development and maintenance of anxiety, particularly much so to social anxiety disorder. We investigated if BI and social anxiety disorder predicted cognitive behavioral therapy (CBT) outcomes for youth anxiety. Youth (N = 179; Mage = 11.6 years) were assessed 4 years following a randomized controlled CBT effectiveness trial. BI was measured by the parent-reported Behavioral Inhibition Questionnaire at baseline. The outcomes were diagnostic recovery, youth- and parent-reported anxiety symptoms, and clinical severity at post-treatment, 1-year, and 4-year follow-up. Having social anxiety disorder negatively predicted diagnostic recovery and predicted higher clinical severity at all assessment points and was the only significant predictor of outcomes at 4-year follow-up. Higher BI negatively predicted diagnostic recovery and predicted higher clinical severity and parent-reported symptom levels at post-treatment and 1-year follow-up, and predicted higher youth-reported anxiety levels at 1-year follow-up. Higher BI was the only predictor of youth- and parent-reported anxiety symptoms. BI and social anxiety disorder seem to be unique predictors of CBT outcomes among youth with anxiety disorders. CBT adaptations may be indicated for youth with high BI and social anxiety disorder.
Tynset Child and Adolescents Mental Health Service, Innlandet Hospital Trust, Tynset, Norway. Toril.Skumsnes@sykehuset-innlandet.no.Department of Mental Health, Norwegian University of Science and Technology, Trondheim, Norway. Toril.Skumsnes@sykehuset-innlandet.no.
Department of Psychology, University of Oslo, Oslo, Norway.
Department of Child and Adolescent Psychiatry, Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.Department of Clinical Medicine, Faculty of Medicine, University of Bergen, Bergen, Norway.
Department for Research and Development, Division of Mental Health and Substance Use, Akershus University Hospital, Oslo, Norway.
Tynset Child and Adolescents Mental Health Service, Innlandet Hospital Trust, Tynset, Norway.
Regional Centre for Child and Youth Mental Health and Child Welfare, NORCE Norwegian Research Centre, Bergen, Norway.
Department of Mental Health, Norwegian University of Science and Technology, Trondheim, Norway.
Research on child and adolescent psychopathology
Res Child Adolesc Psychopathol. 2024-09;52(9):1427-1439.
Behavioral Inhibition and Social Anxiety Disorder as Predictors of Long-Term Outcomes of Cognitive Behavioral Therapy for Youth Anxiety Disorders.
Department of Neurology, Cleveland Clinic, Cleveland, Ohio, USA.
Epilepsy Center, Department of Neurology, Cleveland Clinic, Cleveland, Ohio, USA.
Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, Ohio, USA.
Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, Ohio, USA ABBATEJ2@ccf.org.
Episodic aphasia following a motor vehicle collision.
This study explores the corrosion resistance and antibacterial properties of a PTFE + TiO2/Ag coating applied to 316 L stainless steel. To enhance adhesion, a polydopamine interlayer was chemically deposited onto the steel surface. The PTFE + TiO2 coating was subsequently applied through immersion, followed by the deposition of silver nanoparticles using a chemical method. Optimization of the polydopamine interlayer involved varying temperature, time, stirring speed, and drying parameters. The optimal conditions for the polydopamine interlayer were determined to be 60 °C for 1 h, 300 rpm stirring, and 24-h drying in a freeze dryer. Analytical results demonstrated that both the PTFE + TiO2 and PTFE/PTFE + TiO2/Ag coatings exhibited exceptional corrosion resistance, with corrosion currents of 3.3 × 10-5 and 3.2 × 10-4 μA/cm2, respectively. Antibacterial assessments showcased the remarkable ability of the PTFE/PTFE + TiO2/Ag coating, containing 5% silver content, to effectively inhibit bacterial penetration within a 6.5 mm radius. Furthermore, this coating displayed a water contact angle of 143°, classifying it as a hydrophobic coating. The photocatalytic efficiency (Rs) was determined to be 3.18 × 10-3 A/W, a performance level comparable to that of a standard UV sensor. These findings underscore the substantial enhancements in corrosion resistance, antibacterial performance, and hydrophobic characteristics achieved with the PTFE + TiO2/Ag coating, particularly through the novel optimization of the polydopamine interlayer. This coating exhibits great promise for multifunctional protective applications in diverse fields, particularly demonstrating its suitability for implants and bio-coatings.
Department of Materials Science and Engineering, Sharif University of Technology, Tehran, Iran.
Fabrication of PTFE + TiO2/Ag coatings on 316L/polydopamine with advanced mechanical, bio-corrosion, and antibacterial properties for stainless steel Catheters.
Molecularly imprinted polymers (MIPs) have garnered the interest of researchers in the drug delivery due to their advantages, such as exceptional durability, stability, and selectivity. In this study, a biocompatible MIP drug adsorption and delivery system with high loading capacity and controlled release, was prepared based on chitosan (CS) and graphene quantum dots (GQDs) as the matrix, and the anticancer drug oxaliplatin (OXAL) as the template. Additionally, samples without the drug (non-imprinted polymers, NIPs) were created for comparison. GQDs were produced using the hydrothermal method, and samples underwent characterization through FTIR, XRD, FESEM, and TGA. Various experiments were conducted to determine the optimal pH for drug adsorption, along with kinetic and isotherm studies, selectivity assessments, in vitro drug release and kinetic evaluations. The highest drug binding capacity was observed at pH 6.5. The results indicated the Lagergren-first-order kinetic model (with rate constant of 0.038 min-1) and the Langmuir isotherm (with maximum adsorption capacity of 17.15 mg g-1) exhibited better alignment with the experimental data. The developed MIPs displayed significant selectivity towards OXAL, by an imprinting factor of 2.88, in comparison to two similar drugs (cisplatin and carboplatin). Furthermore, the analysis of the drug release profile showed a burst release for CS-Drug (87% within 3 h) at pH 7.4, where the release from the CS-GQD-Drug did not occur at pH 7.4 and 10; instead, the release was observed at pH 1.2 in a controlled manner (100% within 28 h). Consequently, this specific OXAL adsorption and delivery system holds promise for cancer treatment.
Department of Chemistry, Faculty of Basic Sciences, Azarbaijan Shahid Madani University, Tabriz, Iran.
Chitosan-graphene quantum dot-based molecular imprinted polymer for oxaliplatin release.
The ongoing emergence of SARS-CoV-2 variants poses challenges to the immunity induced by infections and vaccination. We conduct a 6-month longitudinal evaluation of antibody binding and neutralization of sera from individuals with six different combinations of vaccination and infection against BA.5, XBB.1.5, EG.5.1, and BA.2.86. We find that most individuals produce spike-binding IgG or neutralizing antibodies against BA.5, XBB.1.5, EG.5.1, and BA.2.86 2 months after infection or vaccination. However, compared to ancestral strain and BA.5 variant, XBB.1.5, EG.5.1, and BA.2.86 exhibit comparable but significant immune evasion. The spike-binding IgG and neutralizing antibody titers decrease in individuals without additional antigen exposure, and <50% of individuals neutralize XBB.1.5, EG.5.1, and BA.2.86 during the 6-month follow-up. Approximately 57% of the 107 followed up individuals experienced an additional infection, leading to improved binding IgG and neutralizing antibody levels against these variants. These findings provide insights into the impact of SARS-CoV-2 variants on immunity following repeated exposure.
Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.
Shandong Provincial Key Laboratory of Infectious Disease Control and Prevention, Shandong Provincial Center for Disease Control and Prevention, Jinan 250014, China.
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China; Department of Laboratory Medicine, Handan Central Hospital, Hebei Medical University, Handan 056001, China; Hebei Key Laboratory of Immune Mechanism of Major Infectious Diseases and New Technology of Diagnosis and Treatment, The Fifth Hospital of Shijiazhuang, Shijiazhuang 050021, China.
Department of Infectious Disease Control and Prevention, Wuxi Center for Disease Control and Prevention, Wuxi 214023, China.
Department of Microbiological Laboratory Technology, School of Public Health, Cheeloo College of Medicine, Shandong University, Key Laboratory of Prevention and Control of Emerging Infectious Diseases and Biosafety in Universities of Shandong, Jinan 250012, China.
Bioinformatics Center of Academy of Military Medical Science, Beijing 100850, China.
Department of Infectious Disease Control and Prevention, Binzhou Center for Disease Control and Prevention, Binzhou 256613, China.
School of Public Health, Weifang Medical University, Weifang 261053, China.
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China.
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China; School of Public Health, Zhengzhou University, Zhengzhou 450001, China.
Hebei Key Laboratory of Immune Mechanism of Major Infectious Diseases and New Technology of Diagnosis and Treatment, The Fifth Hospital of Shijiazhuang, Shijiazhuang 050021, China.
Department of Infectious Disease Control and Prevention, Wuxi Center for Disease Control and Prevention, Wuxi 214023, China. Electronic address: sarayshen@163.com.
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China. Electronic address: donggang@bmi.ac.cn.
Hebei Key Laboratory of Immune Mechanism of Major Infectious Diseases and New Technology of Diagnosis and Treatment, The Fifth Hospital of Shijiazhuang, Shijiazhuang 050021, China. Electronic address: 1149497466@qq.com.
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China; Department of Microbiological Laboratory Technology, School of Public Health, Cheeloo College of Medicine, Shandong University, Key Laboratory of Prevention and Control of Emerging Infectious Diseases and Biosafety in Universities of Shandong, Jinan 250012, China; School of Public Health, Zhengzhou University, Zhengzhou 450001, China. Electronic address: mjma@163.com.
Variant-specific antibody response following repeated SARS-CoV-2 vaccination and infection.
Methotrexate is a potent anticancer drug whose strong efflux is facilitated by the brain's efflux transporter. As an efflux transporter blocker, albumin increased the drug's concentration in the brain. Methotrexate-loaded nanoparticles were produced by evaporating the emulsification fluid. Improvements and analyses were made to the following aspects of the generated nanoparticles: size, polydispersity, zeta potential, entrapment efficiency, percentage yield, scanning electron microscopy, in vitro drug release studies, and sterilization. The particle size was determined to be in the nano range, and homogeneity of particle size was suggested by a low polydispersity index result. Particle diameters of 168 nm were observed in the F5 preparation, and zeta potential values of -1.5 mV suggested that the preparation produced adequate repulsive interactions between the nanoparticles. Albumin and dopamine HCl were employed to coat the methotrexate-loaded nanoparticles to guarantee that the brain received an adequate amount of them. The homogeneity of albumin coated nanoparticles was demonstrated by the low% PDI values of 0.129 and 0.122 for albumin coated nanoparticles (MNPs-Alb) and polymerized dopamine HCl and albumin coated nanoparticles (MNPs-PMD-Alb), respectively. After 48 h of incubation, the cell viability measured at the same drug concentration (5 mg) decreased for the F5, albumin coated nanoparticles, polymerized dopamine HCl coated nanoparticles, and polymerized dopamine HCl and albumin coated nanoparticles, respectively. Our primary findings demonstrate that the albumin nanoparticles containing methotrexate are designed to deliver the drug gradually. With minimal cytotoxicity, the intended preparation might give the brain an appropriate dosage of methotrexate.
Department of Pharmacy, PSIT-Pranveer Singh Institute of Technology (Pharmacy), Bhauti, Kanpur, U.P, India.
Department of Pharmaceutics, KLE College of Pharmacy, II Block Rajajinagar, Bengaluru, Karnataka, India.
Department of Pharmacology, College of Pharmacy, Shri Venkateshwara University affiliation, Gajraula, India.
Department of Pharmacy, Jai Institute of Pharmaceutical Sciences and Research, Gwalior, M.P, India.
Department of Pharmacy, Faculty of Pharmacy, Integral University Lucknow, India.
Department of Pharmacology, School of Pharmaceutical Sciences, Jaipur National University, Jaipur, Rajasthan, India.
Department of Pharmaceutical Medicine, Maharashtra University of Health Sciences, Nashik, Maharashtra, India.
Design, optimization, and evaluation of methotrexate loaded and albumin coated polymeric nanoparticles.
Bone tissue represents the most frequent site of cancer metastasis. We developed a hemichannel-activating antibody, Cx43-M2. Cx43-M2, directly targeting osteocytes in situ, activates osteocytic hemichannels and elevates extracellular ATP, thereby inhibiting the growth and migration of cultured breast and osteosarcoma cancer cells. Cx43-M2 significantly decreases breast cancer metastasis, osteosarcoma growth, and osteolytic activity, while improving survival rates in mice. The antibody's inhibition of breast cancer and osteosarcoma is dose dependent in both mouse and human cancer metastatic models. Furthermore, Cx43-M2 enhances anti-tumor immunity by increasing the population and activation of tumor-infiltrating immune-promoting effector T lymphocytes, while reducing immune-suppressive regulatory T cells. Our results suggest that the Cx43-M2 antibody, by activating Cx43 hemichannels and facilitating ATP release and purinergic signaling, transforms the cancer microenvironment from a supportive to a suppressive state. Collectively, our study underscores the potential of Cx43-M2 as a therapeutic for treating breast cancer bone metastasis and osteosarcoma.
Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.
Departments of Biochemistry and Structural Biology, Microbiology, University of Texas Health Science Center, San Antonio, TX 78229-3900, USA.
The Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030, USA.
Immunology & Molecular Genetics, University of Texas Health Science Center, San Antonio, TX 78229-3900, USA.
Greehey Children's Cancer Research Institute, University of Texas Health Science Center, San Antonio, TX 78229-3900, USA; Cell Systems and Anatomy, University of Texas Health Science Center, San Antonio, TX 78229-3900, USA.
Cell Systems and Anatomy, University of Texas Health Science Center, San Antonio, TX 78229-3900, USA.
Immunology & Molecular Genetics, University of Texas Health Science Center, San Antonio, TX 78229-3900, USA; South Texas Veterans Health Care System, San Antonio, TX 78229, USA.
The Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030, USA. Electronic address: zhiqiang.an@uth.tmc.edu.
Departments of Biochemistry and Structural Biology, Microbiology, University of Texas Health Science Center, San Antonio, TX 78229-3900, USA. Electronic address: jiangj@uthscsa.edu.
Antibody-activation of connexin hemichannels in bone osteocytes with ATP release suppresses breast cancer and osteosarcoma malignancy.
The protein phosphatase 2A (PP2A) regulatory subunit PPP2R2A is involved in the regulation of immune response. We report that lupus-prone mice with T cells deficient in PPP2R2A display less autoimmunity and nephritis. PPP2R2A deficiency promotes NAD+ biosynthesis through the nicotinamide riboside (NR)-directed salvage pathway in T cells. NR inhibits murine Th17 and promotes Treg cell differentiation, in vitro, by PΑRylating histone H1.2 and causing its reduced occupancy in the Foxp3 loci and increased occupancy in the Il17a loci, leading to increased Foxp3 and decreased Il17a transcription. NR treatment suppresses disease in MRL.lpr mice and restores NAD+-dependent poly [ADP-ribose] polymerase 1 (PARP1) activity in CD4 T cells from patients with systemic lupus erythematosus (SLE), while reducing interferon (IFN)-γ and interleukin (IL)-17 production. We conclude that PPP2R2A controls the level of NAD+ through the NR-directed salvage pathway and promotes systemic autoimmunity. Translationally, NR suppresses lupus nephritis in mice and limits the production of proinflammatory cytokines by SLE T cells.
Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA. Electronic address: wpan2@bidmc.harvard.edu.
Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA; Rheumatology Department, Strasbourg University Hospital of Hautepierre, Strasbourg, France.
Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA. Electronic address: gtsokos@bidmc.harvard.edu.
The PP2A regulatory subunit PPP2R2A controls NAD+ biosynthesis to regulate T cell subset differentiation in systemic autoimmunity.
Biomolecular condensates have emerged as major drivers of cellular organization. It remains largely unexplored, however, whether these condensates can impart mechanical function(s) to the cell. The heterochromatin protein HP1α (Swi6 in Schizosaccharomyces pombe) crosslinks histone H3K9 methylated nucleosomes and has been proposed to undergo condensation to drive the liquid-like clustering of heterochromatin domains. Here, we leverage the genetically tractable S. pombe model and a separation-of-function allele to elucidate a mechanical function imparted by Swi6 condensation. Using single-molecule imaging, force spectroscopy, and high-resolution live-cell imaging, we show that Swi6 is critical for nuclear resistance to external force. Strikingly, it is the condensed yet dynamic pool of Swi6, rather than the chromatin-bound molecules, that is essential to imparting mechanical stiffness. Our findings suggest that Swi6 condensates embedded in the chromatin meshwork establish the emergent mechanical behavior of the nucleus as a whole, revealing that biomolecular condensation can influence organelle and cell mechanics.
Department of Cell Biology, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
Department of Cell Biology, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; Department of Physics, Yale University, 217 Prospect Street, New Haven, CT 06511, USA.
Department of Biophysics, University of Michigan, Ann Arbor, MI 48109, USA.
Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
Department of Biophysics, University of Michigan, Ann Arbor, MI 48109, USA; Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
Department of Physics, Yale University, 217 Prospect Street, New Haven, CT 06511, USA.
Department of Biology, Brandeis University, Waltham, MA 02453, USA. Electronic address: kaushikr@brandeis.edu.
Department of Cell Biology, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA. Electronic address: megan.king@yale.edu.
The condensation of HP1α/Swi6 imparts nuclear stiffness.
Cancer cells experiencing hypoxic stress employ epithelial-mesenchymal transition (EMT) to undergo metastasis through rewiring of the chromatin landscape, epigenetics, and importantly, gene expression. Here, we showed that hypoxia modulates the epigenetic landscape on CTCF promoter and upregulates its expression. Hypoxia-driven epigenetic regulation, specifically DNA demethylation mediated by TET2, is a prerequisite for CTCF induction. Mechanistically, in hypoxic conditions, Hypoxia-inducible factor 1-alpha (HIF1α) binds to the unmethylated CTCF promoter, causing transcriptional upregulation. Further, we uncover the pivotal role of CTCF in promoting EMT as loss of CTCF abrogated invasiveness of hypoxic breast cancer cells. These findings highlight the functional contribution of HIF1α-CTCF axis in promoting EMT in hypoxic breast cancer cells. Lastly, CTCF expression is alleviated and the potential for EMT is diminished when the HIF1α binding is particularly disrupted through the dCas9-DNMT3A system-mediated maintenance of DNA methylation on the CTCF promoter. This axis may offer a unique therapeutic target in breast cancer.
Department of Biological Sciences, Indian Institute of Science Education and Research Bhopal, Bhopal, Madhya Pradesh 462066, India.
Department of Pathology, Bansal Hospital, Bhopal, Madhya Pradesh 462016, India.
Department of Surgical Oncology, Bansal Hospital, Bhopal, Madhya Pradesh 462016, India.
Department of Biological Sciences, Indian Institute of Science Education and Research Bhopal, Bhopal, Madhya Pradesh 462066, India. Electronic address: sanjeevs@iiserb.ac.in.
Hypoxia-induced CTCF promotes EMT in breast cancer.
Morphological studies of skeletal muscle tissue provide insights into the architecture of muscle fibers, the surrounding cells, and the extracellular matrix (ECM). However, a spatial proteomics analysis of the skeletal muscle including the muscle-tendon transition zone is lacking. Here, we prepare cryotome muscle sections of the mouse soleus muscle and measure each slice using short liquid chromatography-mass spectrometry (LC-MS) gradients. We generate 3,000 high-resolution protein profiles that serve as the basis for a network analysis to reveal the complex architecture of the muscle-tendon junction. Among the protein profiles that increase from muscle to tendon, we find proteins related to neuronal activity, fatty acid biosynthesis, and the renin-angiotensin system (RAS). Blocking the RAS in cultured mouse tenocytes using losartan reduces the ECM synthesis. Overall, our analysis of thin cryotome sections provides a spatial proteome of skeletal muscle and reveals that the RAS acts as an additional regulator of the matrix within muscle-tendon junctions.
Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany.
Institute of Sports Medicine Copenhagen, Department of Orthopaedic Surgery, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark; Part of IOC Research Center Copenhagen and Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Bruker Daltonics GmbH & Co. KG, Bremen, Germany.
Institute for Dental Research and Oral Musculoskeletal Biology, Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany.
Department of Pediatrics and Adolescent Medicine, Experimental Neonatology, Medical Faculty, University of Cologne, Cologne, Germany; Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany.
Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany; Center for Molecular Medicine (CMMC), University of Cologne, 50931 Cologne, Germany. Electronic address: pantczak@uni-koeln.de.
Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany; Center for Molecular Medicine (CMMC), University of Cologne, 50931 Cologne, Germany. Electronic address: marcus.krueger@uni-koeln.de.
Spatial proteomics of skeletal muscle using thin cryosections reveals metabolic adaptation at the muscle-tendon transition zone.
Timed feeding drives adipose browning, although the integrative mechanisms for the same remain unclear. Here, we show that twice-a-night (TAN) feeding generates biphasic oscillations of circulating insulin and leptin, representing their entrainment by timed feeding. Insulin and leptin surges lead to marked cellular, functional, and metabolic remodeling of subcutaneous white adipose tissue (sWAT), resulting in increased energy expenditure. Single-cell RNA-sequencing (scRNA-seq) analyses and flow cytometry demonstrate a role for insulin and leptin surges in innate lymphoid type 2 (ILC2) cell recruitment and sWAT browning, since sWAT depot denervation or loss of leptin or insulin receptor signaling or ILC2 recruitment each dampens TAN feeding-induced sWAT remodeling and energy expenditure. Consistently, recreating insulin and leptin oscillations via once-a-day timed co-injections is sufficient to favorably remodel innervated sWAT. Innervation is necessary for sWAT remodeling, since denervation of sWAT, but not brown adipose tissue (BAT), blocks TAN-induced sWAT remodeling and resolution of inflammation. In sum, reorganization of nutrient-sensitive pathways remodels sWAT and drives the metabolic benefits of timed feeding.
Department of Medicine, Division of Digestive Diseases, University of Los Angeles, Los Angeles, CA, USA.
Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY, USA.
Department of Medicine, Division of Digestive Diseases, University of Los Angeles, Los Angeles, CA, USA; Comprehensive Liver Research Center at UCLA, University of Los Angeles, Los Angeles, CA, USA.
Radiation Oncology, Albert Einstein College of Medicine, Bronx, NY, USA.
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA.
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA.
Department of Medicine, Diabetes, Obesity, and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Medicine, Division of Digestive Diseases, University of Los Angeles, Los Angeles, CA, USA; Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY, USA; Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA; Comprehensive Liver Research Center at UCLA, University of Los Angeles, Los Angeles, CA, USA. Electronic address: rajatsingh@mednet.ucla.edu.
Insulin and leptin oscillations license food-entrained browning and metabolic flexibility.
DOT1L mediates the methylation of histone H3 at lysine 79 and, in turn, the transcriptional activation or repression in a context-dependent manner, yet the regulatory mechanisms and functions of DOT1L/H3K79me remain to be fully explored. Following peptide affinity purification and proteomic analysis, we identified that DCAF1-a component of the E3 ligase complex involved in HIV regulation-is associated with H3K79me2 and DOT1L. Interestingly, blocking the expression or catalytic activity of DOT1L or repressing the expression of DCAF1 significantly enhances the tumor necrosis factor alpha (TNF-α)/nuclear factor κB (NF-κB)-induced reactivation of the latent HIV-1 genome. Mechanistically, upon TNF-α/NF-κB activation, DCAF1 is recruited to the HIV-1 long terminal repeat (LTR) by DOT1L and H3K79me2. Recruited DCAF1 subsequently induces the ubiquitination of NF-κB and restricts its accumulation at the HIV-1 LTR. Altogether, our findings reveal a feedback modulation of HIV reactivation by DOT1L-mediated histone modification regulation and highlight the potential of targeting the DOT1L/DCAF1 axis as a therapeutic strategy for HIV treatment.
RNA Institute, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan 430072, China.
State Key Laboratory of Experimental Hematology, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Key Laboratory of Cellular Homeostasis and Human Diseases, Department of Cell Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
State Key Laboratory of Experimental Hematology, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Key Laboratory of Cellular Homeostasis and Human Diseases, Department of Cell Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China; Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Cancer Institute and Hospital of Tianjin Medical University, Tianjin 300060, China. Electronic address: hudq@tmu.edu.cn.
RNA Institute, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address: liang_chen@whu.edu.cn.
DOT1L/H3K79me2 represses HIV-1 reactivation via recruiting DCAF1.
Protective immunity to dengue virus (DENV) requires antibody response to all four serotypes. Systems vaccinology identifies a multi-OMICs pre-vaccination signature and mechanisms predictive of broad antibody responses after immunization with a tetravalent live attenuated DENV vaccine candidate (Butantan-DV/TV003). Anti-inflammatory pathways, including TGF-β signaling expressed by CD68low monocytes, and the metabolites phosphatidylcholine (PC) and phosphatidylethanolamine (PE) positively correlate with broadly neutralizing antibody responses against DENV. In contrast, expression of pro-inflammatory pathways and cytokines (IFN and IL-1) in CD68hi monocytes and primary and secondary bile acids negatively correlates with broad DENV-specific antibody responses. Induction of TGF-β and IFNs is done respectively by PC/PE and bile acids in CD68low and CD68hi monocytes. The inhibition of viral sensing by PC/PE-induced TGF-β is confirmed in vitro. Our studies show that the balance between metabolites and the pro- or anti-inflammatory state of innate immune cells drives broad and protective B cell response to a live attenuated dengue vaccine.
RPM Bioinfo Solutions, Sainte-Thérèse, QC, Canada; Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Pathology Advanced Translational Research Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA; Hospital Israelita Albert Einstein, São Paulo, SP, Brazil.
Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada.
Instituto Adolfo Lutz, São Paulo, Brazil.
Laboratory of Immunology, Heart Institute (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, SP, Brazil; Institute for Investigation in Immunology-Instituto Nacional de Ciência e Tecnologia-iii-INCT, São Paulo, SP, Brazil.
Departments of Medicine, Molecular Microbiology, and Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Department of Medicine and Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USA.
Instituto Butantan, São Paulo, Brazil; Department of Infectious and Parasitic Diseases, Hospital das Clínicas, School of Medicine, University of Sao Paulo, São Paulo 01246-903, Brazil.
Pathology Advanced Translational Research Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA. Electronic address: rafick.sekaly@emory.edu.
A pre-vaccination immune metabolic interplay determines the protective antibody response to a dengue virus vaccine.
The dentate gyrus plays a key role in the discrimination of memories by segregating and storing similar episodes. Whether hilar mossy cells, which constitute a major excitatory principal cell type in the mammalian hippocampus, contribute to this decorrelation function has remained largely unclear. Using two-photon calcium imaging of head-fixed mice performing a spatial virtual reality task, we show that mossy cell populations robustly discriminate between familiar and novel environments. The degree of discrimination depends on the extent of visual cue differences between contexts. A context decoder revealed that successful environmental classification is explained mainly by activity difference scores of mossy cells. By decoding mouse position, we reveal that in addition to place cells, the coordinated activity among active mossy cells markedly contributes to the encoding of space. Thus, by decorrelating context information according to the degree of environmental differences, mossy cell populations support pattern separation processes within the dentate gyrus.
Institute for Physiology I, University of Freiburg, Medical Faculty, 79104 Freiburg, Germany.
Institute for Physiology I, University of Freiburg, Medical Faculty, 79104 Freiburg, Germany; University of Freiburg, Faculty of Biology, 79104 Freiburg, Germany.
Institute for Physiology I, University of Freiburg, Medical Faculty, 79104 Freiburg, Germany; BrainLinks-BrainTools, University of Freiburg, 79104 Freiburg, Germany. Electronic address: hung-ling.chen@physiologie.uni-freiburg.de.
Institute for Physiology I, University of Freiburg, Medical Faculty, 79104 Freiburg, Germany. Electronic address: marlene.bartos@physiologie.uni-freiburg.de.
Context and space coding in mossy cell population activity.
CEO and Director, Neuroscience Research Australia; University of New South Wales and the South Eastern Sydney Local Health District, Sydney, New South Wales, Australia m.kiernan@unsw.edu.au.
Melbourne Brain Centre, Royal Melbourne Hospital and University of Melbourne, Parkville, Victoria, Australia.
Stroke is not optional for neurologists.
The main objective of this work is to synthesize multifunctional nanodendritic structural molecules that can effectively encapsulate hydrophilic as well as hydrophobic therapeutic agents. Four different types of fourth-generation lysine-citric acid based dendrimer have been synthesized in this work: PE-MC-Lys-CA-PEG, TMP-MC-Lys-CA-PEG, PE-MS-Lys-CA-PEG, and TMP-MS-Lys-CA-PEG. The antibacterial drug cefotaxime (CFTX) was further conjugated to these dendrimers. The dendrimer and drug-dendrimer conjugate structures were characterized with the help of FTIR,1H-NMR, and 13C-NMR spectroscopy. Zeta sizer, AFM, and HR-TEM techniques were used to investigate the particle size, surface topography, and structural characteristics of drug-dendrimer conjugates. In vitro drug release was then investigated using dialysis method. Various kinetic drug release models were examined to evaluate the type of kinetic drug release mechanism of the formulations. Cytotoxicity study revealed that the dendrimers encapsulated with CFTX exhibited 2-3% toxicity against healthy epithelial cells, indicating their safe use. Plain dendrimers show 10-15% hemolytic toxicity against red blood cells (RBC), and the toxicity was reduced to 2-3% when CFTX was conjugated to the same dendrimers. The 3rd and 4th generation synthesized drug-dendrimer conjugates exhibit a significantly effective zone of inhibition (ZOI) against both Gram-positive and Gram-negative bacteria. For Gram-positive bacteria, the lower concentration of 0.1 mg/mL showed more than 98% inhibition of drug-dendrimer conjugate samples against B. subtilis and more than 50% inhibition against S. aureus using 0.2 mg/mL, respectively. Moreover, samples with concentrations of 0.5 and 1.0 mg/mL exhibited more than 50% inhibition against S. typhimurium and E. coli, respectively.
Chemistry Department, National Institute of Technology, Hamirpur,Himachal Pradesh, India.
Biotechnology Division, CSIR- Institute of Himalayan Bioresource Technology, Palampur, Palampur, Himachal Pradesh, India.
Pharmacology and Toxicology Lab, Dietetics and Nutrition Technology Division, CSIR- Institute of Himalayan Bioresource Technology (CSIR-IHBT), Palampur, Himachal Pradesh, India.
Lysine and citric acid based pegylated polymeric dendritic nano drug delivery carrier and their bioactivity evaluation.
Here, we examine how prenatal inflammation shapes tissue function and immunity in the lung by reprogramming tissue-resident immune cells from early development. Maternal, but not fetal, type I interferon-mediated inflammation provokes expansion and hyperactivation of group 2 innate lymphoid cells (ILC2s) seeding the developing lung. Hyperactivated ILC2s produce increased IL-5 and IL-13 and are associated with acute Th2 bias, decreased Tregs, and persistent lung eosinophilia into adulthood. ILC2 hyperactivation is recapitulated by adoptive transfer of fetal liver precursors following prenatal inflammation, indicative of developmental programming at the fetal progenitor level. Reprogrammed ILC2 hyperactivation and subsequent lung immune remodeling, including persistent eosinophilia, is concomitant with worsened histopathology and increased airway dysfunction equivalent to papain exposure, indicating increased asthma susceptibility in offspring. Our data elucidate a mechanism by which early-life inflammation results in increased asthma susceptibility in the presence of hyperactivated ILC2s that drive persistent changes to lung immunity during perinatal development.
Department of Pathology, University of Utah, Salt Lake City, UT, USA.
Department of Biomedical Engineering, University of Utah, Salt Lake City, UT, USA.
Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USA.
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT, USA.
Department of Neurology, University of Utah, Salt Lake City, UT, USA.
Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA.
Department of Medicine, University of Alabama, Birmingham, AL, USA.
Department of Pathology, University of Utah, Salt Lake City, UT, USA; Department of Internal Medicine and Program in Molecular Medicine, University of Utah, Salt Lake City, UT, USA. Electronic address: anna.beaudin@hsc.utah.edu.
Prenatal inflammation remodels lung immunity and function by programming ILC2 hyperactivation.
Many diseases are accompanied by symptoms that can impair the ability to perform complex everyday tasks, such as active participation in road traffic. If a cure is not possible, the aim of drug therapy is to alleviate the symptoms to such an extent that the patient no longer has any restrictions in everyday life. However, around 20% of the approximately 100,000 medicines licensed in Germany have traffic-relevant side effects that can also lead to driving impairment.It is assumed that the effect of a drug is at least partially responsible for one in four traffic accidents and that one in ten victims of fatal road accidents has taken psychotropic drugs before driving. In addition to alcohol and drugs, medications from the benzodiazepine, opioid, and antidepressant groups are suspected of impairing driving safety in particular. The effects of these substances on young people have been described many times, but this review deals specifically with the traffic-relevant (side) effects of various classes of drugs on elderly people (aged 65 and over).Older people in particular often have to take different medications, which are metabolized differently compared to younger people due to underlying diseases and can also interact with each other. It was found that (1) older people often react more sensitively to substances, (2) not all representatives of a drug class have the same effect on driving safety, and (3) a general assessment of a drug's safety is not possible, since the effects also depend on other factors such as underlying diseases, treatment regimen, and the time of day the medication is taken.
Institut für Rechtsmedizin, Forensische Toxikologie, Universitätsklinikum Essen, Hufelandstraße 55, 45122, Essen, Deutschland. TheresaSophia.Boedefeld@uk-essen.de.
Institut für Rechtsmedizin, Universitätsklinikum Essen, Essen, Deutschland.
Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz
Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz
Viele Grunderkrankungen gehen mit Symptomen einher, die die Fähigkeit, komplexe Aufgaben des Alltags zu lösen, beeinträchtigen können. Hierzu gehört auch die aktive Teilnahme am Straßenverkehr. Das Ziel von Arzneimitteltherapien ist es, sofern keine Heilung möglich ist, die Symptome soweit zu lindern, dass der Patient im Alltag so wenig Einschränkungen wie möglich erfährt. Jedoch haben etwa 20 % der ca. 100.000 in Deutschland zugelassenen Arzneimittel verkehrsrelevante Nebenwirkungen, die die Fahrsicherheit ihrerseits ebenfalls beeinträchtigen können.So wird davon ausgegangen, dass an jedem 4. Verkehrsunfall die Wirkung eines Arzneimittels zumindest mitursächlich ist und jeder 10. Verkehrstote Psychopharmaka vor Fahrtantritt eingenommen hat. Neben Alkohol und Drogen stehen insbesondere Medikamente aus der Gruppe der Benzodiazepine, Opioide und Antidepressiva im Verdacht, die Fahrsicherheit zu beeinträchtigen. Die Effekte dieser Substanzen auf junge Menschen sind vielfach beschrieben. In dieser Übersichtsarbeit sollen speziell die verkehrsrelevanten (Neben‑)Wirkungen verschiedener Wirkstoffklassen auf betagte Personen ab 65 Jahren dargestellt werden.Insbesondere Ältere müssen häufig verschiedene Medikamente einnehmen, die aufgrund von Grunderkrankungen anders metabolisiert werden als bei Jüngeren und darüber hinaus interagieren können. Es kann festgestellt werden, dass (1) ältere Personen häufig sensibler auf Substanzen reagieren, (2) nicht alle Vertreter einer Wirkstoffklasse den gleichen Effekt auf die Fahrsicherheit haben und (3) eine pauschale Beurteilung nicht möglich ist, sondern die Wirkungen von weiteren Faktoren, wie zum Beispiel Grunderkrankungen, Therapieregime und Einnahmezeit der Medikation, abhängen.
Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2024-08;67(8):903-909.
[Reduced mobility in the elderly due to medication, alcohol, and cannabinoids].
A key strategy in enhancing the efficacy of collagen-based hydrogels involves incorporating polysaccharides, which have shown great promise for wound healing. In this study, semi-interpenetrating polymeric network (semi-IPN) hydrogels comprised of collagen (Col) with the macrocyclic oligosaccharide β-cyclodextrin (β-CD) (20-80 wt.%) were synthesised. Fourier-transform infrared (FTIR) spectroscopy confirmed the successful fabrication of these Col/β-CD hydrogels, evidenced by the presence of characteristic absorption bands, including the urea bond band at ∼1740 cm-1, related with collagen crosslinking. Higher β-CD content was associated with increased crosslinking, higher swelling, and faster gelation. The β-CD content directly influenced the morphology and semi-crystallinity. All Col/β-CD hydrogels displayed superabsorbent properties, enhanced thermal stability, and exhibited slow degradation rates. Mechanical properties were significantly improved with contents higher than β-CD 40 wt.%. These hydrogels inhibited the growth of Escherichia coli bacteria and facilitated the controlled release of agents, such as malachite green, methylene blue, and ketorolac. The chemical composition of the Col/β-CD hydrogels did not induce cytotoxic effects on monocytes and fibroblast cells. Instead, they actively promoted cellular metabolic activity, encouraging cell growth and proliferation. Moreover, cell signalling modulation was observed, leading to changes in the expression of TNF-α and IL-10 cytokines. In summary, the results of this research indicate that these novel hydrogels possess multifunctional characteristics, including biocompatibility, super-swelling capacity, good thermal, hydrolytic, and enzymatic degradation resistance, antibacterial activity, inflammation modulation, and the ability to be used for controlled delivery of therapeutic agents, indicating high potential for application in advanced wound dressings.
Facultad de Ciencias Químicas, Universidad Autónoma de Coahuila, Saltillo, Mexico.
Centro de Investigación en Química Aplicada, Saltillo, Mexico.
Collagen-β-cyclodextrin hydrogels for advanced wound dressings: super-swelling, antibacterial action, inflammation modulation, and controlled drug release.
Succinate, a citric acid cycle intermediate, serves important functions in energy homeostasis and metabolic regulation. Extracellular succinate acts as a stress signal through succinate receptor (SUCNR1), a class A G protein-coupled receptor. Research on succinate signaling is hampered by the lack of high-resolution structures of the agonist-bound receptor. We present cryoelectron microscopy (cryo-EM) structures of SUCNR1-Gi complexes bound to succinate and its non-metabolite derivative cis-epoxysuccinate. Key determinants for the recognition of succinate in cis conformation include R2817.39 and Y832.64, while Y301.39 and R993.29 participate in the binding of both succinate and cis-epoxysuccinate. Extracellular loop 2, through F175ECL2 in its β-hairpin, forms a hydrogen bond with succinate and caps the binding pocket. At the receptor-Gi interface, agonist binding induces the rearrangement of a hydrophobic network on transmembrane (TM)5 and TM6, leading to TM signaling through TM3 and TM7. These findings extend our understanding of succinate recognition by SUCNR1, aiding the development of therapeutics for the succinate receptor.
Dongguan Songshan Lake Central Hospital, Dongguan Third People's Hospital, The Affiliated Dongguan Songshan Lake Central Hospital, Guangdong Medical University, Dongguan, Guangdong 523326, China; Kobilka Institute of Innovative Drug Discovery, School of Medicine, The Chinese University of Hong Kong, Shenzhen, Guangdong 518172, China; The Chinese University of Hong Kong, Shenzhen Futian Biomedical Innovation R&D Center, Shenzhen, Guangdong 518000, China. Electronic address: liuaijun@cuhk.edu.cn.
Kobilka Institute of Innovative Drug Discovery, School of Medicine, The Chinese University of Hong Kong, Shenzhen, Guangdong 518172, China; The Chinese University of Hong Kong, Shenzhen Futian Biomedical Innovation R&D Center, Shenzhen, Guangdong 518000, China.
Kobilka Institute of Innovative Drug Discovery, School of Medicine, The Chinese University of Hong Kong, Shenzhen, Guangdong 518172, China.
Kobilka Institute of Innovative Drug Discovery, School of Medicine, The Chinese University of Hong Kong, Shenzhen, Guangdong 518172, China; The Chinese University of Hong Kong, Shenzhen Futian Biomedical Innovation R&D Center, Shenzhen, Guangdong 518000, China. Electronic address: richardye@cuhk.edu.cn.
Structural insights into ligand recognition and activation of the succinate receptor SUCNR1.
Growing evidence highlights the impact of e-cigarette use on cardiovascular health, prompting a crucial examination of its association with cardiovascular disease (CVD) in both exclusive e-cigarette and dual use scenarios with combustible cigarettes. This meta-analysis assessed the association between e-cigarette use and CVD by synthesizing the existing literature.Pertinent observational studies were identified using multiple electronic databases, from August 22nd, 2006, to April 10th, 2024. A meta-analysis was conducted using random-effect models. Risk of bias was assessed using the National Institutes of Health (NIH) Study Quality Assessment Tools.A total of 20 observational studies involving 8,499,444 participants were included in the meta-analysis. Dual use (e-cigarettes and combustible cigarette) increased the odds of CVD by 2.56 times (95 % CI: 2.11, 3.11) compared to never use of both. Current e-cigarette use combined with former combustible cigarette increased the odds of CVD by 2.02 times (95 % CI: 1.58, 2.58) compared to never use of either. Exclusive current e-cigarette use did not show a statistically significant association with CVD odds compared to never use of either (OR = 1.24, 95 % CI: 0.93, 1.67).Dual use of e-cigarettes and combustible cigarettes was significantly associated with CVD, but results failed to show a significant association between exclusive e-cigarette use and CVD. Robust and longitudinal studies are needed to understand the long-term implications of e-cigarette use and CVD. Public health efforts should focus on awareness, smoking cessation, and regulating both e-cigarettes and combustible cigarettes.
Copyright © 2024 Elsevier Ltd. All rights reserved.
Department of Epidemiology and Biostatistics, Indiana University School of Public Health-Bloomington, Bloomington, IN, USA. Electronic address: cc18@iu.edu.
Department of Epidemiology and Biostatistics, Indiana University School of Public Health-Bloomington, Bloomington, IN, USA. Electronic address: cuiqhuo@iu.edu.
Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address: pamattey@iu.edu.
Department of Epidemiology and Biostatistics, Indiana University School of Public Health-Bloomington, Bloomington, IN, USA. Electronic address: abidules@indiana.edu.
Department of Epidemiology and Biostatistics, Indiana University School of Public Health-Bloomington, Bloomington, IN, USA. Electronic address: map2@iu.edu.
Assessing the association between e-cigarette use and cardiovascular disease: A meta-analysis of exclusive and dual use with combustible cigarettes.
The previous concept of self-administration as a regulatory body in healthcare in Germany has been repeatedly called into question by politicians. Different approaches can be recognized in various examples. In the author's view, healthcare provision based on legal ordinances and action geared towards legislative periods cannot replace the solutions found by self-administration-neither in terms of content, expertise nor quality. It is precisely the separation of roles and responsibilities between the state and self-administration that has so far ensured that decisions are made close to the healthcare system in order to further develop the healthcare system in Germany based on evidence and without losing sight of the costs.
© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.
Gemeinsamer Bundesausschuss (G-BA), Gutenbergstraße 13, 10587, Berlin, Deutschland. info@g-ba.de.
Das bisherige Konzept der Selbstverwaltung als Regelungsinstanz in der Gesundheitsversorgung in Deutschland wird von politischer Seite wiederholt in Frage gestellt. An verschiedenen Beispielen lassen sich unterschiedliche Vorgehensweisen erkennen. Aus Sicht des Autors kann eine Gesundheitsversorgung auf Basis von Rechtsverordnungen und ein an Legislaturperioden ausgerichtetes Agieren die gefundenen Lösungen der Selbstverwaltung nicht ersetzen – weder inhaltlich-fachlich, noch qualitativ. Gerade die Trennung der Rollen und Verantwortlichkeiten von Staat und Selbstverwaltung gewährleistet bisher, dass versorgungsnahe Entscheidungen getroffen werden, um das Gesundheitssystem in Deutschland evidenzbasiert weiterzuentwickeln und die Kosten nicht aus dem Blick zu verlieren.
[State-organized healthcare instead of patient-organized?]
The intricate interplay between resident cells and the extracellular matrix (ECM) profoundly influences cancer progression. In triple-negative breast cancer (TNBC), ECM architecture evolves due to the enrichment of lysyl oxidase, fibronectin, and collagen, promoting distant metastasis. Here we uncover a pivotal transcription regulatory mechanism involving the epigenetic regulator UBR7 and histone methyltransferase EZH2 in regulating transforming growth factor (TGF)-β/Smad signaling, affecting the expression of ECM genes. UBR7 loss leads to a dramatic reduction in facultative heterochromatin mark H3K27me3, activating ECM genes. UBR7 plays a crucial role in matrix deposition in adherent cancer cells and spheroids, altering collagen content and lysyl oxidase activity, directly affecting matrix stiffness and invasiveness. These findings are further validated in vivo in mice models and TNBC patients, where reduced UBR7 levels are accompanied by increased ECM component expression and activity, leading to fibrosis-mediated matrix stiffness. Thus, UBR7 is a master regulator of matrix stiffening, influencing the metastatic potential of TNBC.
Copyright © 2024 Saha Institute Of Nuclear Physics, Kolkata, India. Published by Elsevier Inc. All rights reserved.
Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064, India; Homi Bhabha National Institute, Mumbai, India.
Chemical Sciences Division, Saha Institute of Nuclear Physics, HBNI, 1/AF Bidhannagar, Kolkata 700064, India; Homi Bhabha National Institute, Mumbai, India.
National Centre for Biological Sciences, TIFR, Bangalore, India.
Chromosome Biology Lab (CBL), Indian Institute of Science Education and Research, Pune, Maharashtra, India.
Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064, India.
Theomics International Pvt Ltd., Bangalore, India.
Department of Surgery, Medical College and Hospital, Kolkata, West Bengal, India.
Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064, India; Homi Bhabha National Institute, Mumbai, India. Electronic address: chandrima.das@saha.ac.in.
UBR7 in concert with EZH2 inhibits the TGF-β signaling leading to extracellular matrix remodeling.
High-dimensional brain activity is often organized into lower-dimensional neural manifolds. However, the neural manifolds of the visual cortex remain understudied. Here, we study large-scale multi-electrode electrophysiological recordings of macaque (Macaca mulatta) areas V1, V4, and DP with a high spatiotemporal resolution. We find that the population activity of V1 contains two separate neural manifolds, which correlate strongly with eye closure (eyes open/closed) and have distinct dimensionalities. Moreover, we find strong top-down signals from V4 to V1, particularly to the foveal region of V1, which are significantly stronger during the eyes-open periods. Finally, in silico simulations of a balanced spiking neuron network qualitatively reproduce the experimental findings. Taken together, our analyses and simulations suggest that top-down signals modulate the population activity of V1. We postulate that the top-down modulation during the eyes-open periods prepares V1 for fast and efficient visual responses, resulting in a type of visual stand-by state.
Copyright © 2024 Forschungszentrum Juelich GmbH. Published by Elsevier Inc. All rights reserved.
Institute for Advanced Simulation (IAS-6), Jülich Research Centre, Jülich, Germany; Institute of Zoology, University of Cologne, Cologne, Germany. Electronic address: a.morales-gregorio@fz-juelich.com.
Institute for Advanced Simulation (IAS-6), Jülich Research Centre, Jülich, Germany; RWTH Aachen University, Aachen, Germany.
Institute for Advanced Simulation (IAS-6), Jülich Research Centre, Jülich, Germany.
Institute for Advanced Simulation (IAS-6), Jülich Research Centre, Jülich, Germany; Theoretical Systems Neurobiology, RWTH Aachen University, Aachen, Germany.
Institute for Advanced Simulation (IAS-6), Jülich Research Centre, Jülich, Germany; Institut de Neurosciences de la Timone (INT), CNRS and Aix-Marseille Université, Marseille, France.
Institut de Neurosciences de la Timone (INT), CNRS and Aix-Marseille Université, Marseille, France.
Institute for Advanced Simulation (IAS-6), Jülich Research Centre, Jülich, Germany; Theoretical Systems Neurobiology, RWTH Aachen University, Aachen, Germany; JARA-Institut Brain Structure-Function Relationships (INM-10), Jülich Research Centre, Jülich, Germany.
Institute for Advanced Simulation (IAS-6), Jülich Research Centre, Jülich, Germany; Institute of Zoology, University of Cologne, Cologne, Germany.
Neural manifolds in V1 change with top-down signals from V4 targeting the foveal region.
Uncertainties still existed about the effect of high-quality protein supplementation on cardiovascular disease (CVD) risk factors, although high-quality proteins such as soy and milk proteins have proposed to be beneficial for cardiometabolic health.A systematic search in PubMed, Web of Science, Cochrane Library, Scopus, and Embase was conducted to quantify the impact of high-quality protein on CVD risk factors.63 RCTs on 4 types of high-quality protein including soy protein, milk protein, whey, and casein were evaluated. Soy protein supplementation decreased systolic blood pressure (SBP, -1.42 [-2.68, -0.17] mmHg), total cholesterol (TC, -0.18 [-0.30, -0.07] mmol/L), and low-density lipoprotein cholesterol (LDL-C, -0.16 [-0.27, -0.05] mmol/L). Milk protein supplementation decreased SBP (-2.30 [-3.45, -1.15] mmHg) and total cholesterol (-0.27 [-0.51, -0.03] mmol/L). Whey supplementation decreased SBP (-2.20 [-3.89, -0.51] mmHg), diastolic blood pressure (DBP, -1.07 [-1.98, -0.16] mmHg), triglycerides (-0.10 [-0.17, -0.03] mmol/L), TC (-0.18 [-0.35, -0.01] mmol/L), LDL-C (-0.09 [-0.16, -0.01] mmol/L) and fasting blood insulin (FBI, -2.02 [-3.75, -0.29] pmol/L). Casein supplementation decreased SBP (-4.10 [-8.05, -0.14] mmHg). In the pooled analysis of four high-quality proteins, differential effects were seen in individuals with different health status. In hypertensive individuals, high-quality proteins decreased both SBP (-2.69 [-3.50, -1.87] mmHg) and DBP (-1.34 [-2.09, -0.60] mmHg). In overweight/obese individuals, high-quality proteins improved SBP (-1.40 [-2.22, -0.59] mmHg), DBP (-2.59 [-3.20, -1.98] mmHg), triglycerides (-0.09 [-0.15, -0.02] mmol/L), TC (-0.14 [-0.22, -0.05] mmol/L), LDL-C (-0.12 [-0.16, -0.07] mmol/L), and HDL-C levels (0.02 [0.01, 0.04] mmol/L). According to the benefits on CVD risks factors, whey ranked top for improving cardiometabolic health in hypertensive or overweight/obese individuals.Our study supports a beneficial role of high-quality protein supplementation to reduce CVD risk factors. Further studies are still warranted to investigate the effects of different high-quality proteins on CVD risks in individuals with cardiometabolic disorders.
Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
Department of Nutrition and Health, China Agricultural University, Beijing 100193, China.
Institute of Medical Technology, Peking University Health Science Center, Beijing 100191, China.
National Center of Technology Innovation for Dairy, Hohhot 010110, China.
Beijing Hospital/National Center of Gerontology of National Health Commission, Beijing 100730, China.
Department of Nutrition and Health, China Agricultural University, Beijing 100193, China. Electronic address: luojj@cau.edu.cn.
Department of Nutrition and Health, China Agricultural University, Beijing 100193, China. Electronic address: luo_yongting@163.com.
Department of Nutrition and Health, China Agricultural University, Beijing 100193, China. Electronic address: an-peng@cau.edu.cn.
Clinical nutrition (Edinburgh, Scotland)
Effects of high-quality protein supplementation on cardiovascular risk factors in individuals with metabolic diseases: A systematic review and meta-analysis of randomized controlled trials.
Inhibition of nucleic acid targets is mediated by Argonaute (Ago) proteins guided by RNA or DNA. Although the mechanisms underpinning the functions of eukaryotic and long prokaryotic Ago proteins (pAgos) are well understood, those for short pAgos remain enigmatic. Here, we determine two cryoelectron microscopy structures of short pAgos in association with the NADase-domain-containing protein Sir2-APAZ from Geobacter sulfurreducens (GsSir2/Ago): the guide RNA-target DNA-loaded GsSir2/Ago quaternary complex (2.58 Å) and the dimer of the quaternary complex (2.93Å). These structures show that the nucleic acid binding causes profound conformational changes that result in disorder or partial dissociation of the Sir2 domain, suggesting that it adopts a NADase-active conformation. Subsequently, two RNA-/DNA-loaded GsSir2/Ago complexes form a dimer through their MID domains, further enhancing NADase activity through synergistic effects. The findings provide a structural basis for short-pAgo-mediated defense against invading nucleic acids.
Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China.
NHC Key Laboratory of Systems Biology of Pathogens, State Key Laboratory of Respiratory Health and Multimorbidity, National Institute of Pathogen Biology and Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China; Key Laboratory of Pathogen Infection Prevention and Control (Ministry of Education), National Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China.
NHC Key Laboratory of Systems Biology of Pathogens, State Key Laboratory of Respiratory Health and Multimorbidity, National Institute of Pathogen Biology and Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China; Medical School, Yan'an University, Yan'an, Shaanxi 716000, China.
NHC Key Laboratory of Systems Biology of Pathogens, State Key Laboratory of Respiratory Health and Multimorbidity, National Institute of Pathogen Biology and Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China; Key Laboratory of Pathogen Infection Prevention and Control (Ministry of Education), National Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China. Electronic address: gaoxiaopan@pumc.edu.cn.
Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China; Songshan Lake Materials Laboratory, Dongguan, Guangdong 523808, China. Electronic address: wangym@iphy.ac.cn.
NHC Key Laboratory of Systems Biology of Pathogens, State Key Laboratory of Respiratory Health and Multimorbidity, National Institute of Pathogen Biology and Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China; Key Laboratory of Pathogen Infection Prevention and Control (Ministry of Education), National Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China. Electronic address: cui.sheng@ipb.pumc.edu.cn.
Nucleic acid-induced NADase activation of a short Sir2-associated prokaryotic Argonaute system.
During behavior, the motor cortex sends copies of motor-related signals to sensory cortices. Here, we combine closed-loop behavior with large-scale physiology, projection-pattern-specific recordings, and circuit perturbations to show that neurons in mouse secondary motor cortex (M2) encode sensation and are influenced by expectation. When a movement unexpectedly produces a sound, M2 becomes dominated by sound-evoked activity. Sound responses in M2 are inherited partially from the auditory cortex and are routed back to the auditory cortex, providing a path for the reciprocal exchange of sensory-motor information during behavior. When the acoustic consequences of a movement become predictable, M2 responses to self-generated sounds are selectively gated off. These changes in single-cell responses are reflected in population dynamics, which are influenced by both sensation and expectation. Together, these findings reveal the embedding of sensory and expectation signals in motor cortical activity.
Center for Neural Science, New York University, New York, NY 10003, USA; Neuroscience Institute, NYU Medical Center, New York, NY 10016, USA.
Center for Neural Science, New York University, New York, NY 10003, USA. Electronic address: david.schneider@nyu.edu.
Sensation and expectation are embedded in mouse motor cortical activity.
Alcohol is the most widely used addictive substance, potentially leading to brain damage and genetic abnormalities. Despite its prevalence and associated risks, current treatments have yet to identify effective methods for reducing cravings and preventing relapse. In this study, we find that 4-Hz alternating bilateral sensory stimulation (ABS) effectively reduces ethanol-induced conditioned place preference (CPP) in male mice, while 4-Hz flash light does not exhibit therapeutic effects. Whole-brain c-Fos mapping demonstrates that 4-Hz ABS triggers notable activation in superior colliculus GABAergic neurons (SCGABA). SCGABA forms monosynaptic connections with ventral tegmental area dopaminergic neurons (VTADA), which is implicated in ethanol-induced CPP. Bidirectional chemogenetic manipulation of SC-VTA circuit either replicates or blocks the therapeutic effects of 4-Hz ABS on ethanol-induced CPP. These findings elucidate the role of SC-VTA circuit for alleviating ethanol-related CPP by 4-Hz ABS and point to a non-drug and non-invasive approach that might have potential for treating alcohol use disorder.
Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China; Institute for Brain Research, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China; Key Laboratory of Neurological Diseases, Ministry of Education, Wuhan, Hubei, P.R. China. Electronic address: zhangpei@hust.edu.cn.
Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China; School of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei, P.R. China; Institute for Brain Research, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China; Key Laboratory of Neurological Diseases, Ministry of Education, Wuhan, Hubei, P.R. China. Electronic address: tianbo@mails.tjmu.edu.cn.
Alternating bilateral sensory stimulation alleviates alcohol-induced conditioned place preference via a superior colliculus-VTA circuit.
Polymyxins are often the only effective antibiotics against the Critical pathogen Acinetobacter baumannii. Worryingly, highly polymyxin-resistant A. baumannii displaying dependence on polymyxins has emerged in the clinic, leading to diagnosis and treatment failures. Here, we report that arginine metabolism is essential for polymyxin-dependent A. baumannii. Specifically, the arginine degradation pathway was significantly altered in polymyxin-dependent strains compared to wild-type strains, with critical metabolites (e.g., L-arginine and L-glutamate) severely depleted and expression of the astABCDE operon significantly increased. Supplementation of arginine increased bacterial metabolic activity and suppressed polymyxin dependence. Deletion of astA, the first gene in the arginine degradation pathway, decreased phosphatidylglycerol and increased phosphatidylethanolamine levels in the outer membrane, thereby reducing the interaction with polymyxins. This study elucidates the molecular mechanism by which arginine metabolism impacts polymyxin dependence in A. baumannii, underscoring its critical role in improving diagnosis and treatment of life-threatening infections caused by undetectable polymyxin-dependent A. baumannii.
Infection Program and Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; Centre to Impact AMR, Monash University, Clayton, VIC 3800, Australia. Electronic address: meiling.han@monash.edu.
Infection Program and Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; Centre to Impact AMR, Monash University, Clayton, VIC 3800, Australia.
National Glycoengineering Research Centre, Shandong University, Qingdao 266237, China.
Australian Centre for Neutron Scattering, Australian Nuclear Science and Technology Organisation, Locked Bag 2001, Kirrawee DC, NSW 2232, Australia.
Monash Proteomics and Metabolomics Facility, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.
Department of Materials Science and Engineering, Faculty of Engineering, Monash University, Clayton, VIC 3800, Australia.
Monash Proteomics and Metabolomics Facility, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia.
Department of Pharmacology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.
Infection Program and Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; Centre to Impact AMR, Monash University, Clayton, VIC 3800, Australia. Electronic address: jian.li@monash.edu.
Arginine catabolism is essential to polymyxin dependence in Acinetobacter baumannii.
This study aimed to synthesize and characterize chitosan-coated noisomal doxorubicin for the purpose of enhancing its medical application, particularly in the field of cancer treatment. Doxorubicin, a potent chemotherapeutic agent, was encapsulated within noisomes, which are lipid-based nanocarriers known for their ability to efficiently deliver drugs to target sites. Chitosan, a biocompatible and biodegradable polysaccharide, was used to coat the surface of the noisomes to improve their stability and enhance drug release properties. The synthesized chitosan-coated noisomal doxorubicin was subjected to various characterization techniques to evaluate its physicochemical properties. Transmission electron microscopy (TEM) revealed a spherical structure with a diameter of 500-550 ± 5.45 nm and zeta potential of +11 ± 0.13 mV with no aggregation or agglomeration. Chitosan-coated noisomes can loaded doxorubicin with entrapping efficacy 75.19 ± 1.45%. While scanning electron microscopy (SEM) revealed well-defined pores within a fibrous surface. It is observed that chitosan-coated niosomes loading doxorubicin have optimum roughness (22.88 ± 0.71 nm). UV spectroscopy was employed to assess the drug encapsulation efficiency and release profile. Differential scanning calorimetry (DSC) helped determine the thermal behavior, which indicated a broad endotherm peak at 52.4 °C, while X-ray diffraction (XRD) analysis provided information about the crystallinity of the formulation with an intense peak at 23.79°. Fourier-transform infrared spectroscopy (FTIR) indicated the formation of new bonds between the drug and the polymer. The findings from this study will contribute to the knowledge of the physical and chemical properties of the synthesized formulation, which is crucial for ensuring its stability, drug release kinetics, and biological activity. The enhanced chitosan-coated noisomal doxorubicin has the potential to improve the effectiveness and safety of doxorubicin in cancer treatment, offering a promising strategy for enhanced medical applications.
Radiology and Medical Imaging Department, College of Applied Medical Sciences, Prince Sattam Bin Abdul-Aziz University, Al-Kharj, Saudi Arabia.Biophysics Department, Faculty of Science, Cairo University, Cairo, Egypt.
Physics Department, Center of Basics Science, Misr University for Science and Technology, 6th of October City, Egypt.
Biophysics Department, Faculty of Science, Cairo University, Cairo, Egypt.
Preparation and characterization of chitosan-coated noisomal doxorubicin for enhanced its medical application.
Oligodendrocyte death is common in aging and neurodegenerative disease. In these conditions, dying oligodendrocytes must be efficiently removed to allow remyelination and to prevent a feedforward degenerative cascade. Removal of this cellular debris is thought to primarily be carried out by resident microglia. To investigate the cellular dynamics underlying how microglia do this, we use a single-cell cortical demyelination model combined with longitudinal intravital imaging of dual-labeled transgenic mice. Following phagocytosis, single microglia clear the targeted oligodendrocyte and its myelin sheaths in one day via a precise, rapid, and stereotyped sequence. Deletion of the fractalkine receptor, CX3CR1, delays the microglial phagocytosis of the cell soma but has no effect on clearance of myelin sheaths. Unexpectedly, deletion of the phosphatidylserine receptor, MERTK, has no effect on oligodendrocyte or myelin sheath clearance. Thus, separate molecular signals are used to detect, engage, and clear distinct sub-compartments of dying oligodendrocytes to maintain tissue homeostasis.
Department of Biological Sciences, Dartmouth College, Hanover, NH 03755, USA.
Department of Biological Sciences, Dartmouth College, Hanover, NH 03755, USA. Electronic address: robert.hill@dartmouth.edu.
Microglial phagocytosis of single dying oligodendrocytes is mediated by CX3CR1 but not MERTK.
Mechanosensitive Piezo channels regulate cell division, cell extrusion, and cell death. However, systems-level functions of Piezo in regulating organogenesis remain poorly understood. Here, we demonstrate that Piezo controls epithelial cell topology to ensure precise organ growth by integrating live-imaging experiments with pharmacological and genetic perturbations and computational modeling. Notably, the knockout or knockdown of Piezo increases bilateral asymmetry in wing size. Piezo's multifaceted functions can be deconstructed as either autonomous or non-autonomous based on a comparison between tissue-compartment-level perturbations or between genetic perturbation populations at the whole-tissue level. A computational model that posits cell proliferation and apoptosis regulation through modulation of the cutoff tension required for Piezo channel activation explains key cell and tissue phenotypes arising from perturbations of Piezo expression levels. Our findings demonstrate that Piezo promotes robustness in regulating epithelial topology and is necessary for precise organ size control.
Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, IN 46556, USA; Bioengineering Graduate Program, University of Notre Dame, Notre Dame, IN 46556, USA.
Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, IN 46556, USA.
Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, IN 46556, USA; Bioengineering Graduate Program, University of Notre Dame, Notre Dame, IN 46556, USA; Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556, USA. Electronic address: jzartman@nd.edu.
Piezo regulates epithelial topology and promotes precision in organ size control.
In contrast to most hematopoietic lineages, megakaryocytes (MKs) can derive rapidly and directly from hematopoietic stem cells (HSCs). The underlying mechanism is unclear, however. Here, we show that DNA damage induces MK markers in HSCs and that G2 arrest, an integral part of the DNA damage response, suffices for MK priming followed by irreversible MK differentiation in HSCs, but not in progenitors. We also show that replication stress causes DNA damage in HSCs and is at least in part due to uracil misincorporation in vitro and in vivo. Consistent with this notion, thymidine attenuated DNA damage, improved HSC maintenance, and reduced the generation of CD41+ MK-committed HSCs. Replication stress and concomitant MK differentiation is therefore one of the barriers to HSC maintenance. DNA damage-induced MK priming may allow rapid generation of a lineage essential to immediate organismal survival, while also removing damaged cells from the HSC pool.
Columbia Center for Human Development/Center for Stem Cell Therapies, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA; Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA; Department of Genetics and Development, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
Columbia Center for Human Development/Center for Stem Cell Therapies, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA; Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA.
Department of Microbiology and Immunology, University of Illinois at Chicago College of Medicine, Chicago, IL 60612, USA.
Columbia Center for Human Development/Center for Stem Cell Therapies, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA; Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA; Department of Microbiology and Immunology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA. Electronic address: hs2680@columbia.edu.
G2 arrest primes hematopoietic stem cells for megakaryopoiesis.
Kisspeptin signaling through its G protein-coupled receptor, KISS1R, plays an indispensable role in regulating reproduction via the hypothalamic-pituitary-gonadal axis. Dysregulation of this pathway underlies severe disorders like infertility and precocious puberty. Here, we present cryo-EM structures of KISS1R bound to the endogenous agonist kisspeptin-10 and a synthetic analog TAK-448. These structures reveal pivotal interactions between peptide ligands and KISS1R extracellular loops for receptor activation. Both peptides exhibit a conserved binding mode, unveiling their common activation mechanism. Intriguingly, KISS1R displays a distinct 40° angular deviation in its intracellular TM6 region compared to other Gq-coupled receptors, enabling distinct interactions with Gq. This study reveals the molecular intricacies governing ligand binding and activation of KISS1R, while highlighting its exceptional ability to couple with Gq. Our findings pave the way for structure-guided design of therapeutics targeting this physiologically indispensable receptor.
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China.
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China. Electronic address: eric.xu@simm.ac.cn.
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: duanjia@simm.ac.cn.
Structural basis for hormone recognition and distinctive Gq protein coupling by the kisspeptin receptor.
ADAR1-mediated RNA editing establishes immune tolerance to endogenous double-stranded RNA (dsRNA) by preventing its sensing, primarily by MDA5. Although deleting Ifih1 (encoding MDA5) rescues embryonic lethality in ADAR1-deficient mice, they still experience early postnatal death, and removing other MDA5 signaling proteins does not yield the same rescue. Here, we show that ablation of MDA5 in a liver-specific Adar knockout (KO) murine model fails to rescue hepatic abnormalities caused by ADAR1 loss. Ifih1;Adar double KO (dKO) hepatocytes accumulate endogenous dsRNAs, leading to aberrant transition to a highly inflammatory state and recruitment of macrophages into dKO livers. Mechanistically, progranulin (PGRN) appears to mediate ADAR1 deficiency-induced liver pathology, promoting interferon signaling and attracting epidermal growth factor receptor (EGFR)+ macrophages into dKO liver, exacerbating hepatic inflammation. Notably, the PGRN-EGFR crosstalk communication and consequent immune responses are significantly repressed in ADAR1high tumors, revealing that pre-neoplastic or neoplastic cells can exploit ADAR1-dependent immune tolerance to facilitate immune evasion.
Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore; School of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou, P.R. China.
Genome Institute of Singapore, Agency for Science Technology and Research, 60 Biopolis Street, Genome, #02-01, Singapore, Singapore.
School of Biological Sciences, Nanyang Technological University, Singapore, Singapore; NTU Institute of Structural Biology, Nanyang Technological University, Singapore, Singapore.
Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore; Division of Gastroenterology and Hepatology, National University Health System, Singapore, Singapore.
Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore; NUS Center for Cancer Research, Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore; Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. Electronic address: polly_chen@nus.edu.sg.
Hepatocyte-macrophage crosstalk via the PGRN-EGFR axis modulates ADAR1-mediated immunity in the liver.
Circadian rhythms are internal biological rhythms driving temporal tissue-specific, metabolic programs. Loss of the circadian transcription factor BMAL1 in the paraventricular nucleus (PVN) of the hypothalamus reveals its importance in metabolic rhythms, but its functions in individual PVN cells are poorly understood. Here, loss of BMAL1 in the PVN results in arrhythmicity of processes controlling energy balance and alters peripheral diurnal gene expression. BMAL1 chromatin immunoprecipitation sequencing (ChIP-seq) and single-nucleus RNA sequencing (snRNA-seq) reveal its temporal regulation of target genes, including oxytocin (OXT), and restoring circulating OXT peaks in BMAL1-PVN knockout (KO) mice rescues absent activity rhythms. While glutamatergic neurons undergo day/night changes in expression of genes involved in cell morphogenesis, astrocytes and oligodendrocytes show gene expression changes in cytoskeletal organization and oxidative phosphorylation. Collectively, our findings show diurnal gene regulation in neuronal and non-neuronal PVN cells and that BMAL1 contributes to diurnal OXT secretion, which is important for systemic diurnal rhythms.
UT Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; MD Anderson Cancer Center/UTHealth Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Center for Precision Health, McWilliams School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
UT Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Department of Neurosurgery, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
UT Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
MD Anderson Cancer Center/UTHealth Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Department of Biochemistry and Cell Biology, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
UT Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; MD Anderson Cancer Center/UTHealth Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Department of Integrative Biology and Pharmacology, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
UT Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; MD Anderson Cancer Center/UTHealth Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Department of Neurosurgery, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
UT Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; MD Anderson Cancer Center/UTHealth Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, Houston, TX 77030, USA. Electronic address: kristin.l.mahan@uth.tmc.edu.
Cell-specific regulation of the circadian clock by BMAL1 in the paraventricular nucleus: Implications for regulation of systemic biological rhythms.
Honeybees are important pollinators worldwide, with their gut microbiota playing a crucial role in maintaining their health. The gut bacteria of honeybees consist of primarily five core lineages that are spread through social interactions. Previous studies have provided a basic understanding of the composition and function of the honeybee gut microbiota, with recent advancements focusing on analyzing diversity at the strain level and changes in bacterial functional genes. Research on honeybee gut microbiota across different regions globally has provided insights into microbial ecology. Additionally, recent findings have shed light on the mechanisms of host specificity of honeybee gut bacteria. This review explores the temporospatial dynamics in honeybee gut microbiota, discussing the reasons and mechanisms behind these fluctuations. This synopsis provides insights into host-microbe interactions and is invaluable for honeybee health.
Department of Entomology, College of Plant Protection, China Agricultural University, Beijing 100193, China.
Department of Entomology, College of Plant Protection, China Agricultural University, Beijing 100193, China. Electronic address: xinzhou@cau.edu.cn.
Temporospatial dynamics and host specificity of honeybee gut bacteria.
The internet has become an integral part of daily life, impacting various aspects, especially among children and adolescents. Internet overuse has been associated with numerous physical and mental health issues. Despite its significant implications, there is no universally accepted assessment tool for internet addiction. This study focuses on validating the Georgian version of the Internet Addiction Test (IAT) among pediatric patients aged 9 to 17, specifically the Internet Addiction Test - Adolescence (IAT - A).The study, conducted in 2022-2023, involved pediatric patients from Givi Zhvania Pediatric Academic Clinic, generally healthy but with parental concerns about screen time. The IAT-A, a self-administered questionnaire, was adapted for cultural relevance. Translation-back-translation was employed for linguistic validation. Data was collected twice, with a 6-month interval. Statistical analyses included the Kappa coefficient, Kendall's tau test, paired t-test, and Bland-Altman plots.The translation process ensured linguistic accuracy and cultural relevance. The study included 100 participants (59 % boys, 41 % girls) with a mean age of 12 years. The mean IAT - A score remained consistently high over both testing periods. Kendall's tau correlation coefficient indicated a strong correlation (0.97), and Bland-Altman plots confirmed repeatability. The cut-off of 40 points identified 84 % as problematic internet users. Individual question analysis showed strong correlation and agreement.The Georgian version of the IAT - A demonstrated reliability and consistency in assessing internet addiction among pediatric patients. The prevalence of problematic internet use among children referred to a university hospital because parents were worried about their internet use was indeed high. The study contributes valuable insights into internet addiction research in Georgia and underscores the importance of a standardized assessment tool. The repeatability of the scores of each question was strong among both groups of problematic internet users and non-problematic internet users, confirming that the Georgian version of IAT - A has high level of accuracy and can be used in internet addiction research.
Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.
Department of Pediatric Neurology, Tbilisi State Medical University, Tbilisi, Georgia. Electronic address: T.nadiradze@tsmu.edu.
Department of Pediatric Neurology, Tbilisi State Medical University, Tbilisi, Georgia.
Department of Physiology, Tbilisi State Medical University, Tbilisi, Georgia.
European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society
Validation of the Internet Addiction Test for Adolescents (IAT-A) in the Georgian language.
Macrophages play crucial roles in organ-specific functions and homeostasis. In the adrenal gland, macrophages closely associate with sinusoidal capillaries in the aldosterone-producing zona glomerulosa. We demonstrate that macrophages preserve capillary specialization and modulate aldosterone secretion. Using macrophage-specific deletion of VEGF-A, single-cell transcriptomics, and functional phenotyping, we found that the loss of VEGF-A depletes PLVAP+ fenestrated endothelial cells in the zona glomerulosa, leading to increased basement membrane collagen IV deposition and subendothelial fibrosis. This results in increased aldosterone secretion, called haptosecretagogue signaling. Human aldosterone-producing adenomas also show capillary rarefaction and basement membrane thickening. Mice with myeloid cell-specific VEGF-A deletion exhibit elevated serum aldosterone, hypokalemia, and hypertension, mimicking primary aldosteronism. These findings underscore macrophage-to-endothelial cell signaling as essential for endothelial cell specialization, adrenal gland function, and blood pressure regulation, with broader implications for other endocrine organs.
University of Zurich, Institute of Anatomy, 8057 Zurich, Switzerland. Electronic address: zheng.fan@anatomy.uzh.ch.
University of Zurich, Institute of Anatomy, 8057 Zurich, Switzerland.
Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
University of Zurich, Institute for Experimental Immunology, 8057 Zurich, Switzerland.
Laboratory of Nutrition and Metabolic Epigenetics, Institute for Food, Nutrition and Health, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.
Department of Translational Medical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy.
Electrophysiology Facility (e-phac), Department of Molecular Life Sciences, University of Zurich (UZH), 8057 Zürich, Switzerland.
Cardiovascular Research Center and Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT, USA.
INSERM U970, Paris Cardiovascular Research Center, Paris, France.
Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, Japan.
Institute of Pharmacology and Clinical Pharmacology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
Klinik für Endokrinologie, Diabetologie, und Klinische Ernährung, UniversitätsSpital Zürich (USZ) and UZH, Raemistrasse 100, 8091 Zurich, Switzerland; Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-University (LMU), Munich, Germany.
Klinik für Endokrinologie, Diabetologie, und Klinische Ernährung, UniversitätsSpital Zürich (USZ) and UZH, Raemistrasse 100, 8091 Zurich, Switzerland.
University of Zurich, Institute of Anatomy, 8057 Zurich, Switzerland; INSERM U970, Paris Cardiovascular Research Center, Paris, France. Electronic address: christian.stockmann@anatomy.uzh.ch.
Macrophages preserve endothelial cell specialization in the adrenal gland to modulate aldosterone secretion and blood pressure.
Rationale: Prone positioning for ⩾16 hours in moderate-to-severe acute respiratory distress syndrome (ARDS) improves survival. However, the optimal duration of proning is unknown. Objectives: To estimate the effect of extended versus standard proning duration on patients with moderate-to-severe coronavirus disease (COVID-19) ARDS. Methods: Data were extracted from a five-hospital electronic medical record registry. Patients who were proned within 72 hours of mechanical ventilation were categorized as receiving extended (⩾24 h) versus standard (16-24 h) proning based on the first proning session length. We used a target trial emulation design to estimate the effect of extended versus standard proning on the primary outcome of 90-day mortality and secondary outcomes of ventilator liberation and intensive care unit (ICU) discharge. Analytically, we used inverse probability of treatment weighted (IPTW) Cox or Fine-Gray regression models. Results: A total of 314 patients were included; 234 received extended proning, and 80 received standard-duration proning. Patients who received extended proning were older, had greater comorbidity, were more often at an academic hospital, and had shorter time from admission to mechanical ventilation. After IPTW, characteristics were well balanced. Unadjusted 90-day mortality in the extended versus standard proning groups was 39% versus 58%. In doubly robust IPTW analyses, we found no significant effects of extended versus standard proning duration on mortality (hazard ratio [95% confidence interval], 0.95 [0.51-1.77]), ventilator liberation (subdistribution hazard, 1.60 [0.97-2.64], or ICU discharge (subdistribution hazard, 1.31 [0.82-2.10]). Conclusions: Using target trial emulation, we found no significant effect of extended versus standard proning duration on mortality, ventilator liberation, or ICU discharge. However, given the imprecision of estimates, further study is justified.
Division of Pulmonary and Critical Care Medicine, Department of Medicine.
Department of Biostatistics, Bloomberg School of Public Health.Outcomes After Critical Illness and Surgery (OACIS) Group.
Division of Pulmonary and Critical Care Medicine, Department of Medicine.Outcomes After Critical Illness and Surgery (OACIS) Group.
Interdepartmental Division of Critical Care Medicine, University Health Network and Sinai Health System, University of Toronto, Toronto, Ontario, Canada.
Department of Pediatrics, School of Medicine.
Division of Pulmonary and Critical Care Medicine, Department of Medicine.Bloomberg School of Public Health, and.
Division of Pulmonary and Critical Care Medicine, Department of Medicine.Outcomes After Critical Illness and Surgery (OACIS) Group.Department of Physical Medicine and Rehabilitation, School of Medicine, Johns Hopkins University, Baltimore, Maryland; and.
Extended versus Standard Proning Duration for COVID-19-associated Acute Respiratory Distress Syndrome: A Target Trial Emulation Study.
GGGGCC (G4C2) repeat expansion in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). How this genetic mutation leads to neurodegeneration remains largely unknown. Using CRISPR-Cas9 technology, we deleted EXOC2, which encodes an essential exocyst subunit, in induced pluripotent stem cells (iPSCs) derived from C9ORF72-ALS/FTD patients. These cells are viable owing to the presence of truncated EXOC2, suggesting that exocyst function is partially maintained. Several disease-relevant cellular phenotypes in C9ORF72 iPSC-derived motor neurons are rescued due to, surprisingly, the decreased levels of dipeptide repeat (DPR) proteins and expanded G4C2 repeats-containing RNA. The treatment of fully differentiated C9ORF72 neurons with EXOC2 antisense oligonucleotides also decreases expanded G4C2 repeats-containing RNA and partially rescued disease phenotypes. These results indicate that EXOC2 directly or indirectly regulates the level of G4C2 repeats-containing RNA, making it a potential therapeutic target in C9ORF72-ALS/FTD.
Frontotemporal Dementia Research Center, RNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA; Graduate Program in Neuroscience, Morningside Graduate School of Biomedical Sciences, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Frontotemporal Dementia Research Center, RNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Department of Molecular, Cell, and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Department of Neurology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Neuromuscular & Muscle Disorders, Biogen, Cambridge, MA 02142, USA.
Frontotemporal Dementia Research Center, RNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA; Graduate Program in Neuroscience, Morningside Graduate School of Biomedical Sciences, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA; Department of Neurology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA. Electronic address: fen-biao.gao@umassmed.edu.
The exocyst subunit EXOC2 regulates the toxicity of expanded GGGGCC repeats in C9ORF72-ALS/FTD.
The intestinal environment facilitates HIV-1 infection via mechanisms involving the gut-homing vitamin A-derived retinoic acid (RA), which transcriptionally reprograms CD4+ T cells for increased HIV-1 replication/outgrowth. Consistently, colon-infiltrating CD4+ T cells carry replication-competent viral reservoirs in people with HIV-1 (PWH) receiving antiretroviral therapy (ART). Intriguingly, integrative infection in colon macrophages, a pool replenished by monocytes, represents a rare event in ART-treated PWH, thus questioning the effect of RA on macrophages. Here, we demonstrate that RA enhances R5 but not X4 HIV-1 replication in monocyte-derived macrophages (MDMs). RNA sequencing, gene set variation analysis, and HIV interactor NCBI database interrogation reveal RA-mediated transcriptional reprogramming associated with metabolic/inflammatory processes and HIV-1 resistance/dependency factors. Functional validations uncover post-entry mechanisms of RA action including SAMHD1-modulated reverse transcription and CDK9/RNA polymerase II (RNAPII)-dependent transcription under the control of mammalian target of rapamycin (mTOR). These results support a model in which macrophages residing in the intestine of ART-untreated PWH contribute to viral replication/dissemination in an mTOR-sensitive manner.
Département de microbiologie, infectiologie et immunologie, Faculté de médecine, Université de Montréal, Montréal, QC, Canada; Centre de recherche du centre hospitalier de l'Université de Montréal (CR-CHUM), Montréal, QC, Canada.
Service of Molecular Virology, Department of Molecular Biology (DBM), Université libre de Bruxelles (ULB), 6041 Gosselies, Belgium.
Institut de recherches cliniques de Montréal, Montréal, QC, Canada.
Centre de recherche du centre hospitalier de l'Université de Montréal (CR-CHUM), Montréal, QC, Canada.
Centre de recherche du centre hospitalier de l'Université de Montréal (CR-CHUM), Montréal, QC, Canada; Department of Microbiology and Immunology, McGill University Health Centre, Montréal, QC, Canada.
Infectious Diseases and Immunity in Global Health Program, Research Institute, McGill University Health Centre, Montréal, QC, Canada; Chronic Viral Illness Service, McGill University Health Centre, Montréal, QC, Canada; Division of Hematology, McGill University Health Centre, Montreal, QC, Canada.
Département de microbiologie, infectiologie et immunologie, Faculté de médecine, Université de Montréal, Montréal, QC, Canada; Institut de recherches cliniques de Montréal, Montréal, QC, Canada.
Service of Molecular Virology, Department of Molecular Biology (DBM), Université libre de Bruxelles (ULB), 6041 Gosselies, Belgium. Electronic address: carine.vanlint@ulb.be.
Département de microbiologie, infectiologie et immunologie, Faculté de médecine, Université de Montréal, Montréal, QC, Canada; Centre de recherche du centre hospitalier de l'Université de Montréal (CR-CHUM), Montréal, QC, Canada. Electronic address: petronela.ancuta@umontreal.ca.
Retinoic acid enhances HIV-1 reverse transcription and transcription in macrophages via mTOR-modulated mechanisms.
Innovation chemotherapeutic nano drug delivery systems (NDDSs) with various pharmacological achievement have become one of the hopeful therapeutic strategies in cancer therapy. This study focused on low pH, and high levels of glutathione (GSH) as two prominent characteristics of the tumor microenvironment (TME) to design a novel TME-targeted pH/redox dual-responsive P (AMA-co-DMAEMA)-b-PCL-SS-PCL-b-P (AMA-co-DMAEMA) nanoparticles (NPs) for deep tumor penetration and targeted anti-tumor therapy. The positively charged NPs exhibit strong electrostatic interactions with negatively charged cell membranes, significantly enhancing cellular uptake. Moreover, these NPs possess the unique size-shrinkable property, transitioning from 98.24 ± 27.78 to 45.56 ± 20.62 nm within the TME. This remarkable size change fosters an impressive uptake of approximately 100% by MDA-MB-231 cells within just 30 min, thereby greatly improving drug delivery efficiency. This size switchability enables passive targeting through the enhanced permeability and retention (EPR) effect, facilitating deep penetration into tumors. The NPs also demonstrate improved pH/redox-triggered drug release (∼70% at 24 h) within the TME and exhibit no toxicity in cell viability test. The cell cycle results of treated cells with docetaxel (DTX)-loaded NPs revealed G2/M (84.6 ± 1.16%) arrest. The DTX-loaded NPs showed more apoptosis (62.6 ± 3.7%) than the free DTX (51.8 ± 3.2%) in treated cells. The western blot and RT-PCR assays revealed that apoptotic genes and proteins expression of treated cells were significantly upregulated with the DTX-loaded NPs vs. the free DTX (Pvalue<.001). In conclusion, these findings suggest that this novel-engineered NPs holds promise as a TME-targeted NDDS.
Department of Organic Chemistry, Faculty of Chemistry, Urmia University, Urmia, Iran.
Clinical Research Development Unite of Tabriz Valiasr Hospital, Tabriz University of Medical Sciences, Tabriz, Iran.Drug Applied Research Center and Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Molecular Mediciene, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Applied Cell Science, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
Dual pH/redox-responsive size-switchable polymeric nano-carrier system for tumor microenvironment DTX release.
Basal dendrites of layer 5 cortical pyramidal neurons exhibit Na+ and N-methyl-D-aspartate receptor (NMDAR) regenerative spikes and are uniquely poised to influence somatic output. Nevertheless, due to technical limitations, how multibranch basal dendritic integration shapes and enables multiplexed barcoding of synaptic streams remains poorly mapped. Here, we combine 3D two-photon holographic transmitter uncaging, whole-cell dynamic clamp, and biophysical modeling to reveal how synchronously activated synapses (distributed and clustered) across multiple basal dendritic branches are multiplexed under quiescent and in vivo-like conditions. While dendritic regenerative Na+ spikes promote millisecond somatic spike precision, distributed synaptic inputs and NMDAR spikes regulate gain. These concomitantly occurring dendritic nonlinearities enable multiplexed information transfer amid an ongoing noisy background, including under back-propagating voltage resets, by barcoding the axo-somatic spike structure. Our results unveil a multibranch dendritic integration framework in which dendritic nonlinearities are critical for multiplexing different spatial-temporal synaptic input patterns, enabling optimal feature binding.
Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA.
Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA; Purdue Institute for Integrative Neuroscience, Purdue University, West Lafayette, IN, USA. Electronic address: kjayant@purdue.edu.
Probing multiplexed basal dendritic computations using two-photon 3D holographic uncaging.
Human CD8 tumor-infiltrating lymphocytes (TILs) with impaired effector functions and PD-1 expression are categorized as exhausted. However, the exhaustion-like features reported in TILs might stem from their activation rather than the consequence of T cell exhaustion itself. Using CRISPR-Cas9 and lentiviral overexpression in CD8 T cells from non-cancerous donors, we show that the T cell receptor (TCR)-induced transcription factor interferon regulatory factor 4 (IRF4) promotes cell proliferation and PD-1 expression and hampers effector functions and expression of nuclear factor κB (NF-κB)-regulated genes. While CD8 TILs with impaired interferon γ (IFNγ) production exhibit activation markers IRF4 and CD137 and exhaustion markers thymocyte selection associated high mobility group box (TOX) and PD-1, activated T cells in patients with COVID-19 do not demonstrate elevated levels of TOX and PD-1. These results confirm that IRF4+ TILs are exhausted rather than solely activated. Our study indicates, however, that PD-1 expression, low IFNγ production, and active cycling in TILs are all influenced by IRF4 upregulation after T cell activation.
De Duve Institute, Université Catholique de Louvain, Brussels, Belgium. Electronic address: thibault.hirsch@uclouvain.be.
De Duve Institute, Université Catholique de Louvain, Brussels, Belgium.
De Duve Institute, Université Catholique de Louvain, Brussels, Belgium; Département de Gynécologie, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
Flow Cytometry Facility, University of Lausanne, Lausanne, Switzerland.
Département de Gynécologie, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
Unité de Soins Intensifs, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
De Duve Institute, Université Catholique de Louvain, Brussels, Belgium; WELBIO Department, WEL Research Institute, Wavre, Belgium.
IRF4 impedes human CD8 T cell function and promotes cell proliferation and PD-1 expression.
Platelet-activating factor (PAF) is a potent phospholipid mediator crucial in multiple inflammatory and immune responses through binding and activating the PAF receptor (PAFR). However, drug development targeting the PAFR has been limited, partly due to an incomplete understanding of its activation mechanism. Here, we present a 2.9-Å structure of the PAF-bound PAFR-Gi complex. Structural and mutagenesis analyses unveil a specific binding mode of PAF, with the choline head forming cation-π interactions within PAFR hydrophobic pocket, while the alkyl tail penetrates deeply into an aromatic cleft between TM4 and TM5. Binding of PAF modulates conformational changes in key motifs of PAFR, triggering the outward movement of TM6, TM7, and helix 8 for G protein coupling. Molecular dynamics simulation suggests a membrane-side pathway for PAF entry into PAFR via the TM4-TM5 cavity. By providing molecular insights into PAFR signaling, this work contributes a foundation for developing therapeutic interventions targeting PAF signal axis.
School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210046, China; The State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
The State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
The State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China.
The State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; The Shanghai Advanced Electron Microscope Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
The State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: wangyue1@simm.ac.cn.
School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210046, China; The State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: eric.xu@simm.ac.cn.
The State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; Medicinal Bioinformatics Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China. Electronic address: youwen_zhuang@sjtu.edu.cn.
Molecular basis for the activation of PAF receptor by PAF.
Harsh environments in poorly perfused tumor regions may select for traits driving cancer aggressiveness. Here, we investigated whether tumor acidosis interacts with driver mutations to exacerbate cancer hallmarks. We adapted mouse organoids from normal pancreatic duct (mN10) and early pancreatic cancer (mP4, KRAS-G12D mutation, ± p53 knockout) from extracellular pH 7.4 to 6.7, representing acidic niches. Viability was increased by acid adaptation, a pattern most apparent in wild-type (WT) p53 organoids, and exacerbated upon return to pH 7.4. This led to increased survival of acid-adapted organoids treated with gemcitabine and/or erlotinib, and, in WT p53 organoids, acid-induced attenuation of drug effects. New genetic variants became dominant during adaptation, yet they were unlikely to be its main drivers. Transcriptional changes induced by acid and drug adaptation differed overall, but acid adaptation increased the expression of gemcitabine resistance genes. Thus, adaptation to acidosis increases cancer cell viability after chemotherapy.
Section for Computational and RNA Biology, Department of Biology, University of Copenhagen, Copenhagen, DK2200 Copenhagen N, Denmark; Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, DK2200 Copenhagen N, Denmark.
Section for Cell Biology and Physiology, Department of Biology, University of Copenhagen, Copenhagen, DK2100 Copenhagen Ø, Denmark.
Section for Computational and RNA Biology, Department of Biology, University of Copenhagen, Copenhagen, DK2200 Copenhagen N, Denmark.
Section for Cell Biology and Physiology, Department of Biology, University of Copenhagen, Copenhagen, DK2100 Copenhagen Ø, Denmark. Electronic address: sfpedersen@bio.ku.dk.
Section for Computational and RNA Biology, Department of Biology, University of Copenhagen, Copenhagen, DK2200 Copenhagen N, Denmark; Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, DK2200 Copenhagen N, Denmark. Electronic address: albin@bio.ku.dk.
Adaptation to an acid microenvironment promotes pancreatic cancer organoid growth and drug resistance.
Ferroptosis is a type of regulated cell death characterized by iron-dependent lipid peroxidation. A model cell system is constructed to induce ferroptosis by re-expressing the transcription factor BACH1, a potent ferroptosis inducer, in immortalized mouse embryonic fibroblasts (iMEFs). The transfer of the culture supernatant from ferroptotic iMEFs activates the proliferation of hepatoma cells and other fibroblasts and suppresses cellular senescence-like features. The BACH1-dependent secretion of the longevity factor FGF21 is increased in ferroptotic iMEFs. The anti-senescent effects of the culture supernatant from these iMEFs are abrogated by Fgf21 knockout. BACH1 activates the transcription of Fgf21 by promoting ferroptotic stress and increases FGF21 protein expression by suppressing its autophagic degradation through transcriptional Sqstm1 and Lamp2 repression. The BACH1-induced ferroptotic FGF21 secretion suppresses obesity in high-fat diet-fed mice and the short lifespan of progeria mice. The inhibition of these aging-related phenotypes can be physiologically significant regarding ferroptosis.
Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan. Electronic address: hnishizawa@med.tohoku.ac.jp.
Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan; Center for Regulatory Epigenome and Diseases, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan.
Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan; Gladstone Institute of Neurological Disease, Gladstone Institute, San Francisco, CA 94158, USA.
Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan.
Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan; Department of Pediatric Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan.
Laboratory of Microbial Chemistry, Kobe Pharmaceutical University, Kobe, Hyogo 658-8558, Japan.
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo, Kyoto 606-8501, Japan.
Center for Regulatory Epigenome and Diseases, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan; Department of Cell Proliferation, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan.
Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan; Center for Regulatory Epigenome and Diseases, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8575, Japan. Electronic address: igarashi@med.tohoku.ac.jp.
BACH1 inhibits senescence, obesity, and short lifespan by ferroptotic FGF21 secretion.
The interest in wound dressings increased ten years ago. Wound care practitioners can now use interactive/bioactive dressings and tissue-engineered skin substitutes. Several bandages can heal burns, but none can treat all chronic wounds. This study formulates a composite material from 70% polyvinyl alcohol (PVA) and 30% polyethylene glycol (PEG) with 0.2, 0.4, and 0.6 wt% magnesium oxide nanoparticles. This study aims to create a biodegradable wound dressing. A Fourier Transform Infrared (FTIR) study shows that PVA, PEG, and MgO create hydrogen bonding interactions. Hydrophilic characteristics are shown by the polymeric blend's 56.289° contact angle. MgO also lowers the contact angle, making the film more hydrophilic. Hydrophilicity improves film biocompatibility, live cell adhesion, wound healing, and wound dressing degradability. Differential Scanning Calorimeter (DSC) findings suggest the PVA/PEG combination melted at 53.16 °C. However, adding different weight fractions of MgO nanoparticles increased the nanocomposite's melting temperature (Tm). These nanoparticles improve the film's thermal stability, increasing Tm. In addition, MgO nanoparticles in the polymer blend increased tensile strength and elastic modulus. This is due to the blend's strong adherence to the reinforcing phase and MgO nanoparticles' ceramic material which has a great mechanical strength. The combination of 70% PVA + 30% PEG exhibited good antibacterial spatially at 0.2% MgO, according to antibacterial test results.
Department of Polymer and Petrochemical Industries, College of Materials Engineering, University of Babylon, Hilla, Iraq.
The effect of MgO nanoparticle on PVA/PEG-based membranes for potential application in wound healing.
Behavioral differences exist between countries, regions, and religions. With rapid development in recent decades, an increasing number of international immigrants from different regions with different religions have settled in China. The degrees to which sexual behaviors-particularly risky sexual behaviors-differ by religion and geographical areas are not known.We aim to estimate the associations of religion and geographical areas with sexual behaviors of international immigrants and provide evidence for promoting the sexual health of international immigrants.A cross-sectional study was conducted via the internet with a snowball sampling method among international immigrants in China. In our study, risky sexual behaviors included having multiple sexual partners and engaging in unprotected sex. Descriptive analysis was used to analyze the basic characteristics of international immigrants as well as their sexual behaviors, religious affiliations, and geographical regions of origin. Multivariate binary logistic regression analyses with multiplicative and additive interactions were used to identify aspects of religion and geography that were associated with risky sexual behaviors among international immigrants.A total of 1433 international immigrants were included in the study. South Americans and nonreligious immigrants were more likely to engage in risky sexual behaviors, and Asian and Buddhist immigrants were less likely to engage in risky sexual behaviors. The majority of the Muslims had sexually transmitted infection and HIV testing experiences; however, Muslims had a low willingness to do these tests in the future. The multivariate analysis showed that Muslim (adjusted odds ratio [AOR] 0.453, 95% CI 0.228-0.897), Hindu (AOR 0.280, 95% CI 0.082-0.961), and Buddhist (AOR 0.097, 95% CI 0.012-0.811) immigrants were less likely to report engaging in unprotected sexual behaviors. Buddhist immigrants (AOR 0.292, 95% CI 0.086-0.990) were also less likely to have multiple sexual partners. With regard to geography, compared to Asians, South Americans (AOR 2.642, 95% CI 1.034-6.755), Europeans (AOR 2.310, 95% CI 1.022-5.221), and North Africans (AOR 3.524, 95% CI 1.104-11.248) had a higher probability of having multiple sexual partners.The rates of risky sexual behaviors among international immigrants living in China differed depending on their religions and geographical areas of origin. South Americans and nonreligious immigrants were more likely to engage in risky sexual behaviors. It is necessary to promote measures, including HIV self-testing, pre-exposure prophylaxis implementation, and targeted sexual health education, among international immigrants in China.
© Yuyin Zhou, Feng Cheng, Junfang Xu. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org).
1, Department of Pharmacy, Second Affiliated Hospital, School of Public Health, Zhejiang University School of Medicine, Hangzhou, China.
Vanke School of Public Health, Tsinghua University, Beijing, China.Institute for Healthy China, Tsinghua University, Beijing, China.
JMIR Public Health Surveill. 2024-06-28;10():e44616.
Religion, Geography, and Risky Sexual Behaviors Among International Immigrants Living in China: Cross-Sectional Study.
The basement membrane (BM) is an extracellular matrix that plays important roles in animal development. A spatial heterogeneity in composition and structural properties of the BM provide cells with vital cues for morphogenetic processes such as cell migration or cell polarization. Here, using the Drosophila egg chamber as a model system, we show that the BM becomes heterogeneous during development, with a reduction in Collagen IV density at the posterior pole and differences in the micropattern of aligned fiber-like structures. We identified two AdamTS matrix proteases required for the proper elongated shape of the egg chamber, yet the molecular mechanisms by which they act are different. Stall is required to establish BM heterogeneity by locally limiting Collagen IV protein density, whereas AdamTS-A alters the micropattern of fiber-like structures within the BM at the posterior pole. Our results suggest that AdamTS proteases control BM heterogeneity required for organ shape.
Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; School of Science, Technische Universität Dresden, 01062 Dresden, Germany. Electronic address: utoepfer@mail.ubc.ca.
School of Science, Technische Universität Dresden, 01062 Dresden, Germany.
School of Science, Technische Universität Dresden, 01062 Dresden, Germany; Cluster of Excellence Physics of Life, Technische Universität Dresden, 01062 Dresden, Germany.
Cluster of Excellence Physics of Life, Technische Universität Dresden, 01062 Dresden, Germany; Biotechnology Center, Technische Universität Dresden, 01062 Dresden, Germany.
Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
School of Science, Technische Universität Dresden, 01062 Dresden, Germany; Cluster of Excellence Physics of Life, Technische Universität Dresden, 01062 Dresden, Germany. Electronic address: christian.dahmann@tu-dresden.de.
AdamTS proteases control basement membrane heterogeneity and organ shape in Drosophila.
Heterogeneous resistance to immunotherapy remains a major challenge in cancer treatment, often leading to disease progression and death. Using CITE-seq and matched 40-plex PhenoCycler tissue imaging, we performed longitudinal multimodal single-cell analysis of tumors from metastatic melanoma patients with innate resistance, acquired resistance, or response to immunotherapy. We established the multimodal integration toolkit to align transcriptomic features, cellular epitopes, and spatial information to provide deeper insights into the tumors. With longitudinal analysis, we identified an immune-striving tumor microenvironment marked by peri-tumor lymphoid aggregates and low infiltration of T cells in the tumor and the emergence of MITF+SPARCL1+ and CENPF+ melanoma subclones after therapy. The enrichment of B cell-associated signatures in the molecular composition of lymphoid aggregates was associated with better survival. These findings provide further insights into the establishment of microenvironmental cell interactions and molecular composition of spatial structures that could inform therapeutic intervention.
Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia; Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia. Electronic address: camelia.quek@melanoma.org.au.
Akoya Biosciences, Marlborough, MA, USA.
Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia; Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
Cancer Ecosystems Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia; School of Clinical Medicine, St Vincent's Clinical Campus, UNSW Medicine & Health, UNSW Sydney, NSW, Australia.
Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia; Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia; Crown Princess Mary Cancer Centre, Westmead and Blacktown Hospitals, Sydney, Australia.
Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA; Department of Bioengineering, Stanford University, Stanford, CA, USA; Enable Medicine, Stanford, CA, USA.
Cancer Ecosystems Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia; Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia; Centenary Institute, The University of Sydney, Sydney, NSW, Australia.
Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia; Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia; Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Sydney, NSW, Australia; Sydney Head & Neck Cancer Institute, Chris O'Brien Lifehouse Cancer Centre, Sydney, NSW, Australia.
Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia; Department of Medical Oncology, Royal North Shore and Mater Hospitals, Sydney, NSW, Australia.
Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia; Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia; Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital & NSW Health Pathology, Sydney, NSW, Australia.
Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia; Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia; Department of Medical Oncology, Royal North Shore and Mater Hospitals, Sydney, NSW, Australia.
Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia; Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia. Electronic address: james.wilmott@sydney.edu.au.
Single-cell spatial multiomics reveals tumor microenvironment vulnerabilities in cancer resistance to immunotherapy.
The unfolded protein response (UPR) relieves endoplasmic reticulum (ER) stress through multiple strategies, including reducing protein synthesis, increasing protein folding capabilities, and enhancing misfolded protein degradation. After a multi-omics analysis, we find that signal recognition particle 14 (SRP14), an essential component of the SRP, is markedly reduced in cells undergoing ER stress. Further experiments indicate that SRP14 reduction requires PRKR-like ER kinase (PERK)-mediated eukaryotic translation initiation factor 2α (eIF2α) phosphorylation but is independent of ATF4 or ATF3 transcription factors. The decrease of SRP14 correlates with reduced translocation of fusion proteins and endogenous cathepsin D. Enforced expression of an SRP14 variant with elongation arrest capability prevents the reduced translocation of cathepsin D in stressed cells, whereas an SRP14 mutant without the activity does not. Finally, overexpression of SRP14 augments the UPR and aggravates ER-stress-induced cell death. These data suggest that translocational attenuation mediated by the PERK-SRP14 axis is a protective measure for the UPR to mitigate ER stress.
China Regional Research Centre, International Centre for Genetic Engineering and Biotechnology (ICGEB), Taizhou, Jiangsu 225316, China; School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, Zhejiang 310024, China; Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
China Regional Research Centre, International Centre for Genetic Engineering and Biotechnology (ICGEB), Taizhou, Jiangsu 225316, China.
Academy of Pharmacy, Xi'an Jiaotong-Liverpool University, Suzhou, Jiangsu 215123, China.
Academy of Pharmacy, Xi'an Jiaotong-Liverpool University, Suzhou, Jiangsu 215123, China. Electronic address: mu.wang@xjtlu.edu.cn.
Center for Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. Electronic address: sfang@som.umaryland.edu.
China Regional Research Centre, International Centre for Genetic Engineering and Biotechnology (ICGEB), Taizhou, Jiangsu 225316, China. Electronic address: nathanyang@icgeb.cn.
Translocational attenuation mediated by the PERK-SRP14 axis is a protective mechanism of unfolded protein response.
Vitamin D receptor (VDR) has been implicated in fatty liver pathogenesis, but its role in the regulation of organismal energy usage remains unclear. Here, we illuminate the evolutionary function of VDR by demonstrating that zebrafish Vdr coordinates hepatic and organismal energy homeostasis through antagonistic regulation of nutrient storage and tissue growth. Hepatocyte-specific Vdr impairment increases hepatic lipid storage, partially through acsl4a induction, while simultaneously diminishing fatty acid oxidation and liver growth. Importantly, Vdr impairment exacerbates the starvation-induced hepatic storage of systemic fatty acids, indicating that loss of Vdr signaling elicits hepatocellular energy deficiency. Strikingly, hepatocyte Vdr impairment diminishes diet-induced systemic growth while increasing hepatic and visceral fat in adult fish, revealing that hepatic Vdr signaling is required for complete adaptation to food availability. These data establish hepatocyte Vdr as a regulator of organismal energy expenditure and define an evolutionary function for VDR as a transcriptional effector of environmental nutrient supply.
Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Cutaneous Biology Research Center, Department of Dermatology and Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; HCEMM-SU Translational Dermatology Research Group, Department of Physiology, Semmelweis University, 1085 Budapest Hungary; Department of Dermatology, Venereology, and Dermatooncology, Semmelweis University, 1085 Budapest Hungary.
Cutaneous Biology Research Center, Department of Dermatology and Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Huntsman Cancer Institute and Department of Pathology, University of Utah, Salt Lake City, UT 84112, USA.
Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard-MIT Division of Health Sciences and Technology, Boston, MA 02115, USA; Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. Electronic address: wgoessling@mgh.harvard.edu.
Hepatocyte vitamin D receptor functions as a nutrient sensor that regulates energy storage and tissue growth in zebrafish.
Glioma cancer is the primary cause of cancer-related fatalities globally for both men and women. Traditional chemotherapy treatments for this condition frequently result in reduced efficacy and significant adverse effects. This investigation developed a new drug delivery system for the chemotherapeutic drug temozolomide (TMZ) using pH-sensitive drug delivery zeolitic imidazolate frameworks (ZIF-8). These nanoplatforms demonstrate excellent biocompatibility and hold potential for cancer therapy. Utilizing the favorable reaction milieu offered by ZIFs, a 'one-pot method' was employed for the fabrication and loading of drugs, leading to a good capacity for loading. TMZ@TA@ZIF-8 NPs exhibit a notable response to an acidic milieu, resulting in an enhanced drug release pattern characterized by a controlled release outcome. The effectiveness of TMZ@TA@ZIF-8 NPs in inhibiting the migration and invasion of U251 glioma cancer cells, as well as promoting apoptosis, was confirmed through various tests, including MTT (3-(4,5)-dimethylthiahiazo(-z-y1)) assay, DAPI/PI dual staining, and cell scratch assay. The biochemical fluorescent staining assays showed that TMZ@TA@ZIF-8 NPs potentially improved ROS, reduced MMP, and triggered apoptosis in U251 cells. In U251 cells treated with NPs, the p53, Bax, Cyt-C, caspase-3, -8, and -9 expressions were significantly enhanced, while Bcl-2 expression was diminished. These outcomes show the potential of TMZ@TA@ZIF-8 NPs as a therapeutic agent with anti-glioma properties. Overall, the pH-responsive drug delivery systems we fabricated using TMZ@TA@ZIF-8 NPs show great potential for cancer treatment. This approach has the potential to make significant contributions to the improvement of cancer therapy by overcoming the problems associated with TMZ-based treatments.
Department of Neurosurgery, Dongying People's Hospital, Dongying Hospital of Shandong Provincial Hospital Group, Dongying, China.
Department of Emergency, Dongying People's Hospital, Dongying Hospital of Shandong Provincial Hospital Group, Dongying, China.
Fabrication of pH-responsive temozolomide (TMZ)-clacked tannic acid-altered zeolite imidazole nanoframeworks (ZIF-8) enhance anticancer activity and apoptosis induction in glioma cancer cells.
Exposure to stressors has profound effects on sleep that have been linked to serotonin (5-HT) neurons of the dorsal raphe nucleus (DR). However, the DR also comprises glutamatergic neurons expressing vesicular glutamate transporter type 3 (DRVGLUT3), leading us to examine their role. Cell-type-specific tracing revealed that DRVGLUT3 neurons project to brain areas regulating arousal and stress. We found that chemogenetic activation of DRVGLUT3 neurons mimics stress-induced sleep perturbations. Furthermore, deleting VGLUT3 in the DR attenuated stress-induced sleep perturbations, especially after social defeat stress. In the DR, VGLUT3 is found in subsets of 5-HT and non-5-HT neurons. We observed that both populations are activated by acute stress, including those projecting to the ventral tegmental area. However, deleting VGLUT3 in 5-HT neurons minimally affected sleep regulation. These findings suggest that VGLUT3 expression in the DR drives stress-induced sleep perturbations, possibly involving non-5-HT DRVGLUT3 neurons.
Sorbonne Université, CNRS UMR 8246, INSERM U1130 - Neuroscience Paris Seine - Institut de Biologie Paris Seine (NPS - IBPS), 75005 Paris, France.
Université Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative, 75013 Paris, France; Institut Universitaire de France (IUF), Paris, France.
Sorbonne Université, CNRS UMR 8246, INSERM U1130 - Neuroscience Paris Seine - Institut de Biologie Paris Seine (NPS - IBPS), 75005 Paris, France; Sorbonne Université, CNRS UMR 7203, Laboratoire des BioMolécules, 75005 Paris, France.
Sorbonne Université, CNRS UMR 8246, INSERM U1130 - Neuroscience Paris Seine - Institut de Biologie Paris Seine (NPS - IBPS), 75005 Paris, France; Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montréal, QC H4H 1R3, Canada.
Sorbonne Université, CNRS UMR 8246, INSERM U1130 - Neuroscience Paris Seine - Institut de Biologie Paris Seine (NPS - IBPS), 75005 Paris, France. Electronic address: stephanie.daumas@sorbonne-universite.fr.
Sorbonne Université, CNRS UMR 8246, INSERM U1130 - Neuroscience Paris Seine - Institut de Biologie Paris Seine (NPS - IBPS), 75005 Paris, France. Electronic address: veronique.fabre@inserm.fr.
Regulation of stress-induced sleep perturbations by dorsal raphe VGLUT3 neurons in male mice.
In this study, to address the defects of sodium alginate (SA), such as its susceptibility to disintegration, silica was coated on the outer layer of sodium alginate hydrogel beads in order to improve its swelling and slow-release properties. Tetraethyl orthosilicate (TEOS) was used as the hydrolyzed precursor, and the solution of silica precursor was prepared by sol-gel reaction under acidic conditions. Then SA-silica hydrogel beads prepared by ionic crosslinking method were immersed into the SiO2 precursor solution to prepare SA-silica hydrogel beads. The chemical structure and morphology of the hydrogel beads were characterized by XRD, FTIR, and SEM, and the results showed that the surface of SA-silica beads was successfully encapsulated with the outer layer of SiO2, and the surface was smooth and dense. The swelling experiments showed that the swelling performance effectively decreased with the increase of TEOS molar concentration, and the maximum swelling ratio of the hydrogel beads decreased from 41.07 to 14.3, and the time to reach the maximum swelling ratio was prolonged from 4 h to 8 h. The sustained-release experiments showed that the SA-silica hydrogel beads possessed a good pH sensitivity, and the time of sustained-release was significantly prolonged in vitro. Hemolysis and cytotoxicity experiments showed that the SA-silica hydrogel beads were biocompatible when the TEOS molar concentration was lower than 0.375 M. The SA-silica-2 hydrogel beads had good biocompatibility, swelling properties, and slow-release properties at the same time.
College of Materials Science and Engineering, Taiyuan University of Technology, Taiyuan, PR China.Key Laboratory of Interface Science and Engineering in Advanced Materials, Taiyuan University of Technology, Ministry of Education, Taiyuan, PR China.
First Hospital of Shanxi Medical University, Taiyuan, PR China.
Shanxi Cardiovascular Hospital, Taiyuan, PR China.
Preparation and Characterization of Silica-Coated Sodium Alginate Hydrogel Beads and the Delivery of Curcumin.
To analyze waste from intraocular lens (IOL) packaging across a variety of brands.Private clinical practice.Prospective weight and composition analysis of all elements of unopened packages of IOLs sold in the United States-both preloaded and non-preloaded.Samples were collected from multiple IOL companies in 2023. The primary end point for comparison was the total weight of each IOL package, because this generally correlates with the carbon footprint. The percentage of total weight contributed by paper, plastic, Tyvek, foil, sterile saline solution (fluid), metal, or glossy paper material was also calculated.The non-preloaded IOL package weights ranged from 29 g (Zeiss Lucia) to 80 g (RxSIGHT LAL). Most of the weight was attributable to paper, including the box and instructions for use (IFUs) pamphlet. The latter was generally the largest component within the box. The weights of preloaded IOL packages were generally higher than those of their non-preloaded counterparts and ranged from 67 g (Hoya iSert) to 116 g (Rayner RayOne Spheric).Meaningful differences in IOL packaging weight and waste were noted across different models and manufacturers. Electronic IFUs linked to QR codes could replace the need for an IFU pamphlet within every box, significantly reducing the box's size, weight, and carbon footprint. Pairing preloaded IOL cartridges with autoclavable injectors could reduce associated waste. Because of the enormous global volume of IOL implantation, these waste-reducing strategies should be prioritized by IOL manufacturers.
Copyright © 2024 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.
From the Harvard Eye Associates, Laguna Hills, California (Keyser, Hovanesian); Altos Eye Physicians, Los Altos, California (Chang); Population Health, NYU Langone Health, New York, New York (Thiel); Ophthalmology, NYU Langone Health, New York, New York (Thiel).
Journal of cataract and refractive surgery
Analysis of intraocular lens packaging weight and waste.
Fe-Ca-SAPO-34/CS/PANI, a novel hybrid bio-composite scaffold with potential application in dental tissue engineering, was prepared by freeze drying technique. The scaffold was characterized using FT-IR and SEM methods. The effects of PANI on the physicochemical properties of the Fe-Ca-SAPO-34/CS scaffold were investigated, including changes in swelling ratio, mechanical behavior, density, porosity, biodegradation, and biomineralization. Compared to the Fe-Ca-SAPO-34/CS scaffold, adding PANI decreased the pore size, porosity, swelling ratio, and biodegradation, while increasing the mechanical strength and biomineralization. Cell viability, cytotoxicity, and adhesion of human dental pulp stem cells (hDPSCs) on the scaffolds were investigated by MTT assay and SEM. The Fe-Ca-SAPO-34/CS/PANI scaffold promoted hDPSC proliferation and osteogenic differentiation compared to the Fe-Ca-SAPO-34/CS scaffold. Alizarin red staining, alkaline phosphatase activity, and qRT-PCR results revealed that Fe-Ca-SAPO-34/CS/PANI triggered osteoblast/odontoblast differentiation in hDPSCs through the up-regulation of osteogenic marker genes BGLAP, RUNX2, and SPARC. The significance of this study lies in developing a novel scaffold that synergistically combines the beneficial properties of Fe-Ca-SAPO-34, chitosan, and PANI to create an optimized microenvironment for dental tissue regeneration. These findings highlight the potential of the Fe-Ca-SAPO-34/CS/PANI scaffold as a promising biomaterial for dental tissue engineering applications, paving the way for future research and clinical translation in regenerative dentistry.
Brozek Lab, Chemistry and Biochemistry Department, University of OR, Eugene, Oregon.
Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran.
Organosilicon Research Laboratory, Faculty of Chemistry, University of Tabriz, Tabriz, Iran.Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Chemistry, Faculty of Science, University of Zanjan, Zanjan, Iran.
Organosilicon Research Laboratory, Faculty of Chemistry, University of Tabriz, Tabriz, Iran.
Development of novel hybrid nanomaterials with potential application in bone/dental tissue engineering: design, fabrication and characterization enriched-SAPO-34/CS/PANI scaffold.
Understanding the role of B cells in tuberculosis (TB) is crucial for developing new TB vaccines. However, the changes in B cell immune landscapes during TB and their functional implications remain incompletely explored. Using high-dimensional flow cytometry to map the immune landscape in response to Mycobacterium tuberculosis (Mtb) infection, our results show an accumulation of marginal zone B (MZB) cells and other unconventional B cell subsets in the lungs and spleen, shaping an unconventional B cell landscape. These MZB cells exhibit activated and memory-like phenotypes, distinguishing their functional profiles from those of conventional B cells. Notably, functional studies show that MZB cells produce multiple cytokines and contribute to systemic protection against TB by shaping cytokine patterns and cell-mediated immunity. These changes in the immune landscape are reversible upon successful TB chemotherapy. Our study suggests that, beyond antibody production, targeting the regulatory function of B cells may be a valuable strategy for TB vaccine development.
Center for Discovery and Innovation (CDI), Hackensack Meridian Health, 111 Ideation Way, Nutley, NJ 07110, USA.
Biosafety Level 3 Core, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Level 15, Centre for Translational Medicine (MD6), NUS, 14 Medical Drive, Singapore 117599, Singapore.
Infectious Diseases Translational Research Programme and Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Level 2, Blk MD4, 5 Science Drive 2, Singapore 117545, Singapore.
Singapore Immunology Network (SIgN), Agency for Science Technology and Research, Biopolis, 8A Biomedical Grove, Level 3 & 4, Immunos Building, Singapore 138648, Singapore; Centre for Biomedical Informatics, Lee Kong Chian School of Medicine, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore; A(∗)STAR Infectious Diseases Labs, Agency for Science, Technology and Research, 8A Biomedical Grove #05-13, Immunos, Singapore 138648, Singapore.
Center for Discovery and Innovation (CDI), Hackensack Meridian Health, 111 Ideation Way, Nutley, NJ 07110, USA; Hackensack Meridian School of Medicine, Nutley, NJ 07110, USA.
Singapore Immunology Network (SIgN), Agency for Science Technology and Research, Biopolis, 8A Biomedical Grove, Level 3 & 4, Immunos Building, Singapore 138648, Singapore.
Center for Discovery and Innovation (CDI), Hackensack Meridian Health, 111 Ideation Way, Nutley, NJ 07110, USA; Hackensack Meridian School of Medicine, Nutley, NJ 07110, USA. Electronic address: martin.gengenbacher@gmail.com.
Splenic marginal zone B cells restrict Mycobacterium tuberculosis infection by shaping the cytokine pattern and cell-mediated immunity.
Cancer is ranked among the top causes of mortality throughout the world. Conventional therapies are associated with toxicity and undesirable side effects, rendering them unsuitable for prolonged use. Additionally, there is a high occurrence of resistance to anticancer drugs and recurrence in certain circumstances. Hence, it is essential to discover potent anticancer drugs that exhibit specificity and minimal unwanted effects. Curcumin, a polyphenol derivative, is present in the turmeric plant (Curcuma longa L.) and has chemopreventive, anticancer, radio-, and chemo-sensitizing activities. Curcumin exerts its anti-tumor effects on cancer cells by modulating the disrupted cell cycle through p53-dependent, p53-independent, and cyclin-dependent mechanisms. This review provides a summary of the formulations of curcumin based on nanospheres, since there is increasing interest in its medicinal usage for treating malignancies and tumors. Nanospheres are composed of a dense polymeric matrix, and have a size ranging from 10 to 200 nm. Lactic acid polymers, glycolic acid polymers, or mixtures of them, together with poly (methyl methacrylate), are primarily used as matrices in nanospheres. Nanospheres are suitable for local, oral, and systemic delivery due to their minuscule particle size. The majority of nanospheres are created using polymers that are both biocompatible and biodegradable. Previous investigations have shown that the use of a nanosphere delivery method can enhance tumor targeting, therapeutic efficacy, and biocompatibility of different anticancer agents. Moreover, these nanospheres can be easily taken up by mammalian cells. This review discusses the many curcumin nanosphere formulations used in cancer treatment.
School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India.
Center for Global Health Research, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India.Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Nanospheres for curcumin delivery as a precision nanomedicine in cancer therapy.
Metabolic reprogramming dictates tumor molecular attributes and therapeutic potentials. However, the comprehensive metabolic characteristics in gastric cancer (GC) remain obscure. Here, metabolic signature-based clustering analysis identifies three subtypes with distinct molecular and clinical features: MSC1 showed better prognosis and upregulation of the tricarboxylic acid (TCA) cycle and lipid metabolism, combined with frequent TP53 and RHOA mutation; MSC2 had moderate prognosis and elevated nucleotide and amino acid metabolism, enriched by intestinal histology and mismatch repair deficient (dMMR); and MSC3 exhibited poor prognosis and enhanced glycan and energy metabolism, accompanied by diffuse histology and frequent CDH1 mutation. The Shandong Provincial Hospital (SDPH) in-house dataset with matched transcriptomic, metabolomic, and spatial-metabolomic analysis also validated these findings. Further, we constructed the metabolic subtype-related prognosis gene (MSPG) scoring model to quantify the activity of individual tumors and found a positive correlation with cuproptosis signaling. In conclusion, comprehensive recognition of the metabolite signature can enhance the understanding of diversity and heterogeneity in GC.
Clinical Research Center of Shandong University, Clinical Epidemiology Unit, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China. Electronic address: qiluchenhao@email.sdu.edu.cn.
Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Key Laboratory of Engineering of Shandong Province, Shandong Provincial Hospital, Jinan 250021, China; Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250021, China.
Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, China.
Clinical Research Center of Shandong University, Clinical Epidemiology Unit, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China.
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.
Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Key Laboratory of Engineering of Shandong Province, Shandong Provincial Hospital, Jinan 250021, China; Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250021, China. Electronic address: chongwei.good@163.com.
Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Key Laboratory of Engineering of Shandong Province, Shandong Provincial Hospital, Jinan 250021, China; Department of Gastrointestinal Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250021, China. Electronic address: lileping@medmail.com.cn.
Molecular characterization and clinical relevance of metabolic signature subtypes in gastric cancer.
Cancer cells undergo major epigenetic alterations and transcriptomic changes, including ectopic expression of tissue- and cell-type-specific genes. Here, we show that the germline-specific RNA helicase DDX4 forms germ-granule-like cytoplasmic ribonucleoprotein granules in various human tumors, but not in cultured cancer cells. These cancerous DDX4 complexes contain RNA-binding proteins and splicing regulators, including many known germ granule components. The deletion of DDX4 in cancer cells induces transcriptomic changes and affects the alternative splicing landscape of a number of genes involved in cancer growth and invasiveness, leading to compromised capability of DDX4-null cancer cells to form xenograft tumors in immunocompromised mice. Importantly, the occurrence of DDX4 granules is associated with poor survival in patients with head and neck squamous cell carcinoma and higher histological grade of prostate cancer. Taken together, these results show that the germ-granule-resembling cancerous DDX4 granules control gene expression and promote malignant and invasive properties of cancer cells.
Institute of Biomedicine, Integrative Physiology and Pharmacology Unit, University of Turku, 20520 Turku, Finland.
Department of Pathology, Laboratory Division, Turku University Hospital and University of Turku, 20520 Turku, Finland.
Institute of Biomedicine, Integrative Physiology and Pharmacology Unit, University of Turku, 20520 Turku, Finland; Faculty of Science and Engineering, Cell Biology, Åbo Akademi University, 20500 Turku, Finland; Turku Bioscience, University of Turku and Åbo Akademi University, 20520 Turku, Finland.
Institute of Biomedicine, Integrative Physiology and Pharmacology Unit, University of Turku, 20520 Turku, Finland; Centre for Population Health Research, Turku University Hospital and University of Turku, 20520 Turku, Finland.
Department of Biochemistry and Molecular Biology, Medical University of Lublin, 20-093 Lublin, Poland.
Department of Biostatistics, University of Turku and Turku University Hospital, 20520 Turku, Finland.
Faculty of Science and Engineering, Cell Biology, Åbo Akademi University, 20500 Turku, Finland; Turku Bioscience, University of Turku and Åbo Akademi University, 20520 Turku, Finland.
Institute of Biomedicine, Integrative Physiology and Pharmacology Unit, University of Turku, 20520 Turku, Finland; Turku Bioscience, University of Turku and Åbo Akademi University, 20520 Turku, Finland.
Turku Bioscience, University of Turku and Åbo Akademi University, 20520 Turku, Finland; Department for Otorhinolaryngology, Head, and Neck Surgery, University of Turku and Turku University Hospital, 20520 Turku, Finland.
Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere University Hospital, 33520 Tampere, Finland; Fimlab Laboratories, Tampere University Hospital, 33520 Tampere, Finland.
Institute of Biomedicine, Integrative Physiology and Pharmacology Unit, University of Turku, 20520 Turku, Finland; Turku Center for Disease Modeling, University of Turku, 20520 Turku, Finland; FICAN West Cancer Center, University of Turku, Turku University Hospital, 20500 Turku, Finland.
Institute of Biomedicine, Integrative Physiology and Pharmacology Unit, University of Turku, 20520 Turku, Finland. Electronic address: noora.kotaja@utu.fi.
Germline-specific RNA helicase DDX4 forms cytoplasmic granules in cancer cells and promotes tumor growth.
In this study, a novel bio-composite material that allow sustained release of plant derived antimicrobial compound was developed for the biomedical applications to prevent the infections caused by microorganisms resistant to commercial antimicrobials agents. With this aim, bacterial cellulose (BC)-p(HEMA) nanocomposite film that imprinted with eugenol (EU) via metal chelated monomer, MAH was prepared. Firstly, characterization studies were utilized by FTIR, SEM and BET analysis. Then antimicrobial assays, drug release studies and in vitro cytotoxicity test were performed. A significant antimicrobial effect against both Gram (+) Staphylococcus aureus and Gram (-) Escherichia coli bacteria and a yeast Candida albicans were observed even in low exposure time periods. When antimicrobial effect of EU compared with commercially used agents, both antifungal and antibacterial activity of EU were found to be higher. Then, sustained drug release studies showed that approximately 55% of EU was released up to 50 h. This result proved the achievement of the molecular imprinting for an immobilization of molecules that desired to release on an area in a long-time interval. Finally, the in vitro cytotoxicity experiment performed with the mouse L929 cell line determined that the synthesized EU-imprinted BC nanocomposite was biocompatible.
Department of Biology, Hacettepe University, Ankara, Türkiye.
Department of Chemistry, Bursa Uludag University, Bursa, Türkiye.
Department of Chemistry, Hacettepe University, Ankara, Türkiye.
Antimicrobial assay and controlled drug release studies with novel eugenol imprinted p(HEMA)-bacterial cellulose nanocomposite, designed for biomedical applications.
Obesity and type 2 diabetes cause a loss in brown adipose tissue (BAT) activity, but the molecular mechanisms that drive BAT cell remodeling remain largely unexplored. Using a multilayered approach, we comprehensively mapped a reorganization in BAT cells. We uncovered a subset of macrophages as lipid-associated macrophages (LAMs), which were massively increased in genetic and dietary model of BAT expansion. LAMs participate in this scenario by capturing extracellular vesicles carrying damaged lipids and mitochondria released from metabolically stressed brown adipocytes. CD36 scavenger receptor drove LAM phenotype, and CD36-deficient LAMs were able to increase brown fat genes in adipocytes. LAMs released transforming growth factor β1 (TGF-β1), which promoted the loss of brown adipocyte identity through aldehyde dehydrogenase 1 family member A1 (Aldh1a1) induction. These findings unfold cell dynamic changes in BAT during obesity and identify LAMs as key responders to tissue metabolic stress and drivers of loss of brown adipocyte identity.
IRCCS Santa Lucia Foundation, Rome, Italy.
Department of Biology, University of Rome Tor Vergata, Rome, Italy; PhD Program in Evolutionary Biology and Ecology, Department of Biology, University of Rome Tor Vergata, Rome, Italy.
Laboratory of Resolution of Neuroinflammation, IRCCS Santa Lucia Foundation, Rome, Italy; Institute of Translational Pharmacology, National Research Council, Rome, Italy.
Université Côte d'Azur, CNRS, LP2M, Nice, France.
Department of Immunology, School of Medicine, University of Connecticut, Farmington, CT, USA.
Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO, USA.
Department of Biology, University of Rome Tor Vergata, Rome, Italy.
NOMIS Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
IRCCS Santa Lucia Foundation, Rome, Italy; Department of Biology, University of Rome Tor Vergata, Rome, Italy; PhD Program in Evolutionary Biology and Ecology, Department of Biology, University of Rome Tor Vergata, Rome, Italy.
Laboratory of Resolution of Neuroinflammation, IRCCS Santa Lucia Foundation, Rome, Italy.
Department of Nutrition & Integrative Physiology, University of Utah, Salt Lake City, UT, USA.
Integrated Research Center (PRAAB), Campus Biomedico University of Rome, Rome, Italy.
Department of Nutrition & Integrative Physiology, University of Utah, Salt Lake City, UT, USA; Molecular Medicine Program (U2M2), University of Utah, Salt Lake City, UT, USA.
Telethon Institute of Genetics and Medicine, Pozzuoli, Italy; Department of Clinical Medicine and Surgery, University Federico II, Naples, Italy.
Department of Immunology, School of Medicine, University of Connecticut, Farmington, CT, USA; Institute for Systems Genomics, University of Connecticut, Farmington, CT, USA.
Department of Biology, University of Rome Tor Vergata, Rome, Italy; IRCCS Fondazione Bietti, Rome, Italy. Electronic address: daniele.lettieri.barbato@uniroma2.it.
Lipid-associated macrophages reshape BAT cell identity in obesity.
Development of type 2 diabetes mellitus (T2DM) is associated with low-grade chronic type 2 inflammation and disturbance of glucose homeostasis. Group 2 innate lymphoid cells (ILC2s) play a critical role in maintaining adipose homeostasis via the production of type 2 cytokines. Here, we demonstrate that CB2, a G-protein-coupled receptor (GPCR) and member of the endocannabinoid system, is expressed on both visceral adipose tissue (VAT)-derived murine and human ILC2s. Moreover, we utilize a combination of ex vivo and in vivo approaches to explore the functional and therapeutic impacts of CB2 engagement on VAT ILC2s in a T2DM model. Our results show that CB2 stimulation of ILC2s protects against insulin-resistance onset, ameliorates glucose tolerance, and reverses established insulin resistance. Our mechanistic studies reveal that the therapeutic effects of CB2 are mediated through activation of the AKT, ERK1/2, and CREB pathways on ILC2s. The results reveal that the CB2 agonist can serve as a candidate for the prevention and treatment of T2DM.
Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. Electronic address: akbari@usc.edu.
CB2 stimulation of adipose resident ILC2s orchestrates immune balance and ameliorates type 2 diabetes mellitus.
The human pathogen Streptococcus pneumoniae (Spn) encodes several cell-cell communication systems, notably multiple members of the Rgg/SHP and the Tpr/Phr families. Until now, members of these diverse communication systems were thought to work independently. Our study reveals that the ABC transporter PptAB and the transmembrane enzyme Eep act as a molecular link between Rgg/SHP and TprA/PhrA systems. We demonstrate that PptAB/Eep activates the Rgg/SHP systems and represses the TprA/PhrA system. Specifically, they regulate the respective precursor peptides (SHP and PhrA) before these leave the cell. This dual mode of action leads to temporal coordination of these systems, producing an overlap between their respective regulons during host cell infection. Thus, we have identified a single molecular mechanism that targets diverse cell-cell communication systems in Spn. Moreover, these molecular components are encoded by many gram-positive bacteria, suggesting that this mechanism may be broadly conserved.
Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA.
Department of Respiratory Sciences, University of Leicester, Leicester, UK.
Department of Host-Microbe Interactions, St. Jude Children's Research Hospital, Memphis, TN, USA.
Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA. Electronic address: lhiller@andrew.cmu.edu.
Peptide maturation molecules act as molecular gatekeepers to coordinate cell-cell communication in Streptococcus pneumoniae.
Pro-survival metabolic adaptations to stress in tumorigenesis remain less well defined. We find that multiple myeloma (MM) is unexpectedly dependent on beta-oxidation of long-chain fatty acids (FAs) for survival under both basal and stress conditions. However, under stress conditions, a second pro-survival signal is required to sustain FA oxidation (FAO). We previously found that CD28 is expressed on MM cells and transduces a significant pro-survival/chemotherapy resistance signal. We now find that CD28 signaling regulates autophagy/lipophagy that involves activation of the Ca2+→AMPK→ULK1 axis and regulates the translation of ATG5 through HuR, resulting in sustained lipophagy, increased FAO, and enhanced MM survival. Conversely, blocking autophagy/lipophagy sensitizes MM to chemotherapy in vivo. Our findings link a pro-survival signal to FA availability needed to sustain the FAO required for cancer cell survival under stress conditions and identify lipophagy as a therapeutic target to overcome treatment resistance in MM.
Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
Department of Pediatrics, State University of New York at Buffalo, Buffalo, NY, USA.
Indiana University Simon Comprehensive Cancer Center, and the Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, IN, USA.
Indiana University Simon Comprehensive Cancer Center, and the Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address: kplee@iu.edu.
Pro-survival signaling regulates lipophagy essential for multiple myeloma resistance to stress-induced death.
Actin assembly and dynamics are crucial for maintaining cell structure and changing physiological states. The broad impact of actin on various cellular processes makes it challenging to dissect the specific role of actin regulatory proteins. Using actin waves that propagate on the cortex of mast cells as a model, we discovered that formins (FMNL1 and mDia3) are recruited before the Arp2/3 complex in actin waves. GTPase Cdc42 interactions drive FMNL1 oscillations, with active Cdc42 and the constitutively active mutant of FMNL1 capable of forming waves on the plasma membrane independently of actin waves. Additionally, the delayed recruitment of Arp2/3 antagonizes FMNL1 and active Cdc42. This antagonism is not due to competition for monomeric actin but rather for their common upstream regulator, active Cdc42, whose levels are negatively regulated by Arp2/3 via SHIP1 recruitment. Collectively, our study highlights the complex feedback loops in the dynamic control of the actin cytoskeletal network.
Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510, USA; Department of Biological Sciences, Centre for Bioimaging Sciences, Singapore 117557, Singapore.
Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510, USA; Department of Biological Sciences, Centre for Bioimaging Sciences, Singapore 117557, Singapore; Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.
Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510, USA; Department of Physics, Yale University, New Haven, CT 06511, USA.
Department of Biological Sciences, Centre for Bioimaging Sciences, Singapore 117557, Singapore.
School of Life Sciences, Westlake University, Hangzhou 310024, China.
Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510, USA; Department of Biological Sciences, Centre for Bioimaging Sciences, Singapore 117557, Singapore; Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore. Electronic address: wu.min@yale.edu.
Competition and synergy of Arp2/3 and formins in nucleating actin waves.
Single-gene missense mutations remain challenging to interpret. Here, we deploy scalable functional screening by sequencing (SEUSS), a Perturb-seq method, to generate mutations at protein interfaces of RUNX1 and quantify their effect on activities of downstream cellular programs. We evaluate single-cell RNA profiles of 115 mutations in myelogenous leukemia cells and categorize them into three functionally distinct groups, wild-type (WT)-like, loss-of-function (LoF)-like, and hypomorphic, that we validate in orthogonal assays. LoF-like variants dominate the DNA-binding site and are recurrent in cancer; however, recurrence alone does not predict functional impact. Hypomorphic variants share characteristics with LoF-like but favor protein interactions, promoting gene expression indicative of nerve growth factor (NGF) response and cytokine recruitment of neutrophils. Accessible DNA near differentially expressed genes frequently contains RUNX1-binding motifs. Finally, we reclassify 16 variants of uncertain significance and train a classifier to predict 103 more. Our work demonstrates the potential of targeting protein interactions to better define the landscape of phenotypes reachable by missense mutations.
Division of Medical Genetics, Department of Medicine, University of California, San Diego, La Jolla, CA, USA; Bioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, CA, USA.
Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA.
School of Biological Sciences, University of California, San Diego, La Jolla, CA, USA.
School of Biological Sciences, University of California, San Diego, La Jolla, CA, USA; Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
MLL Munich Leukemia Laboratory, Max-Lebsche-Platz 31, 81377 Munich, Germany.
Division of Medical Genetics, Department of Medicine, University of California, San Diego, La Jolla, CA, USA; Bioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, CA, USA; Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA. Electronic address: pmali@ucsd.edu.
Division of Medical Genetics, Department of Medicine, University of California, San Diego, La Jolla, CA, USA; Bioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, CA, USA; Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA. Electronic address: hkcarter@health.ucsd.edu.
Interface-guided phenotyping of coding variants in the transcription factor RUNX1.
When the peritoneal cavity cannot serve as the distal shunt terminus, nonperitoneal shunts, typically terminating in the atrium or pleural space, are used. The comparative effectiveness of these two terminus options has not been evaluated. The authors directly compared shunt survival and complication rates for ventriculoatrial (VA) and ventriculopleural (VPl) shunts in a pediatric cohort.The Hydrocephalus Clinical Research Network Core Data Project was used to identify children ≤ 18 years of age who underwent either VA or VPl shunt insertion. The primary outcome was time to shunt failure. Secondary outcomes included distal site complications and frequency of shunt failure at 6, 12, and 24 months.The search criteria yielded 416 children from 14 centers with either a VA (n = 318) or VPl (n = 98) shunt, including those converted from ventriculoperitoneal shunts. Children with VA shunts had a lower median age at insertion (6.1 years vs 12.4 years, p < 0.001). Among those children with VA shunts, a hydrocephalus etiology of intraventricular hemorrhage (IVH) secondary to prematurity comprised a higher proportion (47.0% vs 31.2%) and myelomeningocele comprised a lower proportion (17.8% vs 27.3%) (p = 0.024) compared with those with VPl shunts. At 24 months, there was a higher cumulative number of revisions for VA shunts (48.6% vs 38.9%, p = 0.038). When stratified by patient age at shunt insertion, VA shunts in children < 6 years had the lowest shunt survival rate (p < 0.001, log-rank test). After controlling for age and etiology, multivariable analysis did not find that shunt type (VA vs VPl) was predictive of time to shunt failure. No differences were found in the cumulative frequency of complications (VA 6.0% vs VPl 9.2%, p = 0.257), but there was a higher rate of pneumothorax in the VPl cohort (3.1% vs 0%, p = 0.013).Shunt survival was similar between VA and VPl shunts, although VA shunts are used more often, particularly in younger patients. Children < 6 years with VA shunts appeared to have the shortest shunt survival, which may be a result of the VA group having more cases of IVH secondary to prematurity; however, when age and etiology were included in a multivariable model, shunt location (atrium vs pleural space) was not associated with time to failure. The baseline differences between children treated with a VA versus a VPl shunt likely explain current practice patterns.
1Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake City, Utah.2Department of Neurosurgery, University of California, San Diego, California.3Division of Pediatric Neurosurgery, Rady Children's Hospital, San Diego, California.4Department of Neurosurgery, Naval Medical Center, San Diego, California.
5Department of Clinical Neurosciences, University of Calgary, Alberta, Canada.
6Department of Pediatrics, University of Utah, Salt Lake City, Utah.
7Department of Neurosurgery, Division of Pediatric Neurosurgery, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas.
8Division of Neurosurgery, The Hospital for Sick Children, University of Toronto, Ontario, Canada.
9Department of Neurosurgery, Virginia Commonwealth University, Richmond, Virginia.
10Department of Neurological Surgery, Division of Pediatric Neurosurgery, Vanderbilt University Medical Center, Nashville, Tennessee.
11Division of Neurosurgery, Section of Pediatric Neurosurgery, Children's Hospital of Alabama, University of Alabama-Birmingham, Alabama.
12Division of Neurosurgery, Children's Hospital of Pittsburgh, Pennsylvania.
13Department of Surgery, Division of Neurosurgery, British Columbia Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada.
14Department of Neurosurgery, University of Washington, Seattle Children's Hospital, Seattle, Washington.
15Department of Neurosurgery, Nationwide Children's Hospital, Columbus, Ohio.
16Department of Surgery, Section of Neurosurgery, University of Manitoba, Winnipeg, Manitoba, Canada.
17Department of Neurosurgery, Division of Pediatric Neurosurgery, University of Colorado School of Medicine, Aurora, Colorado.
18Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
19Department of Neurosurgery, Division of Neurosurgery, Children's Hospital Los Angeles, University of Southern California, Los Angeles, California.
20Department of Pediatrics, Children's Hospital Los Angeles, University of Southern California, Los Angeles, California; and.
21Department of Neurosurgery, St. Louis Children's Hospital, Washington University in St. Louis, Missouri.
1Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake City, Utah.
Comparing ventriculoatrial and ventriculopleural shunts in pediatric hydrocephalus: a Hydrocephalus Clinical Research Network study.
Non-alcoholic fatty liver disease (NAFLD1) is the most frequent chronic liver disorder worldwide. Currently, no pharmacological treatment has been approved for NAFLD. Probiotics have been suggested as a potential therapy for NAFLD. The aim of this systematic review and meta-analysis was to assess the impact of probiotic intake on liver tests, lipids, glycemic parameters and inflammatory markers in NAFLD patients.We searched electronic databases using related terms. Meta-analysis was performed using random-effects models. Clinical outcomes were presented as standard mean difference (SMD2) with a 95 % confidence interval (CI3). Publication bias and heterogeneity were evaluated in eligible studies.Fifteen randomized clinical trials comprising 899 participants were included in our meta-analysis. Probiotic supplementation improved alanine transaminase [SMD -0.796; 95 % CI (-1.419, -0.172); p = 0.012], Homeostatic Model Assessment for Insulin Resistance (HOMA-IR4) [SMD -0.596; 95 % CI (-1.071, -0.121); p = 0.01] and insulin levels [SMD -1.10; 95 % CI (-2.121, -0.087); p = 0.03]. No significant effects were observed on fasting glucose, hemoglobin A1c, aspartate transaminase, lipid profile, interleukin-6 and tumor necrosis factor-α.Probiotic intake may improve insulin sensitivity and alanine transaminase in NAFLD patients.
Copyright © 2024 Elsevier Inc. All rights reserved.
Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Biochemistry Department, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Department of Nutritional Sciences and Dietetics, International Hellenic University, 57400 Thessaloniki, Greece; School of Medicine, European University Cyprus, Nicosia 2404, Cyprus. Electronic address: nikikatsiki@hotmail.com.
Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: panahig@yandex.com.
Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: sahebkara@mums.ac.ir.
Journal of diabetes and its complications
J Diabetes Complications. 2024-08;38(8):108780.
The effect of probiotic consumption on lipid profile, glycemic index, inflammatory markers, and liver function in NAFLD patients: A systematic review and meta-analysis of randomized controlled trials.
Social deficits are frequently observed in patients suffering from neurodevelopmental disorders, but the molecular mechanisms regulating sociability are still poorly understood. We recently reported that the loss of the microRNA (miRNA) cluster miR-379-410 leads to hypersocial behavior and anxiety in mice. Here, we show that ablating miR-379-410 in excitatory neurons of the postnatal mouse hippocampus recapitulates hypersociability, but not anxiety. At the cellular level, miR-379-410 loss in excitatory neurons leads to larger dendritic spines, increased excitatory synaptic transmission, and upregulation of an actomyosin gene network. Re-expression of three cluster miRNAs, as well as pharmacological inhibition of the actomyosin activator ROCK, is sufficient to reinstate normal sociability in miR-379-410 knockout mice. Several actomyosin genes and miR-379-410 family members are reciprocally dysregulated in isogenic human induced pluripotent stem cell (iPSC)-derived neurons harboring a deletion present in patients with Williams-Beuren syndrome, characterized by hypersocial behavior. Together, our results show an miRNA-actomyosin pathway involved in social behavior regulation.
Laboratory of Systems Neuroscience, Institute for Neuroscience, Department of Health Science and Technology, ETH-Zürich, Zürich, Switzerland.
Laboratory of Systems Neuroscience, Institute for Neuroscience, Department of Health Science and Technology, ETH-Zürich, Zürich, Switzerland; Laboratory of Molecular and Behavioural Neuroscience, Institute for Neuroscience, Department of Health Science and Technology, ETH-Zürich, Zürich, Switzerland; Laboratory of Statistical Bioinformatics, IMLS, University of Zürich, Zürich, Switzerland.
European Institute of Oncology (IEO) IRCCS, Milan, Italy; Human Technopole, Milan, Italy.
European Institute of Oncology (IEO) IRCCS, Milan, Italy; Human Technopole, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
Laboratory of Systems Neuroscience, Institute for Neuroscience, Department of Health Science and Technology, ETH-Zürich, Zürich, Switzerland. Electronic address: gerhard.schratt@hest.ethz.ch.
miRNA-mediated inhibition of an actomyosin network in hippocampal pyramidal neurons restricts sociability in adult male mice.
Recent advancements in tissue engineering have witnessed luffa-derived scaffolds, exhibiting their exceptional potential in cellular proliferation, biocompatibility, appropriate interconnectivity, and biomechanical strength. In vivo studies involved implanting fabricated scaffolds subcutaneously in Wistar rats to evaluate their impact on the heart, liver, and kidneys. This approach provided a safe and minimally invasive means to evaluate scaffold compatibility with surrounding tissues. Male Wistar rats were categorized into four distinct groups, Group A, B, C, and D are referred to as 3% LC implanted scaffolds, 5% LC implanted scaffolds, control (without luffa scaffolds), and Sham (without any scaffold implantation), respectively. Histological analysis in all the groups indicated that the animal models did not exhibit any signs of inflammation or toxicity, suggesting favorable tissue response to the implanted scaffolds. Initial observations revealed elevated levels of enzymes and biomarkers in the experimental groups after a 24 h interval, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin, creatine kinase-MB (CK-MB), and serum creatinine. However, these parameters normalized 3 weeks post-implantation, with no significant increase compared to the control groups, suggesting that the implanted luffa-based scaffolds did not induce adverse effects on the heart, liver, and kidneys. Furthermore, the scaffold's significant pore size and porosity enable it to release drugs, including antibacterial medications. This study demonstrates promising results, indicating excellent scaffold porosity, sustained drug release, affirming the in vivo biocompatibility, absence of inflammatory responses, and overall tissue compatibility highlighting the immense potential of these luffa-based scaffolds in various tissue engineering and regenerative medicine applications.
Tissue Engineering and Biomicrofluidics Laboratory, School of Biomedical Engineering, Indian Institute of Technology (Banaras Hindu University), Varanasi, India.
Department of Biomedical Engineering, University of Engineering (UCE), Osmania University, Hyderabad, India.
Tissue Engineering and Biomicrofluidics Laboratory, School of Biomedical Engineering, Indian Institute of Technology (Banaras Hindu University), Varanasi, India.Centre for Advanced Biomaterials and Tissue Engineering, Indian Institute of Technology (Banaras Hindu University), Varanasi, India.
In vivo characterization of a luffa-based composite scaffold for subcutaneous implantation in rats.
G-protein-coupled receptors are integral membrane proteins that transduce chemical signals from the extracellular matrix into the cell. Traditional drug design has considered ligand-receptor interactions only under normal conditions. However, studies on opioids indicate that such interactions are very different in diseased tissues. In such microenvironments, protons play an important role in structural and functional alterations of both ligands and receptors. The pertinent literature strongly suggests that future drug design should take these aspects into account in order to reduce adverse side effects while preserving desired effects of novel compounds.
Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Experimental Anaesthesiology, Berlin, Germany. Electronic address: christoph.stein@charite.de.
Effects of pH on opioid receptor activation and implications for drug design.
Omicron surged as a variant of concern in late 2021. Several distinct Omicron variants appeared and overtook each other. We combined variant frequencies and infection estimates from a nowcasting model for each US state to estimate variant-specific infections, attack rates, and effective reproduction numbers (Rt). BA.1 rapidly emerged, and we estimate that it infected 47.7% of the US population before it was replaced by BA.2. We estimate that BA.5 infected 35.7% of the US population, persisting in circulation for nearly 6 months. Other variants-BA.2, BA.4, and XBB-together infected 30.7% of the US population. We found a positive correlation between the state-level BA.1 attack rate and social vulnerability and a negative correlation between the BA.1 and BA.2 attack rates. Our findings illustrate the complex interplay between viral evolution, population susceptibility, and social factors during the Omicron emergence in the US.
Department of Epidemiology of Microbial Diseases and Public Health Modeling Unit, Yale School of Public Health, New Haven, CT, USA. Electronic address: rafael.lopes@yale.edu.
Department of Epidemiology of Microbial Diseases and Public Health Modeling Unit, Yale School of Public Health, New Haven, CT, USA.
Department of Global Health and Population, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
Department of Health Policy, Stanford University School of Medicine, Stanford, CA, USA.
Department of Epidemiology of Microbial Diseases and Public Health Modeling Unit, Yale School of Public Health, New Haven, CT, USA. Electronic address: theodore.cohen@yale.edu.
Department of Epidemiology of Microbial Diseases and Public Health Modeling Unit, Yale School of Public Health, New Haven, CT, USA; Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT, USA. Electronic address: nathan.grubaugh@yale.edu.
Combining genomic data and infection estimates to characterize the complex dynamics of SARS-CoV-2 Omicron variants in the US.
A stimulus held in working memory is perceived as contracted toward the average stimulus. This contraction bias has been extensively studied in psychophysics, but little is known about its origin from neural activity. By training recurrent networks of spiking neurons to discriminate temporal intervals, we explored the causes of this bias and how behavior relates to population firing activity. We found that the trained networks exhibited animal-like behavior. Various geometric features of neural trajectories in state space encoded warped representations of the durations of the first interval modulated by sensory history. Formulating a normative model, we showed that these representations conveyed a Bayesian estimate of the interval durations, thus relating activity and behavior. Importantly, our findings demonstrate that Bayesian computations already occur during the sensory phase of the first stimulus and persist throughout its maintenance in working memory, until the time of stimulus comparison.
Departamento de Física Teórica, Universidad Autónoma de Madrid, 28049 Madrid, Spain; Centro de Investigación Avanzada en Física Fundamental, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
Center for Theoretical Neuroscience, Zuckerman Institute, Columbia University, New York, NY, USA.
Departamento de Física Teórica, Universidad Autónoma de Madrid, 28049 Madrid, Spain; Centro de Investigación Avanzada en Física Fundamental, Universidad Autónoma de Madrid, 28049 Madrid, Spain. Electronic address: nestor.parga@uam.es.
Emergent perceptual biases from state-space geometry in trained spiking recurrent neural networks.
Obesity is a global health challenge with limited therapeutic solutions. Here, we demonstrate the engineering of an energy-dissipating hybrid tissue (EDHT) in the body for weight control. EDHT is constructed by implanting a synthetic gel matrix comprising immunomodulatory signals and functional cells into the recipient mouse. The immunomodulatory signals induce the host stromal cells to create an immunosuppressive niche that protects the functional cells, which are overexpressing the uncoupling protein 1 (UCP1), from immune rejection. Consequently, these endogenous and exogenous cells co-develop a hybrid tissue that sustainedly produces UCP1 to accelerate the host's energy expenditure. Systematic experiments in high-fat diet (HFD) and transgenic (ob/ob) mice show that EDHT efficiently reduces body weight and relieves obesity-associated pathological conditions. Importantly, an 18-month observation for safety assessment excludes cell leakage from EDHT and reports no adverse physiological responses. Overall, EDHT demonstrates convincing efficacy and safety in controlling body weight.
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing 210093, China; School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing 210093, China.
Medical School, Nanjing University, Nanjing 210093, China.
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR, China.
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing 210093, China; School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China; Medical School, Nanjing University, Nanjing 210093, China. Electronic address: jfzhang@nju.edu.cn.
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR, China; Department of Pharmaceutical Sciences, Faculty of Health Science, University of Macau, Taipa, Macau SAR, China. Electronic address: cmwang@umac.mo.
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing 210093, China; Chemistry and Biomedicine Innovation Center, Nanjing University, Nanjing 210093, China; National Resource Center for Mutant Mice, Nanjing, Jiangsu 210023, China. Electronic address: leidong@nju.edu.cn.
Engineering an energy-dissipating hybrid tissue in vivo for obesity treatment.
Microbial plant pathogens deploy amphipathic cyclic lipopeptides to reduce surface tension in their environment. While plants can detect these molecules to activate cellular stress responses, the role of these lipopeptides or associated host responses in pathogenesis are not fully clear. The gramillin cyclic lipopeptide is produced by the Fusarium graminearum fungus and is a virulence factor and toxin in maize. Here, we show that gramillin promotes virulence and necrosis in both monocots and dicots by disrupting ion balance across membranes. Gramillin is a cation-conducting ionophore and causes plasma membrane depolarization. This disruption triggers cellular signaling, including a burst of reactive oxygen species (ROS), transcriptional reprogramming, and callose production. Gramillin-induced ROS depends on expression of host ILK1 and RBOHD genes, which promote fungal induction of virulence genes during infection and host susceptibility. We conclude that gramillin's ionophore activity targets plant membranes to coordinate attack by the F. graminearum fungus.
Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.
Ottawa Research and Development Center, Agriculture and Agri-Food Canada, Ottawa, ON K1A 0C6, Canada; Department of Biology, University of Ottawa, Ottawa, ON K1N 9A7, Canada. Electronic address: elizabeth.brauer@agr.gc.ca.
Ottawa Research and Development Center, Agriculture and Agri-Food Canada, Ottawa, ON K1A 0C6, Canada.
Boyce Thompson Institute for Plant Research, Cornell University, Ithaca, NY 14853, USA.
Ottawa Research and Development Center, Agriculture and Agri-Food Canada, Ottawa, ON K1A 0C6, Canada; Department of Biology, University of Ottawa, Ottawa, ON K1N 9A7, Canada.
Biology Department, Queen's University, Biological Sciences Complex, 116 Barrie St., Kingston, ON K7L 3N6, Canada.
Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada.
Boyce Thompson Institute for Plant Research, Cornell University, Ithaca, NY 14853, USA; Robert W. Holley Center for Agriculture and Health, United States Department of Agriculture-Agricultural Research Service, Cornell University, Ithaca, NY 14853, USA.
A cyclic lipopeptide from Fusarium graminearum targets plant membranes to promote virulence.
The compaction of chromatin into mitotic chromosomes is essential for faithful transmission of the genome during cell division. In eukaryotes, chromosome morphogenesis is regulated by the condensin complex, though the exact mechanism used to target condensin to chromatin and initiate condensation is not understood. Here, we reveal that condensin contains an intrinsically disordered region (IDR) that modulates its association with chromatin in early mitosis and exhibits phase separation. We describe DNA-binding motifs within the IDR that, upon deletion, inflict striking defects in chromosome condensation and segregation, ill-timed condensin turnover on chromatin, and cell death. Importantly, we demonstrate that the condensin IDR can impart cell cycle regulatory functions when transferred to other subunits within the complex, indicating its autonomous nature. Collectively, our study unveils the molecular basis for the initiation of chromosome condensation in early mitosis and how this process ultimately promotes genomic stability and faultless cell division.
Ottawa Institute of Systems Biology, Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Molecular Medicine Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada.
Ottawa Institute of Systems Biology, Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada. Electronic address: damien.damours@uottawa.ca.
Chromosome compaction is triggered by an autonomous DNA-binding module within condensin.
To evaluate the incidence of skin-related complications attributable to incontinence-associated dermatitis (IAD) using an external female urinary catheter device strategy for urinary incontinent (UI) patients in acute care.Multicenter quality improvement study.Randomized allocation of two commercially available external female urinary catheter devices was used in hospitalized UI female patients. Daily nursing skin assessments were documented in the electronic health record before, during and after external catheter device application. Methods and results were reported following SQUIRE guidelines.Three hundred and eighty-one patients from 57 inpatient care units were included in the analysis. Both catheter devices were associated with an overall low risk (5 %) of new or worsening skin breakdown.The overall benefit of external catheters is most persuasive for skin integrity, rather than infection prevention.Significant negative outcomes are associated with UI patients. External female urinary catheters are a non-invasive alternative strategy to reduce exposure of regional skin to urine contamination and IAD-related skin complications. Use of external female urinary catheters in hospitalized UI female patients offers low risk (5%) of new or worsening overall skin breakdown.Hospitalized UI female patients were screened for external catheter device eligibility by the bedside nurse. The quality improvement review committee waved consent because the intervention was considered standard care.
© 2024 The Author(s). Journal of Clinical Nursing published by John Wiley & Sons Ltd.
Quality, Safety, and Innovation, Wolff Center-UPMC, Pittsburgh, Pennsylvania, USA.
Wound Care, UPMC Presbyterian/Shadyside, Pittsburgh, Pennsylvania, USA.
Wound Care, UPMC Passavant, Pittsburgh, Pennsylvania, USA.
Supply Chain Management, UPMC, Pittsburgh, Pennsylvania, USA.
Infection Prevention and Control, UPMC Mercy, Pittsburgh, Pennsylvania, USA.
Infection Prevention and Control, UPMC Presbyterian, Pittsburgh, Pennsylvania, USA.Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Implementation of an external female urinary catheter strategy on prevention of skin breakdown in acute care: A quality improvement study.
This research investigated the in vivo gelation, biodegradation, and drug release efficiency of a novel injectable sensitive drug delivery system for human growth hormone (HGh). This composite system comprises pH- and temperature-sensitive hydrogel, designated as oligomer serine-b-poly(lactide)-b-poly(ethylene glycol)-b-poly(lactide)-b-oligomer serine (OS-PLA-PEG-PLA-OS) pentablock copolymer, as matrix and electrosprayed HGh-loaded chitosan (HGh@CS) nanoparticles (NPs) as principal material. The proton nuclear magnetic resonance spectrum of the pH- and temperature-sensitive OS-PLA-PEG-PLA-OS pentablock copolymer hydrogel proved that this copolymer was successfully synthesized. The HGh was encapsulated in chitosan (CS) NPs by an electrospraying system in acetic acid with appropriate granulation parameters. The scanning electron microscopy images and size distribution showed that the HGh@CS NPs formed had an average diameter of 366.1 ± 214.5 nm with a discrete spherical shape and dispersed morphology. The sol-gel transition of complex gel based on HGh@CS NPs and OS-PLA-PEG-PLA-OS pentablock hydrogel was investigated at 15 °C and pH 7.8 in the sol state and gelled at 37 °C and pH 7.4, which is suitable for the physiological conditions of the human body. The HGh release experiment of the composite system was performed in an in vivo environment, which demonstrated the ability to release HGh, and underwent biodegradation within 32 days. The findings of the investigation revealed that the distribution of HGh@CS NPs into the hydrogel matrix not only improved the mechanical properties of the gel matrix but also controlled the drug release kinetics into the systematic bloodstream, which ultimately promotes the desired therapeutic body growth depending on the distinct concentration used.
Faculty of Materials Technology, Ho Chi Minh City University of Technology, Ho Chi Minh City, Vietnam.Research Center for Polymeric Materials, Ho Chi Minh City University of Technology, Ho Chi Minh City, Vietnam.Vietnam National University Ho Chi Minh City, Ho Chi Minh City, Vietnam.
Research Center for Polymeric Materials, Ho Chi Minh City University of Technology, Ho Chi Minh City, Vietnam.Vietnam National University Ho Chi Minh City, Ho Chi Minh City, Vietnam.
Faculty of Applied Sciences, Ho Chi Minh City University of Technology and Education, Ho Chi Minh City, Vietnam.
Preparation and characterization of the injectable pH- and temperature-sensitive pentablock hydrogel containing human growth hormone-loaded chitosan nanoparticles via electrospraying.
Lung adenocarcinoma (LUAD) remains a predominant cause of cancer-related mortality globally, underscoring the urgency for targeted therapeutic strategies. The specific role and impact of the SEC61 translocon gamma subunit (SEC61G) in LUAD progression and metastasis remain largely unexplored. In this study, we use a multifaceted approach, combining bioinformatics analysis with experimental validation, to elucidate the pivotal role of SEC61G and its associated molecular mechanisms in LUAD. Our integrated analyses reveal a significant positive correlation between SEC61G expression and the glycolytic activity of LUAD, as evidenced by increased fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET)/CT scans. Further investigations show the potential influence of SEC61G on metabolic reprogramming, which contributes to the immunosuppressive tumor microenvironment (TME). Remarkably, we identify a negative association between SEC61G expression levels and the infiltration of critical immune cell populations within the TME, along with correlations with immune checkpoint gene expression and tumor heterogeneity scores in LUAD. Functional studies demonstrate that SEC61G knockdown markedly inhibits the migration of A549 and H2030 LUAD cells. This inhibitory effect is accompanied by a significant downregulation of key regulators of tumor progression, including hypoxia-inducible factor-1 alpha (HIF-1α), lactate dehydrogenase A, and genes involved in the epithelial-mesenchymal transition pathway. In conclusion, our comprehensive analyses position SEC61G as a potential prognostic biomarker intricately linked to glycolytic metabolism, the EMT pathway, and the establishment of an immune-suppressive phenotype in LUAD. These findings underscore the potential of SEC61G as a therapeutic target and predictive marker for immunotherapeutic responses in LUAD patients.
Department of Neurosurgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
SEC61 translocon gamma subunit is correlated with glycolytic activity, epithelial mesenchymal transition and the immune suppressive phenotype of lung adenocarcinoma.
Cell membranes mediate interactions between life and its environment, with lipids determining their properties. Understanding how cells adjust their lipidomes to tune membrane properties is crucial yet poorly defined due to the complexity of most organisms. We used quantitative shotgun lipidomics to study temperature adaptation in the simple organism Mycoplasma mycoides and the minimal cell JCVI-syn3B. We show that lipid abundances follow a universal logarithmic distribution across eukaryotes and bacteria, with comparable degrees of lipid remodeling for adaptation regardless of lipidomic or organismal complexity. Lipid features analysis demonstrates head-group-specific acyl chain remodeling as characteristic of lipidome adaptation; its deficiency in Syn3B is associated with impaired homeoviscous adaptation. Temporal analysis reveals a two-stage cold adaptation process: swift cholesterol and cardiolipin shifts followed by gradual acyl chain modifications. This work provides an in-depth analysis of lipidome adaptation in minimal cells, laying a foundation to probe the design principles of living membranes.
B CUBE Center for Molecular Bioengineering, Technische Universität Dresden, 01062 Dresden, Germany.
B CUBE Center for Molecular Bioengineering, Technische Universität Dresden, 01062 Dresden, Germany; Faculty of Medicine, Technische Universität Dresden, 01062 Dresden, Germany. Electronic address: james.saenz@tu-dresden.de.
Temperature change elicits lipidome adaptation in the simple organisms Mycoplasma mycoides and JCVI-syn3B.
ADP-ribosylation (ADPr) signaling plays a crucial role in DNA damage response. Inhibitors against the main enzyme catalyzing ADPr after DNA damage, poly(ADP-ribose) polymerase 1 (PARP1), are used to treat patients with breast cancer harboring BRCA1/2 mutations. However, resistance to PARP inhibitors (PARPi) is a major obstacle in treating patients. To understand the role of ADPr in PARPi sensitivity, we use liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyze ADPr in six breast cancer cell lines exhibiting different PARPi sensitivities. We identify 1,632 sites on 777 proteins across all cell lines, primarily on serine residues, with site-specific overlap of targeted residues across DNA-damage-related proteins across all cell lines, demonstrating high conservation of serine ADPr-signaling networks upon DNA damage. Furthermore, we observe site-specific differences in ADPr intensities in PARPi-sensitive BRCA mutants and unique ADPr sites in PARPi-resistant BRCA-mutant HCC1937 cells, which have low poly(ADP-ribose) glycohydrolase (PARG) levels and longer ADPr chains on PARP1.
Department of Proteomics, Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Faculty of Health and Medical Sciences, 2200 Copenhagen, Denmark.
Danish Cancer Institute, Copenhagen, Denmark.
Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, Université Toulouse III - Paul Sabatier (UT3), Toulouse, France.
Danish Cancer Institute, Copenhagen, Denmark; Computational Health Informatics Program, Boston Children's Hospital, Boston, MA, USA.
Department of Proteomics, Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Faculty of Health and Medical Sciences, 2200 Copenhagen, Denmark. Electronic address: michael.lund.nielsen@cpr.ku.dk.
ADP-ribosylome analysis reveals homogeneous DNA-damage-induced serine ADP-ribosylation across wild-type and BRCA-mutant breast cancer cell lines.
Some microbial toxins also target the producer species itself, necessitating a means of self-protection. The M2 double-stranded RNA (dsRNA) killer virus in Saccharomyces cerevisiae contains a single open reading frame (ORF) encoding both the secreted pore-forming toxin K2 as well as a cognate immunity factor. Here, we show that expression of a 49-amino acid N-terminal peptide from the K2 precursor is both necessary and sufficient for immunity. This immunity peptide simultaneously functions as a signal peptide for toxin secretion and protects the cell against the cytotoxic K2 α subunit. The K2 toxin and immunity factor can be functionally separated into two ORFs, yielding a modular toxin-immunity system. This case further shows how a (signal) peptide can carry the potential for providing cellular protection against an antimicrobial toxin.
Molecular Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, 9747 AG Groningen, the Netherlands.
Molecular Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, 9747 AG Groningen, the Netherlands. Electronic address: s.k.billerbeck@rug.nl.
The signal peptide of yeast killer toxin K2 confers producer self-protection and allows conversion into a modular toxin-immunity system.
Kainate (KA)-type glutamate receptors (KARs) are implicated in various neuropsychiatric and neurological disorders through their ionotropic and metabotropic actions. However, compared to AMPA- and NMDA-type receptor functions, many aspects of KAR biology remain incompletely understood. Our study demonstrates an important role of KARs in organizing climbing fiber (CF)-Purkinje cell (PC) synapses and synaptic plasticity in the cerebellum, independently of their ion channel or metabotropic functions. The amino-terminal domain (ATD) of the GluK4 KAR subunit binds to C1ql1, provided by CFs, and associates with Bai3, an adhesion-type G protein-coupled receptor expressed in PC dendrites. Mice lacking GluK4 exhibit no KAR-mediated responses, reduced C1ql1 and Bai3 levels, and fewer CF-PC synapses, along with impaired long-term depression and oculomotor learning. Remarkably, introduction of the ATD of GluK4 significantly improves all these phenotypes. These findings demonstrate that KARs act as synaptic scaffolds, orchestrating synapses by forming a KAR-C1ql1-Bai3 complex in the cerebellum.
Department of Neurophysiology, Keio University School of Medicine, Tokyo 160-8582, Japan. Electronic address: wkake@keio.jp.
Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas and Universidad Miguel Hernández, 03550 San Juan de Alicante, Spain.
Department of Neurophysiology, Keio University School of Medicine, Tokyo 160-8582, Japan.
Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Meguro, Tokyo 153-8902, Japan; Department of Animal Model Development, Brain Research Institute, Niigata University, Niigata 951-8585, Japan.
Department of Animal Model Development, Brain Research Institute, Niigata University, Niigata 951-8585, Japan.
Department of Neurophysiology, Keio University School of Medicine, Tokyo 160-8582, Japan. Electronic address: myuzaki@keio.jp.
Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas and Universidad Miguel Hernández, 03550 San Juan de Alicante, Spain. Electronic address: jlerma@umh.es.
Kainate receptors regulate synaptic integrity and plasticity by forming a complex with synaptic organizers in the cerebellum.
Cartilage tissue engineering holds great promise for efficient cartilage regeneration. However, early inflammatory reactions to seed cells and/or scaffolds impede this process. Consequently, managing inflammation is of paramount importance. Moreover, due to the body's restricted chondrogenic capacity, inducing cartilage regeneration becomes imperative. Thus, a controlled platform is essential to establish an anti-inflammatory microenvironment before initiating the cartilage regeneration process. In this study, we utilized fifth-generation polyamidoamine dendrimers (G5) as a vehicle for drugs to create composite nanoparticles known as G5-Dic/Sr. These nanoparticles were generated by surface modification with diclofenac (Dic), known for its potent anti-inflammatory effects, and encapsulating strontium (Sr), which effectively induces chondrogenesis, within the core. Our findings indicated that the G5-Dic/Sr nanoparticle exhibited selective Dic release during the initial 9 days and gradual Sr release from days 3 to 15. Subsequently, these nanoparticles were incorporated into a gelatin methacryloyl (GelMA) hydrogel, resulting in GelMA@G5-Dic/Sr. In vitro assessments demonstrated GelMA@G5-Dic/Sr's biocompatibility with bone marrow stem cells (BMSCs). The enclosed nanoparticles effectively mitigated inflammation in lipopolysaccharide-induced RAW264.7 macrophages and significantly augmented chondrogenesis in BMSCs cocultures. Implanting BMSCs-loaded GelMA@G5-Dic/Sr hydrogels in immunocompetent rabbits for 2 and 6 weeks revealed diminished inflammation and enhanced cartilage formation compared to GelMA, GelMA@G5, GelMA@G5-Dic, and GelMA@G5/Sr hydrogels. Collectively, this study introduces an innovative strategy to advance cartilage regeneration by temporally modulating inflammation and chondrogenesis in immunocompetent animals. Through the development of a platform addressing the temporal modulation of inflammation and the limited chondrogenic capacity, we offer valuable insights to the field of cartilage tissue engineering.
Department of Thoracic Surgery, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, China.
Department of Pathology, Anhui Medical College, Hefei, China.
Department of Thoracic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Spine Surgery, Ningbo Sixth Hospital, Ningbo, China.
Department of Orthopedics, Shanghai Eighth People's Hospital, Shanghai, China.
Temporal modulation of inflammation and chondrogenesis through dendritic nanoparticle-mediated therapy with diclofenac surface modification and strontium ion encapsulation.
The emergence of novel traits is often preceded by a potentiation phase, when all the genetic components necessary for producing the trait are assembled. However, elucidating these potentiating factors is challenging. We have previously shown that an anthocyanin-activating R2R3-MYB, STRIPY, triggers the emergence of a distinct foliar pigmentation pattern in the monkeyflower Mimulus verbenaceus. Here, using forward and reverse genetics approaches, we identify three potentiating factors that pattern STRIPY expression: MvHY5, a master regulator of light signaling that activates STRIPY and is expressed throughout the leaf, and two leaf developmental regulators, MvALOG1 and MvTCP5, that are expressed in opposing gradients along the leaf proximodistal axis and negatively regulate STRIPY. These results provide strong empirical evidence that phenotypic novelties can be potentiated through incorporation into preexisting genetic regulatory networks and highlight the importance of positional information in patterning the novel foliar stripe.
Department of Ecology and Evolutionary Biology, University of Connecticut, 75 North Eagleville Road, Storrs, CT 06269-3043, USA. Electronic address: amy.lafountain@uconn.edu.
Department of Ecology and Evolutionary Biology, University of Connecticut, 75 North Eagleville Road, Storrs, CT 06269-3043, USA.
Department of Ecology and Evolutionary Biology, University of Connecticut, 75 North Eagleville Road, Storrs, CT 06269-3043, USA; Institute for Systems Genomics, University of Connecticut, 67 North Eagleville Road, Storrs, CT 06269, USA. Electronic address: yaowu.yuan@uconn.edu.
A distinct foliar pigmentation pattern formed by activator-repressor gradients upstream of an anthocyanin-activating R2R3-MYB.
The gene encoding the NUAK family kinase 1 (NUAK1) is frequently amplified and its expression is upregulated, activating oncogenic signaling in various cancers. However, little is known about its role in gastric cancer (GC). We investigate the mechanistic links among NUAK1, Hedgehog signaling, and tumorigenesis in GC. NUAK1 overexpression is validated in local and public GC cohorts. Patient-derived xenograft and transgenic mouse models demonstrate that NUAK1 depletion or inhibition dramatically ameliorates gastric tumorigenesis. NUAK1 upregulates GLI1 expression by activating STAT5-mediated transcription and stabilizing GLI1 protein. NUAK1 depletion or inhibition impairs cancer cell expansion, tumor formation, and chemotherapy resistance in in vitro and in vivo models. Clinicopathological analysis confirms that upregulated NUAK1 expression correlates with poor prognosis and chemotherapy resistance in human GC. Our findings demonstrate that the signaling axis NUAK1/STAT5/GLI1 promotes cancer cell expansion and tumorigenesis and indicate that NUAK1 is an attractive therapeutic target and prognostic factor in GC.
Copyright © 2024. Published by Elsevier Inc.
Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian, China; Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, Fujian, China. Electronic address: lxc1122@fjmu.edu.cn.
Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian, China; Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, Fujian, China.
Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian, China; Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, Fujian, China. Electronic address: hcmlr2002@163.com.
Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China; Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian, China; Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, Fujian, China. Electronic address: xjwhw2019@163.com.
NUAK1 activates STAT5/GLI1/SOX2 signaling to enhance cancer cell expansion and drives chemoresistance in gastric cancer.
The authors evaluated the impact of the timing of epilepsy surgery on postoperative neurocognitive outcomes in a cohort of children followed in the multiinstitutional Tuberous Sclerosis Complex (TSC) Autism Center of Excellence Research Network (TACERN) study.Twenty-seven of 159 patients in the TACERN cohort had drug-refractory epilepsy and underwent surgery. Ages at surgery ranged from 15.86 to 154.14 weeks (median 91.93 weeks). Changes in patients' first preoperative (10-58 weeks) to last postoperative (155-188 weeks) scores on three neuropsychological tests-the Mullen Scales of Early Learning (MSEL), the Vineland Adaptive Behavior Scales, 2nd edition (VABS-2), and the Preschool Language Scales, 5th edition (PLS-5)-were calculated. Pearson correlation and multivariate linear regression models were used to correlate test outcomes separately with age at surgery and duration of epilepsy prior to surgery. Analyses were separately conducted for patients whose seizure burdens decreased postoperatively (n = 21) and those whose seizure burdens did not (n = 6). Regression analysis was specifically focused on the 21 patients who achieved successful seizure control.Age at surgery was significantly negatively correlated with the change in the combined verbal subtests of the MSEL (R = -0.45, p = 0.039) and predicted this score in a multivariate linear regression model (β = -0.09, p = 0.035). Similar trends were seen in the total language score of the PLS-5 (R = -0.4, p = 0.089; β = -0.12, p = 0.014) and in analyses examining the duration of epilepsy prior to surgery as the independent variable of interest. Associations between age at surgery and duration of epilepsy prior to surgery with changes in the verbal subscores of VABS-2 were more variable (R = -0.15, p = 0.52; β = -0.05, p = 0.482).Earlier surgery and shorter epilepsy duration prior to surgery were associated with greater improvement in postoperative language in patients with TSC. Prospective or comparative effectiveness clinical trials are needed to further elucidate surgical timing impacts on neurocognitive outcomes.
2Department of Neurology, Harvard Medical School, Boston, Massachusetts; and.
3Neurology, Stanford University School of Medicine, Stanford, California.
4Department of Pediatrics, Division of Neurology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Association of earlier surgery with improved postoperative language development in children with tuberous sclerosis complex.
Department of Neurology, Queen's Hospital, BHR University Hospitals NHS Trust, Romford, UK rawannn@gmail.com.
Department of Neurology, Queen's Hospital, BHR University Hospitals NHS Trust, Romford, UK.
NHS North Thames Genomic Laboratory Hub, London, UK.
Glucose transporter type 1 deficiency syndrome and paroxysmal exercise-induced dyskinesia.
To assess the effects of 1% azithromycin ophthalmic solution (AZM) in patients with bacterial blepharitis accompanied by meibomian gland dysfunction (MGD).A multicenter, single arm, prospective interventional study.AZM was administered to the affected eyes twice daily for the first 2 days and once daily for the subsequent 12 days. Lid margin hyperaemia/redness, collarette at the root of the eyelashes, conjunctival hyperaemia, foreign body sensation, and epiphora were assessed on Days 1, 14, and 28. The Dry Eye-related Quality of Life Score (DEQS) and objectives related to MGD, including lid vascularity, lid margin irregularity, foaming, lid plugging, keratoconjunctival disorders, Marx line, meibum grade, and tear breakup time, were also assessed. Bacterial culture of the conjunctival sac and meibum was performed on Days 1 and 14.Twenty-four eyes of 24 patients (10 men/14 women, mean age 72.3 ± 13.2) were included. On Days 14 and 28, the total score, lid vascularity, lid plugging, and meibum grade showed significant improvement (p < 0.05). On Day 1, 71 strains were isolated from 22 of the 24 eyes (91.7%). Cutibacterium acnes, Corynebacterium spp., and Staphylococci were detected at high frequencies. The overall disappearance rates of the bacteria in the conjunctival sac and meibum at the end of treatment were 65.7% and 58.3%, respectively. No serious ocular or systemic adverse events were observed.Fourteen-day treatment with AZM was effective in patients with blepharitis accompanied by MGD, and the efficacy of AZM persisted for a period after the treatment.
Department of Ophthalmology, Tokyo Dental College Ichikawa General Hospital, 5-11-13 Sugano, Ichikawa, Chiba, 272-8513, Japan. meishano1@gmail.com.Shimazaki Eye Clinic, Tokyo, Japan. meishano1@gmail.com.
Senju pharmaceutical Co., Ltd, Osaka, Japan.
Department of Ophthalmology, Tokyo Dental College Ichikawa General Hospital, 5-11-13 Sugano, Ichikawa, Chiba, 272-8513, Japan.Satake Eye Clinic, Chiba, Japan.
Efficacy and safety of topical azithromycin therapy in patients with blepharitis and meibomian gland dysfunction.
Defense systems that recognize viruses provide important insights into both prokaryotic and eukaryotic innate immunity mechanisms. Such systems that restrict foreign DNA or trigger cell death have recently been recognized, but the molecular signals that activate many of these remain largely unknown. Here, we characterize one such system in pandemic Vibrio cholerae responsible for triggering cell density-dependent death (CDD) of cells in response to the presence of certain genetic elements. We show that the key component is the Lamassu DdmABC anti-phage/plasmid defense system. We demonstrate that signals that trigger CDD were palindromic DNA sequences in phages and plasmids that are predicted to form stem-loop hairpins from single-stranded DNA. Our results suggest that agents that damage DNA also trigger DdmABC activation and inhibit cell growth. Thus, any infectious process that results in damaged DNA, particularly during DNA replication, can in theory trigger DNA restriction and death through the DdmABC abortive infection system.
Department of Microbiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. Electronic address: william_robins@hms.harvard.edu.
Department of Microbiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Department of Microbiology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. Electronic address: john_mekalanos@hms.harvard.edu.
DdmABC-dependent death triggered by viral palindromic DNA sequences.
Noonan syndrome patients harboring causative variants in LZTR1 are particularly at risk to develop severe and early-onset hypertrophic cardiomyopathy. In this study, we investigate the mechanistic consequences of a homozygous variant LZTR1L580P by using patient-specific and CRISPR-Cas9-corrected induced pluripotent stem cell (iPSC) cardiomyocytes. Molecular, cellular, and functional phenotyping in combination with in silico prediction identify an LZTR1L580P-specific disease mechanism provoking cardiac hypertrophy. The variant is predicted to alter the binding affinity of the dimerization domains facilitating the formation of linear LZTR1 polymers. LZTR1 complex dysfunction results in the accumulation of RAS GTPases, thereby provoking global pathological changes of the proteomic landscape ultimately leading to cellular hypertrophy. Furthermore, our data show that cardiomyocyte-specific MRAS degradation is mediated by LZTR1 via non-proteasomal pathways, whereas RIT1 degradation is mediated by both LZTR1-dependent and LZTR1-independent pathways. Uni- or biallelic genetic correction of the LZTR1L580P missense variant rescues the molecular and cellular disease phenotype, providing proof of concept for CRISPR-based therapies.
Stem Cell Unit, Clinic for Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany; DZHK (German Center for Cardiovascular Research), Göttingen, Germany; Cluster of Excellence Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells (MBExC), University of Göttingen, Göttingen, Germany.
Stem Cell Unit, Clinic for Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany; DZHK (German Center for Cardiovascular Research), Göttingen, Germany.
DZHK (German Center for Cardiovascular Research), Greifswald, Germany; Interfaculty Institute of Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
Institute of Biochemistry and Molecular Biology II, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
School of Biological Sciences, Seoul National University, Seoul, South Korea.
Cluster of Excellence Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells (MBExC), University of Göttingen, Göttingen, Germany; Institute of Computer Science, Georg-August University Göttingen, Göttingen, Germany.
Stem Cell Unit, Clinic for Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany.
NMR Signal Enhancement Group, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
Institute of Applied Physiology, University of Ulm, Ulm, Germany.
Institute of Physical Biology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany; Institute of Biological Information Processing, Structural Biochemistry (IBI-7), Forschungszentrum Jülich GmbH, Jülich, Germany.
Cologne Center for Genomics, University of Cologne, Faculty of Medicine, and University Hospital Cologne, Cologne, Germany; Genomics Platform, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine-Berlin, Berlin, Germany.
Institute of Human Genetics, University Hospital Cologne, Cologne, Germany; Institute of Human Genetics, Heidelberg University, Heidelberg, Germany.
DZHK (German Center for Cardiovascular Research), Göttingen, Germany; Cluster of Excellence Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells (MBExC), University of Göttingen, Göttingen, Germany; Institute of Pharmacology and Toxicology, University Medical Center Göttingen, Göttingen, Germany; Translational Neuroinflammation and Automated Microscopy, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Göttingen, Germany.
DZHK (German Center for Cardiovascular Research), Göttingen, Germany; Cluster of Excellence Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells (MBExC), University of Göttingen, Göttingen, Germany; Institute of Human Genetics, University Medical Center Göttingen, Göttingen, Germany.
Stem Cell Unit, Clinic for Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany; DZHK (German Center for Cardiovascular Research), Göttingen, Germany; Cluster of Excellence Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells (MBExC), University of Göttingen, Göttingen, Germany; Translational Neuroinflammation and Automated Microscopy, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Göttingen, Germany. Electronic address: lukas.cyganek@gwdg.de.
Mutation-induced LZTR1 polymerization provokes cardiac pathology in recessive Noonan syndrome.
Introduction. The WPAI-UC/CD-Caregiver questionnaires assess the impact of ulcerative colitis (UC) or Crohn's disease (CD) on parents'/caregivers' work life and daily activities. Our objective was to adapt and validate these questionnaires in the Spanish population. Methods. A translation and back-translation were done. The document was assessed by an expert committee and a pilot group of families of patients with pediatric inflammatory bowel disease (p-IBD). For validation, the parents/caregivers of patients with p-IBD (10-18 years old) were recruited. The expert committee and the pilot group conducted a subjective assessment of the format and time necessary to complete the questionnaires. Cronbach's alpha coefficient was estimated and a factor analysis with varimax rotation was done. Kaiser- Meyer-Olkin (KMO) coefficients and Bartlett's sphericity test were estimated to test the adequacy of the factor analysis. Results. A total of 370 patients (median age: 14.1 years) and 263 parents/caregivers of patients with UC or unclassified IBD and 261 parents/caregivers of patients with CD were included. The KMO coefficients (0.6947 and 0.7179) and Bartlett's sphericity test (p < 0.001) confirmed the adequacy of the factor analysis. The 6 items targeted the same domain. The factor model accounted for 99.99% and 94.68% of variance, and Cronbach's alpha coefficients (0.6581 and 0.6968) showed an adequate consistency. The format and the median time of 2 minutes to complete the questionnaires were considered optimal. Conclusions. The versions of the WPAI-Caregiver questionnaires validated in the Spanish population may be used in families whose children have IBD.
Department of Pediatric Gastroenterology and Nutrition, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.
Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Hospital Sant Joan de Déu, Barcelona, Spain.
Department of Pediatric Gastroenterology and Nutrition, Hospital Regional Universitario de Málaga, Málaga, Spain.
Unit of Pediatric Gastroenterology, Hospital Universitario de Fuenlabrada, Madrid, Spain.
Task Force for Pediatric Inflammatory Bowel Disease of the Spanish Society of Pediatric Gastroenterology, Hepatology, and Nutrition (SEGHNP)
Unit of Pediatric Gastroenterology and Nutrition, Hospital Doce de Octubre, Madrid
Unit of Pediatric Gastroenterology, Hepatology, and Nutrition, Hospital Materno-Infantil Teresa Herrera, Complejo Hospitalario Universitario A Coruña, A Coruña
Department of Pediatric Gastroenterology and Nutrition, Hospital Universitario La Paz, Madrid
Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Hospital Sant Joan de Déu, Barcelona
Division of Pediatric Gastroenterology and Nutrition, Hospital Regional Universitario de Málaga, Málaga
Unit of Pediatric Gastroenterology, Hospital Germans Trias i Pujol, Badalona
Division of Pediatric Gastroenterology and Nutrition, Complejo Hospitalario Universitario Insular Materno Infantil, Universidad de Las Palmas de Gran Canaria
Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Hospital Universitario Virgen del Rocío, Sevilla
Division of Pediatric Gastroenterology, Hospital Universitario Fundación Alcorcón, Madrid
Division of Pediatric Gastroenterology, Hospital Clínico Universitario de Valladolid, Valladolid
Division of Pediatric Gastroenterology, Hospital Universitario de Canarias, Santa Cruz de Tenerife
Division of Pediatric Gastroenterology and Hepatology, Hospital Universitari i Politècnic la Fe, Valencia
Division of Pediatric Gastroenterology, Complexo Hospitalario de Ourense, Ourense
Division of Pediatric Gastroenterology, Hospital General Universitario Gregorio Marañón, Madrid
Division of Pediatric Gastroenterology, Hospital Parc Taulí, Sabadell
Unit of Pediatric Gastroenterology and Nutrition, Hospital Vall d’Hebron, Barcelona
Division of Pediatric Gastroenterology, Complejo Hospitalario de Navarra, Pamplona
Unit of Pediatric Gastroenterology and Nutrition, Complejo Asistencial Universitario de Salamanca, Salamanca
Division of Pediatric Gastroenterology and Nutrition, Hospital Clínico Universitario de Valencia, Valencia
Division of Pediatric Gastroenterology, Hospital Universitario de Valme, Universidad de Sevilla, Sevilla
Division of Pediatric Gastroenterology, Hospital General Universitario de Castellón, Castellón de la Plana
Division of Pediatric Gastroenterology, Hospital Universitario Ramón y Cajal, Madrid
Division of Pediatric Gastroenterology, Hospital Infantil Miguel Servet, Zaragoza
Division of Pediatric Gastroenterology, Hospital Universitario Virgen Macarena, Sevilla
Division of Pediatric Gastroenterology, Hospital Clínico Universitario Lozano Blesa, Zaragoza
Division of Pediatric Gastroenterology, Hospital Clínico Universitario de Santiago, Santiago de Compostela
Division of Pediatric Gastroenterology, Hospital Universitario Infanta Leonor, Madrid
Division of Pediatric Gastroenterology, Hospital General de Granollers, Barcelona
Division of Pediatric Gastroenterology, Hospital Universitario Río Hortega, Valladolid
Division of Pediatric Gastroenterology, Hospital Universitario de Getafe, Madrid
Division of Pediatric Gastroenterology, Hospital Universitario Infanta Elena, Valdemoro
Division of Pediatric Gastroenterology, Hospital Universitario Los Arcos del Mar Menor, Murcia
Division of Pediatric Gastroenterology, Complexo Hospitalario de Pontevedra, Pontevedra
Division of Pediatric Gastroenterology, Hospital Obispo Polanco, Teruel
Division of Pediatric Gastroenterology, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife
Fundación para la Investigación Biomédica, Hospital Infantil Universitario Niño Jesús, Madrid.
Introducción. Los cuestionarios WPAI-UC/CD-Caregiver evalúan la repercusión laboral y en actividades cotidianas de los padres/cuidadores de pacientes con colitis ulcerosa (CU) o enfermedad de Crohn (EC). El objetivo fue adaptar y validar estos cuestionarios en la población española. Métodos. Se realizó la traducción y la retrotraducción. El documento fue evaluado por un comité de expertos y por un grupo piloto de familias de pacientes con enfermedad inflamatoria intestinal pediátrica (EII-p). Para la validación, se reclutaron padres/cuidadores de pacientes con EII-p (10-18 años). El comité de expertos y el grupo piloto evaluaron subjetivamente el formato y el tiempo necesario para completar los cuestionarios. Se calculó el coeficiente alfa de Cronbach y se realizó el análisis factorial con rotación Varimax. Se calcularon los coeficientes de Kaiser-Meyer-Olkin (KMO) y la prueba de esfericidad de Bartlett para comprobar la adecuación del análisis factorial. Resultados. Se incluyeron 370 pacientes (mediana 14,1 años), y 263 padres/cuidadores de pacientes con colitis ulcerosa o EII no clasificada y 261 padres/cuidadores de pacientes con enfermedad de Crohn. Los coeficientes KMO (0,6947 y 0,7179) y la prueba de esfericidad de Barttlet (p <0,001) confirmaron la adecuación del análisis factorial. Los 6 ítems se dirigieron a la misma dimensión. El modelo factorial explicó el 99,99 % y el 94,68 % de la varianza, y los alfa de Cronbach (0,6581 y 0,6968) indicaron buena consistencia. El formato y la mediana de 2 minutos para completarlos se consideraron óptimos. Conclusiones. Las versiones validadas en la población española de los cuestionarios WPAI-Caregiver pueden considerarse para su uso en familias con hijos con EII.
Cross-cultural adaptation and validation of Work Productivity and Activity Impairment questionnaires for caregivers of patients with pediatric inflammatory bowel disease in Spain. A multicenter study.
Yale School of Nursing, Orange, Connecticut, USA.Adelphi University, Garden City, New York, USA.
Visitation Restrictions in Inpatient Psychiatric Settings: A Call for Connected Healing.
This randomized, placebo-controlled, double-blind, parallel trial investigated whether generally healthy adult, nonelite runners would have a greater time-to-exhaustion during submaximal treadmill running with probiotic versus placebo supplementation. It was hypothesized that the probiotic would impact training progression by reducing gastrointestinal (GI) and cold/flu symptoms. Participants who typically ran ≥24 km/week, ran or cross-trained 3-5 days per week, and had a maximal oxygen intake (V̇O2 max) in the 60-85th percentile were enrolled. V̇O2 max was used to establish individualized workload settings (85% of V̇O2 max) for the submaximal endurance tests at baseline and following 6 weeks of supplementation with a probiotic (Lactobacillus helveticus Lafti L10, 5×109 CFU/capsule/day) or placebo. Participants self-reported GI and cold/flu symptoms and physical activity via daily and weekly questionnaires. Outcomes were tested using a linear model to determine if mean response values adjusted for baseline differed between groups. Twenty-eight participants (n = 14/group), aged 25 ± 5 years (mean ± SD) with a body mass index of 23 ± 3 kg/m2, completed the study. At the final visit the probiotic group had a lower time-to-exhaustion versus the placebo group (P = 0.01) due to an increase in time-to-exhaustion with the placebo (1344 ± 188 to 1565 ± 219 s, P = 0.01) with no change with the probiotic (1655 ± 230 to 1547 ± 215 s, P = 0.23). During the intervention, the probiotic group completed fewer aerobic training sessions per week (P = 0.02) and trained at a lower intensity (P = 0.007) versus the placebo group. Few GI and cold/flu symptoms were reported with no differences between groups. Time-to-exhaustion increased in the placebo group, possibly due to differences in training habits.
Food Science and Human Nutrition Department, University of Florida, 572 Newell Drive, Gainesville, FL 32611, USA.
UF Health Sports Performance Center, Department of Physical Medicine and Rehabilitation, University of Florida, 3450 Hull Road, Gainesville, FL 32611, USA.
Department of Medicine, University of Florida, PO Box 100277, Gainesville, FL 32610, USA.
Institute of Food and Agricultural Statistical Consulting Unit, University of Florida, Gainesville, FL 32611, USA.
Impact of probiotic supplementation on exercise endurance among nonelite athletes: a randomized, placebo-controlled, double-blind, clinical trial.
This article discusses the personal experiences of the parents regarding their child's medication journey. Parents can play a vital role in their child's overall mental well-being, ensuring they receive the care and support they need. To navigate these difficult circumstances, it is crucial for parents to maintain open lines of communication with their child as well as with the health care professionals involved in their care. Professionals should be aware that parents' perspectives toward mental health medication can evolve over time, influenced by the experiences and challenges faced by both child and family. Excluding parents from their child's treatment limits the potential for a comprehensive and holistic treatment approach. By recognizing the value of parental input, health care professionals can create a collaborative environment that maximizes the chances of finding the most suitable treatment strategy. It is important for health care professionals to engage families in a respectful and empathetic manner, recognizing the challenges they face. Providing them with the necessary support and guidance can help reduce feelings of helplessness and ensure their active involvement in their child's mental health journey (PsycInfo Database Record (c) 2024 APA, all rights reserved).
Department of Community Mental Health, University of Haifa.
My child's medication journey: A parent's view.
The current guidelines recommend continuation of antipsychotic medication for a minimum of at least 1 year following a first episode of psychosis (FEP). There have been several trials investigating whether early dose reduction or cessation leads to improved functional outcomes. The aim of this study was to explore the experience of consenting to and participating in a randomized controlled trial (RCT) of antipsychotic medication cessation.Five participants in the Reduce trial-an RCT evaluating early antipsychotic medication dose reduction/cessation following FEP-aged 22-24 years completed a semistructured qualitative interview following the RCT. Interpretive phenomenological analysis was undertaken to understand the key themes.A superordinate theme was derived from interviews: the Liminal Space of FEP and treatment. Themes within the Liminal Space included: rejection versus identification with psychosis, medication as symbolic of illness versus wellness, embodiment of wellness and illness with medication, medication as symbolic of independence versus dependence, discovery of independence when autonomously choosing medication, the Reduce trial offered safety to navigate the liminal space, and self-exploration versus altruism.The experience and treatment of FEP involves young people feeling torn between multiple, competing perspectives, demands, and priorities. Participation in an RCT exploring dose reduction provided additional supports contributing to the perception of greater safety to navigate their own experiences of treatment that was appropriate for them. When treatment is experienced as collaborative, involves shared decision making and support, other than medication, young people feel more equipped to navigate the liminal space. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
Centre for Mental Health, Melbourne School of Population and Global Health, University of Melbourne.
Healthy Brain and Mind Research Centre, Australian Catholic University.
The liminal space of first-episode psychosis and its treatment: A qualitative study exploring the experience of young people participating in an antipsychotic dose reduction randomized controlled trial.
To determine whether dropless, injection-based cataract surgery prophylaxis with intracameral antibiotic and subconjunctival steroid may reduce healthcare system costs and patient out-of-pocket costs compared with topical medication regimens.U.S. national medical expenditures database.Retrospective cost analysis.Costs were analyzed for topical ophthalmics from the 2020 Medical Expenditure Panel Survey (MEPS) and for dropless medications from pharmaceutical invoices/catalogs. Main outcomes included system costs, from insurance and patient payments, and out-of-pocket costs for cataract surgery topical and dropless, injection-based prophylactic medication regimens, per eye and nationally. System costs for individual topical medications and same-class dropless, injection-based medications were compared using 2-sided, 1-sample t tests.There were 583 prophylactic topical ophthalmic purchases in MEPS. Mean system costs per eye were $76.20 ± SD 39.07 for the lowest cost topical steroid (prednisolone) compared with $4.01 for the lowest cost subconjunctival steroid (triamcinolone acetonide) ( P < .001). Per eye, the lowest cost dropless, injection-based regimen, at $15.91, results in an $87.99 (84.7%) reduction in overall healthcare costs and a $43.64 (100%) reduction in patient out-of-pocket costs relative to the lowest cost topical regimen ($103.90 ± 43.14 mean system cost and $43.64 ± 37.32 mean out-of-pocket cost per eye). Use of intracameral moxifloxacin and subconjunctival triamcinolone acetonide can reduce annual national healthcare system and out-of-pocket costs up to $450 000 000 and $225 000 000, respectively.An evidence-based cataract surgery prophylactic medication regimen of intracameral moxifloxacin and subconjunctival triamcinolone acetonide can reduce healthcare system and patient out-of-pocket costs in comparison with various topical regimens.
From the Department of Ophthalmology, New York University Grossman School of Medicine, New York, New York (Massa, Patil, Parikh); Cheyenne Eye Clinic and Surgery Center, Cheyenne, Wyoming (Smits); Department of Ophthalmology, Yale New Haven Health, New Haven, Connecticut (Nguyen); The Eye Care Group, Waterbury, Connecticut (Nguyen); Department of Ophthalmology, University of California, San Francisco School of Medicine, San Francisco, California (Chen); Seva Foundation, Berkeley, California (Shorstein); Florida Retina Consultants, Lakeland, Florida (Friedman); Manhattan Retina and Eye Consultants, New York, New York (Parikh).
Cost analysis of dropless cataract surgery prophylaxis with intracameral antibiotics and subconjunctival steroids.
Traditionally, renal cell carcinoma (RCC) was considered a radioresistant tumor, thereby limiting definitive radiation therapy management options. However, several recent studies have demonstrated that stereotactic body radiation therapy (SBRT) can achieve high rates of local control for the treatment of primary RCC. In the setting of expanding use of SBRT for primary RCC, it is crucial to provide guidance on practical considerations such as patient selection, fractionation, target delineation, and response assessment. This is particularly important in challenging scenarios where a paucity of evidence exists, such as in patients with a solitary kidney, bulky tumors, or tumor thrombus. The Radiosurgery Society endorses this case-based guide to provide a practical framework for delivering SBRT to primary RCC, exemplified by 3 cases. This article explores topics of tumor size and dose fractionation, impact on renal function and treatment in the setting of a solitary kidney, and radiation's role in the management of inferior vena cava tumor thrombus. Additionally, we review existing evidence and expert opinion on target delineation, advanced techniques such as magnetic resonance imaging guided SBRT, and SBRT response assessment.
Copyright © 2024 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.
Department of Radiation Oncology, Fred Hutchinson Cancer Center, University of Washington, Seattle, Washington.
Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, Ohio.
Department of Radiation Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, Florida.
Department of Radiation Oncology, Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey.
Department of Urology, Fred Hutchinson Cancer Center, University of Washington, Seattle, Washington.
Department of Radiation Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, New York.
Department of Radiation Oncology, Montefiore Medical Center, Bronx, New York.
Department of Radiation Oncology, Amsterdam University Medical Center, Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Department of Radiation Oncology, London Health Sciences Centre, London, Ontario, Canada.
Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, Florida.
Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York.
Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas.
Department of Radiation Oncology, Sunnybrook Health Sciences Centre and the University of Toronto, Toronto, Ontario, Canada.
Division of Radiation Oncology, Juravinski Cancer Centre, McMaster University, Hamilton, Ontario, Canada.
Department of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas.
Department of Radiation Oncology, Cancer Center and Research Institute, Houston Methodist Hospital, Houston, Texas.
Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve, Cleveland, Ohio.
Department of Radiation Oncology, Fred Hutchinson Cancer Center, University of Washington, Seattle, Washington. Electronic address: simonslo@uw.edu.
Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Center, University of Melbourne, Melbourne, Victoria, Australia.
Stereotactic Body Radiation Therapy for Primary Renal Cell Carcinoma: A Case-Based Radiosurgery Society Practice Guide.
Recent breakthroughs in artificial intelligence (AI) have caught the attention of many fields, including health care. The vision for AI is that a computer model can process information and provide output that is indistinguishable from that of a human and, in specific repetitive tasks, outperform a human's capability. The 2 critical underlying technologies in AI are used for supervised and unsupervised machine learning. Machine learning uses neural networks and deep learning modeled after the human brain from structured or unstructured data sets to learn, make decisions, and continuously improve the model. Natural language processing, used for supervised learning, is understanding, interpreting, and generating information using human language in chatbots and generative and conversational AI. These breakthroughs result from increased computing power and access to large data sets, setting the stage for releasing large language models, such as ChatGPT and others, and new imaging models using computer vision. Hypertension management involves using blood pressure and other biometric data from connected devices and generative AI to communicate with patients and health care professionals. AI can potentially improve hypertension diagnosis and treatment through remote patient monitoring and digital therapeutics.
American Heart Association, Center for Health Technology & Innovation, Dallas, TX (P.D.).
University of Texas Health Science Center, Houston (A.A.).
University of Texas at Austin, Dell Medical School (A.P.).
School of Health Sciences and Public Policy, Walden University, Minneapolis, MN (S.B.).
Brief Review and Primer of Key Terminology for Artificial Intelligence and Machine Learning in Hypertension.
Panax notoginseng has the effect of stimulating circulation to end stasis. Our study was designed to evaluate the anti-thrombotic effect of protoparaxotriol saponins (PTS) from P. notoginseng and the involved mechanisms. A thrombosis model was constructed, and the anti-thrombotic activity of PTS was determined by erythrocyte staining, heart rate, and blood flow velocity. In addition, quantitative real-time polymerase chain reaction was used to identify changes in the expression of genes related to coagulation, inflammation, and apoptosis. PTS alleviated arachidonic acid-induced caudal vein thrombosis, restored blood flow, and increased the area of cardiac erythrocyte staining, heart rate, and blood flow velocity. It reduced the ponatinib-induced cerebral thrombus area and decreased the intensity of erythrocyte staining. The quantitative polymerase chain reaction data showed that the anti-thrombotic effect of PTS was mediated by suppression of genes related to coagulation, inflammation, and apoptosis and also involved inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathways.
Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Qilu University of Technology (Shandong Academy of Sciences), Jinan, China .
Anti-Thrombotic Effect of Protoparaxotriol Saponins From Panax notoginseng Using Zebrafish Model.
Prescribed contraception is used worldwide by over 400 million women of reproductive age. Monitoring contraceptive use is a major public health issue that usually relies on population-based surveys. However, these surveys are conducted on average every 6 years and do not allow close follow-up of contraceptive use. Moreover, their sample size is often too limited for the study of specific population subgroups such as people with low income. Health administrative data could be an innovative and less costly source to study contraceptive use.We aimed to explore the potential of health administrative data to study prescribed contraceptive use and compare these data with observations based on survey data.We selected all women aged 15-49 years, covered by French health insurance and living in France, in the health administrative database, which covers 98% of the resident population (n=14,788,124), and in the last French population-based representative survey, the Health Barometer Survey, conducted in 2016 (n=4285). In health administrative data, contraceptive use was recorded with detailed information on the product delivered, whereas in the survey, it was self-declared by the women. In both sources, the prevalence of contraceptive use was estimated globally for all prescribed contraceptives and by type of contraceptive: oral contraceptives, intrauterine devices (IUDs), and implants. Prevalences were analyzed by age.There were more low-income women in health administrative data than in the population-based survey (1,576,066/14,770,256, 11% vs 188/4285, 7%, respectively; P<.001). In health administrative data, 47.6% (7034,710/14,770,256; 95% CI 47.6%-47.7%) of women aged 15-49 years used a prescribed contraceptive versus 50.5% (2297/4285; 95% CI 49.1%-52.0%) in the population-based survey. Considering prevalences by the type of contraceptive in health administrative data versus survey data, they were 26.9% (95% CI 26.9%-26.9%) versus 27.7% (95% CI 26.4%-29.0%) for oral contraceptives, 17.7% (95% CI 17.7%-17.8%) versus 19.6% (95% CI 18.5%-20.8%) for IUDs, and 3% (95% CI 3.0%-3.0%) versus 3.2% (95% CI 2.7%-3.7%) for implants. In both sources, the same overall tendency in prevalence was observed for these 3 contraceptives. Implants remained little used at all ages, oral contraceptives were highly used among young women, whereas IUD use was low among young women.Compared with survey data, health administrative data exhibited the same overall tendencies for oral contraceptives, IUDs, and implants. One of the main strengths of health administrative data is the high quality of information on contraceptive use and the large number of observations, allowing studies of subgroups of population. Health administrative data therefore appear as a promising new source to monitor contraception in a population-based approach. They could open new perspectives for research and be a valuable new asset to guide public policies on reproductive and sexual health.
©Juliette Congy, Delphine Rahib, Céline Leroy, Jean Bouyer, Elise de La Rochebrochard. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 22.07.2024.
Sexual and Reproductive Health and Rights Unit, Institut National d'Etudes Démographiques, Aubervilliers, France.
Sexual Health Unit, Santé Publique France, Saint-Maurice, France.
Agence Régionale de Santé, Caen, France.
Sexual and Reproductive Health and Rights Unit, Institut National d'Etudes Démographiques, Aubervilliers, France.Centre de Recherche en Epidémiologie et Santé des Populations, Institut national de la santé et de la recherche médicale, Université de Versailles Saint-Quentin-en-Yvelines, Université Paris-Saclay, Villejuif, France.
JMIR Public Health Surveill. 2024-07-22;10():e45030.
Contraceptive Use Measured in a National Population-Based Approach: Cross-Sectional Study of Administrative Versus Survey Data.
Personalized dose optimization is desirable to improve subjective well-being and support rehabilitation. Therefore, N = 1 trials investigating tools to self-manage functional outcomes during dose optimization are necessary. The aim of this pilot study was to determine in two N = 1 trials whether an experience sampling method (ESM) smartphone app could be used to monitor and detect changes in subjective well-being and psychotic experiences during and after dose reduction.Two participants with a psychotic disorder in remission underwent gradual dose reduction under a longitudinal self-monitoring paradigm, accompanied by regular clinical monitoring by the attending physician. Subjective well-being was monitored with an (ESM) app through momentary affective experience (positive and negative affect) and physical well-being (tiredness, feeling unwell, and pain). Momentary psychotic experiences were assessed with four items. Time-series linear regression models were used to detect changes in reduction phases compared to baseline.Whereas significant improvements in subjective well-being and psychotic experiences during dose reduction were detected in one participant, the opposite was demonstrated for the other participant, showing worsened subjective well-being and increased psychotic experiences in the reduction phase compared to baseline.Self-monitoring with an ESM smartphone app offers a tool for detecting changes in subjective well-being and psychotic experiences during antipsychotic dose reduction. In this way, ESM may increase an individual's sense of control and empowerment. It may further facilitate dose optimization and shared decision-making at an individual level, which is required considering the high heterogeneity in psychotic disorders. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
Geestelijke Gezondheidszorg Eindhoven, Institute of Mental Health Care.
Monitoring momentary subjective well-being and psychotic experiences during antipsychotic dose reduction: Two single-case time series experience sampling method pilot study.
The prevalence of the medical model in the field of mental health care has undoubtedly contributed to significant scientific progress. However, it is important to recognize that it may not represent the sole perspective for comprehending mental distress. Rather than endorsing particular paradigms, I advocate for a pluralistic approach that empowers individuals to discover their unique narratives, the stories that may save them. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
Copenhagen Research Center for Mental Health, Copenhagen University Hospital.
Stories that trap us and stories that save us.
Though the psychiatric field has primarily focused on medication and symptom amelioration via medication adherence, contemporary approaches that incorporate recovery-oriented care and shared decision-making (SDM) could provide a more holistic and effective approach to serving individuals experiencing psychosis. This article explores the implementation of such innovative and collaborative practices while highlighting their benefits and challenges. Furthermore, it aims to offer practical implementations of SDM in prescribing practices.This article presents innovative strategies for prescribing antipsychotics utilizing SDM and recovery-oriented care approaches for those who experience psychosis. The study explores the clinical applications of these approaches within an inpatient psychiatric setting.The article emphasizes the numerous challenges for those who experience psychosis in adhering to antipsychotic medication and proposes a recovery-oriented approach facilitated by SDM. It emphasizes the importance of therapeutic alliance and collaboration while providing practical clinical applications of this approach.The article advocates for collaborative approaches in antipsychotic prescribing, such as SDM and recovery-oriented care, to support those experiencing psychosis in constructing a life of meaning as they define it, including in how they choose to take medications. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
Department of Psychiatry, Yale University School of Medicine.
All paths do not lead to Rome or adherence: Innovative antipsychotic prescribing in partnership with people in recovery as they define.
To evaluate the efficacy and safety of upadacitinib in the treatment of moderate-to-severe atopic dermatitis (AD), and provide reference for rational clinical medication.PubMed, Medline, Embase, Web of Science, Clinical Trials Website, and Cochrane Library databases were searched from the time of establishment until January 6, 2024, to compile a list of all randomized controlled trials (RCTs) including upadacitinib in the treatment of moderate-to-severe AD. The quality of the included studies was evaluated using the Cochrane Systematic Review. Review Manager 5.3 software was utilized for statistical analysis of outcome measures.A total of five studies were included in the meta-analysis. The results revealed that the 15 mg and 30 mg upadacitinib significantly improved Eczema Area and Severity Index (EASI) 75% {[Odds Ratio (OR) = 8.58, 95% confidence interval (CI) (5.84-12.60), P < 0.00001] [OR = 15.62, 95% CI (10.89-22.42), P < 0.00001]}, Numerical Rating Scale (NRS) ≥ 4 {[OR = 7.13, 95% CI (5.63-9.01), P < 0.00001] [OR = 11.30, 95% CI (8.93-14.31), P < 0.00001]}, and Investigator's Global Assessment (IGA) 0/1 {[OR = 8.63, 95% CI (6.60-11.27), P < 0.00001] [OR = 16.04, 95% CI (12.26-20.99), P < 0.00001]} compared to placebo. In terms of safety, although 15 mg and 30 mg upadacitinib significantly increased the overall adverse events rate compared to placebo {[OR = 1.31, 95% CI (1.09-1.58), P = 0.004] [OR = 1.85, 95% CI (1.54-2.21), P < 0.00001]}, there was no significant difference in the serious adverse events rate {[OR = 0.73, 95% CI (0.41-1.29), P = 0.28] [OR = 0.69, 95% CI (0.39-1.23), P = 0.21]} and withdrawal rate due to adverse events {[OR = 0.66, 95% CI (0.39-1.11), P = 0.12] [OR = 0.85, 95% CI (0.52-1.38), P = 0.50]} compared to placebo.This meta-analysis preliminarily suggests that upadacitinib is effective and safe for usage in the treatment of moderate-to-severe AD. Additionally, upadacitinib can instantly relieve itchiness and effectively reduce symptoms and signs, with its 30-mg dose being more effective than the 15-mg dose.
Copyright: © 2024 Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Department of Pharmacology, The First People's Hospital of Shuangliu District, West China (Airport) Hospital of Sichuan University, Chengdu, Sichuan, China.
Department of TCM Pharmacy, Chengdu Integrated TCM and Western Medicine Hospital, Chengdu, Sichuan, China.
Efficacy and safety of upadacitinib in the treatment of moderate-to-severe atopic dermatitis: A systematic review.
This work explores astaxanthin (AXT), a valuable xanthophyll ketocarotenoid pigment with significant health benefits and diverse applications across various industries. It discusses the prevalence of synthetic AXT, and the development of natural-based alternatives derived from microorganisms such as microalgae, bacteria, and yeast. The chapter examines the potential of microbial AXT production, highlighting the advantages and challenges associated with natural AXT. Key microorganisms like Haematococcus pluvialis, Paracoccus carotinifaciens, and Phaffia rhodozyma are emphasized for their role in commercially producing this valuable ketocarotenoid. The narrative covers the complexities and opportunities in microbial AXT production, from cell structure implications to downstream processing strategies. Additionally, the chapter addresses current applications, commercialization trends, and market dynamics of natural microbial AXT, emphasizing the importance of cost-effective production, regulatory compliance, and technological advancements to reduce the market cost of the final product. As demand for natural microbial-based AXT rises, this chapter envisions a future where research, innovation, and collaboration drive sustainable and competitive microbial AXT production, fostering growth in this dynamic market.
Escuela de Agronomía, Facultad de Ciencias Agronómicas y de los Alimentos, Pontificia Universidad Católica de Valparaíso, Quillota, Chile. Electronic address: cassamo.mussagy@pucv.cl.
Advances in microbial astaxanthin production.
Pulmonary rehabilitation (PR) is an intervention aimed at the comprehensive care of individuals with chronic respiratory diseases. Patients with chronic obstructive pulmonary disease (COPD) and asthma present low levels of physical fitness because they avoid physical exercises due to the fear of triggering recurrent symptoms. Wearable devices have been integrated into behavioral modification interventions for physical activity in PR protocols. Therefore, this review aims to identify how wearable devices are being utilized for monitoring chronic respiratory diseases in pulmonary rehabilitation programs.Searches will be conducted on Medline, Cochrane Central Register of Controlled Trials, Embase (CENTRAL), CINAHL and PEDro electronic databases, as well as a search in the grey literature. We will include baseline data from randomized clinical trials reporting the use of wearable devices for monitoring physical activity in protocols for pulmonary rehabilitation programs for chronic respiratory diseases. Studies that discuss only the development of algorithms or applications for the assessment of diseases or unavailable full texts will be excluded. The main reviewer will conduct the initial search and exclusion of duplicates, while two independent reviewers will select studies, extract data, and assess the methodological quality using the PEDro tool.CRD42024504137.
Copyright: © 2024 Oliveira et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Departament of Physical Therapy, Federal University of Rio Grande do Norte, Natal, RN, Brazil.
Ana Tereza do Nascimento Sales Figueiredo
Departament of Physical Therapy, State University of Paraíba, Campina Grande, PB, Brazil.
School of Physical & Occupational Therapy, McGill University Montreal, Montreal, Québec, Canada.
Effects of using wearable devices to monitoring physical activity in pulmonary rehabilitation programs for chronic respiratory diseases: A systematic review protocol.
Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor derived from parafollicular thyroid gland cells. In both hereditary MTC and sporadic forms, genetic changes result in fundamental changes, and prognosis and mutational status are highly correlated. In this work, biomarker genes (DEGs and DEmiRNAs) for MTC will be computationally identified in order to help in their diagnosis and treatment. The gene expression profiles of two different types of studies, namely without-treatment (wo-trt) and with-treatment (w-trt), are considered for discovering biomarkers. The datasets were retrieved from the GEO database, and the DEGs and DEmiRNAs were analyzed using ExpressAnalyst and GEO2R. The functional analysis of DEGs and DEmiRNAs was performed, and most of the pathways enriched related to thyroid oncological pathways such as MAPK pathway,mTOR pathway, and PI3K-AKT Signaling pathway. Through this conclusion, the RET gene was upregulated wo-trt; the dinaciclib treatment RET gene was down-regulated computationally. To optimize the therapeutic targeting of RET, greater research into the mechanisms regulating RET transcription is necessary.
Laboratory of Integrative Genomics, Department of Integrative Biology, School of BioSciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, India.
Laboratory of Integrative Genomics, Department of Integrative Biology, School of BioSciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu, India. Electronic address: georgepriyadoss@vit.ac.in.
Advances in protein chemistry and structural biology
Adv Protein Chem Struct Biol. 2024;142():367-396.
Biomarker identification of medullary thyroid carcinoma from gene expression profiles considering without-treatment and with-treatment studies-A bioinformatics approach.
Neurology, Manchester Centre for Clinical Neurosciences, Salford Royal Hospital, Salford, UK christopher.hutchcroft@nca.nhs.uk.
Neurology, Manchester Centre for Clinical Neurosciences, Salford Royal Hospital, Salford, UK.
Neurology, Royal Preston Hospital, Preston, UK.Lancaster University School of Health and Medicine, Lancaster, UK.
Neurology, Manchester Centre for Clinical Neurosciences, Salford Royal Hospital, Salford, UK.The University of Manchester Faculty of Medical and Human Sciences, Manchester, UK.
Neurology, Manchester Centre for Clinical Neurosciences, Salford Royal Hospital, Salford, UK.The University of Manchester Division of Musculoskeletal and Dermatological Sciences, Manchester, UK.
Neurology, Manchester Centre for Clinical Neurosciences, Salford Royal Hospital, Salford, UK.Division of Neuroscience and Experimental Psychology, The University of Manchester Faculty of Biology Medicine and Health, Manchester, UK.
To provide reference for clinical development of ADCs in the industry, we analyzed the landscape and characteristics of clinical trials about antibody-drug conjugates (ADCs).Clinical trials to study ADCs used for the pharmacotherapy of cancers initiated by the sponsor were searched in the Cite line Pharma Intelligence (Trialtrove database), and the landscape and characteristics of these clinical trials were analyzed from multiple perspectives, such as the number, phases, status, indications, and targets of the clinical trials.As of December 31, 2022, a total of 431 clinical trials have been initiated to study ADCs used for the pharmacotherapy of cancers, and the number of the last 10 years was 5.5 times as large as the first 11 years. These clinical trials involved 47 indications, including breast cancer, lymphoma (lymphoma, non-Hodgkin's and lymphoma, Hodgkin's), unspecified solid tumor, bladder cancer and lung cancer (lung, non-small cell cancer and lung, small cell cancer). As for each of these five indications, 50 + clinical trials have been carried out, accounting for as high as 48.50% (454/936). ADCs involve 38 targets, which are relatively concentrated. Among them, ERBB2 (HER2) and TNFRSF8 (CD30) involve in 100 + registered clinical trials, and TNFRSF17 (BCMA), NECTIN4 and CD19 in 10 + trials. The clinical trials for these five targets account for 79.02% (354/448) of the total number. Up to 93.97% (405/431) of these clinical trials explored the correlation between biomarkers and efficacy. Up to 45.91% (292/636) of Lots (lines of treatment) applied in the clinical trials were the second line. Until December 31, 2022, 54.52% (235/431) of the clinical trials have been completed or terminated.ADCs are a hotspot of research and development in oncology clinical trials, but the indications, targets, phases, and Lot that have been registered are seemingly relatively concentrated at present. This study provides a comprehensive analysis which can assist researchers/developer quickly grasp relevant knowledge to assess a product and also providing new clues and ideas for future research.
Department of Clinical Trials Center, The University of Hong Kong-Shenzhen Hospital, Haiyuan 1st Road, Futian District, Shenzhen, 518000, P. R. China. zhouwj@hku-szh.org.
Department of Clinical Oncology Center, The University of Hong Kong-Shenzhen Hospital, Shenzhen, 518000, P. R. China.
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.
Department of Clinical Trials Center, The University of Hong Kong-Shenzhen Hospital, Haiyuan 1st Road, Futian District, Shenzhen, 518000, P. R. China.
School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, 211198, P. R. China.
Department of Pharmacy, The University of Hong Kong-Shenzhen Hospital, Shenzhen, 518000, P. R. China.
Department of Chinese Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, 518000, P. R. China.
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China. huanghb@sysucc.org.cn.
Landscape of clinical drug development of ADCs used for the pharmacotherapy of cancers: an overview of clinical trial registry data from 2002 to 2022.
This study aims to analyze the efficacy of metformin on carotid intima media thickness (CIMT) and flow-mediated dilation (FMD) for patients with polycystic ovary syndrome (PCOS).A literature search of PubMed, Embase, and the Cochrane Library from inception to December 2023 was conducted. Then, after studies selection and data extraction, the mean difference (MD) with a 95% confidence interval (CI) was used to evaluate metformin efficacy in CIMT and FMD for PCOS patients. Heterogeneity was investigated through subgroup and sensitivity analysis. The protocol of our study has been registered in PROSPERO (CRD42024497239).A total of 12 studies with 248 patients were included. CIMT was lower in the endpoint group (after metformin) compared with the baseline group (before metformin) (MD = -0.11, 95% CI = -0.21 to -0.01, p = 0.04). FMD was higher in the endpoint group compared with the baseline group (MD = 3.25, 95% CI = 1.85 to 4.66, p < 0.01). No statistically significant difference was observed in nitroglycerin-mediated dilation (NMD) between the two groups (MD = 0.65, p = 0.51). Subgroup analysis showed that a relatively lower MD of CIMT in PCOS patients from Europe in the endpoint group compared with the baseline group (MD = -0.09, 95% CI = -0.14 to -0.04, p < 0.001). However, the MD in CIMT was not significantly different between the endpoint group and baseline group in PCOS patients from Asia (p = 0.270).Metformin may have a beneficial effect on CIMT and FMD, but not on NMD, suggesting that metformin may help reduce cardiovascular events in PCOS patients. Notably, the clinical efficacy of metformin can be influenced by regional differences and study types.
Obstetric and Gynecologic Department, Hangzhou Women's Hospital, Hangzhou, Zhejiang, China.
The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China.
The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Department of Nephrology, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang, China.
Obstetric and Gynecologic Department, Changxing Maternal and Child Health Hospital, No.861, Mingzhu Road, Changxing, Huzhou, 313100, Zhejiang, China. metpcos@163.com.
Effects of Metformin on CIMT and FMD in PCOS patients: a systematic review and meta-analysis.
To investigate the effects of cylinder axis-flip after toric intraocular lens (TIOL) implantation on vision and patient-reported outcome measures (PROMs).Teaching hospital in the United Kingdom.Post hoc analysis of data from patients who participated in a prospective randomized study of TIOLs.Axis-flip was defined as a change in postoperative refractive cylinder (RC) axis of 90 ± 22.5 degrees from the preoperative biometric axis. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), residual RC, and CATPROM-5 and EQ-5D-3L quality-of-life scores were analyzed.At 6 months, axis-flip occurred in 29 (34.5%) of 84 eyes of which 28 had with-the-rule (WTR) astigmatism preoperatively. Mean (±SD) UDVA (logMAR) was 0.13 (0.16) in flipped cases (FCs) and 0.10 (0.14) in unflipped cases (UFs) ( P = .88). CDVA was 0.01 (0.11) in FC and was 0.00 (0.09) in UF ( P = .68). Mean RC was 0.74 diopters (D) (0.41) in FC and 0.93 D (0.47) in UF ( P = .08). Mean CATPROM-5 score was -6.22 (2.56) in FC and -5.52 (3.03) in UF ( P = .29). Mean EQ-5D-3L calibrated score was 0.89 (0.19) in FC and 0.85 (0.19) in UF ( P = .35). Retrospectively applying coefficients of adjustment to account for posterior corneal astigmatism (PCA) suggested that 6 eyes (21%) of FC with WTR might have avoided axis-flip.Axis flipping after TIOL implantation did not adversely influence visual acuity or PROMs scores. Most FC had WTR preoperatively. Adjusting for PCA might have reduced axis-flip in some of these eyes.
From the Department of Ophthalmology, St. Thomas' Hospital, London, United Kingdom (Naderi, Jameel, Chow, O'Brart); King's College, London, United Kingdom (Naderi, Jameel, O'Brart); Department of Optometry and Visual Science, University of London, London, United Kingdom (Hull).
Effects of axis-flip of the refractive cylinder on vision and patient-reported outcome measures after toric intraocular lens implantation.
Alloimmunization against red blood cell (RBC) antigen is an important concern in myelodysplastic syndromes (MDSs) patients with chronic transfusion, causing potential risk for hemolytic reaction and limited supply of compatible blood. However, there is little data addressing RBC alloimmunization in this patient cohort among the Chinese population. This study aims to evaluate the incidence, specificity of antibodies, and RBC units transfused before antibody formation and its significance in a population of patients consistently receiving RhD-matched RBC units.We retrospectively reviewed the transfusion and clinical information of all transfused patients with MDS enrolled in our hospital from 2012 to 2022. The cumulative incidence of alloimmunization was analyzed by a Kaplan-Meier plot. Alloimmunization incidence was compared based on different transfused RBC units using the log-rank test.A total of 103 patients with MDS were included in this study; alloantibody formed in 8 (7.8%) patients. Before reaching 32 RBC units, 87.5% of the alloimmunized patients had developed their alloantibodies. All but 1 of the alloantibodies developed were antibodies to Rh antigens. The RBC transfusion intensity and frequency were significantly higher following alloimmunization in the alloimmunized patients (P = .008, P = .008, respectively).The antibodies detected mostly involve the Rh system among MDS patients in China. The alloimmunization tended to occur early prior to reaching 32 RBC units in patients with MDS. Rh antigen matching should be considered early in the patient's transfusion history and completed before receiving 32 RBC units.
© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.
Department of Blood Transfusion, Tianjin 4th Central Hospital, Tianjin, China.
Department of Blood Transfusion, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
Red blood cell alloimmunization in transfused patients with myelodysplastic syndromes: a retrospective study from northern China.
The main protease (M pro) of coronaviruses plays a key role in viral replication, thus serving as a hot target for drug design. PF-00835231 is a promising inhibitor of SARS-CoV-2 M pro. Here, we report the inhibitory potency of PF-00835231 against SARS-CoV-2 M pro and seven M pro mutants (G15S, M49I, Y54C, K90R, P132H, S46F, and V186F) from SARS-CoV-2 variants. The results confirm that PF-00835231 has broad-spectrum inhibition against various coronaviral M pros. In addition, the crystal structures of SARS-CoV-2 M pro, SARS-CoV M pro, MERS-CoV M pro, and seven SARS-CoV-2 M pro mutants (G15S, M49I, Y54C, K90R, P132H, S46F, and V186F) in complex with PF-00835231 are solved. A detailed analysis of these structures reveals key determinants essential for inhibition and elucidates the binding modes of different coronaviral M pros. Given the importance of the main protease for the treatment of coronaviral infection, structural insights into M pro inhibition by PF-00835231 can accelerate the design of novel antivirals with broad-spectrum efficacy against different human coronaviruses.
College of Pharmacy, Gannan Medical University, Ganzhou 341000, China.
Shenzhen Crystalo Biopharmaceutical Co., Ltd., Shenzhen 518118, China.
Jiangxi Jmerry Biopharmaceutical Co., Ltd., Ganzhou 341000, China.
Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, 201204, China.
School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang 330031, China.
Structural basis for the inhibition of coronaviral main proteases by PF-00835231.
To investigate whether phacoemulsification (PE) experience impacts and transfers to the skill acquisition of novices in manual small-incision cataract surgery (MSICS) within a simulation environment.Copenhagen Academy for Medical Education and Simulation, Copenhagen, Denmark.Prospective controlled experimental study.The study included 29 residents or specialist in ophthalmology with no prior MSICS experience. Participants were required to have either (1) proficiency on the EyeSi surgical simulator (PE group [PG]) or (2) no prior extensive exposure to the EyeSi simulator or any PE surgery experience as a primary surgeon (control group [CG]). Possible skill transfer was assessed using a test on the HelpMeSee virtual-reality simulator, including 9 modules and 30 steps (points). A pass/fail score was determined at 20 points (of 30 points). Performance scores were analyzed using independent samples t tests, pass rates using the Fisher exact test, and individual modules using Fisher-Freeman-Halton analysis.The PG performed significantly better in overall performance score (mean ± SD, PG; 21.8 points ± 2.3 vs CG; 18.9 points ± 2.2, P = .002, t -value = -3.39) and pass rates (PG; 72% vs CG; 22%, P = .018). The subanalysis for individual modules demonstrated significant differences exclusively in the capsulorhexis and cortex removal modules.The results suggest a positive interprocedural transfer of skills between PE and MSICS. Pretraining and experience in PE demonstrated a significant effect on the performance of MSICS within a simulation environment. These findings suggest that PE experience provides an advantage before MSICS training in surgical residency programs.
From the Copenhagen Academy for Medical Education and Simulation, Copenhagen, Denmark (Le, Konge, Thomsen); Department of Ophthalmology, Innlandet Hospital Trust, Brumunddal, Norway (Boberg-Ans); Department of Ophthalmology, Rigshospitalet, Glostrup, Denmark (la Cour, Thomsen); Department of Ophthalmology, Strasbourg University Hospital, University of Strasbourg, Strasbourg, France (Bourcier); Gepromed, Education Department, Strasbourg, France (Bourcier); Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark (Thomsen).
Phacoemulsification to manual small-incision cataract surgery: transfer of skills study in a simulated environment.
To compare the refractive prediction errors (PEs) of formulas included in the ESCRS intraocular lens (IOL) power calculator to aid in informed decisions on IOL power selection based on the output of this tool.Cullen Eye Institute, Baylor College of Medicine, Houston, Texas.Retrospective case-series.748 eyes of 748 patients after implantation of 1 of 3 lenses were included, single-piece: the SN60WF, PCB00/ZCB00 and 3-piece: MA60MA. IOL constants recommended by the calculator were used for the study. We performed analysis for the whole dataset, short (<22 mm) and long eyes (>25 mm) as well as in subgroups based on the type of the implanted IOL. SD and root mean square absolute error (RMSAE) were selected as the primary endpoints.Cooke K6 had the lowest SD of PEs in the whole dataset ( P < .05) when compared with Barrett, EVO, and Hoffer QST. In the subgroup of long eyes, the Kane formula had the lowest RMSAE ( P < .05) when compared with Barrett and EVO. No significant differences in primary endpoints for implantation of the 3 types of IOLs were found. However, the median absolute error after implantation of the MA60MA was significantly higher for Hoffer QST than for all other formulas except for Pearl-DGS.Significant differences in the performance of formulas included in the calculator were found. In the whole dataset, Cooke K6 had the lowest SD of PEs among the analyzed formulas.
From the Department of Experimental Physiology and Pathophysiology, Medical University of Warsaw, Warsaw, Poland (Skrzypecki); Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas (Koch, Wang).
Performance of formulas included in the ESCRS intraocular lens power calculator.
To compare time and resource saving with integration of digital cataract workflow to the existing workflow in high-volume cataract surgery clinics.L V Prasad Eye Institute, Hyderabad, India (site 1), and Narayana Nethralaya, Bengaluru, India (site 2).Prospective, time and motion.The total time to complete each step (preoperative measurements, surgical planning, and surgical procedures) of the cataract workflow, number of data fields entered, and support staff required for both workflows were recorded. All study measurements were determined first for existing electronic medical record (EMR) cataract workflow followed by digital workflow (integrated data management system with data reviewer, surgical planner, and data transfer to operating room) at both sites.A total of 85 (site 1, 44; site 2, 41) cataract workflows were analyzed. The integration of digital workflow into the site's existing EMR workflow reduced the mean time for preoperative measurements by 25.3% ( P = .006), surgical planning by 55.1% ( P = .008), and surgical procedures by 22.6% ( P = .002). The mean ± SD overall time for the surgery was significantly shorter in the digital group (887.3 ± 103.3 vs 1271.3 ± 300.7 seconds; P < .0001). For both sites, the number of data fields recorded and number of support staff needed were significantly lesser for the digital workflow ( P < .0001, for both).Integration of digital workflow significantly reduced the overall cataract surgery time, variability of overall time, number of data fields recorded, and resource utilization. Complete digitalization has important implications for improving the efficiency and standardization of cataract surgery workflow.
Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of ASCRS and ESCRS.
From the Narayana Nethralaya, Bengaluru, India (Shetty, Saxena); L V Prasad Eye Institute, Hyderabad, India (Singh, Fernandes, Garg); Carl Zeiss Meditec USA, Inc., Dublin, California (Venkiteshwar).
Effect of digital cataract workflow on time and resource efficiencies in cataract surgery: time and motion study.
Gallium-phosphate (GaPO4) is one of the ultra-high thermally stable piezoelectric materials with a high critical temperature of 1206 K. Here, first principles calculations with quasi-harmonic approximation are performed to study thermal and other physical properties of α-GaPO4. For the electronic structure, we focus on the electron-phonon interaction and lattice expansion effects on the temperature-dependent band gap, which plays a significant role in zero-point renormalization. Significantly, the large piezoelectric constants e11 primarily comes from intrinsic sensitivity of Ga and O sites to axial strain, while P atoms contribute little, which remains true in other quartz-like type APO4 (A = B, Al, In). Our work provides an insight into the temperature-dependent electronic and piezoelectric properties of α-GaPO4 and motivates its applications in a high temperature environment.
School of Physics and National Laboratory of Solid State Microstructures, Nanjing University, Nanjing 210093, China.Physics Department, Materials Genome Institute, State Key Laboratory of Advanced Special Steel, Shanghai Key Laboratory of High Temperature Superconductors, International Centre for Quantum and Molecular Structures, Shanghai University, Shanghai 200444, China. renwei@shu.edu.cn.
Physics Department, Materials Genome Institute, State Key Laboratory of Advanced Special Steel, Shanghai Key Laboratory of High Temperature Superconductors, International Centre for Quantum and Molecular Structures, Shanghai University, Shanghai 200444, China. renwei@shu.edu.cn.
State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an 710049, China.
European Theoretical Spectroscopy Facility, Institute of Condensed Matter and Nanosciences, Université Catholique de Louvain, Chemin des Étoiles 8, B-1348 Louvain-la-Neuve, Belgium.WEL Research Institute, avenue Pasteur, 6, 1300 Wavre, Belgium.
School of Physics and National Laboratory of Solid State Microstructures, Nanjing University, Nanjing 210093, China.
Physical chemistry chemical physics : PCCP
Ab initio study of temperature-dependent piezoelectric and electronic properties of thermally stable GaPO4.
To investigate the relationship between the fundus sex index obtained from fundus photographs and body height or axial length in the Kumejima population.Prospective cross-sectional observational population study.Using color fundus photographs obtained from the Kumejima population, 1,653 healthy right eyes with reliable fundus parameter measurements were included in this study. The tessellation fundus index was calculated as R/(R + G + B) using the mean value of the red-green-blue intensity in the eight locations around the optic disc and foveal region. The optic disc ovality ratio, papillomacular angle, and retinal vessel angle were quantified as previously described. The masculine or feminine fundus was quantified using machine learning (L2 regularized binominal logistic regression and leave one out cross validation), with the range of 0-1 as the predictive value, and defined as the fundus sex index. The relationship between the fundus sex index and body height or axial length was investigated using Spearman's correlation.The mean age of the 838 men and 815 women included in this study was 52.8 and 54.0 years, respectively. The correlation coefficient between fundus sex index and body height was - 0.40 (p < 0.001) in all, 0.01 (p = 0.89) in men, and - 0.04 (p = 0.30) in women, and that between fundus sex index and axial length was - 0.23 (p < 0.001) in all, - 0.12 (p < 0.001) in men, and - 0.13 (p < 0.001) in women.This study shows that a larger number of masculine fundi tend to have longer axial lengths in each sex group. However, sex index was not significantly related with body height either in men or in women.
Department of Ophthalmology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Department of Ophthalmology, Seirei Hamamatsu General Hospital, Shizuoka, Japan.
Urasoe Sakai Eye Clinic, Okinawa, Japan.
Department of Ophthalmology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan. tsakamot@m3.kufm.kagoshima-u.ac.jp.
Department of Ophthalmology, Kanto Central Hospital, Tokyo, Japan.
Relationship between fundus sex index obtained using color fundus parameters and body height or axial length in the Kumejima population.
Cadmium (Cd) is readily absorbed by tobacco and accumulates in the human body through smoke inhalation, posing threat to human health. While there have been many studies on the negative impact of cadmium in tobacco on human health, the specific adaptive mechanism of tobacco roots to cadmium stress is not well understood. In order to comprehensively investigate the effects of Cd stress on the root system of tobacco, the combination of transcriptomic, biochemical, and physiological methods was utilized. In this study, tobacco growth was significantly inhibited by 50 μM of Cd, which was mainly attributed to the destruction of root cellular structure. By comparing the transcriptome between CK and Cd treatment, there were 3232 up-regulated deferentially expressed genes (DEGs) and 3278 down-regulated DEGs. The obvious differential expression of genes related to the nitrogen metabolism, metal transporters and the transcription factors families. In order to mitigate the harmful effects of Cd, the root system enhances Cd accumulation in the cell wall, thereby reducing the Cd content in the cytoplasm. This result may be mediated by plant hormones and transcription factor (TF). Correlational statistical analysis revealed significant negative correlations between IAA and GA with cadmium accumulation, indicated by correlation coefficients of -0.91 and -0.93, respectively. Conversely, ABA exhibited a positive correlation with a coefficient of 0.96. In addition, it was anticipated that 3 WRKY TFs would lead to a reduction in Cd accumulation. Our research provides a theoretical basis for the systematic study of the specific physiological processes of plant roots under Cd stress.
College of Plant Protection, Shandong Agricultural University, Taian, 271018, Shandong province, China.
Department of Botany, GDC Pulwama-192301, Jammu and Kashmir, India.
Botany and Microbiology Department, College of Science, King Saud University, Riyadh, 11451, Saudi Arabia.
Faculty of Science and Technology, Madhyanchal Professional University, Ratibad, Bhopal, 462044, India; Environmental and Atmospheric Sciences Research Group, Scientific Research Center, Al-Ayen University, Thi-Qar, Nasiriyah, 64001, Iraq.
Departamento de Procesos Químicos, Facultad de Ciencias Matemáticas, Físicas y Químicas, Universidad Técnica de Manabí, Portoviejo, Manabí, Ecuador.
College of Plant Protection, Shandong Agricultural University, Taian, 271018, Shandong province, China. Electronic address: liupeng2003@sdau.edu.cn.
Comprehensive transcriptome, physiological and biochemical analyses reveal that key role of transcription factor WRKY and plant hormone in responding cadmium stress.
Telemedicine has shown promising results, allowing specialists to provide rapid and effective care in remote locations. However, to our knowledge, current evidence is not robust enough to prove the effectiveness of this tool. This cluster-randomized trial (CRT) aimed to evaluate the impact of telemedicine on clinical care indicators in pediatric intensive care units (PICUs).An open-label CRT was conducted in 16 PICUs within the Brazilian public health system. The trial took place from August 2022 to December 2023 and compared an intervention group, which received telemedicine support, with a control group, which received usual PICU care. The primary outcome was the PICU length of stay. The main secondary outcomes were mortality rate and ventilator-free days.A total of 1393 participants were included, 657 in the control group and 736 in the intervention group. The mean PICU length of stay was 10.42 (SD, 10.71) days for the control group and 11.52 (SD, 10.80) days for the intervention group. The overall mean of ventilator-free days was 6.82 (SD, 7.71) days. Regarding mortality, 7.54% of participants died in total. No significant difference was found in the outcomes between the groups.Despite the potential benefits of telemedicine, its effective implementation in the Brazilian public health system faces considerable challenges, highlighting the continued importance of investigating and improving the role of telemedicine in pediatric critical care.ClinicalTrials.gov NCT05260710 and ReBEC - RBR-7×j4wyp.
Responsabilidade Social, Hospital Moinhos de Vento, Porto Alegre, Brasil.
Instituto de Pesquisa, Hospital Moinhos de Vento - Porto Alegre (RS), Porto Alegre, Brasil.
Evaluation of the use of telemedicine in pediatric intensive care units: a cluster-randomized trial.
Mouthwashes, as a form of antimicrobial delivery system, rank among the safest and most effective vehicles, particularly in the case of young children. This is attributed to their ability to distribute therapeutic components across all accessible oral surfaces, including interproximal areas.To evaluate the antibacterial efficacy of recently introduced Ayurvedic (Hiora) and triclosan-based mouthwashes among children.A total of 45 healthy children aged 10-15 years were randomly assigned to three groups: Herbal mouthwash (Hiora), triclosan-based mouthwash (Kidodent), and normal saline as the control group. Saliva samples were collected pre-rinse, 2 minutes, 30 minutes, and 60 minutes post-rinsing with the study mouthwashes. These samples were then inoculated onto Petri dishes containing blood agar culture media, followed by incubation under both aerobic and anaerobic conditions at 37°C for 48 hours. The resulting bacterial colonies of Streptococcus spp. and Lactobacillus spp. were counted (CFU/ml x 105). Statistical analysis, including ANOVA, Newman Keul's Post-hoc test, and a two-tailed 't' test, was conducted to determine the significance of the results.The Ayurvedic Hiora mouthwash demonstrated the most substantial reduction in salivary bacterial colony counts of Streptococcus spp. and Lactobacillus spp. with statistically significant results (p<0.01).The Ayurvedic Hiora mouthwash exhibited the highest antibacterial effectiveness, followed by the triclosan-based mouthwash in decreasing order, with saline showing the least efficacy.
Department of Pedodontics & Preventive Dentistry, Sardar Patel Post Graduate Institute of Dental & Medical Sciences, Lucknow, Uttar Pradesh, India.
Annagiri Surgical and Dental Clinic, Tezpur, Assam, India.
Department of Dentistry, Autonomous State Medical College, Shahjahanpur, Uttar Pradesh, India.
Department of Paediatric & Preventive Dentistry, JSS Dental College & Hospital, JSS Academy of Higher Education & Research, Mysore, Karnataka, India.
Department of Oral Pathology & Microbiology, JSS Dental College, Hospital, JSS Academy of Higher Education and Research, Mysore, Karnataka 5870015, India.
Antibacterial Efficacy of Hiora: An Ayurvedic Mouthwash in Children.
To evaluate and compare dynamic vault range (DVR) and asymmetry of the vault during a 3-month follow-up after the implantation of 2 posterior chamber phakic intraocular lenses (pIOLs).Aver Clinic, Madrid, Spain.Prospective comparative study.119 eyes (65 patients) that underwent refractive surgical correction with implantation of 1 of 2 distinct pIOLs were enrolled: Eyecryl Phakic from Biotech Vision Care (Eyecryl group, 72 eyes) and Evo Visian Implantable Contact Lens from Staar Surgical (ICL group, 47 eyes). Besides evaluation of visual acuity, refraction, and ocular integrity, the pIOL vault centrally and at 2 mm nasally and temporally as well as the DVR from photopic (50 lux) to mesopic (10 lux) illumination conditions were measured.No significant differences were found between the pIOL groups in visual and refractive outcomes ( P ≥ .454). No significant differences between the groups were found in central (523.72 ± 168.4 vs 494.16 ± 156.7 μm, P = .248) and temporal (499.43 ± 155.8 vs 431.28 ± 150.5 μm, P = .067) vaults. However, nasal vault was significantly lower in the ICL group (465.6 ± 149.1 vs 375.4 ± 144.0 μm, P = .045). A trend of a larger DVR was observed in the ICL group, although differences between groups did not reach statistical significance (54.00 ± 36.39 vs 86.5 ± 57.9 μm, P = .070). The pIOL diameter only correlated significantly with vault measurements in the ICL group ( r ≥ 0.650, P < .001).The Eyecryl pIOL showed more symmetric vaults and a trend of fewer light-induced changes in the central vault compared with the ICL pIOL. The clinical relevance of this finding should be investigated further.
From the Clínica AVER, Madrid, Spain (Paredes, Mora de Oñate, Martín Sánchez); Department of Optics, Pharmacology and Anatomy, University of Alicante, Alicante, Spain (Piñero).
Characterization of vault with two models of posterior chamber phakic intraocular lenses.
To report functional and refractive outcomes of manual arcuate keratotomy (AK) with compression sutures for high regular postkeratoplasty astigmatism.Department of Ophthalmology, Saarland University Medical Center, Homburg/Saar, Germany.Retrospective analysis.This study included 90 eyes with high regular postkeratoplasty astigmatism (>4 diopters [D]) who received AK with compression sutures between 2010 and 2022. Functional and refractive outcomes were assessed by evaluating topographic indices and by performing vector astigmatism and Fourier analysis.At last follow-up (mean 13.7 ± 16.6 months), corrected distance visual acuity improved from 0.59 ± 0.28 to 0.34 ± 0.25 logMAR. Cylinder magnitude decreased from 9.91 ± 2.88 to 5.42 ± 3.35 D. Surface asymmetry index, irregular astigmatism index, and corneal eccentricity index were equal to preoperative values, whereas surface regularity index approached normal values at last follow-up. Fourier analysis indicated a decrease in the regular astigmatic component, whereas nonregular components (asymmetry and higher-order irregularity) remained stable. In vector astigmatism analysis, target-induced astigmatism magnitude was 9.92 ± 2.86 D and surgically induced astigmatism magnitude was 10.16 ± 4.86 D (correction index of 0.91 ± 0.48) with a difference vector of 5.42 ± 3.35 D at last follow-up. Correction of astigmatism magnitude was adequate in 40% of the eyes, undercorrected in 30%, and overcorrected in 30%. Angle of error was <|22.5 degrees| in 88% resulting in a low risk of off-axis treatment.AK with compression sutures is a simple, relatively effective, and safe surgical procedure for astigmatism reduction after keratoplasty. In case of regular astigmatism, the procedure does not increase corneal irregularities. The remaining refractive error might be further corrected by spectacles, contact lenses, or toric intraocular lens implantation (in-the-bag/add-on), thus reducing the need for repeat keratoplasty.
From the Department of Ophthalmology, Saarland University Medical Center, Homburg/Saar, Germany (Berger, Abu Dail, Seitz, Khattabi, Flockerzi, Hamon, Daas); Department of Experimental Ophthalmology, Saarland University, Homburg/Saar, Germany (Langenbucher).
Outcomes of manual arcuate keratotomy with compression sutures for high regular postkeratoplasty astigmatism.
The pathogen of community-acquired pneumonia (CAP) in children is typically uncertain during initial treatment, leading to systematic empiric antibiotic use. This study investigates if having rapid multiplex PCR results in the emergency department (ED) improves empiric treatment.OPTIPAC, a French multicentre study (2016-2018), enrolled patients consulting for CAP at the paediatric ED in 11 centres. Patients were randomized to either receive a multiplex PCR test plus usual care or usual care alone and followed for 15 days. The primary outcome was the appropriateness of initial antimicrobial management, determined by a blinded committee.Of the 499 randomized patients, 248 were tested with the multiplex PCR. Appropriateness of the antibiotic treatment was higher in the PCR group (168/245, 68.6% vs. 120/249, 48.2%; Relative risk 1.42 [1.22-1.66]; p < 0.0001), chiefly by reducing unnecessary antibiotics in viral pneumonia (RR 3.29 [2.20-4.90]). No adverse events were identified.The multiplex PCR assay result at the ED improves paediatric CAP's antimicrobial stewardship, by both reducing antibiotic prescriptions and enhancing treatment appropriateness.
Copyright © 2024 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Department of Paediatric Emergencies, Hospital University of Saint-Etienne, Saint-Etienne, France; Centre International de Recherche en Infectiologie (CIRI), Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne, Lyon, France. Electronic address: aymeric.cantais@chu-st-etienne.fr.
Centre International de Recherche en Infectiologie (CIRI), Université de Lyon, Université Claude Bernard Lyon 1, INSERM U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne, Lyon, France; Department of Infectious Agents and Hygiene, University-Hospital of Saint-Etienne, Saint-Etienne, France.
Department of Paediatrics, Hospital University Robert Debré, Paris, France.
Department of Paediatric Emergencies, Hospital University of Nantes, Nantes, France.
Department of Paediatrics, Hospital University of Brest, Brest, France.
Department of Paediatric Emergencies, Hospital University of Saint-Etienne, Saint-Etienne, France.
Unit of Clinical Research, Hospital University of Saint-Etienne, Saint-Etienne, France.
Department of Paediatric Emergencies, Hospital University of Toulouse, Toulouse, France.
Department of Virology, Hospital University of Toulouse, Toulouse, France.
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
Impact of respiratory pathogens detection by a rapid multiplex polymerase chain reaction assay on the management of community-acquired pneumonia for children at the paediatric emergency department. A randomized controlled trial, the Optimization of Pneumonia Acute Care (OPTIPAC) study.
Systemically administered cytokines are potent immunotherapeutics but can cause severe dose-limiting toxicities. To overcome this challenge, cytokines have been engineered for intratumoral retention after local delivery. However, despite inducing regression of treated lesions, tumor-localized cytokines often elicit only modest responses at distal untreated tumors. In the present study, we report a localized cytokine therapy that safely elicits systemic antitumor immunity by targeting the ubiquitous leukocyte receptor CD45. CD45-targeted immunocytokines have lower internalization rates relative to wild-type counterparts, leading to sustained downstream cis and trans signaling between lymphocytes. A single intratumoral dose of αCD45-interleukin (IL)-12 followed by a single dose of αCD45-IL-15 eradicated treated tumors and untreated distal lesions in multiple syngeneic mouse tumor models without toxicity. Mechanistically, CD45-targeted cytokines reprogrammed tumor-specific CD8+ T cells in the tumor-draining lymph nodes to have an antiviral transcriptional signature. CD45 anchoring represents a broad platform for protein retention by host immune cells for use in immunotherapy.
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.Howard Hughes Medical Institute, Chevy Chase, MD, USA.
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. wittrup@mit.edu.Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA. wittrup@mit.edu.Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. wittrup@mit.edu.
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA. djirvine@mit.edu.Howard Hughes Medical Institute, Chevy Chase, MD, USA. djirvine@mit.edu.Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. djirvine@mit.edu.Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA, USA. djirvine@mit.edu.Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. djirvine@mit.edu.
Local delivery of cell surface-targeted immunocytokines programs systemic antitumor immunity.
Aberrant DNA methylation patterns in the promoter region of PLCG2 are associated with dysregulated signaling pathways and cellular functions. Its role in colorectal cancer cells is still unknown. In this study, qRT-PCR is used to measure DNMT3B expression in colorectal cancer. Western blot analysis and immunohistochemistry are used to analyze DNMT3B and PLCG2 protein levels in colorectal tissues and cell lines. Cell Counting Kit-8 (CCK-8) and colony formation assays are used to assess the proliferation of colorectal cancer cells. Methylation-specific PCR (MSP) and bisulfite-sequencing PCR (BSP) are used to measure DNA methylation level. Our results show that DNMT3B is overexpressed in colorectal cells in the TCGA datasets according to Kaplan-Meier plots. DNMT3B is significantly overexpressed in tumor tissues compared to that in adjacent nontumor tissues. Western blot analysis results demonstrate high expression of DNMT3B in tumor tissues. Compared to normal colonic epithelial cells, colorectal cancer cell lines exhibit elevated level of PLCG2 methylation. Overexpression of PLCG2 effectively prevents the growth of colorectal cancer xenograft tumors in vivo. PLCG2 is identified as a key downstream regulatory protein of DNMT3B in colorectal cancer. DNMT3B inhibits PLCG2 transcription through methylation of the PLCG2 promoter region. DNMT3B controls colorectal cancer cell proliferation through PLCG2, which is useful for developing therapeutic approaches that target PLCG2 expression for the treatment of colorectal cancer.
The Yangzhou School of Clinical Medicine of Dalian Medical University, Yangzhou 225001, China.Jingjiang People's Hospital, Jingjiang 214500, China.General Surgery Institute of Yangzhou, Yangzhou University, Yangzhou 225001, China.Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases, Yangzhou 225001, China.
Clinical Medical College, Yangzhou University, Yangzhou 225001, China.General Surgery Institute of Yangzhou, Yangzhou University, Yangzhou 225001, China.Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases, Yangzhou 225001, China.
The Yangzhou School of Clinical Medicine of Dalian Medical University, Yangzhou 225001, China.General Surgery Institute of Yangzhou, Yangzhou University, Yangzhou 225001, China.Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases, Yangzhou 225001, China.
The Yangzhou Clinical Medical College of Xuzhou Medical University, Yangzhou 225001, China.General Surgery Institute of Yangzhou, Yangzhou University, Yangzhou 225001, China.Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases, Yangzhou 225001, China.
The Yangzhou School of Clinical Medicine of Dalian Medical University, Yangzhou 225001, China.Clinical Medical College, Yangzhou University, Yangzhou 225001, China.General Surgery Institute of Yangzhou, Yangzhou University, Yangzhou 225001, China.Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases, Yangzhou 225001, China.
Methyltransferase DNMT3B promotes colorectal cancer cell proliferation by inhibiting PLCG2.
Departments of Advanced Medical and Surgical Sciences, and.Experimental Medicine, University of Campania Luigi Vanvitelli , Naples, IT.
Department of Biology, College of Science and Technology, Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA; and.Division of Cardiology, Department of Medical Translational Sciences, University of Campania Luigi Vanvitelli, Naples, Italy .
Experimental Medicine, University of Campania Luigi Vanvitelli , Naples, IT.
Departments of Advanced Medical and Surgical Sciences, and.
Commentary on Antithrombotic Effect of Protopanaxatriol Saponins from Panax notoginseng Using Zebrafish Model.
Patients undergoing anthracycline-based cancer treatments have an increased risk of heart failure or worsening preexisting heart failure as well as adverse metabolic outcomes such as malnutrition and cachexia. This retrospective study explored the impact of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on these outcomes in patients with heart failure previously treated with anthracyclines. Using the TriNetX research network, we identified 1545 patients with a history of SGLT2i use and 17,681 patients without a history of SGLT2i use. We then performed 1:1 propensity score matching resulting in 1323 patients within each cohort. Patients were analyzed over a 5-year period. SGLT2i use was associated with significantly reduced risks of cachexia {hazard ratio (HR) 0.453, 95% confidence interval (CI) [0.286-0.718]}, malnutrition (HR 0.702, 95% CI [0.547-0.900]), adult failure to thrive (HR 0.489, 95% CI [0.345-0.693]), and all-cause mortality (HR 0.490, 95% CI [0.423-0.568]). These findings call for additional research to determine whether SGLT2i may indeed improve nutritional status and survival in patients with heart failure receiving anthracycline therapy.
Virginia Commonwealth University School of Medicine, Richmond, VA.
Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University Health System.Pauley Heart Center, Virginia Commonwealth University, Richmond, VA; and.
Pauley Heart Center, Virginia Commonwealth University, Richmond, VA; and.Department of Kinesiology and Health Sciences, College of Humanities and Sciences, Virginia Commonwealth University.
Sodium-Glucose Cotransporter 2 Inhibitors, Malnutrition, Cachexia, and Survival in Patients With Heart Failure With a History of Anthracycline Treatment.
To compare intraindividually the incidence and intensity of posterior capsule opacification (PCO) and Nd:YAG capsulotomy rates between 2 similar open-loop single-piece hydrophobic acrylic intraocular lenses (IOLs) differing slightly in their particular material, optic surface, and sharp posterior edge design over a period of 3 years.Department of Ophthalmology, Medical University Vienna, Vienna, Austria.Randomized, prospective, patient-masked and examiner-masked clinical trial with intraindividual comparison.100 patients randomly received a Vivinex XY1 IOL in 1 eye and a Clareon CNA0T0 IOL in the fellow eye. The amount of PCO (score 0 to 10) was assessed subjectively and objectively with digital retroillumination pictures using automated image analysis software (Automated Quantification of After-Cataract). Corrected distance visual acuity and the presence of glistenings, subjective visual symptoms, and Nd:YAG laser capsulotomy rate were noted.67 of 100 patients were available for the 3-year follow-up examination. The objective PCO score of the Vivinex XY1 IOLs was 1.0 ± 1.0 compared with the PCO score of 1.5 ± 1.2 for the Clareon CNA0T0 IOLs ( P < .001). 7.5% of patients had a Nd:YAG capsulotomy in the Vivinex XY1 eye, and 9.0% had a capsulotomy in the Clareon CNA0T0 eye ( P = 1.0).Both hydrophobic acrylic IOLs showed low PCO and YAG rates with a small but significant favor of the Vivinex XY1 IOL compared with the Clareon CNA0T0 IOL. The interaction of various factors such as hydrophobic material, smooth optic surface, and sharp posterior optic edge is the major key for PCO prevention.NCT04369482.
From the Department of Ophthalmology, Medical University of Vienna, Vienna, Austria.
Posterior capsule opacification with two similar-design hydrophobic acrylic intraocular lenses: 3-year results of a randomized controlled trial.
To describe serum fibroblast growth factor 23 (FGF-23) concentrations in young adult cats with remnant kidney model-induced chronic kidney disease (CKD) and to evaluate the effects of orally administered aluminum hydroxide (ALOH) on serum phosphate and FGF-23 concentrations in these cats.17 adult, purpose-bred cats with induced CKD and 13 healthy, age-matched cats.A prospective, randomized study. Cats with induced CKD fed a wet renal diet received treatment with ALOH (90 mg/kg/d, PO) on days 0 to 42 and no treatment on days 43 to 84 (treatment group, n = 9) or no treatment on days 0 to 84 (control group, n = 8). Standard serum and urine biochemical analyses and several parameters reflective of calcium-phosphate balance, including serum parathyroid hormone and FGF-23 concentrations, were evaluated at baseline and various time points, including days 42 and 84. Age-matched, healthy, community-owned cats underwent similar evaluations at a single time point. Baseline data from CKD cats were compared to those of healthy cats. Longitudinal data from CKD cats were compared over time.Serum phosphate, total and ionized calcium, and FGF-23 concentrations were significantly higher in CKD cats at baseline relative to healthy cats (all P ≤ .009). Serum phosphate concentration did not change significantly over time in either CKD group; however, FGF-23 concentrations significantly increased over time in the control group (P < .02) but not the treatment group (P = .059).Aluminum hydroxide did not reduce serum phosphate or FGF-23 concentrations in this small study of cats with induced CKD chronically eating a phosphate-restricted diet.
Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA.
Elanco Animal Health GmbH, Monheim, Germany.
Effect of aluminum hydroxide on serum phosphate and fibroblast growth factor 23 concentrations in young adult cats with surgically induced chronic kidney disease.
One of the most impactful recent developments in the glaucoma community has been the concept of interventional glaucoma. In brief, this paradigm shift involves proactive rather than reactive intervention to address glaucoma earlier in the disease process, including in both standalone and combination-cataract settings. By intervening earlier with minimally invasive surgical, laser, or drug-delivery treatments instead of prolonged topical medications, interventional glaucoma aims to take the burden of medication compliance off the patient. It also allows for standalone surgical interventions rather than letting cataract surgery dictate the glaucoma treatment plan. This interventional mindset has been made possible by the increasing diversity and availability of effective minimally invasive treatment options. With these options as a springboard, it is time to reevaluate and advance the traditional glaucoma treatment paradigm.
From Berkeley Eye Center, Houston, Texas (Micheletti); Matthew Brink LLC, Palm Beach Gardens, Florida (Brink); Sacramento Eye Consultants, Sacramento, California (Brubaker); Vance Thompson Vision, Sioux Falls, South Dakota (Ristvedt); Oklahoma Eye Surgeons, Oklahoma City, Oklahoma (Sarkisian).
Standalone interventional glaucoma: evolution from the combination-cataract paradigm.
Heart failure has always been a prevalent, disabling, and potentially life-threatening disease. For the treatment of heart failure, controlling cardiac remodeling is very important. In recent years, clinical trials have shown that sodium-glucose cotransporter-2 (SGLT-2) inhibitors not only excel in lowering glucose levels but also demonstrate favorable cardiovascular protective effects. However, the precise mechanisms behind the cardiovascular benefits of SGLT-2 inhibitors remain elusive. In this research, we assessed the impact of canagliflozin (CANA, an SGLT-2 inhibitor) on cardiac remodeling progression in mice and preliminarily elucidated the possible mechanism of action of the SGLT-2 inhibitor. Our results indicate that the administration of canagliflozin significantly attenuates myocardial hypertrophy and fibrosis and enhances cardiac ejection function in mice with isoprenaline (ISO)-induced cardiac remodeling. Notably, excessive mitophagy, along with mitochondrial structural abnormalities observed in ISO-induced cardiac remodeling, was mitigated by canagliflozin treatment, thereby attenuating cardiac remodeling progression. Furthermore, the differential expression of AMPK/PINK1/Parkin pathway-related proteins in ISO-induced cardiac remodeling was effectively reversed by canagliflozin, suggesting the therapeutic potential of targeting this pathway with the drug. Thus, our study indicates that canagliflozin holds promise in mitigating cardiac injury, enhancing cardiac function, and potentially exerting cardioprotective effects by modulating mitochondrial function and mitophagy through the AMPK/PINK1/Parkin pathway.
Department of Cardiology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China ; and.
Department of Cardiology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China ; and.Center of Reproduction, Development and Aging and Institute of Translation Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau, China .
Canagliflozin Mediates Mitophagy Through the AMPK/PINK1/Parkin Pathway to Alleviate ISO-induced Cardiac Remodeling.
Continuity is considered essential for high-quality maternal and child health care services, but studies to show this effect on parental well-being are still rare. We studied whether receiving support from the same public health nurse has a beneficial effect on parental perceptions of health care professionals and the use of childcare support services.Maternal and child health care services were provided by different nurses in a Japanese municipality until March 2019. From April 2019, all families with infants received continuous support from the same assigned nurse. A questionnaire covering parental perception and the use of services was sent by postal mail to 1,341 families with infants. The data were analyzed using χ2-test, t-test and logistic regression producing odds ratios (OR) with 95% confidence intervals (CI).Parental perceptions of the availability of professionals to discuss children's issues, the degree of understanding about available other childcare support services, the degree of utilizing other services, and satisfaction with health care services were higher in parents who received continuous support from the same assigned nurse compared to those who did not receive continuous support. Continuous support was associated with parental perceptions of the availability of professionals to discuss children's issues (OR = 1.97, 95% CI 1.34-2.91) and the degree of understanding about available other child-care support services (OR = 1.65, 95% CI 1.11-2.44) after adjusting the results for socioeconomic factors.Continuous support from the same assigned nurse has benefits for parents. This offers a cost-effective way to improve parental well-being.
© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Health Promotion Care Science, Osaka Metropolitan University, 1-5-17 Asahi-machi, Abeno-ku, Osaka, 545-0051, Japan. yyokoyama@omu.ac.jp.
Health Promotion Care Science, Osaka Metropolitan University, 1-5-17 Asahi-machi, Abeno-ku, Osaka, 545-0051, Japan.Bukkyo University, Kyoto, Japan.
Shimada City Public Health Center, Shimada, Japan.
Center for Birth Cohort Studies, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi, Japan.
Center for Birth Cohort Studies, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi, Japan.Department of Health Sciences, Basic Science for Clinical Medicine, Division of Medicine, Graduate School Department of Interdisciplinary Research, University of Yamanashi, Yamanashi, Japan.
Department of Social Epidemiology, School of Public Health, Kyoto University, Kyoto, Japan.
Population Research Unit, Faculty of Social Sciences, University of Helsinki, Helsinki, Finland.
Continuous Support from the Same Public Health Nurse and Parental Perception and Use of Health Care Services: A Retrospective Observational Study.
To investigate whether there is a dose-dependent association between empiric dexamethasone and outcome in viral meningitis.Observational cohort study of adults hospitalized for viral meningitis, both with and without a microbiologically confirmed diagnosis, in Denmark between 2015 and 2020. Dose-dependent associations between dexamethasone (one dose = 10 mg) and an unfavourable outcome (Glasgow Outcome Scale score 1-4) at 30 days after discharge were assessed using weighted logistic regression. Entropy balancing was used to compute weights.Of 1025 included patients, 658 (64%) did not receive dexamethasone, 115 (11%) received 1-2 doses, 131 (13%) received 3-4 doses, and 121 (12%) received ≥5 doses. Among patients treated with dexamethasone, the median number of doses was higher for those without an identified pathogen than for those with a microbiologically confirmed viral aetiology (5 [interquartile range (IQR) 3-8] vs. 3 [IQR 2-5]; p < 0.001). Using no doses of dexamethasone as a reference, the weighted OR for an unfavourable outcome were 0.55 (95% CI, 0.29-1.07) for 1-2 doses, 1.13 (95% CI, 0.67-1.89) for 3-4 doses, and 1.43 (95% CI, 0.77-2.64) for ≥5 doses. In the subgroup of enteroviral meningitis, the weighted OR was 3.08 (95% CI, 1.36-6.94) for ≥5 doses, but decreased to 2.35 (95% CI, 0.65-8.40) when the reference group was restricted to patients treated with antibiotics for suspected bacterial meningitis.This study showed no dose-dependent association between dexamethasone and an unfavourable outcome in patients with viral meningitis. In enteroviral meningitis, ≥5 doses were associated with an increased risk of an unfavourable outcome. However, sensitivity analysis indicated that the association was affected by unmeasured or residual confounding by severity.
Department of Pulmonary and Infectious Diseases, Nordsjællands Hospital, Hillerød, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: pelle.trier.petersen.01@regionh.dk.
Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
Department of Pulmonary and Infectious Diseases, Nordsjællands Hospital, Hillerød, Denmark.
Department of Infectious Diseases, Odense University Hospital, Odense, Denmark.
Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
Department of Infectious Diseases, Hvidovre Hospital, Hvidovre, Denmark.
Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark.
Department of Medicine, Zealand University Hospital, Roskilde, Denmark.
Department of Infectious Diseases, Herlev-Gentofte Hospital, Herlev, Denmark.
Department of Clinical Microbiology, Hvidovre Hospital, Hvidovre, Denmark.
Danish Study Group of Infections of the Brain (DASGIB)
Dexamethasone in adults with viral meningitis: an observational cohort study.
Historical exclusion of females in research has been, in part, due to the perceived influence of natural menstrual (NAT) and oral contraceptive pill (OCP) cycles on vascular outcomes. NAT and OCP cycle phases may influence brachial artery (BA) endothelial function, however, findings are mixed. Minimal research has examined arterial stiffness, smooth muscle, and lower limb endothelial function. The purpose of this study was to investigate the influence of NAT and OCP cycles on cardiovascular outcomes and cellular regulation. Forty-nine premenopausal females (n = 17 NAT, n = 17 second generation OCP, n = 15 third generation OCP) participated in two randomized order visits in the low (LH, early follicular/placebo) and high (HH, midluteal/active) hormone cycle phases. BA and superficial femoral artery (SFA) endothelial function [flow-mediated dilation (FMD) test], smooth muscle function (nitroglycerine-mediated dilation test), and carotid and peripheral (pulse wave velocity) arterial stiffness were assessed. Cultured female human endothelial cells were exposed to participant serum for 24 h to examine endothelial nitric oxide synthase (eNOS) and estrogen receptor-α (ERα) protein content. BA FMD was elevated in the HH vs. LH phase, regardless of group (HH, 7.7 ± 3.5%; LH, 7.0 ± 3.3%; P = 0.02); however, allometric scaling for baseline diameter resulted in no phase effect (HH, 7.6 ± 2.6%; LH, 7.1 ± 2.6%; P = 0.052, d = 0.35). SFA FMD, BA, and SFA smooth muscle function, arterial stiffness, and eNOS and ERα protein content were unaffected. NAT and OCP phases examined have minimal influence on vascular outcomes and ERα-eNOS pathway, apart from a small effect on BA endothelial function partially explained by differences in baseline artery diameter. NEW & NOTEWORTHY Comprehensive evaluation of the cardiovascular system in naturally cycling and second and third generation OCP users indicates no major influence of hormonal phases examined on endothelial function and smooth muscle function in the arteries of the upper and lower limbs, arterial stiffness, or underlying cellular mechanisms. Study findings challenge the historical exclusion of female participants due to potentially confounding hormonal cycles; researchers are encouraged to consider the hormonal environment in future study design.
Vascular Dynamics Lab, Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada.
Molecular Exercise Physiology & Muscle Aging Lab, Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada.
American journal of physiology. Heart and circulatory physiology
Menstrual and oral contraceptive pill cycles minimally influence vascular function and associated cellular regulation in premenopausal females.
To evaluate the effectiveness and safety of Qishen Yiqi Dripping Pill (QSYQ) in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI).This multicentre prospective cohort study was conducted at 40 centers in China. Patients with ACS after PCI entered either the QSYQ or Western medicine (WM) groups naturally based on whether they had received QSYQ before enrollment. QSYQ group received QSYQ (0.52 g, 3 times a day for 12 months) in addition to WM. The primary endpoint included cardiac death, non-fatal myocardial infarction, and urgent revascularization. The secondary endpoint included rehospitalization due to ACS, heart failure, stroke, and other thrombotic events. Quality of life was assessed by the Seattle Angina Questionnaire (SAQ).A total of 936 patients completed follow-up of the primary endpoint from February 2012 to December 2018. Overall, 487 patients received QSYQ and WM. During a median follow-up of 566 days (inter quartile range, IQR, 517-602), the primary endpoint occurred in 46 (9.45%) and 65 (14.48%) patients in QSYQ and WM groups respectively [adjusted hazard ratio (HR) 0.60, 95% confidence interval (CI) 0.41-0.90; P=0.013]. The secondary endpoint occurred in 61 (12.53%) and 74 (16.48%) patients in QSYQ and WM groups, respectively (adjusted HR 0.76, 95% CI 0.53-1.09; P=0.136). In sensitivity analysis, the results still demonstrated that WM combined with QSYQ reduced the risk of the primary endpoint (HR 0.67, 95% CI 0.46-0.98; P=0.039). Moreover, QSYQ improved the disease perception domain of the SAQ (P<0.05).In patients with ACS after PCI, QSYQ combined with WM reduced the incidence of the primary endpoint. These findings provide a promising option for managing ACS after PCI and suggest the potential treatment for reducing the risk of primary endpoint included cardiac death, non-fatal myocardial infarction, and urgent revascularization through intermittent administration of QSYQ (Registration No. ChiCTR-OOC-14005552).
Department of Cardiovascular, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.National Clinical Research Center for Chinese Medicine Cardiology, Beijing, 100091, China.
Department of Evidence-Based Medicine Basic Research Laboratory, Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
Department of Traditional Chinese Medicine, Beijing Shangdi Hospital, Beijing, 100193, China.
Department of Cardiovascular, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.National Medical Products Administration, Key Laboratory for Clinical Research and Evaluation of Traditional Chinese Medicine, Beijing, 100091, China.
Department of Cardiovascular, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China. shidztcm@163.com.National Clinical Research Center for Chinese Medicine Cardiology, Beijing, 100091, China. shidztcm@163.com.
Effectiveness and Safety of Qishen Yiqi Dripping Pill in Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention: 3-Year Results from a Multicentre Cohort Study.
College of Osteopathic Medicine, Michigan State University, East Lansing, MI, USA.
Department of Neurology, Henry Ford Health, Detroit, MI, USA. lzeidma1@hfhs.org.Department of Neurology and Ophthalmology, College of Human Medicine, Michigan State University, East Lansing, MI, USA. lzeidma1@hfhs.org.
Cancer cells edit gene expression to evade immunosurveillance. However, genome-wide studies of gene editing during early tumorigenesis are lacking. Here we used single-cell RNA sequencing in a breast cancer genetically engineered mouse model (GEMM) to identify edited genes without bias. Late tumors repressed antitumor immunity genes, reducing infiltrating immune cells and tumor-immune cell communications. Innate immune genes, especially interferon-stimulated genes, dominated the list of downregulated tumor genes, while genes that regulate cell-intrinsic malignancy were mostly unedited. Naive and activated CD8+ T cells in early tumors were replaced with exhausted or precursor-exhausted cells in late tumors. Repression of immune genes was reversed by inhibiting DNA methylation using low-dose decitabine, which suppressed tumor growth and restored immune control, increasing the number, functionality and memory of tumor-infiltrating lymphocytes and reducing the number of myeloid suppressor cells. Decitabine induced important interferon, pyroptosis and necroptosis genes, inflammatory cell death and immune control in GEMM and implanted breast and melanoma tumors.
© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.
Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA. ying.zhang@pku.edu.cn.Department of Pediatrics, Harvard Medical School, Boston, MA, USA. ying.zhang@pku.edu.cn.Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, School of Life Sciences, Peking University, Beijing, China. ying.zhang@pku.edu.cn.Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China. ying.zhang@pku.edu.cn.
Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA.Harvard Medical School, Boston, MA, USA.
Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
Department of Pediatrics, Harvard Medical School, Boston, MA, USA.Division of Newborn Medicine, Boston Children's Hospital, Boston, MA, USA.
Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.Department of Pediatrics, Harvard Medical School, Boston, MA, USA.Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Harvard Medical School, Boston, MA, USA.Spatial Technologies Unit, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
Department of Pediatrics, Harvard Medical School, Boston, MA, USA.Division of Newborn Medicine, Boston Children's Hospital, Boston, MA, USA.Departments of Pediatrics and Genetics, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA. whide@bidmc.harvard.edu.Harvard Medical School, Boston, MA, USA. whide@bidmc.harvard.edu.
Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA. judy.lieberman@childrens.harvard.edu.Department of Pediatrics, Harvard Medical School, Boston, MA, USA. judy.lieberman@childrens.harvard.edu.
Tumor editing suppresses innate and adaptive antitumor immunity and is reversed by inhibiting DNA methylation.
The drivers of immune evasion are not entirely clear, limiting the success of cancer immunotherapies. Here we applied single-cell spatial and perturbational transcriptomics to delineate immune evasion in high-grade serous tubo-ovarian cancer. To this end, we first mapped the spatial organization of high-grade serous tubo-ovarian cancer by profiling more than 2.5 million cells in situ in 130 tumors from 94 patients. This revealed a malignant cell state that reflects tumor genetics and is predictive of T cell and natural killer cell infiltration levels and response to immune checkpoint blockade. We then performed Perturb-seq screens and identified genetic perturbations-including knockout of PTPN1 and ACTR8-that trigger this malignant cell state. Finally, we show that these perturbations, as well as a PTPN1/PTPN2 inhibitor, sensitize ovarian cancer cells to T cell and natural killer cell cytotoxicity, as predicted. This study thus identifies ways to study and target immune evasion by linking genetic variation, cell-state regulators and spatial biology.
Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, USA.Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.Cancer Biology Program, Stanford University, Stanford, CA, USA.Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Department of Pathology, California Pacific Medical Center, San Francisco, CA, USA.
Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, USA.Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.
Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA. bhowitt@stanford.edu.
Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA. ljerby@stanford.edu.Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA. ljerby@stanford.edu.Chan Zuckerberg Biohub, San Francisco, CA, USA. ljerby@stanford.edu.
Mapping spatial organization and genetic cell-state regulators to target immune evasion in ovarian cancer.
The aim of this study was to explore the incidence of new-onset erectile dysfunction (ED) in diabetes mellitus (DM) patients with sodium-glucose cotransporter 2 inhibitors (SGLT2I) use compared with a control group of non-SGLT2I use by propensity score matching approach. Cox proportional hazards regression models were used to examine the effect of SGLT2I and risk factors on the risk of developing ED, presented as a hazard ratio with a 95% confidence interval. One lakhs fifty nine thousand seven hundred seventy three patients with DM using SGLT2I and 159,773 propensity score matching patients with DM who had never used SGLT2I were included. SGLT2I users had a higher risk of ED than the non-SGLT2I users (adjusted hazard ratio = 1.55, 95% confidence interval = 1.40-1.72). The likelihood of developing ED was higher in patients with SGLT2I use was found.
School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan.Division of Cardiovascular Medicine, Department of Medicine, China Medical University Hospital, Taichung, Taiwan; and.
Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan.
Erectile Dysfunction Risk Among Patients With Diabetes Mellitus Using Sodium-Glucose Cotransporter 2 Inhibitors.
To compare reproductive history and postmenopausal health by birth status (preterm vs. full term) in a U.S. longitudinal study of postmenopausal women. Birth status was examined according to region of residence, household, and neighborhood socioeconomic status (SES).In the Women's Health Initiative Observational Study, 2271 women were born prematurely (< 37 weeks). ANOVA and Chi-square determined birth status differences of reproductive history, pregnancy, and postmenopausal health. Odds ratios were calculated using either binary logistic or multinomial logistic regression. SES and U.S. region of residence were examined as potential effect modifiers.Preterm-born women compared to term-born women had higher risk of delivering a premature infant (aOR 1.68, 95% CI [1.46, 1.93]), higher odds of later-age first pregnancy (aOR 1.27 95% CI [1.02, 1.58]), longer duration to become pregnant (> 1 year to pregnancy) (aOR 1.10 95% CI [1.01, 1.21]), more miscarriages (aOR 1.23 95% CI [1.11, 1.37]), and more pregnancy complications including hypertension (aOR 1.58 95% CI (1.13, 2.21)], preeclampsia (aOR 1.64 95% CI [1.24, 2.16]), and gestational diabetes (aOR 1.68 95% CI [1.11, 2.53]). Preterm-born women had higher odds of menopause before age 50 (aOR 1.09 95% CI [1.05, 1.14]). Post-menopause, they had higher rates of diabetes (p = .01), hypertension (p = .01), hysterectomy (p = .045), and higher Charlson Comorbidity Index scores (p = .01).Preterm-born women had higher reproductive and pregnancy risks which when coupled with early menopause, may indicate a shorter childbearing period than term-born women. Guidelines for integration of preterm history in women's health care across the life course are needed to identify and manage their higher risk.
College of Nursing, University of Rhode Island, Providence, RI, USA. mcsullivan@uri.edu.
College of Nursing, University of Rhode Island, Providence, RI, USA.
Care New England Medical Group/Primary Care and Specialty Services, Center for Primary Care and Prevention, Pawtucket, RI, USA.
Departments of Biostatistics and Epidemiology, Oklahoma City, OK, USA.Obstetrics and Gynecology, Oklahoma University Health Sciences Center, Oklahoma City, OK, USA.
Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, CA, USA.
College of Public Health, Ohio State University, Columbus, OH, USA.
Department of Epidemiology, Brown University, Providence, RI, USA.Department of Family Medicine, Warren Alpert Medical School of Brown University, Providence, RI, USA.
Intergenerational Occurrence of Premature Birth and Reproductive Health in Prematurely-Born Women in the Women's Health Initiative.
Radiation-induced heart disease (RIHD) is a severe delayed complication of thoracic irradiation (IR). Endonuclease/exonuclease/phosphatase family domain-containing 1 ( EEPD1) plays an important role in DNA damage repair, but its role in RIHD is less known. In this study, EEPD1 global knockout mice, C57BL/6J mice, and C57BL/6J mice overexpressing EEPD1 are treated with radiation at a total dose of 20 Gy or 0 Gy. After 9 weeks, echocardiography is used to assess cardiac hypertrophy and apoptosis. The results show that EEPD1 deletion exacerbates radiation-induced cardiac hypertrophy and apoptosis, while EEPD1 overexpression has the opposite effect. Further mechanistic investigations reveal that EEPD1 interacts with FOXO3A and destabilizes it by catalyzing its deubiquitination. Inhibition of FOXO3A ameliorates cardiac hypertrophy and apoptosis after EEPD1 knockdown. Thus, EEPD1 protects against radiation-induced cardiac hypertrophy and apoptosis via destabilization of FOXO3A, which may offer new insight into therapeutic strategies for RIHD.
Department of Cardiology, Shanghai Jiao Tong University Affiliated Chest Hospital, Shanghai 200030, China.
Radiotherapy Department of Shanghai Jiao Tong University Affiliated Chest Hospital, Shanghai 200030, China.
EEPD1 attenuates radiation-induced cardiac hypertrophy and apoptosis by degrading FOXO3A in cardiomyocytes.
CD8+ T cells control tumors but inevitably become dysfunctional in the tumor microenvironment. Here, we show that sodium chloride (NaCl) counteracts T cell dysfunction to promote cancer regression. NaCl supplementation during CD8+ T cell culture induced effector differentiation, IFN-γ production and cytotoxicity while maintaining the gene networks responsible for stem-like plasticity. Accordingly, adoptive transfer of tumor-specific T cells resulted in superior anti-tumor immunity in a humanized mouse model. In mice, a high-salt diet reduced the growth of experimental tumors in a CD8+ T cell-dependent manner by inhibiting terminal differentiation and enhancing the effector potency of CD8+ T cells. Mechanistically, NaCl enhanced glutamine consumption, which was critical for transcriptional, epigenetic and functional reprogramming. In humans, CD8+ T cells undergoing antigen recognition in tumors and predicting favorable responses to checkpoint blockade immunotherapy resembled those induced by NaCl. Thus, NaCl metabolism is a regulator of CD8+ T cell effector function, with potential implications for cancer immunotherapy.
IRCCS Humanitas Research Hospital, Milan, Italy.
IRCCS Humanitas Research Hospital, Milan, Italy.Institute of Genetic and Biomedical Research, UoS Milan, National Research Council, Milan, Italy.
Division of Functional Immune Cell Modulation, Leibniz Institute for Immunotherapy (LIT), Regensburg, Germany.University of Regensburg, Regensburg, Germany.Center for Immunomedicine in Transplantation and Oncology (CITO), University Hospital Regensburg, Regensburg, Germany.
Department of Pathology, University of Cambridge, Cambridge, UK.Immunology Programme, Babraham Institute, Babraham Research Campus, Cambridge, UK.
Department of Biomedical Sciences, Humanitas University, Milan, Italy.Division of Thoracic, IRCCS Humanitas Research Hospital, Milan, Italy.
IRCCS Humanitas Research Hospital, Milan, Italy.Department of Biomedical Sciences, Humanitas University, Milan, Italy.
The Peter Doherty Institute for Infection and Immunity and Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia.
IRCCS Humanitas Research Hospital, Milan, Italy.Institute of Neuroscience, National Research Council of Italy (CNR) c/o Humanitas Mirasole S.p.A, Milan, Italy.
Department of Sciences and Technological Innovation, University of Piemonte Orientale, Alessandria, Italy.
Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy.
IRCCS Humanitas Research Hospital, Milan, Italy. enrico.lugli@humanitasresearch.it.
NaCl enhances CD8+ T cell effector functions in cancer immunotherapy.
Cleveland Clinic, Cleveland, Ohio, USA uchinok@ccf.org.
Journal of neurology, neurosurgery, and psychiatry
J Neurol Neurosurg Psychiatry. 2025-01-16;96(2):104.
Ischaemic stroke in the young-is it time to consider alcohol reduction for stroke prevention?
The efficacy of antitumor immunity is associated with the metabolic state of cytotoxic T cells, which is sensitive to the tumor microenvironment. Whether ionic signals affect adaptive antitumor immune responses is unclear. In the present study, we show that there is an enrichment of sodium in solid tumors from patients with breast cancer. Sodium chloride (NaCl) enhances the activation state and effector functions of human CD8+ T cells, which is associated with enhanced metabolic fitness. These NaCl-induced effects translate into increased tumor cell killing in vitro and in vivo. Mechanistically, NaCl-induced changes in CD8+ T cells are linked to sodium-induced upregulation of Na+/K+-ATPase activity, followed by membrane hyperpolarization, which magnifies the electromotive force for T cell receptor (TCR)-induced calcium influx and downstream TCR signaling. We therefore propose that NaCl is a positive regulator of acute antitumor immunity that might be modulated for ex vivo conditioning of therapeutic T cells, such as CAR T cells.
Technical University of Munich, Munich, Germany.
Department of Infection Immunology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, Germany.
Institute of Systems Immunology, Philipps-University Marburg, Marburg, Germany.
Department of Microbiome Dynamics, Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, Germany.
Institute of Biology III, Faculty of Biology and Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.Center of Chronic Immunodeficiency, University Clinics and Medical Faculty, University of Freiburg, Freiburg, Germany.Spemann Graduate School of Biology and Medicine, University of Freiburg, Freiburg, Germany.
Department of Bioinformatics and Biochemistry, Braunschweig Integrated Centre of Systems Biology, Technical University of Braunschweig, Braunschweig, Germany.
Leibniz Institute for Aging, Jena, Germany.
Research Unit Analytical BioGeoChemistry, Helmholtz Center Munich-German Research Center for Environmental Health (GmbH), Neuherberg, Germany.
Department of Microbiome Dynamics, Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, Germany.Jena University Hospital, Friedrich Schiller University, Jena, Germany.
Chair for Cellular Immunotherapy, Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany.
Medical University of Vienna, Center for Pathophysiology, Infectiology and Immunology, Institute for Hygiene and Applied Immunology, Vienna, Austria.
Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen und Friedrich-Alexander-Universität Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany.FAU Profile Center Immunomedicine, FAU Erlangen-Nürnberg, Erlangen, Germany.
Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen und Friedrich-Alexander-Universität Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany.
Institute of Biology III, Faculty of Biology and Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.Center of Chronic Immunodeficiency, University Clinics and Medical Faculty, University of Freiburg, Freiburg, Germany.
Technical University of Munich, Munich, Germany. christina.zielinski@uni-jena.de.Department of Infection Immunology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, Germany. christina.zielinski@uni-jena.de.Institute of Microbiology, Faculty of Biological Sciences, Friedrich Schiller University Jena, Jena, Germany. christina.zielinski@uni-jena.de.
Sodium chloride in the tumor microenvironment enhances T cell metabolic fitness and cytotoxicity.
This study investigated the effect of menthol (MEN) mouth rinsing (MR) on cycling performance during a modified variable cycle test (M-VCT) in adolescent athletes under hot conditions (31.4 ± 0.9 °C, 23.4 ± 3.7% relative humidity).Trained adolescent male cyclists (n = 11, 16.7 ± 1.3 years, height 176.6 ± 8.8 cm, body mass 65.8 ± 11.6 kg, maximal oxygen uptake 62.97 ± 7.47 ml·kg-1·min-1) voluntarily completed three trials (familiarization and two experimental) of a 30-min M-VCT, which included five 6-min laps consisting of three 6-s accelerations and three 10-s sprints throughout each lap. In a randomized crossover design, MEN (0.01%) or placebo (PLA) (crystal-light), was swilled for 5 s before the start of each lap (total of 6 MR). Power output, distance (in kilometers), core temperature, heart rate, perceptual exertion, thermal stimulation (thermal comfort and thermal sensation), and blood lactate concentration were recorded.MEN MR significantly improved M-VCT mean power output by 1.81 ± 1.57% compared to PLA (MEN, 177.8 ± 31.4 W; PLA, 174.7 ± 30.5 W, p < .001, 95% confidence interval [1.73, 4.46], d = 1.53). For maximal intermittent sprints, 6- and 10-s mean power output was significantly higher with MEN than PLA (6 s, p = .041, 95% confidence interval [0.73, 27.19], d = 0.71; 10 s, p = .002, 95% confidence interval [11.08, 35.22], d = 1.29). There was no significant difference in core temperature, heart rate, blood lactate concentration, or any perceptual measure between trials (p > .05) despite significantly higher work with MEN.64% of athletes (7/11) improved M-VCT performance with MEN. The results of this investigation suggest that a MEN MR may improve power output during a sport-specific stochastic cycling task in elite adolescent male cyclists.
Faculty of Health Sciences, Ontario Tech University, Oshawa, ON, Canada.
International journal of sport nutrition and exercise metabolism
Menthol Mouth Rinsing Improves Cycling Performance in Trained Adolescent Males Under Heat Stress.
Deciphering the composition of the tumor microenvironment (TME) is critical for understanding tumorigenesis and to design immunotherapies. In the present study, we mapped genetic effects on cell-type proportions using single-cell and bulk RNA sequencing data, identifying 3,494 immunity quantitative trait loci (immunQTLs) across 23 cancer types from The Cancer Genome Atlas. Functional annotation revealed regulatory potential and we further assigned 1,668 genes that regulate TME composition. We constructed a combined immunQTL map by integrating data from European and Chinese colorectal cancer (CRC) samples. A polygenic risk score that incorporates these immunQTLs and hits on a genome-wide association study outperformed in CRC risk stratification within 447,495 multiethnic individuals. Using large-scale population cohorts, we identified that the immunQTL rs1360948 is associated with CRC risk and prognosis. Mechanistically, the rs1360948-G-allele increases CCL2 expression, recruiting regulatory T cells that can exert immunosuppressive effects on CRC progression. Blocking the CCL2-CCR2 axis enhanced anti-programmed cell death protein 1 ligand therapy. Finally, we have established a database (CancerlmmunityQTL2) to serve the research community and advance our understanding of immunogenomic interactions in cancer pathogenesis.
Department of Epidemiology and Biostatistics, School of Public Health, Research Center of Public Health, Renmin hospital of Wuhan University, Department of Gastrointestinal Oncology, Zhongnan Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, China.
Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan, China.
Cancer Center, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, China.
Department of Gastrointestinal Cancer Research Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Department of Cancer Epidemiology, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Henan Engineering Research Center of Cancer Prevention and Control, Henan International Joint Laboratory of Cancer Prevention, Zhengzhou, China.
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.
Department of Epidemiology and Biostatistics, School of Public Health, Research Center of Public Health, Renmin hospital of Wuhan University, Department of Gastrointestinal Oncology, Zhongnan Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, China. tianjb@whu.edu.cn.
Department of Epidemiology and Biostatistics, School of Public Health, Research Center of Public Health, Renmin hospital of Wuhan University, Department of Gastrointestinal Oncology, Zhongnan Hospital of Wuhan University, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, China. xpmiao@whu.edu.cn.Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, China. xpmiao@whu.edu.cn.Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China. xpmiao@whu.edu.cn.
An atlas of genetic effects on cellular composition of the tumor microenvironment.
Lung cancer and tuberculosis share similar risk factors, clinical spectrum, radiological features and it is difficult to differentiate but it is important to diagnose both conditions for targeted therapy and better outcome.Our primary objective was to estimate the proportion of TB in primary biopsy proven non-small cell lung carcinoma (NSCLC) cases.This prospective observational study was conducted in the Departments of Medicine/Pulmonary Medicine/Medical Oncology and Microbiology at the All India Institute of Medical Sciences, New Delhi for a period of 2 years (January 2020-December 2021). Patients with biopsy proven, primary non-small cell lung cancer were recruited and sputum samples were subjected to microbiological investigations to confirm tuberculosis. Comparison was done in two groups of lung cancer patients with confirmed TB (Group A) and without confirmed tuberculosis (Group B).Total 75 patients with biopsy proven, primary NSCLC were recruited and 16 % (12/75) were diagnosed with confirmed TB. Adenocarcinoma (36.48 %) and Squamous cell carcinoma (33.44 %) were the two predominant histopathological subtypes of NSCLC. About 57 (76 %) of them were found to be in stage IV of Lung cancer at initial presentation itself (75 % in group A & 74.6 % in group B; p value < 0.80). A majority of patients (11/12 cases; 91 %) of group A were males with a mean age of 59 ± 7.5 years. The upper lobes of the lung were involved in 65 % (49/75) of the cases and showing a mass lesion on imaging (75 % in group A & 65 % in group B; p value < 0.52). Kaplan Meier survival revealed a median survival time of 11 months in subjects with only NSCLC and a median survival time of 4 months in the group with concomitant TB and NSCLC (p value < 0.44).
Copyright © 2024 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.
Department of Medicine & Microbiology, All India Institute of Medical Sciences, New Delhi, India. Electronic address: niranjanmahishi1987@gmail.com.
Department of Microbiology, All India Institute of Medical Sciences, New Delhi, India. Electronic address: drkiran.dks@gmail.com.
Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India. Electronic address: drprabhatsm@gmail.com.
Department of General Medicine, All India Institute of Medical Sciences, New Delhi, India. Electronic address: drpiyushdost@gmail.com.
Department of General Medicine, All India Institute of Medical Sciences, New Delhi, India. Electronic address: linktoarvind@gmail.com.
Department of General Medicine, All India Institute of Medical Sciences, New Delhi, India. Electronic address: manishsoneja@gmail.com.
Department of Pulmonary Critical Care & Sleep Disorder, All India Institute of Medical Sciences, New Delhi, India. Electronic address: anantmohan@yahoo.com.
Department of Microbiology, All India Institute of Medical Sciences, New Delhi, India. Electronic address: drurvashi@gmail.com.
The burden of tuberculosis among patients with non-small cell lung carcinoma in a tertiary care center.
Neurological autoimmune peripheral and central nervous system disorders can be associated with anti-sulfatide antibodies. These antibodies are considered potential diagnostic biomarkers, although their additional diagnostic value in neurological fields has been increasingly questioned. Given the little evidence of anti-sulfatide antibodies' frequency and diagnostic value in neurology, we aimed to fill this knowledge gap by investigating 10 years of data.This retrospective study analyzed the results of the anti-ganglioside dot kits (GA Generic Assays GmbH) from 1318 serum samples and 462 cerebrospinal fluid (CSF) samples for the frequency, sensitivity, and specificity of anti-sulfatide antibodies in neurological disorders.Although anti-sulfatide antibodies are rarely present in neurological autoimmune disorders (serum IgM 2.5%, IgG 4.6%), they are also present in non-autoimmune diseases (serum IgM 1.2%, IgG 2.5%) and lack sensitivity and specificity towards being a diagnostic marker. Furthermore, anti-sulfatide antibodies are rarely found in CSF (e.g., no positive results for IgM), and including so-called borderline results ((+)) increases sensitivity and the false-positive rate in serum and CSF.While anti-sulfatide antibodies appear more frequently in neurological autoimmune diseases, they are rare overall and provide very limited diagnostic value in determining specific neurological diseases and-more importantly-if a neurological disease has a potential autoimmune etiology.
Department of Epileptology, Hertie-Institute for Clinical Brain Research, University of Tübingen, Hoppe-Seyler-Str. 3, 72076, Tubingen, Germany. Benedict.Kleiser@med.uni-tuebingen.de.Department of Neural Dynamics and Magnetoencephalography, Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. Benedict.Kleiser@med.uni-tuebingen.de.MEG-Center, University of Tübingen, Tübingen, Germany. Benedict.Kleiser@med.uni-tuebingen.de.
Department of Epileptology, Hertie-Institute for Clinical Brain Research, University of Tübingen, Hoppe-Seyler-Str. 3, 72076, Tubingen, Germany.
Department of Neurology and Stroke, Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
Department of Epileptology, Hertie-Institute for Clinical Brain Research, University of Tübingen, Hoppe-Seyler-Str. 3, 72076, Tubingen, Germany.Department of Neural Dynamics and Magnetoencephalography, Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.MEG-Center, University of Tübingen, Tübingen, Germany.Institute for Modelling and Simulation of Biomechanical Systems, Pfaffenwaldring 5a, 70569, Stuttgart, Germany.
Anti-sulfatide antibodies in neurological disorders: should we test?
To differentiate a normal cornea from a forme fruste keratoconus (FFKC) with the swept-source optical coherence tomography (SS-OCT) topography CASIA 2 using machine learning artificial intelligence algorithms.Monocentric, performed in CHU Bordeaux, Bordeaux, France.Retrospective case-control.3 groups were included: KC group (108 eyes), FFKC (88 eyes), and normal corneas (162 eyes). The data were analyzed and processed using the Dataiku data science platform. Machine learning models (random forest [RF], logistic regression [LR]) were used to develop a multiclass classifier for automated early KC detection. The models were trained using a training database and tested using a test database. Then, algorithms were compared with the Ectasia Screening Index (ESI), which is an OCT-topography inherent screening score for ectasia.The LR and RF detected FFKC with an area under the curve of 0.99 and 0.98, respectively. The sensitivities of LR (100%) and RF (84%) were better than the ESI (28%) for the diagnosis of FFKC. However, ESI has a maximum specificity (100%) compared with the LR (100%) and 90% for RF.This study identified discriminating topographic parameters to be considered in refractive surgery screening on SS-OCT CASIA 2. An algorithm capable of classifying normal eyes vs FFKC cases was developed, with improved performance compared with the ESI score.
From the Ophthalmology Unit, University Hospital Bordeaux, Bordeaux, France (Mourgues, Saunier, Touboul, Valentine Saunier); Department of Ophthalmology, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel (Smadja).
Forme fruste keratoconus detection with OCT corneal topography using artificial intelligence algorithms.
Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing, China.Changping Laboratory, Beijing, China.College of Chemistry and Molecular Engineering, Peking University, Beijing, China.
Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing, China. yunlongcao@pku.edu.cn.Changping Laboratory, Beijing, China. yunlongcao@pku.edu.cn.
The delivery device of SARS-CoV-2 mucosal vaccine matters.
To evaluate the rotational stability and visual performance of the enVista toric intraocular lens (IOL) (MX60ET) in cataract patients with preexisting astigmatism.6 U.S. sites.Prospective, multicenter.Cataract patients 18 years and older with preexisting astigmatism (0.77 to 4.53 diopters [D]) underwent phacoemulsification and implantation of enVista toric IOL (MX60ET). Outcome measures were the proportion of patients with absolute IOL axis rotation of ≤5 degrees, uncorrected and corrected distance visual acuities (UDVA and CDVA) at 4 m, uncorrected intermediate visual acuity (UIVA) at 66 cm, manifest refraction, and adverse events. The patients were followed up on days 1 to 2, 7 to 14, 30 to 60, and 120 to 180.Mean astigmatism of 101 eyes (101 patients) reduced from 1.47 ± 0.64 D preoperatively to 0.38 ± 0.38 D at days 120 to 180 ( P < .001), with 88.1% (N = 89/101) of eyes achieving astigmatism within 0.75 D. Mean postoperative UDVA and UIVA were 0.10 ± 0.16 and 0.25 ± 0.15 logMAR, respectively. While 79.2% (N = 80/101) of patients had postoperative UDVA of 20/32 or better, 63.9% (N = 62/97) had UIVA of 20/40 or better. The mean toric IOL rotation from the operative visit to days 30 to 60 was 1.97 ± 2.06 degrees, with 97.4% (N = 74/76) of eyes showing toric IOL rotation of 5 degrees or less.The enhanced enVista toric IOL (MX60ET) demonstrated excellent rotational stability and astigmatic outcomes indicating good efficacy of the IOL for the correction of astigmatism during cataract surgery.
From the Cleveland Eye Clinic, Elyria, Ohio (Wiley); The Eye Center of Columbus, Columbus, Ohio (Epitropoulos); Key-Whitman Eye Center, Dallas, Texas; Center For Sight, Las Vegas, Nevada (Liang); Visionary Eye Institute, Newport Beach, California (Sadri); Bausch & Lomb, Inc., Bridgewater, New Jersey (Lau).
Rotational stability and visual performance of aberration-free, hydrophobic acrylic monofocal toric intraocular lens with enhanced material.
Emerging tumor repression of immune recognition is reversed by inhibiting DNA methylation.
Neurosurgery, Hospital Universitario Marques de Valdecilla, Santander, Spain.
Faculty of Medicine, Universidad de Cantabria, Santander, Spain.
Neurosurgery, Hospital Universitario Marques de Valdecilla, Santander, Spain.Department of Anatomy and Cell Biology, Universidad de Cantabria, Santander, Spain.Marques de Valdecilla Research Institute Foundation, Santander, Spain.
Neurosurgery, Hospital Universitario Marques de Valdecilla, Santander, Spain patricia91lpz@gmail.com.
Bulbar oedema complicating surgery for Chiari malformation.
Nature Immunology, . l.dempsey@us.nature.com.
A mucosal route of vaccination could prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication at the site of infection and limit transmission. We compared protection against heterologous XBB.1.16 challenge in nonhuman primates (NHPs) ~5 months following intramuscular boosting with bivalent mRNA encoding WA1 and BA.5 spike proteins or mucosal boosting with a WA1-BA.5 bivalent chimpanzee adenoviral-vectored vaccine delivered by intranasal or aerosol device. NHPs boosted by either mucosal route had minimal virus replication in the nose and lungs, respectively. By contrast, protection by intramuscular mRNA was limited to the lower airways. The mucosally delivered vaccine elicited durable airway IgG and IgA responses and, unlike the intramuscular mRNA vaccine, induced spike-specific B cells in the lungs. IgG, IgA and T cell responses correlated with protection in the lungs, whereas mucosal IgA alone correlated with upper airway protection. This study highlights differential mucosal and serum correlates of protection and how mucosal vaccines can durably prevent infection against SARS-CoV-2.
© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Department of Pediatrics, Center for Childhood Infections and Vaccines of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA.Emory Vaccine Center, Emory University, Atlanta, GA, USA.Emory National Primate Research Center, Atlanta, GA, USA.
Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, USA.
Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA.Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.The Andrew M. and Jane M. Bursky Center for Human Immunology & Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA.Center for Vaccines & Immunity to Microbial Pathogens, Washington University School of Medicine, St. Louis, MO, USA.
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. ddouek@mail.nih.gov.
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. rseder@mail.nih.gov.
Mucosal adenovirus vaccine boosting elicits IgA and durably prevents XBB.1.16 infection in nonhuman primates.
Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.Translational Center of Excellence in Hematopoietic Stem Cell Engineering, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. saar.gill2@pennmedicine.upenn.edu.Translational Center of Excellence in Hematopoietic Stem Cell Engineering, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. saar.gill2@pennmedicine.upenn.edu.Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA. saar.gill2@pennmedicine.upenn.edu.Center for Cellular Therapy and Transplantation, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA. saar.gill2@pennmedicine.upenn.edu.
CD45 threads the needle of cytokine cancer immunotherapy.
Division of Experimental Medicine, University of California San Francisco, San Francisco, CA, USA. sara.suliman@ucsf.edu.Chan Zuckerberg Biohub, San Francisco, CA, USA. sara.suliman@ucsf.edu.
Division of Experimental Medicine, University of California San Francisco, San Francisco, CA, USA.
Division of Experimental Medicine, University of California San Francisco, San Francisco, CA, USA. timothy.henrich@ucsf.edu.
The promise and reality of new immune profiling technologies.
Bruce Lefroy Centre, Murdoch Children's Research Institute, 50 Flemington Road, Parkville, VIC, 3052, Australia.Department of Paediatrics, The University of Melbourne, Parkville, 3052, Australia.
Bruce Lefroy Centre, Murdoch Children's Research Institute, 50 Flemington Road, Parkville, VIC, 3052, Australia.Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, 3052, Australia.Department of Medical Biology, The University of Melbourne, Parkville, 3052, Australia.
Bruce Lefroy Centre, Murdoch Children's Research Institute, 50 Flemington Road, Parkville, VIC, 3052, Australia.
Department of Neurology, Wellington Hospital, Wellington, 6242, New Zealand.
Capital and Coast District Health Board, Wellington Regional Hospital, Wellington, 6021, New Zealand.
Genetic Health Service New Zealand, Wellington Hospital, Wellington, 6242, New Zealand.
Bruce Lefroy Centre, Murdoch Children's Research Institute, 50 Flemington Road, Parkville, VIC, 3052, Australia.Department of Paediatrics, The University of Melbourne, Parkville, 3052, Australia.Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Parkville, 3052, Australia.
Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, 3052, Australia.Department of Medical Biology, The University of Melbourne, Parkville, 3052, Australia.
Bruce Lefroy Centre, Murdoch Children's Research Institute, 50 Flemington Road, Parkville, VIC, 3052, Australia. paul.lockhart@mcri.edu.au.Department of Paediatrics, The University of Melbourne, Parkville, 3052, Australia. paul.lockhart@mcri.edu.au.
A multi-exon RFC1 deletion in a case of CANVAS: expanding the genetic mechanism of disease.
Department of Immunology, Guangzhou Institute of Paediatrics, Guangzhou Women and Children's Medical Centre, and State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, China.Department of Medical Microbiology, Faculty of Medicine, University of Science and Technology, Aden, Yemen.
Department of Immunology, Guangzhou Institute of Paediatrics, Guangzhou Women and Children's Medical Centre, and State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, China.Department of Therapy and Nursing, Bashkir State Medical University, Ufa, Russia.
Department of Immunology, Guangzhou Institute of Paediatrics, Guangzhou Women and Children's Medical Centre, and State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, China.
Inflammation Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
State Key Laboratory of Respiratory Diseases, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China.
Department of Immunology, Guangzhou Institute of Paediatrics, Guangzhou Women and Children's Medical Centre, and State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, China.Center for Mitochondrial Genetics and Health, Greater Bay Area Institute of Precision Medicine (Guangzhou), Guangzhou, China.
Clinical Laboratory, Guangzhou Women and Children's Medical Centre, Guangzhou Medical University, Guangdong, China.
Department of Immunology, Guangzhou Institute of Paediatrics, Guangzhou Women and Children's Medical Centre, and State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, China.National Children Medical Center, Department of Clinical Immunology, Children's Hospital of Fudan University, Shanghai, China.
School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
Department of Immunology, Guangzhou Institute of Paediatrics, Guangzhou Women and Children's Medical Centre, and State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, China. yuxia.zhang@gwcmc.org.
Department of Immunology, Guangzhou Institute of Paediatrics, Guangzhou Women and Children's Medical Centre, and State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, China. seth.masters@hudson.org.au.Inflammation Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia. seth.masters@hudson.org.au.Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia. seth.masters@hudson.org.au.Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Victoria, Australia. seth.masters@hudson.org.au.Department of Molecular and Translational Science, Monash University, Clayton, Victoria, Australia. seth.masters@hudson.org.au.
Author Correction: Genetic variants in UNC93B1 predispose to childhood-onset systemic lupus erythematosus.
From the Dean McGee Eye Institute, University of Oklahoma, Oklahoma City, Oklahoma (Riaz); Department of Experimental Ophthalmology, Saarland University, Homburg, Germany (Wendelstein); Department of Ophthalmology, Johannes Kepler University Linz, Linz, Austria (Wendelstein); Institut für Refraktive und Ophthalmochirurgie (IROC), Zurich, Switzerland (Wendelstein); Cullen Eye Institute, Baylor College of Medicine, Houston, Texas (Koch).
Developing theoretical understanding of complex reactions and processes at interfaces requires using methods that go beyond semilocal density functional theory to accurately describe the interactions between solvent, reactants and substrates. Methods based on many-body perturbation theory, such as the random phase approximation (RPA), have previously been limited due to their computational complexity. However, this is now a surmountable barrier due to the advances in computational power available, in particular through modern GPU-based supercomputers. In this work, we describe the implementation of RPA calculations within BerkeleyGW and show its favorable computational performance on large complex systems relevant for catalysis and electrochemistry applications. Our implementation builds off of the static subspace approximation which, by employing a compressed representation of the frequency dependent polarizability, enables the evaluation of the RPA correlation energy with significant acceleration and systematically controllable accuracy. We find that the computational cost of calculating the RPA correlation energy scales only linearly with system size for systems containing up to 50 thousand bands, and is expected to scale quadratically thereafter. We also show excellent strong scaling results across several supercomputers, demonstrating the performance and portability of this implementation.
Applied Mathematics & Computational Research Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720-8099, United States.
Materials, Chemical, and Computational Science Directorate, National Renewable Energy Laboratory, Golden, Colorado 80401, United States.
Department of Materials Science and Engineering, Rensselaer Polytechnic Institute, Troy, New York 12180-3522, United States.
Journal of chemical theory and computation
Static Subspace Approximation for Random Phase Approximation Correlation Energies: Implementation and Performance.
The prognostic role of plasma neurofilament light chain (NfL), phospho-tau, beta-amyloid, and GFAP is still debated in Parkinson's disease (PD).Plasma p-tau181, p-tau231, Aβ1-40, Aβ1-42, GFAP, and NfL were measured by SIMOA in 136 PD with 2.9 + 1.7 years of follow-up and 76 controls. Differences in plasma levels between controls and PD and their correlation with clinical severity and progression rates were evaluated using linear regression analyses.Patients exhibited similar distribution of plasma biomarkers but higher P-tau181, P-tau231 and lower Aβ1-42 compared with controls. NfL and GFAP correlated with baseline motor and non-motor severity measures. At follow-up, NfL emerged as the best predictor of progression with marginal effect of GFAP and p-tau181 adjusting for age, sex, disease duration, and baseline motor severity.The present findings confirmed plasma NfL as best predictor of progression in PD, with a marginal role of p-tau181 and GFAP.
Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, P.Zzale Spedali Civili, 1, 25123, Brescia, Italy. Andrea.pilotto@unibs.it.Department of Continuity of Care and Frailty, Neurology Unit, ASST Spedali Civili Hospital, Brescia, Italy. Andrea.pilotto@unibs.it.Neurobiorepository and Laboratory of Advanced Biological Markers, University of Brescia and ASST Spedali Civili Hospital, Brescia, Italy. Andrea.pilotto@unibs.it.
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.Wallenberg Centre for Molecular and Translational Medicine, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.King's College London, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Clinical Neuroscience Institute, London, UK.NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK.
Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, P.Zzale Spedali Civili, 1, 25123, Brescia, Italy.
Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, P.Zzale Spedali Civili, 1, 25123, Brescia, Italy.Department of Continuity of Care and Frailty, Neurology Unit, ASST Spedali Civili Hospital, Brescia, Italy.Neurobiorepository and Laboratory of Advanced Biological Markers, University of Brescia and ASST Spedali Civili Hospital, Brescia, Italy.
Department of Continuity of Care and Frailty, Neurology Unit, ASST Spedali Civili Hospital, Brescia, Italy.
Division of Biology and Genetics, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Division of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Department of Statistical Sciences, University of Padova, Padua, Italy.
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.Paris Brain Institute, ICM, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France.Neurodegenerative Disorder Research Center, Division of Life Sciences and Medicine, Department of Neurology, Institute On Aging and Brain Disorders, University of Science and Technology of China and First Affiliated Hospital of USTC, Hefei, People's Republic of China.Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.UK Dementia Research Institute at UCL, London, UK.Department of Old Age Psychiatry, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.Hong Kong Center for Neurodegenerative Diseases, Hong Kong, People's Republic of China.Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, P.Zzale Spedali Civili, 1, 25123, Brescia, Italy.Department of Continuity of Care and Frailty, Neurology Unit, ASST Spedali Civili Hospital, Brescia, Italy.Neurobiorepository and Laboratory of Advanced Biological Markers, University of Brescia and ASST Spedali Civili Hospital, Brescia, Italy.Brain Health Center, University of Brescia, Brescia, Italy.
Plasma NfL, GFAP, amyloid, and p-tau species as Prognostic biomarkers in Parkinson's disease.
Beta-blockers are a crucial part of post-myocardial infarction (MI) pharmacological therapy. Recent studies have raised questions about their efficacy in patients without reduced left ventricular ejection fraction (LVEF). This study aims to assess adherence to beta-blockers after discharge for ST-segment elevation myocardial infarction (STEMI) and the impact of adherence on outcomes based on LVEF at discharge. The retrospective registry FAST-STEMI evaluated real-world adherence to main cardiovascular drugs in patients with STEMI between 2012 and 2017 by comparing purchased tablets with expected ones at 1 year through pharmacy registries. Optimal adherence was defined as ≥80%. Primary outcomes included all-cause and cardiovascular death while secondary outcomes were MI, major/minor bleeding events, and ischemic stroke. The study included 4688 patients discharged on beta-blockers. The mean age was 64 ± 12.3 years, 76% were male, and the mean LVEF was 49.2 ± 8.8%. The mean adherence at 1 year was 87.1%. Optimal adherence was associated with lower all-cause (adjusted hazard ratio, 0.62, 95% confidence interval, 0.41-0.92, P : 0.02) and cardiovascular (adjusted hazards ratio, 0.55, 95% confidence interval, 0.26-0.98, P : 0.043) mortality. In patients with LVEF ≤40%, optimal adherence was linked to reduced all-cause and cardiovascular mortality, but this was not found in patients with either preserved or mildly reduced LVEF. Predictors of cardiovascular mortality included older age, chronic kidney disease, male gender, and atrial fibrillation. Optimal adherence to beta-blocker therapy in patients with all-comers STEMI reduced all-cause and cardiovascular mortality at 1 year; once stratified by LVEF, this effect was confirmed only in patients with reduced LVEF (<40%) at hospital discharge. Impact of adherence to beta-blockers in all-comers STEMI patients and according to LVEF at discharge: results from the real-world registry FAST-STEMI.
Department of Medical Sciences, University of Turin, Turin, Italy.Division of Cardiology, Cardiovascular and Thoracic Department, Citta della Salute e della Scienza Hospital, Turin, Italy.
Civic Hospital of Cirié, Cirié, Italy ; and.
Department of Medical Sciences, University of Turin, Turin, Italy.
Impact of Adherence to Beta-Blockers in Patients With All-Comers ST-Segment Elevation Myocardial Infarction and According to Left Ventricular Ejection Fraction at Discharge: Results From the Real-World Registry FAST-STEMI.
Cataracts can cause visual impairment in diabetic patients. Diabetes mellitus affects different parts of the eye and causes many complications and problems before, during, and after intraocular surgeries. In this review, we will discuss the effects of diabetes on different aspects of cataract surgery and review the current management of diabetic cataracts. Careful preoperative examination of the patient's ocular surface, cornea, iris, and posterior segment, as well as the use of advanced phacoemulsification techniques, new intraocular lenses and the appropriate use of auxiliary medications such as nonsteroidal anti-inflammatory drugs and anti-vascular endothelial growth factors have improved the outcomes of cataract surgery in diabetic patients.
From the Department of Ophthalmology, Eye Research Center, Mashhad University of Medical Sciences, Mashhad, Iran (Zarei-Ghanavati); Eye Research Center, Five Senses Institute, Rassoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran (Hadi, Habibi, Ashraf Khorasani); Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida (Yoo).
Cataract and diabetes: review of the literature.
Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli , Naples, IT.Department of Experimental Medicine, University of Campania Luigi Vanvitelli , Naples, IT.
Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli , Naples, IT.
Data Collection G-STeP Research Core Facility, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy.
Department of Biology, College of Science and Technology, Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA.Division of Cardiology, Department of Medical Translational Sciences, University of Campania Luigi Vanvitelli, Naples, Italy; and.
Department of Experimental Medicine, University of Campania Luigi Vanvitelli , Naples, IT.
Department of Medicine and Health Sciences Vincenzo Tiberio , Università degli Studi del Molise, Campobasso, Italy.
Editorial on: Canagliflozin Mediates Mitophagy Through the AMPK/PINK1/PARKIN Pathway to Alleviate Isoprenaline-Induced Cardiac Remodeling.
Extracorporeal membrane oxygenation (ECMO) is a mechanical support treatment modality used in patients with refractory cardiac and/or pulmonary failure. Bleeding and thrombotic complications associated with ECMO are inherent concerns that require careful management. Anticoagulation optimization may help mitigate these risks by providing more adequate therapeutic anticoagulation and lessen the bleed risk. Heparin, the most used anticoagulant, carries concerns for heparin-induced thrombocytopenia and possible resistance given its dependence on cofactors and circulating proteins to exert its pharmacologic effect. In contrast, bivalirudin, a direct thrombin inhibitor, exerts its effect independent of cofactors or plasma proteins, and possesses thrombin-binding and metabolism features that may confer advantages in ECMO management. This review of the evidence for bivalirudin utilization in ECMO suggests favorable outcomes in circuit-related thrombosis, bleeding, and dosing reliability. In addition, blood product utilization, circuit interventions, and success in ECMO decannulation and survival were positive findings associated with bivalirudin that merit consideration. Common questions and concerns relative to bivalirudin utilization, including laboratory monitoring, utilization in low-flow states, dosing considerations in renal replacement therapy, reversibility, and cost are also discussed in this review. Moreover, this review suggests that bivalirudin utilization presents the opportunity for ECMO management simplification.
Department of Pharmacy Services, University of Michigan Health, Ann Arbor, MI.
Department of Pharmacy, Mayo Clinic, Rochester, MN.Department of Anesthesiology, Mayo Clinic, Rochester, MN; and.
Department of Pharmacy, Wake Forest Baptist Medical Center, Winston Salem, NC.
Bivalirudin in Extracorporeal Membrane Oxygenation.
Department of Clinical and Molecular Medicine, Unit of Cardiology, Sapienza University of Rome, Sant'Andrea Hospital-University Company, Rome, Italy.
Sapienza University of Rome, Rome, Italy.
Department of Geriatrics, Orthopedics, and Rheumatology, Università Cattolica del Sacro Cuore, L.go F. Vito 1, Rome, Italy.Fondazione Policlinico Universitario Agostino Gemelli IRCCS, L.go A. Gemelli 8, Rome, Italy ; and.
Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy .
Rethinking Beta-Blockers After ST-Segment Elevation Myocardial Infarction: Essential for Some, Questionable for Others.
Evolutionary pressures sculpt population genetics, whereas immune adaptation fortifies humans against life-threatening organisms. How the evolution of selective genetic variation in adaptive immune receptors orchestrates the adaptation of human populations to contextual perturbations remains elusive. Here, we show that the G396R coding variant within the human immunoglobulin G1 (IgG1) heavy chain presents a concentrated prevalence in Southeast Asian populations. We uncovered a 190-kb genomic linkage disequilibrium block peaked in close proximity to this variant, suggestive of potential Darwinian selection. This variant confers heightened immune resilience against various pathogens and viper toxins in mice. Mechanistic studies involving severe acute respiratory syndrome coronavirus 2 infection and vaccinated individuals reveal that this variant enhances pathogen-specific IgG1+ memory B cell activation and antibody production. This G396R variant may have arisen on a Neanderthal haplotype background. These findings underscore the importance of an IGHG1 variant in reinforcing IgG1 antibody responses against life-threatening organisms, unraveling the intricate interplay between human evolution and immune adaptation.
School of Life Sciences, Institute for Immunology, State Key Laboratory of Membrane Biology, China Ministry of Education Key Laboratory of Protein Sciences, Beijing Key Lab for Immunological Research on Chronic Diseases, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China.Tsinghua-Peking Center for Life Sciences, Beijing, China.
Tsinghua-Peking Center for Life Sciences, Beijing, China.Biomedical Pioneering Innovation Center (BIOPIC), Beijing Advanced Innovation Center for Genomics (ICG), Peking University, Beijing, China.
Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.Chongqing Key Laboratory for Research of Infectious Diseases, Chongqing, China.Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, China.
School of Life Sciences, Institute for Immunology, State Key Laboratory of Membrane Biology, China Ministry of Education Key Laboratory of Protein Sciences, Beijing Key Lab for Immunological Research on Chronic Diseases, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China.
BGI-Shenzhen, Shenzhen, China.College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
Key Laboratory of Medical Molecular Virology of MOE/NHC/CAMS, School of Basic Medical Sciences, Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Fudan University, Shanghai, China.
Biomedical Pioneering Innovation Center (BIOPIC), Beijing Advanced Innovation Center for Genomics (ICG), Peking University, Beijing, China.
NexVac Research Center, Center for Infectious Disease Research, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China.
Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
The Third People's Hospital of Shenzhen, National Clinical Research Center for Infectious Disease, The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China.
Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, China.
Department of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, Republic of Korea.Biomedical Statistics Center Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea.
NexVac Research Center, Center for Infectious Disease Research, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China.Institute of Biomedical Health Technology and Engineering, Shenzhen Bay Laboratory, Shenzhen, China.Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, China.
Key Laboratory of Medical Molecular Virology of MOE/NHC/CAMS, School of Basic Medical Sciences, Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Fudan University, Shanghai, China. lul@fudan.edu.cn.
Key Laboratory of Protein Sciences (Ministry of Education), State Key Laboratory of Molecular Oncology, School of Life Sciences, Tsinghua University, Beijing, China. xiqiaoran@mail.tsinghua.edu.cn.
Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China. gh_deng@hotmail.com.Chongqing Key Laboratory for Research of Infectious Diseases, Chongqing, China. gh_deng@hotmail.com.
Tsinghua-Peking Center for Life Sciences, Beijing, China. yanyi@pku.edu.cn.Biomedical Pioneering Innovation Center (BIOPIC), Beijing Advanced Innovation Center for Genomics (ICG), Peking University, Beijing, China. yanyi@pku.edu.cn.College of Chemistry and Molecular Engineering, Beijing National Laboratory for Molecular Sciences, Peking University, Beijing, China. yanyi@pku.edu.cn.
BGI-Shenzhen, Shenzhen, China. jinxin@genomics.cn.School of Medicine, South China University of Technology, Guangzhou, China. jinxin@genomics.cn.
Zhejiang Key Laboratory of Multi-Omics in Infection and Immunity, Center for Infectious Disease Research, School of Medicine, Westlake University, Hangzhou, China. chenxiangjun@westlake.edu.cn.Research Center for Industries of the Future, Westlake University, Hangzhou, China. chenxiangjun@westlake.edu.cn.
School of Life Sciences, Institute for Immunology, State Key Laboratory of Membrane Biology, China Ministry of Education Key Laboratory of Protein Sciences, Beijing Key Lab for Immunological Research on Chronic Diseases, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China. LiuLab@Tsinghua.edu.cn.Tsinghua-Peking Center for Life Sciences, Beijing, China. LiuLab@Tsinghua.edu.cn.
An IGHG1 variant exhibits polarized prevalence and confers enhanced IgG1 antibody responses against life-threatening organisms.
Amyotrophic lateral sclerosis (ALS) is known to be associated with varying degrees of autonomic and cardiovascular dysfunction. Recent case reports showed that ALS may be linked to Takotsubo syndrome (TTS). We assessed the frequency of TTS in an incident ALS cohort from Sardinia, Italy, and investigated the relationship of TTS with ALS course.We retrospectively examined a 10-year (2010-2019) incident cohort of ALS patients of Sardinian ancestry, reported TTS frequency and patients' clinical characteristics. Following, we checked for TTS among patients with ALS onset after 2019 and focused on the same features as for the incident cohort.Our incident cohort included 344 ALS patients and 5 of them (1.45%) developed TTS. All were female and their median onset age was 71.5 years (IQR 62.75-77). Two patients had spinal and three bulbar onset, though all patients had bulbar involvement and were at an advanced stage of disease (ALSFRS ≤ 25, King's ≥ 3) at TTS diagnosis. We identified a potential TTS trigger in three patients (hospitalization for PEG placement, pneumonia). Among patients who had ALS onset after 2019, we identified a further TTS case and described it.TTS is not a rare condition in ALS. Female sex, bulbar involvement, and later age of disease onset may be important risk factors for developing this cardiac condition and a physical or psychological trigger is often observed. Despite autonomic dysfunction in ALS has been already demonstrated, the precise physiopathological mechanism underlying TTS needs to be further clarified.
Department of Medical Sciences and Public Health, Institute of Neurology, Policlinico Universitario di Monserrato, University of Cagliari, 09042, Cagliari, Italy. alessandramaccabeo@outlook.it.
Department of Medical Sciences and Public Health, Institute of Neurology, Policlinico Universitario di Monserrato, University of Cagliari, 09042, Cagliari, Italy.
Neurology Unit, AOU Cagliari, Hospital D. Casula Monserrato, Cagliari, Italy.
Department of Neurology, University of Sassari, Viale S. Pietro 10, 07100, Sassari, Italy.
Cardiology Unit, AOU Cagliari, Hospital D. Casula Monserrato, Cagliari, Italy.
Department of Medical Sciences and Public Health, Institute of Cardiology, University of Cagliari, Cagliari, Italy.
Department of Translational Biomedicine and Neurosciences, University of Bari Aldo Moro , Bari, Italy.
Takotsubo syndrome in a Sardinian amyotrophic lateral sclerosis cohort.
Familial progressive hyperpigmentation with or without hypopigmentation (FPHH) is an autosomal dominant disorder characterized by widespread skin hyperpigmentation, café-au-lait spots, and hypopigmented circular macules, resulting from KITLG variants. KITLG, expressed by keratinocytes, binds to KIT on melanocytes, stimulating melanogenesis. Disturbances in the KITLG-KIT interaction result in diffuse hyperpigmentation in FPHH. However, the mechanisms behind hypopigmented macule formation remain unclear. This report presents a unique FPHH case in a patient with a novel KITLG mutation (Ser78Leu). Notably, the patient showed multiple hypopigmented macules and striae along the lines of Blaschko. Digital polymerase chain reaction analysis of the DNA from skin and blood tissues indicated a copy-neutral loss of heterozygosity at the KITLG locus, only in the hypopigmented macule. These findings suggest that the hypopigmented macules might result from revertant mosaicism. Conversely, café-au-lait spots do not follow the lines of Blaschko and can superimpose on the hypopigmented striae, indicating a distinct pathogenesis. This case contributes to the understanding of the genetic mechanisms in FPHH.
© 2024 Japanese Dermatological Association.
Department of Dermatology, Sapporo Medical University School of Medicine, Sapporo, Japan.
Department of Medical Genome Sciences, Cancer Research Institute, Sapporo Medical University School of Medicine, Sapporo, Japan.
Department of Medical Genetics, Sapporo Medical University School of Medicine, Sapporo, Japan.
Center for Vascular Anomalies, Department of Plastic and Reconstructive Surgery, Tonan Hospital, Sapporo, Japan.
A case of familial progressive hyperpigmentation with or without hypopigmentation presenting with hypopigmented striae along the lines of Blaschko.
Lipoprotein(a) [Lp(a)] is a risk factor for coronary disease. Although levels are primarily genetically determined, data from patients with inflammatory diseases indicate that the inflammatory milieu is associated with increased Lp(a) levels. Lp(a) is synthesized in the liver and the LPA gene promoter contains an interleukin-6 (IL-6) responsive binding site, but the regulatory steps linking inflammation with hepatic Lp(a) synthesis are not well clarified. We explored the interplay between IL-6, peroxisome proliferator-activated receptor gamma (PPARγ), and Lp(a) synthesis in HepG2 cells. Through genetic mapping, a regulatory variant within the LPA promoter overlapping with a PPARγ binding site was identified. In in vitro experiments, IL-6-mediated LPA gene transcription was heightened with PPARγ knock-down and suppressed with pioglitazone, a PPARγ agonist. These results demonstrate an important role of PPARγ as a negative regulator of IL-6-induced hepatic Lp(a) production and may represent a new therapeutic target for patients with inflammatory conditions characterized by elevated Lp(a).
Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; and.Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD.
Peroxisome Proliferator-Activated Receptor Gamma Regulates Interleukin-6-Induced Lipoprotein (a) Gene Expression in Human HepG2 Cells.
Neurology, The View Hospital, Doha, Qatar h.ramadan@theviewhospital.com.
Critical Care, Hamad Medical Corporation, Doha, Qatar.
Rehabilitation, The View Hospital, Doha, Qatar.
Department of Neurology, Lenox Hill Hospital, New York, New York, USA.
Influenza A-associated acute necrotising encephalopathy.
Human induced pluripotent stem cells (hiPSC) and atrial hiPSC-derived cardiomyocytes (hiPSC-CM) have entered the arena of preclinical atrial fibrillation research. A central question is whether they reproduce the physiologic contribution of atrial selective potassium currents (such as the ultrarapid potassium current, I Kur ) to repolarization. Of note, 2 studies in single atrial hiPSC-CM reported prolongation of action potential duration by I Kur block indicating that I Kur might in fact represent a valuable target for the treatment of human atrial fibrillation. However, the results and interpretation are at odds with the literature on I Kur block in human atria and the results of clinical studies. We believe that the discrepancies indicate that experiments in single atrial CM (both adult atrial CM and atrial hiPSC-CM) might be misleading. Under particular experimental conditions, atrial hiPSC-CMs may not closely resemble the electrophysiology of the human atrium. Therefore, we recapitulate here methodological issues evaluating potential value of the I Kur as an antiarrhythmic target when investigated in animal models, in human atrial tissues, and finally in atrial hiPSC-CM.
Department of Cardiology, University Heart and Vascular Center Hamburg, Hamburg, Germany.Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany ; and.DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg/Kiel/Luebeck/Greifswald, Hamburg, Germany .
Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany ; and.DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg/Kiel/Luebeck/Greifswald, Hamburg, Germany .
Atrial hiPSC-CM as a Pharmacologic Model to Evaluate Anti-AF Drugs: Some Lessons From I Kur.
Controlling multidrug-resistant microorganisms (MRM) has a long history with the extensive and inappropriate use of antibiotics. At the cost of these drugs being scarce, new possibilities have to be explored to inhibit the growth of microorganisms. Thus, metallic compounds have shown to be promising as a viable alternative to contain pathogens resistant to conventional antimicrobials. Gallium (Ga3+) can be highlighted, which is an antimicrobial agent capable of disrupting the essential activities of microorganisms, such as metabolism, cellular respiration and DNA synthesis. It was observed that this occurs due to the similar properties between Ga3+ and iron (Fe3+), which is a fundamental ion for the correct functioning of bacterial activities. The mimetic effect performed by Ga3+ prevents iron transporters from distinguishing both ions and results in the substitution of Fe3+ for Ga3+ and in adverse metabolic disturbances in rapidly growing cells. This review focuses on analyzing the development of research involving Ga3+, elucidating the intracellular incorporation of the Trojan Horse , summarizing the mechanism of interaction between gallium and iron and comparing the most recent and broad-spectrum studies using gallium-based compounds with antimicrobial scope.
© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
Center of Science and Technology for Sustainability (CCTS), Laboratory of Applied Microbiology, Federal University of São Carlos (UFSCar), Rodovia João Leme dos Santos, km 110, Itinga,, Sorocaba, SP, 18052-780, Brazil. amandajabur@estudante.ufscar.br.
Center of Science and Technology for Sustainability (CCTS), Laboratory of Applied Microbiology, Federal University of São Carlos (UFSCar), Rodovia João Leme dos Santos, km 110, Itinga,, Sorocaba, SP, 18052-780, Brazil.
Center of Human and Biological Sciences (CCHB), Federal University of São Carlos (UFSCar), Rodovia João Leme dos Santos, km 110, Sorocaba, SP, Brazil.
SENAI Innovation Institute for Biotechnology, São Paulo, SP, 04571-050, Brazil.
Antonie Van Leeuwenhoek. 2024-09-13;118(1):3.
Gallium: a decisive Trojan Horse against microorganisms.
A Gram-stain-negative, aerobic, motile and rod-shaped bacterium, the color of the bacterial colony ranges from light yellow to yellow, designated YC-2023-2T, was isolated from sediment sample of Yuncheng salt lake. Growth occurred at 15-45℃ (optimum 37℃), pH 6.0-9.0 (optimum pH 7.0-8.0) and with 0-8.0% NaCl (w/v, optimum 2.0%). The phylogenetic analysis based on 16S rRNA gene sequences showed that strain YC-2023-2T belonged to the family Kordiimonadaceae. The closely related members were Gimibacter soli 6D33T (92.38%), Kordiimonas lipolytica M41T (91.88%), Eilatimonas milleporae DSM 25217T (91.88%) and Kordiimonas gwangyangensis JCM 12864T (91.84%). The genome of strain YC-2023-2T was 2957513 bp, and the genomic DNA G+C content was 63.91%. The main respiratory quinone was Q-10 and the major fatty acids (>10%) were iso-C15:0, C16:0, C19:0 cyclo ω8c, Summed Feature 8 (C18:1 ω6c or C18:1 ω7c) and Summed Feature 9 (iso-C17:1 ω9c or C16:0 10-methyl). The major polar lipids consisted of phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, unidentified glycolipid, unidentified lipid, and two unidentified aminolipids. Based on the phylogenetic, phenotypic and chemotaxonomic characteristics, strain YC-2023-2T is proposed to represent a novel species of a novel genus named Yunchengibacter salinarum gen. nov., sp. nov., within the family Kordiimonadaceae. The type strain is YC-2023-2T (= GDMCC 1.4502T = KCTC 8546T).
College of Food Science and Engineering, Shanxi Agricultural University, Taigu, 030801, Shanxi, People's Republic of China.
Shanxi Key Laboratory of Yuncheng Salt Lake Ecological Protection and Resource Utilization, Yuncheng University, Yuncheng, 044000, Shanxi, People's Republic of China.
State Key Laboratory of Desert and Oasis Ecology, Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, Urumqi, 830011, Xinjiang, People's Republic of China.
Shanxi Key Laboratory of Yuncheng Salt Lake Ecological Protection and Resource Utilization, Yuncheng University, Yuncheng, 044000, Shanxi, People's Republic of China. lixin-eva@163.com.
State Key Laboratory of Desert and Oasis Ecology, Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, Urumqi, 830011, Xinjiang, People's Republic of China. liwenjun3@mail.sysu.edu.cn.State Key Laboratory of Biocontrol, Guangdong Provincial Key Laboratory of Plant Resources and Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), School of Life Sciences, Sun Yat-Sen University, Guangzhou, 510275, People's Republic of China. liwenjun3@mail.sysu.edu.cn.
Antonie Van Leeuwenhoek. 2024-09-13;118(1):4.
Yunchengibacter salinarum gen. nov., sp. nov., a novel bacterium of the family Kordiimonadaceae isolated from sediment in Yuncheng salt lake.
Atrial fibrillation (AF) poses a significant therapeutic challenge with drug interventions showing only limited success. Phosphodiesterases (PDE) regulate cardiac electrical stability and may represent an interesting target. Recently, PDE8 inhibition was proposed as an antiarrhythmic intervention by increasing L-type Ca 2+ current (I Ca,L ) and action potential duration (APD). However, the effect size of PDE8 inhibition on I Ca,L and APD seems discrepant and effects on force are unknown. We investigated the impact of PDE8 inhibition on force using PF-04957325 in right atrial appendages, obtained from patients in sinus rhythm (SR) and with persistent AF (peAF) undergoing cardiac surgery. A computational model was used to predict the effects of PDE8 inhibition on APD in SR and peAF. Results showed no increase in force after exposure to increasing concentrations of the PDE8 inhibitor PF-04957325 in either SR or peAF tissues. Furthermore, PDE8 inhibition did not affect the potency or efficacy of norepinephrine-induced inotropic effects in either group. Arrhythmic events triggered by norepinephrine were observed in both SR and peAF, but their frequency remained unaffected by PF-04957325 treatment. Computational modeling predicted that the reported increase in I Ca,L induced by PDE8 inhibition would lead to substantial APD prolongation at all repolarization states, particularly in peAF. Our findings indicate that PDE8 inhibition does not significantly impact force or arrhythmogenicity in human atrial tissue.
Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.DZHK (German Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Hamburg, Germany.
Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.DZHK (German Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Hamburg, Germany.Department of Cardiovascular Surgery, University Heart and Vascular Center, Hamburg, Germany ; and.
Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.DZHK (German Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Hamburg, Germany.
BioMediTech, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland .
PDE8 Inhibition and Its Impact on ICa,L in Persistent Atrial Fibrillation: Evaluation of PDE8 as a Potential Drug Target.
Despite constituting one-third of suspected autoimmune encephalitis (AE) patients, antibody-negative cases without typical AE features are understudied. We aim to characterize the clinical phenotypes and long-term outcomes of possible only and probable AE cases.We conducted a retrospective analysis of adult patients evaluated at Mayo Clinic's Autoimmune Neurology Clinic (01/01/2006-12/31/2020), meeting diagnostic criteria for possible only or probable but antibody-negative AE, with ≥ 1 year of follow-up. All patients underwent neural antibody testing.Among fifty-one patients, six had a change in diagnosis (non-autoimmune, 2) and were excluded from further analysis. Forty-five patients were analyzed [median age, 61 years (range 20-88); female, 21 (47%); median follow-up, 36 months (range 12-174)]. A nadir modified Rankin Scale (mRS) ≥ 3 was recorded in 41/45 (91%). CSF was inflammatory in 20/44 (45%) and MRI had encephalitic changes in 21/45 (47%). Unclassified neural-specific IgG staining on tissue-based assay was detected in five (11%). Two patients (4%) had paraneoplastic causation. Relapses (> 3 months from onset) were noted in 14 (31%). Memory dysfunction (69%), attention deficits (38%), and gait instability (29%) were the most frequent at the last follow-up. Most patients (76%) were independent at the last follow-up and only two required an assistive device to ambulate; 11 patients (24%) had poor neurological outcome (mRS ≥ 3). Higher mRS score and gait assistance requirement at 3 months were predictive of poor outcome (P ≤ 0.01).Despite significant disability at initial disease stages, most antibody-negative AE patients regain independent functioning. Early functional status and gait assistance requirements may predict long-term prognosis.
© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.
Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 1St ST SW, Rochester, MN, 55905, USA.
Department of Neurology, University of New Mexico, Albuquerque, NM, USA.
Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 1St ST SW, Rochester, MN, 55905, USA.Department of Neurology, Mayo Clinic, Rochester, MN, USA.Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, MN, USA.
Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 1St ST SW, Rochester, MN, 55905, USA. mckeon.andrew@mayo.edu.Department of Neurology, Mayo Clinic, Rochester, MN, USA. mckeon.andrew@mayo.edu.Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, MN, USA. mckeon.andrew@mayo.edu.
Long-term outcomes in antibody-negative autoimmune encephalitis: a retrospective study.
Genomic map of the cellular composition of the tumor microenvironment.
American Indian/Alaska Native (AI/AN) communities continue to experience health disparities and poor health outcomes, which are influenced by social determinants of health. The theory of settler colonialism provides a framework for understanding the structures that affect social determinants of health and the resulting health disparities. Western biomedicine and medical education have been implicated in perpetuating settler colonialism, and as a result Indigenous medical educators and leaders have called for increased education and understanding of the structural and social determinants of health affecting Indigenous populations. One important method is through community-based approaches to curriculum design. In collaboration with community leaders and experts, we identified the need for a curriculum on health in the context of settler colonialism, with a focus on resilience and community-directed efforts to improve wellness and care. Alongside Indigenous leaders and educators, we developed a unique curriculum focused on settler colonialism, the social determinants of health, and the assets inherent to the Native Nation where we work. Developed for non-Native learners and clinicians, the curriculum is designed to help provide context for the historical and political etiologies of health inequities experienced by the local community. Local educators helped shape a video lecture series associated with readings and experiential learning activities in 10 domains, providing an overview of settler colonialism and how it affects the social determinants of health. Our model of education draws upon the strengths and assets of communities and can improve health outcomes as well as learners' understandings of AI/AN-specific needs. We expect that our collaborative approach results in improved relationships among the Non-Native learners and providers and community members.
Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, California, USA.
University of Colorado School of Medicine, Aurora, Colorado, USA.
Office of Academic Affairs/Sanford School of Medicine, University of South Dakota, Vermillion, South Dakota, USA.
Division of General Internal Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Departments of Medicine and Pediatrics, University of Minnesota - Twin Cities, Minneapolis, Minnesota, USA.
Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Community Collaboration to Develop a Curriculum on Settler Colonialism and the Social Determinants of Health.
Physiology and Molecular Laboratory, Phymolab, Collado Hermoso, 40170, Segovia, Spain. phymolab@gmail.com.
Physiological Data of Kilian Jornet During the Victory of UTMB 2022: An Exceptional Report of Maximal Metabolical Limits.
Costs and policy-specific beliefs, such as effectiveness and fairness, are central factors for supporting environmental taxes. Less is known about how much each of these factors is limiting support. Across four experiments, I investigate to which extent high costs, ineffectiveness, and unfairness constrain support for environmental taxes. Results consistently demonstrate that perceived unfairness poses a greater barrier to support than extensive costs or ineffectiveness. These findings were robust across three environmental taxes (meat tax, plastic tax, and carbon tax), across three cultures (USA, UK, and India), and were replicated using a representative US sample. Furthermore, delving deeper into the consequences of perceived unfairness, results showed that distributional unfairness was a stronger barrier to support than procedural unfairness. Beyond limiting support, being presented with an unfair tax proposal led participants to perceive the tax as less effective and to express lower trust in policymakers than when receiving a fairer tax proposal.
Department of Psychology, University of Gothenburg, Haraldsgatan 1, 413 14, Göteborg, Sweden. magnus.bergquist@psy.gu.se.
Limiting support for environmental policies: Unfairness is a more critical barrier than cost and ineffectiveness.
Hypertension is a significant risk factor for cardiovascular and chronic kidney diseases. Its management in young people remains limited. Device-based therapies, such as low-level tragus stimulation (LL-TS), a noninvasive method that reduces sympathetic activity, have recently been explored for resistant hypertension.This trial involved patients with Grade 1 hypertension with no other medical history. LL-TS (20 Hz, 1 mA, 1 h/day) was applied for 3 months on the tragus (Intervention group [IG]) or earlobe (Control group [CG]). Blood pressure and outcomes were assessed at the first, second, and third months. Among 40 patients, 21 were in IG and 19 in CG. Baseline systolic blood pressure was similar between IG (142.62±8.18 mm Hg) and CG (143.00±8.61 mm Hg), P=0.89. Post-LL-TS, systolic blood pressure showed significant reductions in IG compared with CG at the first (IG: 134.47±5.95 mm Hg, CG: 141.28±6.78 mm Hg, P=0.002), second (IG: 132.50±7.51 mm Hg, CG: 140.62±7.15 mm Hg, P=0.001), and third months (IG: 128.81±7.13 mm Hg, CG: 136.51±7.96 mm Hg, P=0.003). diastolic blood pressure also differed significantly: first month (IG: 85.34±5.81 mm Hg, CG: 89.74±6.32 mm Hg, P=0.03), second month (IG: 82.12±5.22 mm Hg, CG: 88.57±7.11 mm Hg, P=0.002), and third month (IG: 80.71±5.96 mm Hg, CG: 87.55±5.26 mm Hg, P=0.001). Heart rate was unchanged (P>0.05). Only 0.01% of IG subjects reported site irritation, with no serious adverse events.LL-TS led to significant blood pressure reductions in young patients with essential hypertension. Further larger trials are needed to confirm the safety and efficacy of LL-TS.URL: https://www.chictr.org.cn/; Unique identifier: ChiCTR2000038448.
Department of Cardiology The First Hospital of China Medical University Shenyang China.
Department of Cardiology The First Hospital of China Medical University Shenyang China.Department of Cardiology Zhongshan Hospital, Fudan University Shanghai China.
Journal of the American Heart Association
Low-Level Tragus Stimulation Attenuates Blood Pressure in Young Individuals With Hypertension: Results From a Small-Scale Single-Blind Controlled Randomized Clinical Trial.
Marfan syndrome (MFS) is a genetic disorder affecting the vascular and musculoskeletal systems. Limited knowledge exists regarding the exercise benefits for this population. This study aimed to explore the impact of a structured exercise program on the quality of life (QoL) and physical capabilities of patients with MFS.This was a randomized, controlled, parallel-group trial. Patients with MFS were randomized in a 1:1 ratio to either a training group or a control group. The trial included a 3-month online supervised training program. Seventy patients with MFS were compared with healthy subjects. They were randomized into a training group (MFS-T) and a control group (MFS-C). The training consisted of 2 supervised online sessions weekly for 3 months. The primary outcome was QoL, assessed using the Medical Outcomes Study Short-Form 36 questionnaire. Baseline QoL in all dimensions was lower in patients with MFS. Their peak oxygen uptake was 25% lower, and muscle elasticity was diminished compared with healthy subjects. Postintervention, significant improvements were observed in the MFS-T group relative to the MFS-C group: QoL (+20.2±14.3 versus +0.7±0.5), peak oxygen uptake (+34% versus +14%), muscle elasticity index (11.5±8.2 versus +1.2±1.7), reduced blood pressures during isometric squats (systolic -19±30 versus 0±6; diastolic -27±39 versus +2±15), and reduced pulse wave velocity at rest (-1.20±1.89 versus -0.40±1.61) and postexercise (-0.42±0.45 versus +0.08±0.48). The aortic diameter remained stable in both groups (MFS-T-0.19±1.1 versus MFS-C+0.11±0.78). After training, QoL remained lower in MFS-T than in healthy subjects, but peak oxygen uptake, pulse wave velocity at rest, and postexercise were similar to those of healthy subjects.The 3-month online training program significantly enhanced QoL and cardiovascular/muscular metrics in patients with MFS without affecting aortic root diameter, suggesting its potential as part of a management strategy for MFS.URL: https://www.clinicaltrials.gov; Unique identifier: NCT04553094.
Université Paris Cité, URP 3625-Institut des Sciences du Sport Santé de Paris (I3SP) Paris France.
Centre national de référence pour le syndrome de Marfan et pathologies apparentés Assistance Publique-Hôpitaux de Paris, Hôpital Bichat Paris France.Service de Cardiologie, Centre National de Référence Pour le Syndrome de Marfan et Apparentés AP-HP, Hôpital Bichat Paris France.
Centre national de référence pour le syndrome de Marfan et pathologies apparentés Assistance Publique-Hôpitaux de Paris, Hôpital Bichat Paris France.Service de Cardiologie, Centre National de Référence Pour le Syndrome de Marfan et Apparentés AP-HP, Hôpital Bichat Paris France.Laboratory for Vascular Translational Science Université Paris Cité, INSERM U1148, Hôpital Bichat-Claude-Bernard Paris France.
Online Personal Training in Patients With Marfan Syndrome: A Randomized Controlled Study of Its Impact on Quality of Life and Physical Capacity.
Corin plays important roles in the regulation of blood volume and pressure and cardiac function by activating natriuretic peptide pathway, exerting multiple cardioprotective effects. But the impacts of soluble corin on clinical outcomes after ischemic stroke are unclear. We aimed to investigate the associations between serum soluble corin and long-term clinical outcomes after acute ischemic stroke.We measured the concentrations of serum soluble corin in 3162 participants (2010 men and 1152 women) from the China Antihypertensive Trial in Acute Ischemic Stroke. The clinical outcomes were recurrent stroke, cardiovascular events, all-cause mortality, and unfavorable functional outcome within 24 months after stroke. Risk reclassification for study clinical outcomes of models with soluble corin were evaluated. Serum soluble corin was inversely associated with recurrent stroke, cardiovascular events, and unfavorable functional outcome after ischemic stroke. After adjusting for multiple covariates, each additional SD of log-corin was associated with a 21% (95% CI, 11-30), 16% (95% CI, 6-26), and 12% (95% CI, 3-21) decreased risk for recurrent stroke, cardiovascular events, and unfavorable functional outcome, respectively. Furthermore, the addition of soluble corin to the basic model with conventional risk factors significantly improved risk discrimination for recurrent stroke, cardiovascular events, and the composite outcome of all-cause mortality and cardiovascular events, as shown by C-statistics (all P<0.05).Serum soluble corin was associated with decreased risks of long-term clinical outcomes, and may be a promising prognostic biomarker for risk stratification in patients with acute ischemic stroke.
Department of Epidemiology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology Suzhou Medical College of Soochow University Suzhou China.
Suzhou Industrial Park Centers for Disease Control and Prevention Suzhou China.
Public Health Research Center and Department of Public Health and Preventive Medicine, Wuxi School of Medicine Jiangnan University Wuxi Jiangsu China.
Department of Neurology Affiliated Hospital of North China University of Science and Technology Tangshan China.
Department of Epidemiology Tulane University School of Public Health and Tropical Medicine New Orleans LA.Department of Medicine Tulane University School of Medicine New Orleans LA.
Serum Soluble Corin and Long-Term Clinical Outcomes After Acute Ischemic Stroke.
A B cell receptor variant confers evolutionary protection against pathogens.
Patients with acute coronary syndrome without standard modifiable cardiovascular risk factors (SMuRFs; hypertension, smoking, dyslipidemia, diabetes) have not been well studied, with little known about their characteristics, quality of care, or outcomes. We sought to systematically analyze patients with ACS without SMuRFs, especially to evaluate the effectiveness of guideline-directed medical therapy for these patients.In the CCC-ACS (Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome) project (2014-2019), we examined the presence and absence of SMuRFs and features among 89 462 patients with initial acute coronary syndrome. The main outcome was in-hospital all-cause mortality. Among eligible patients, 11.0% had none of the SMuRFs (SMuRF-less). SMuRF-less patients had higher in-hospital mortality (unadjusted hazard ratio [HR], 1.49 [95% CI, 1.19-1.87]). After adjustment for clinical characteristics and treatments, the associations between SMuRF status and in-hospital mortality persisted (adjusted HR, 1.35 [95% CI, 1.07-1.70]). Guideline-directed optimal medical therapy (receiving angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β-blockers, and statins) was not associated with lower mortality (adjusted HR, 0.98 [95% CI, 0.58-1.67]) in SMuRF-less patients, unlike the association in patients with SMuRFs (adjusted HR, 0.80 [95% CI, 0.66-0.98]). Sensitivity analyses were consistent with these results.SMuRF-less patients were associated with an increased risk of in-hospital mortality. Guideline-directed medical therapy was less effective in SMuRF-less patients than in patients with SMuRFs. Dedicated studies are needed to confirm the optimal therapy for SMuRF-less patients.URL: https://www.clinicaltrials.gov; Unique identifier: NCT02306616.
Center for Coronary Artery Disease, Division of Cardiology, Beijing Anzhen Hospital Capital Medical University Beijing China.National Clinical Research Center for Cardiovascular Diseases Beijing China.Beijing Institute of Heart Lung, and Blood Vessel Diseases Beijing China.
Department of Epidemiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung, and Blood Vessel Diseases Beijing China.
Division of Cardiology University of North Carolina Chapel Hill NC USA.
Division of Cardiology Geffen School of Medicine at University of California Los Angeles CA USA.
International Quality Improvement Department American Heart Association Dallas TX USA.
National Clinical Research Center for Cardiovascular Diseases Beijing China.Beijing Institute of Heart Lung, and Blood Vessel Diseases Beijing China.
Department of Cardiology General Hospital of Northern Theater Command Shenyang China.
In-Hospital Mortality and Treatment in Patients With Acute Coronary Syndrome With and Without Standard Modifiable Cardiovascular Risk Factors: Findings From the CCC-ACS Project.
Type A aortic dissection presents challenges with postoperative cerebral complications, and this study evaluates the predictive value of quantitative electroencephalography for perioperative brain function prognosis.Amplitude-integrated electroencephalography (aEEG) processes raw signals through filtering, amplitude integration, and time compression, displaying the data in a semilogarithmic format. Using this method, postoperative relative band power (post-RBP) α% and dynamic aEEG (ΔaEEG) grade were significantly associated with neurological dysfunction in univariate and multivariable analyses, with area under the receiver operating characteristic curve of 0.876 (95% CI, 0.825-0.926) for the combined model. Postoperative relative band power α% and ΔaEEG were significantly associated with adverse outcomes, with area under the receiver operating characteristic curve of 0.903 (95% CI, 0.835-0.971) for the combined model. Postoperative relative band power α% and ΔaEEG were significantly associated with transient neurological dysfunction and stroke, with areas under the receiver operating characteristic curve of 0.818 (95% CI, 0.760-0.876) and 0.868 (95% CI, 0.810-0.926) for transient neurological dysfunction, and 0.815 (95% CI, 0.743-0.886) and 0.831 (95% CI, 0.746-0.916) for stroke. Among 56 patients, the Alberta Stroke Program Early Computed Tomography score was superior to ΔaEEG in predicting neurological outcomes (area under the receiver operating characteristic curve of 0.872 versus 0.708 [95% CI, 0.633-0.783]; P<0.05).Perioperative quantitative electroencephalography monitoring offers valuable insights into brain function changes in patients with type A aortic dissection. ∆aEEG grades can aid in early detection of adverse outcomes, while postoperative relative band power and ∆aEEG grades predict transient neurological dysfunction. Quantitative electroencephalography can assist cardiac surgeons in assessing brain function and improving outcomes in patients with type A aortic dissection.URL: https://www.chictr.org.cn; Unique identifier: ChiCTR2200055980.
Department of Cardiac Surgery Nanjing Drum Tower Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College Jiangsu China.
Department of Cardiac Surgery Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School Jiangsu China.
Department of Cardiac Surgery Johns Hopkins University School of Medicine Baltimore MD USA.
Department of Radiology Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University Jiangsu China.
Department of Neurology of Drum Tower Hospital Jiangsu Province Stroke Center for Diagnosis and Therapy Nanjing China.
Department of Anesthesia, Critical Care and Pain Medicine Massachusetts General Hospital, Harvard Medical School Boston MA USA.
Department of Cardiac Surgery Nanjing Drum Tower Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College Jiangsu China.Department of Cardiac Surgery Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School Jiangsu China.
Quantitative Electroencephalography for Predication of Neurological Dysfunction in Type A Aortic Dissection: A Prospective Observational Study.
Magnetic skyrmions are topologically protected spin textures with emergent particle-like behaviors. Their dynamics under external stimuli is of great interest and importance for topological physics and spintronics applications alike. So far, skyrmions are only found to move linearly in response to a linear drive, following the conventional model treating them as isolated quasiparticles. Here, by performing time and spatially resolved resonant elastic X-ray scattering of the insulating chiral magnet Cu2OSeO3, we show that for finite-sized skyrmion crystallites, a purely linear temperature gradient not only propels the skyrmions but also induces continuous rotational motion through a chiral lattice torque. Consequently, a skyrmion crystallite undergoes a rolling motion under a small gradient, while both the rolling speed and the rotational sense can be controlled. Our findings offer a new degree of freedom for manipulating these quasiparticles toward device applications and underscore the fundamental phase difference between the condensed skyrmion lattice and isolated skyrmions.
School of Physical Science and Technology, ShanghaiTech University, Shanghai 200031, China.ShanghaiTech Laboratory for Topological Physics, ShanghaiTech University, Shanghai 200031, China.
School of Physical Science and Technology, ShanghaiTech University, Shanghai 200031, China.
Diamond Light Source, Harwell Science and Innovation Campus, Didcot, OX11 0DE, United Kingdom.
Clarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 3PU, United Kingdom.
Anhui Province Key Laboratory of Low-Energy Quantum Materials and Devices, High Magnetic Field Laboratory, HFIPS, Chinese Academy of Sciences, Hefei, Anhui 230031, China.
School of Physical Science and Technology, ShanghaiTech University, Shanghai 200031, China.ShanghaiTech Laboratory for Topological Physics, ShanghaiTech University, Shanghai 200031, China.Center for Transformative Science, ShanghaiTech University, Shanghai 200031, China.
Rolling Motion of Rigid Skyrmion Crystallites Induced by Chiral Lattice Torque.
Conventional magnetic resonance imaging (MRI) used for detecting possible antibody-negative autoimmune encephalitis (AIE) often fails to meet the diagnostic requirements of this disease. Positron emission tomography (PET) with a translocator protein radioligand can help visualize microglia distribution density in inflammation-related diseases, thereby offering potentially incremental value to conventional MRI for the in vivo assessment of possible antibody-negative AIE.In this prospective study, 15 participants diagnosed with possible antibody-negative AIE and 10 healthy controls were enrolled (ClinicalTrials.gov: NCT05293405, dated March 15, 2022). All participants underwent hybrid 18F-DPA714 PET/MRI and evaluation for modified Rankin scale (mRS) score, clinical assessment scale for AIE (CASE), and appropriate antibodies. A positive finding was defined as the intensity of 18F-DPA714 uptake that was above a threshold of mean standardized uptake value ratio (SUVR) + two standard deviations of SUVR within the corresponding brain regions of healthy controls.The positive detection rate of 18F-DPA714 PET for possible antibody-negative AIE was significantly higher than that of brain MRI (10/15 [67%] vs. 3/15 [20%]; P = 0.039). In addition, both the intensity and extent of 18F-DPA714 uptake were significantly associated with the CASE score (P = 0.002 and 0.001). Meanwhile, SUVR levels in the cerebellar region were significantly higher in patients with ataxia than in those without ataxia (P = 0.006). Furthermore, 18F-DPA714 uptake decreased in 5/10 [50%] patients who underwent follow-up PET/MRI, which mirrored their symptom relief.18F-DPA714 PET demonstrated its potentially incremental value to conventional MRI for detecting possible antibody-negative AIE.
Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, China.Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China.
Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, China.
Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.Shanxi Medical University-Collaborative Innovation Center for Molecular Imaging of Precision Medicine, Shanxi, China.
Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. zm11518@rjh.com.cn.Shanxi Medical University-Collaborative Innovation Center for Molecular Imaging of Precision Medicine, Shanxi, China. zm11518@rjh.com.cn.
Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, China. mztcs@163.com.Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China. mztcs@163.com.Department of Neurology, Xinrui Hospital, Wuxi, China. mztcs@163.com.
18F-DPA714 PET/MRI as a potential imaging tool for detecting possible antibody-negative autoimmune encephalitis: a prospective study.
Fatigue is commonly observed in pediatric multiple sclerosis (pedMS) patients, but its underlying mechanisms remain largely unexplored. We evaluated whether resting-state (RS) functional connectivity (FC) abnormalities in monoaminergic networks contributed to explain fatigue in pedMS.Fifty-five pedMS and twenty-three matched healthy controls (HC) underwent clinical and RS functional MRI assessment. Patients with Fatigue Severity Scale (FSS) score ≥ 4 were classified as fatigued (F). Patterns of dopamine-, noradrenaline- and serotonin-related RS FC were derived by constrained independent component analysis, using PET atlases for dopamine, noradrenaline, and serotonin transporters obtained in HCs' brain.Compared to non-fatigued (NF)-pedMS patients and HC, F-pedMS patients (15/55, 27.3%) showed decreased dopamine-related RS FC in the right postcentral gyrus. They also showed decreased dopamine-related RS FC in the left insula vs. HC and increased dopamine-related RS FC in the left middle temporal gyrus and cerebellum (lobule VI) vs. NF patients. In the noradrenaline-related network, F-pedMS patients showed decreased RS FC in the left superior parietal lobule and increased RS FC in the right thalamus vs. HC and NF-pedMS. Compared to HC, F-pedMS patients also showed decreased RS FC in the right calcarine cortex and increased RS FC in the right middle frontal gyrus. In the serotonin-related network, F-pedMS patients showed decreased RS FC in the right angular gyrus and increased RS FC in the right postcentral gyrus vs. NF-pedMS patients.In pedMS, fatigue is associated with specific monoaminergic network abnormalities, providing pathological markers for this bothersome symptom and putative targets for its treatment.
Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.Neurorehabilitation Unit IRCCS San Raffaele Scientific Institute, Milan, Italy.
Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.Neurorehabilitation Unit IRCCS San Raffaele Scientific Institute, Milan, Italy.Neurophysiology Service, IRCCS San Raffaele Scientific Institute, Milan, Italy.Vita-Salute San Raffaele University, Milan, Italy.
Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy. rocca.mara@hsr.it.Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy. rocca.mara@hsr.it.Vita-Salute San Raffaele University, Milan, Italy. rocca.mara@hsr.it.
Monoaminergic network abnormalities are associated with fatigue in pediatric multiple sclerosis.
Leptospirosis is responsible for various clinical syndromes, classically linked with fever and acute kidney injury.A prospective multicenter observational study was conducted in six health institutions in the region of Urabá, Colombia. Enrollment was based on leptospirosis-compatible clinical syndrome and a positive preliminary serological test, with PCR used to confirm the disease. Clinical data were collected using a standard questionnaire at enrollment, complemented with a review of clinical records. A total of 100 patients were enrolled, 37% (95% CI 27.0-46.9%) had a positive PCR result confirming acute leptospirosis. The most frequent symptoms in patients with a positive PCR test were headache (91.9%; 34/37), chills and sweating (80.6%; 29/37), nausea (75%; 27/37), dizziness (74.3%; 26/37), vomiting (61.1%; 22/37), congestion (56.8%; 21/37), and conjunctival suffusion (51.4%; 19/37). The frequency of clinical signs classically described in leptospirosis was low: jaundice (8.3%; 3/36) and anuria/oliguria (21.6%; 8/37). An increased neutrophile percentage was reported in 60.6% (20/33) of patients. The presence of complications was 21.6% (8/37), with pulmonary complications being the most frequent (75.0% 6/8). One confirmed case died resulting in a fatality of 2.7% (95% CI 0.5-13.8).Leptospirosis should be considered within the differential diagnoses of an undifferentiated acute febrile syndrome. Leptospirosis presents diagnostic challenges due to limitations in both clinical and laboratory diagnosis thus it is important to improve understanding of disease presentation and identify signs and symptoms that might help differentiate it from other causes of febrile illness.
Copyright: © 2024 Uribe-Restrepo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Graduate School, CES University, Medellin, Colombia.
Faculty of Veterinary Medicine and Animal Sciences, CES University, Medellin, Colombia.
Colombian Institute of Tropical Medicine, Apartadó, Colombia.
School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States of America.
Clinical presentation of human leptospirosis in febrile patients: Urabá, Colombia.
Simnotrelvir is a small-molecule highly specific 3C-like protease inhibitor for anti-SARS-CoV-2 and was approved as a combination drug with ritonavir (simnotrelvir/ritonavir) in China. Simnotrelvir is a substrate of cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp), and a weak inhibitor of CYP3A. Ritonavir is a substrate and inhibitor of CYP3A and an inhibitor of P-gp. Hence, the drug-drug interaction potential of simnotrelvir/ritonavir should be investigated.This drug-drug interaction study was an open-label, fixed-sequence, two-period phase I clinical trial in Chinese healthy adult subjects, divided into three cohorts, including simnotrelvir/ritonavir co-administrated with a strong CYP3A and P-gp inhibitor (itraconazole) and inducer (rifampicin), and with a specific CYP3A substrate (midazolam).The results demonstrated that compared with administration of simnotrelvir/ritonavir alone, the co-administration with itraconazole increased the geometric least-square mean ratio (GMR) of the expose (area under the plasma concentration-time curve from time zero to the lowest detectable plasma concentration [AUC0-t]) of simnotrelvir by 25% (GMR 125%, 90% CI 114-137%), whereas co-administration with rifampicin significantly decreased the AUC0-t of simnotrelvir by 81.5% (GMR 18.5%, 90% CI 16.4-20.9%). Notably, simnotrelvir/ritonavir increased the AUC0-t of midazolam by 16.69-fold (GMR 1769%, 90% CI 1551-2018%). The co-administration of simnotrelvir/ritonavir and rifampicin caused the increased amount and severity of treatment-emergent adverse events, especially hepatotoxicity.The co-administration of simnotrelvir/ritonavir with CYP3A and P-gp inhibitors can be safely used, whereas the co-administration with CYP3A and P-gp strong inducer should be avoided to minimize the risk of under-exposure. Co-administration of midazolam with simnotrelvir/ritonavir increased systemic exposure of midazolam.gov Identifier: NCT05665647.
Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Engineering and Technology Research Center for Pediatric Drug Development, Shandong Medicine and Health Key Laboratory of Clinical Pharmacy, Jinan, China.
Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
State Key Laboratory of Neurology and Oncology Drug Development, Nanjing, China; Simcere Zaiming Pharmaceutical Co. Ltd., Nanjing, China.
State Key Laboratory of Neurology and Oncology Drug Development, Nanjing, China; Jiangsu Simcere Pharmaceutical Co., Ltd., Nanjing, China.
Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Engineering and Technology Research Center for Pediatric Drug Development, Shandong Medicine and Health Key Laboratory of Clinical Pharmacy, Jinan, China; Department of Clinical Pharmacy, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China. Electronic address: zhao4wei2@hotmail.com.
Drug-drug interactions of simnotrelvir/ritonavir: an open-label, fixed-sequence, two-period clinical trial.
Proteus faecis is a gram-negative facultative anaerobic rod-shaped bacterium capable of swarming motility. It has been isolated from numerous sources such as humans, animals, and refuse and is considered potentially pathogenic towards humans. In this study, bacteria were isolated from the blowhole of a Yangtze finless porpoise (Neophocaena asiaeorientalis asiaeorientalis; YFP) living in captivity in China. One bacterium, P. faecis porpoise, was isolated and whole genome sequencing done. Biofilm formation, motility and antimicrobial resistance were also investigated. To find putative virulence factors, the genome of P. faecis strain porpoise was compared to the genomic sequences of eight other P. faecis isolates using the Bacterial and Viral Bioinformatics Resource Center (BV-BRC) ( https://www.bv-brc.org/ ). The goal of this study was to initially characterize the pathogenicity of this bacterium isolated from a cetacean species using both pathogenomics and conventional approaches.
Innovation Research Center for Aquatic Mammals; Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China.School of Liberal Arts & Sciences, Gateway Technical College, Kenosha, WI, 53144, USA.
Innovation Research Center for Aquatic Mammals; Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China.University of Chinese Academy of Sciences, Beijing, 101408, China.
State Key Laboratory of Freshwater Ecology and Biotechnology; Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China.University of Chinese Academy of Sciences, Beijing, 101408, China.
State Key Laboratory of Freshwater Ecology and Biotechnology; Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China.
School of Animal Science and Nutritional Engineering, Wuhan Polytechnic University, Wuhan, 430023, China.
Innovation Research Center for Aquatic Mammals; Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China.
Innovation Research Center for Aquatic Mammals; Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China. zhengjinsong@ihb.ac.cn.
Antonie Van Leeuwenhoek. 2024-09-21;118(1):7.
Proteus faecis: a potentially pathogenic bacterium isolated from the freshwater Yangtze finless porpoise.
Vestibular migraine (VM) is a usual trigger of episodic vertigo. Patients with VM often experience spinning, shaking, or unsteady sensations, which are usually also accompanied by photophobia, phonophobia, motor intolerance, and more. VM is often associated with a number of comorbidities. Recurrent episodes of VM can affect the patient's emotions, sleep, and cognitive functioning to varying degrees. Patients with VM may be accompanied by adverse moods such as anxiety, fear, and depression, which can gradually develop into anxiety disorders or depressive disorders. Sleep disorders are also a common concomitant symptom of VM, which significantly lower patients' quality of life. The influence of anxiety disorders and sleep disorders may reduce cognitive functions of VM, such as visuospatial ability, attention, and memory decline. Clinically, it is also common to see VM comorbid with other vestibular disorders, making the diagnosis more difficult. VM episodes are relieved but lingering, in which case VM may coexist with persistent postural-perceptual dizziness (PPPD). Anxiety may be an important bridge between recurrent VM and PPPD. The clinical manifestations of VM and Meniere's disease (MD) overlap considerably, and those who meet the diagnostic criteria for both can be said to have VM/MD comorbidity. VM can also present with positional vertigo, and some patients with VM present with typical benign paroxysmal positional vertigo (BPPV) nystagmus on positional testing. In this paper, we synthesize and analyze the pathomechanisms of VM comorbidity by reviewing the literature. The results show that it may be related to the extensive connectivity of the vestibular system with different brain regions and the close connection of the trigeminovascular system with the periphery of the vestibule. Therefore, it is necessary to pay attention to the diagnosis of comorbidities in VM, synthesize its pathogenesis, and give comprehensive treatment to patients.
The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Zhejiang Province, Hangzhou City, China.
The First Affiliated Hospital of Henan University of Chinese Medicine, Henan Province, Zhengzhou City, China.
Department of Neurology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Province, Hangzhou City, 310053, China. xubin2008.love@163.com.
Why is vestibular migraine associated with many comorbidities?
Social facets linked to conservation corridors and ecological networks have received relatively limited academic attention. This study explores the perspectives of researchers, NGO representatives, and landowners, as well as the community's ideas of conservation efforts and corridor potential in the Vhembe District, Limpopo, South Africa. Surveys and interviews were conducted with communities, regional stakeholders, and landowners. The findings revealed that the community participants strongly support corridor implementation. The results indicate that this support is driven by the anticipated socio-economic benefits in the form of jobs. However, the employment opportunities might not align with the resident's expectations. The study identifies several challenges to corridor establishment, including infrastructure and financial constraints. Moreover, the findings revealed a lack of supportive legislation and highlighted concerns over protected area's accessibility. The study contributes to the global academic discourse by emphasizing the importance of community engagement before corridor and network implementation. It also addresses the complex trade-offs inherent in such projects, regardless of location. The methodological approach employed in this research transcends its regional context and offers actionable insights applicable worldwide.
University of the Witwatersrand, 1 Jan Smuts Avenue, Braamfontein, Johannesburg, South Africa. a.dalziel9@gmail.com.
University of the Witwatersrand, 1 Jan Smuts Avenue, Braamfontein, Johannesburg, South Africa. Mary.evans@wits.ac.za.
Community perceptions and socio-economic implications of conservation corridors and networks in the Vhembe District, Limpopo, South Africa.
Intravenous thrombolysis (IVT) with alteplase (TPA) in hyperglycemic stroke patients is associated with an increased risk of symptomatic intracranial hemorrhage (sICH) and poor functional outcomes. We aimed to explore the association between admission hyperglycemia and sICH in large vessel occlusion stroke (LVOS) patients treated with TNK versus TPA before endovascular thrombectomy (EVT).We reviewed consecutive LVOS patients treated with TPA or TNK before EVT from 01/2020 to 06/2023. EVT was performed across five comprehensive stroke centers (CSCs) in Pennsylvania. Of 569 patients, 462 met inclusion criteria: LVOS, pre-stroke modified Rankin Scale (mRS) 0-2, and last-known-well to IVT (LKW-to-IVT) ≤ 4.5 h. The rates of sICH and parenchymal hematomas (PHs) between TPA and TNK cohorts were assessed.Of 462 patients, 254 (55%) received TNK, and 208 (45%) received TPA. Admission hyperglycemia (≥ 140 mg/dl) was present in 153 (33.1%) patients. Hyperglycemic patients were more frequently diabetic (p < 0.001). Admission hyperglycemia was associated with a significantly increased rate of sICH (5.9% versus 1.6%, p = 0.019) and PH (20.3% versus 11.3%, p = 0.010). Hyperglycemic patients had a significantly higher degree of overall disability as compared to normoglycemic patients (90d-mRS shift aOR 0.611, p = 0.007). Comparable rates of sICH and PH were observed in the hyperglycemic and normoglycemic cohorts among both TNK and TPA groups.In LVOS patients receiving IVT before EVT, admission hyperglycemia significantly increased the risk of sICH and PH and was associated with worse outcomes at 90 days. No differences in sICH or PH were observed between TNK and TPA groups.
Department of Neurosurgery, Geisinger, Danville, PA, USA. Hendrix.philipp@gmail.com.Department of Neurology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. Hendrix.philipp@gmail.com.
Department of Neurosurgery, Geisinger, Danville, PA, USA.
Department of Neurology, Geisinger, Danville, PA, USA.
Department of Molecular and Functional Genomics, Weis Center for Research, Geisinger, Danville, PA, USA.
Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Department of Neurology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Admission hyperglycemia effect on symptomatic intracranial hemorrhage in tenecteplase versus alteplase before large vessel occlusion stroke thrombectomy.
This study aimed to investigate whether serum amyloid A (AA) level can be used as a biomarker in women with hyperemesis gravidarum (HEG). This prospective observational study was conducted at the Antalya Training and Research Hospital Gynecology and Obstetrics Clinic, Türkiye, between July and December 2023. Forty women diagnosed with HEG and 40 healthy women were included. No statistically significant differences were observed between the groups in terms of sociodemographic data such as age, body mass index, family history, educational status, economic level, place of residence, occupation, smoking and alcohol use, or drug habits. However, obstetric characteristics such as number of miscarriages, number of dilatation curettages, and gestational age and laboratory values including complete blood count, hematocrit, leukocyte, neutrophil, lymphocyte, platelet, free T4, albumin, alanine aminotransferase, aspartate aminotransferase, urea, creatinine, hs-C-reactive protein, and sodium (P > .05) all differed significantly. In addition, significant differences were observed between the HEG and healthy groups in terms of numbers of gravidities (2 [1-3] vs 1 [0-1], respectively, P < .001), numbers of parities (1 [0-1] vs 1 [0-1], P < .001), numbers of living children (1 [0-2] vs 1 [0-1], P < .001), presenting complaints (nausea 0 [0%], nausea + vomiting 0 [0%], none 40 [100.0%] vs nausea 27 [67.5%], nausea + vomiting 13 [32.5%], none 0 [0%], P < .001), serum thyroid-stimulating hormone (1.16 ± 0.56 vs 1.81 ± 0.624, P = .004), potassium (4.1 ± 0.7 vs 3.8 ± 0.2, P = .001), and AA values (7.29 ± 2.61 vs 10.74 ± 3.04, P < .001). At receiver operating characteristic analysis, the area under the curve (AUC: 0.881) was statistically significant for serum AA (P: <.001), with a cutoff value of ≥ 8.79 ([95% confidence interval] 0.743-0.919, sensitivity 87.4%, specificity 80.2%). The positive predictive value of serum AA was 81.1% and the negative predictive value was 80.4%. The study results showed that serum AA can be used as a diagnostic biomarker in HEG. Prospective studies involving more participants are now required to confirm our results.
Antalya Training and Research Hospital, Department of Obstetrics and Gynecology, Antalya, Turkey.
Konya City Hospital, Department of Obstetrics and Gynecology, Konya, Turkey.
An evaluation of serum blood parameters and amyloid-A levels in women with hyperemesis gravidarum; A prospective observational study.
The aim of our study was to estimate the frequency of autoimmune comorbidities, in NMOSD patients from the national Serbian NMOSD Registry.Our study comprises 136 patients with NMOSD, diagnosed according to the NMOSD criteria 2015. At the time of the study, in the Registry were collected demographic and clinical data, including those related to the coexisting comorbidities and pathogenic autoantibodies. Not all patients were tested for all autoimmune antibodies. None of the seronegative aquaporin4-IgG (AQP4-IgG) NMOSD patients, included in the Registry, were positive for the myelin oligodendrocyte glycoprotein IgG.Among 136 NMOSD patients, 50 (36.8%) had at least one associated autoimmune disorder. AQP4-IgG was present in the sera from 106 patients (77.9%), the proportion of NMOSD patients with autoimmune comorbidities being significantly higher in the AQP4-IgG positive subgroup in comparison to the AQP4-IgG negative (p = 0.002). AQP4-IgG seropositive NMOSD patients had 5.2-fold higher risk of comorbid autoimmune diseases (OR = 5.2, 95% CI 1.4-18.5, p = 0.012). The most frequently reported diseases were autoimmune thyroid disease (15.4%), Sjogren's syndrome (11.0%), systemic lupus erythematosus (5.1%), myasthenia gravis (4.4%), and primary antiphospholipid antibody syndrome (2.9%). Antinuclear antibodies (ANAs) were frequently detected in the subgroup of NMOSD patients tested for this antibody (50/92; 54.3%). The higher frequency of ANAs and anti-extractable nuclear antigen autoantibodies, in the subgroups of AQP4-IgG-positive patients compared to the AQP4-IgG negative, tested for these antibodies, was statistically significant (p = 0.009, and p = 0.015, respectively).In conclusion, based on our results, in a defined cohort with European ethnical background, a wide spectrum of autoimmune diseases is frequently associated with AQP4-IgG seropositive NMOSD patients.
Institute of Epidemiology, Faculty of Medicine, University of Belgrade, 11000, Belgrade, Serbia. pekmezovic@sezampro.rs.
Clinic of Neurology, University Clinical Center of Serbia, Belgrade, Serbia.
Institute of Epidemiology, Faculty of Medicine, University of Belgrade, 11000, Belgrade, Serbia.Clinic of Neurology, University Clinical Center of Serbia, Belgrade, Serbia.
Clinic of Neurology, Faculty of Medicine, Clinical Center Nis, University of Nis, Nis, Serbia.
Clinic of Neurology, Military Medical Academy, Medical Faculty, Defense University, Belgrade, Serbia.
Institute of Epidemiology, Faculty of Medicine, University of Belgrade, 11000, Belgrade, Serbia.Clinic of Allergology and Immunology, University Clinical Center of Serbia, Belgrade, Serbia.
Aquaporin4-IgG seropositivity significantly increases the risk of comorbid autoimmune diseases in NMOSD patients: population-based registry data.
China has a large population of smokers, with half of them dependent on tobacco and in need of cessation assistance, indicating the need for mobile health (mHealth) to provide cessation support.The study aims to assess the feasibility and preliminary effectiveness of combining chatbot-led support with counselor-led support for smoking cessation among community smokers in China.This is a 2-arm, parallel, assessor-blinded, pilot randomized controlled trial nested in a smoke-free campus campaign in Zhuhai, China. All participants will receive brief face-to-face cessation advice and group cessation support led by a chatbot embedded in WeChat. In addition, participants in the intervention group will receive personalized WeChat-based counseling from trained counselors. Follow-up will occur at 1, 3, and 6 months after treatment initiation. The primary smoking outcome is bioverified abstinence (exhaled carbon monoxide <4 parts per million or salivary cotinine <30 ng/mL) at 6 months. Secondary outcomes include self-reported 7-day point prevalence of abstinence, smoking reduction rate, and quit attempts. Feasibility outcomes include eligibility rate, consent rate, intervention engagement, and retention rate. An intention-to-treat approach and regression models will be used for primary analyses.Participant recruitment began in March 2023, and the intervention began in April 2023. The data collection was completed in June 2024. The results of the study will be published in peer-reviewed journals and presented at international conferences.This study will provide novel insights into the feasibility and preliminary effectiveness of a chatbot-led intervention for smoking cessation in China. The findings of this study will inform the development and optimization of mHealth interventions for smoking cessation in China and other low- and middle-income countries.ClinicalTrials.gov NCT05777005; https://clinicaltrials.gov/study/NCT05777005.DERR1-10.2196/58636.
©Xue Weng, Hua Yin, Kefeng Liu, Chuyu Song, Jiali Xie, Ningyuan Guo, Man Ping Wang. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 23.09.2024.
Institute of Advanced Studies in Humanities and Social Sciences, Beijing Normal University, Zhuhai, China.
Office of Clinical Research Administration, Zhuhai People's Hospital (Zhuhai Hospital Affiliated With Jinan University), Zhuhai, China.
Pulmonary and Critical Care Medicine, Guangdong Provincial Hospital of Chinese Medicine, Zhuhai, China.
School of Sociology, Beijing Normal University, Beijing, China.
School of Nursing, Shanghai Jiao Tong University, Shanghai, China.
LKS Faculty of Medicine, School of Nursing, The University of Hong Kong, Hong Kong SAR, China.
Chatbot-Led Support Combined With Counselor-Led Support on Smoking Cessation in China: Protocol for a Pilot Randomized Controlled Trial.
Interleukin (IL)-6 is a major inflammatory cytokine that predicts mortality after out-of-hospital cardiac arrest (OHCA). Targeted temperature management (TTM) is associated with improved all-cause mortality in patients with OHCA. However, the effect of TTM on IL-6 production remains unclear. This study investigated whether TTM has additional anti-inflammatory effects after OHCA.This prospective cohort study included a total of 141 hospitalized patients with OHCA who were treated between January 2015 and June 2023. The study was conducted in the intensive care unit of China Medical University Hospital, Taichung. Postcardiac arrest care included TTM or the control approach (no TTM). The primary outcomes included the 90-day mortality rate and neurologic outcomes after OHCA. Differences between the TTM and control groups were examined using Student t test, chi-square test, and Kaplan-Meier survival curve analysis. Multivariate analysis of variance model was used to examine interaction effects.Plasma IL-6 and IL-6/soluble IL-6 receptor complex levels were measured at 6 and 24 hours after resuscitation. IL-6 and IL-6/soluble IL-6 receptor complex production was lower in the TTM group than in the control group (-50.0% vs +136.7%, P < .001; +26.3% vs +102.40%, P < .001, respectively). In addition, the 90-day mortality rate and poor neurologic outcomes were lower in the TTM group than in the control group (36.8% vs 63.0%, relative risk 0.39, 95% confidence interval 0.24-0.64, P < .001; 65.5% vs 81.5%, relative risk 0.80, 95% confidence interval 0.66-0.98, P = .04).TTM improves both the mortality rate and neurologic outcomes in patients resuscitated from OHCA, possibly by reducing IL-6-induced proinflammatory responses.
Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.Division of Cardiovascular Medicine, Department of Medicine, China Medical University Hospital, Taichung, Taiwan.
Division of Cardiovascular Medicine, Department of Medicine, China Medical University Hospital, Taichung, Taiwan.Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
Division of Cardiovascular Medicine, Department of Medicine, China Medical University Hospital, Taichung, Taiwan.Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan.
Division of Cardiovascular Medicine, Department of Medicine, China Medical University Hospital, Taichung, Taiwan.Graduate Institute of Chinese Medicine, China Medical University, Taichung, Taiwan.
Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan.
Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.Pharmacy Department, Wizcare Medical Corporation Aggregate, Taichung, Taiwan.School of Medicine, Weifang University of Science and Technology, Weifang, Shandong, China.
Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.Division of Cardiovascular Medicine, Department of Medicine, China Medical University Hospital, Taichung, Taiwan.Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan.
Effect of targeted temperature management on systemic inflammatory responses after out-of-hospital cardiac arrest: A prospective cohort study.
To observe the effect of low temperature plasma ablation combined with collagenase injection on lumbar disc herniation. 90 patients with lumbar disc herniation admitted to the pain department of our hospital and receiving surgical treatment from April 2021 to April 2023 were included in this retrospective study, and were divided into 2 groups according to different treatment plans. One group was treated with low-temperature plasma ablation combined with collagenase injection, and the other group was treated with low-temperature plasma ablation alone. The sample size of both groups was 80 cases. Peripheral blood was collected by fasting in the morning at 5 time points before surgery, 1, 3, 7 and 14 days after surgery, and 5 mL of whole venous blood was collected by disposable vacuum blood collection device. Serum levels of pro-inflammatory factor interleukin (IL)-1α, IL-1β, IL-6, IL-8, tumor necrosis factor-α and anti-inflammatory factor IL-4, IL-10 were detected by ELISA. VAS scores were used to evaluate postoperative low back pain. ODI and Lehmann Lumbar Function Scale were used to evaluate postoperative lumbar function. The contents of IL-1α, IL-1β, IL-6, IL-8, tumor necrosis factor-α and anti-inflammatory factor IL-4, IL-10 in the cryo-plasma ablation combined with collagenase injection group were significantly lower than those in the cryo-plasma ablation group alone (P < .05). The VAS score of cryo-plasma ablation combined with collagenase injection group was significantly lower than that of cryo-plasma ablation group at 1 day and 3 months after treatment, and the difference was statistically significant (P < .05). The ODI score of cryo-plasma ablation combined with collagenase injection group was significantly lower than that of cryo-plasma ablation group at 1 day and 3 months after treatment, and the difference was statistically significant (P < .05). The Lehmann score of cryo-plasma ablation combined with collagenase injection group was significantly higher than that of cryo-plasma ablation group at 1 day and 3 months after treatment, and the difference was statistically significant (P < .05). The overall efficacy of low-temperature plasma ablation combined with collagenase injection is better than that of low-temperature plasma ablation alone. Low temperature plasma ablation combined with collagenase injection in the treatment of patients with lumbar disc herniation has less pain, faster recovery.
Department of Pain, Nanchong Central Hospital (Nanchong Hospital, Beijing Anzhen Hospital)/The Second Clinical School of North Sichuan Medical College, Nanchong, Sichuan, China.
Clinical observation of low temperature plasma ablation combined with collagenase injection in lumbar disc herniation.
Anorectal malformations (ARMs) consist of a range of anomalies that are often associated with other anomalies The purpose of the study is to assess the incidence of associated congenital anomalies that are seen in patients with ARMs. An observational prospective study was conducted on 162 cases with ARM from February 2019 to January 2020, and data were collected on patient demographics, type of ARM, and associated anomalies using a prestructured questionnaire and analysis done using SPSS (IBM), version 23, software. Relevant statistical analysis was done, and the results are presented in tables and charts. Of 162 cases studied, 70 of them were males and 92 were females with a male-to-female ratio of 0.76:1. The majority of male patients (45%) had rectourethral fistulas, whereas 63% of the females had rectovestibular fistula. While 76 (47%) patients presented with isolated ARM, 86 (53%) had ≥1 associated congenital malformations. Forty-eight (30%) patients presented with a single associated anomaly, whereas 20 (12%) patients had≥3 associated anomalies. The commonest associated anomalies were urologic 26.5% followed by genital (22.8%), cardiac 20.4%, and musculoskeletal 16.6%, and 12.3% of them had vertebral; anorectal; cardiac; tracheoesophageal fistula; renal; limb association. More than half of the children have other associated abnormalities. We found urogenital anomalies to be the most common associated congenital defects. A lower incidence of cardiac and spinal cord anomalies was noted suggesting a need for active workup to be in line with the latest standards of care.
Department of Surgery, Division of Pediatric Surgery, Addis Ababa University College of Health Sciences, Addis Ababa, Ethiopia.
Department of Surgery, Unit of Pediatric Surgery, College of Health Sciences, Jig Jiga University, Jig Jiga, Ethiopia.
Incidence of associated anomalies in children with anorectal malformation: A 1-year prospective observational study in a low-income setting.
The aim of this study was to identify independent risk factors for preoperative lower extremity deep vein thrombosis (DVT) in elderly hip fracture patients and to construct a nomogram prediction model based on them. We collected clinical data from elderly hip fracture patients from Ya'an Hospital of Traditional Chinese Medicine (2021-2023), and used univariate and multivariate logistic regression analyses to identify independent risk factors for preoperative DVT. In this way, a nomogram prediction model was established. In addition, external validation of the model was performed by patient data from Ya'an Mingshan District Hospital of Traditional Chinese Medicine. Receiver operating characteristic curve analysis was used to calculate the area under the curve, and calibration and decision curves were plotted to assess the predictive performance of the model. Of the 223 elderly hip fracture patients, 23 (10.31%) developed DVT of the lower extremities before surgery. A total of 6 variables were identified as independent risk factors for preoperative lower extremity DVT in elderly hip fracture patients by logistic regression analysis: age > 75 years (OR = 1.932; 95% CI: 1.230-3.941), diabetes mellitus (OR = 2.139; 95% CI: 1.149-4.342), and prolonged duration of disease (OR. 2.535; 95% CI: 1.378-4.844), surgical treatment (OR = 1.564; 95% CI: 1.389-3.278), D-dimer > 0.5 mg/L (OR = 3.365; 95% CI: 1.229-7.715) fibrinogen > 4 g/L (OR = 3.473; 95% CI: 1.702-7.078). The constructed nomogram model has high accuracy in predicting the risk of preoperative DVT in elderly hip fracture patients, providing an effective tool for clinicians to identify high-risk patients and implement early intervention.
Ya'an Mingshan District Hospital of Traditional Chinese Medicine, Ya'an, China.
Ya'an Hospital of Traditional Chinese Medicine, Ya'an, China.
Construction and validation of a predictive model for preoperative lower extremity deep vein thrombosis risk in elderly hip fracture patients: An observational study.
To investigate the factors influencing glycemic control in gestational diabetes mellitus (GDM) patients and their impacts on pregnancy outcomes, providing insights for GDM management. Pregnant women diagnosed with GDM at a tertiary hospital in western China in 2019. Participants were categorized based on varying levels of glycemic control during pregnancy. A retrospective analysis was conducted, utilizing univariate and multivariate regression analyses, to identify factors influencing glycemic control in GDM patients. Based on various approaches to manage glucose, subjects were categorized into A1 (diet and exercise guidance alone) and A2 (insulin usage) groups. Based on whether glucose levels met the glycemic target in women with GDM, subjects were further divided into satisfactory and unsatisfactory groups. A total of 2621 women meeting the inclusion criteria were enrolled in the study. Independent factors associated with GDM A2 included higher prepregnancy body mass index (odds ratio [OR] = 1.070, 95% confidence interval [CI]: 1.019-1.122, P = .006), a history of GDM (OR = 1.888, 95% CI: 1.052-3.389, P = .033), elevated fasting plasma glucose (FPG) in early pregnancy (OR = 1.828, 95% CI: 1.320-2.532, P < .001), elevated 1-hour postprandial glucose (1-h PG) (OR = 1.126, 95% CI: 1.0091.256, P = .034), and 2-h PG by oral glucose tolerance test (OGTT) (OR = 1.181, 95% CI: 1.046-1.333, P = .007). Higher FPG by OGTT was an independent risk factor for unsatisfactory glycemic control (OR = 1.590, 95% CI: 1.273-1.985, P < .001). Compared with the A1 group, the A2 group has longer hospitalization, higher rates of cesarean section, placenta previa, and neonatal pneumonia (P < .05). Compared with the satisfactory group, the unsatisfactory group has lower gestational age, lower rates of cesarean section and placenta previa, and higher rates of postpartum hemorrhage for mothers; lower length and weight, and higher rates of premature birth, jaundice, hypoglycemia, pneumonia, respiratory distress syndrome, anemia, hospitalization, and hospitalization for more than 15 days in both pediatric unit and neonatal intensive care unit for newborns (P < .05). Elevated prepregnancy body mass index, FPG in early pregnancy, 1-h and 2-h PG during OGTT, and with a history with GDM are independent factors influencing insulin utilization, while elevated 0-h PG is an independent influencing factor of unsatisfactory glycemic control. Poor glycemic control has negative impacts on both maternal and fetal outcomes under 2 classifications.
Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan, China.
Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.Department of Reproductive Medical Center, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
Influencing factors of glycemic control in singleton pregnancies complicated by gestational diabetes mellitus in western China: A retrospective study.
Chronic obstructive pulmonary disease (COPD) stands as one of the leading causes of mortality worldwide. Acute exacerbations of COPD (AECOPD) lead to rapid respiratory function decline and worsened disease status. Despite recent studies, the ability of the neutrophil-to-lymphocyte ratio (NLR) to predict outcomes in patients with COPD remains controversial. We investigated the predictive value of NLR for adverse outcomes in hospitalized patients with AECOPD. A retrospective study was conducted at the Department of Pulmonary Medicine, Cho Ray Hospital (Vietnam) from November 2019 to November 2021. The study extracted data from patients diagnosed with AECOPD at discharge and met the inclusion criteria. NLR is calculated by dividing the number of neutrophils by the number of lymphocytes in the peripheral blood test. Adverse outcomes are defined as invasive mechanical ventilation, admission to intensive care unit, or in-hospital mortality. Multivariable regression analysis was conducted to identify variables predicting adverse outcomes. The cutoff, sensitivity, specificity, area under the curve, and receiver operating characteristic of NLR were determined for predicting adverse outcomes. Two hundred eighty-seven patients with AECOPD were included in the final analysis, with a mean age of 70.9, and males comprising 92.7%. The rate of adverse outcomes was 15.7%. Multivariable logistic regression identified reduced consciousness at admission (adjusted odds ratio = 0.08, 95% confidence interval [CI]: 0.02-0.38, P = .001) and high NLR (adjusted odds ratio = 1.17, 95% CI: 1.10-1.24, P < .001) as predictors of adverse outcomes. The receiver operating characteristic of NLR's predictive value yielded an area under the curve of 0.877 (95% CI: 0.83-0.93). An NLR cutoff of 11.0 predicted adverse outcomes with a sensitivity of 80.0%, specificity of 77.7%, and an odds ratio of 13.9 (95% CI: 6.3-30.7), P < .001. NLR is a simple, routine, and cost-effective tool for predicting adverse outcomes in hospitalized patients with AECOPD. Future studies should evaluate the kinetics of NLR in predicting treatment response in patients with AECOPD.
Faculty of Medicine, Department of Internal Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam.Department of Pulmonary Medicine, Cho Ray Hospital, Ho Chi Minh City, Vietnam.
Faculty of Medicine, Department of Internal Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam.
Faculty of Medicine, Department of Tuberculosis and Pulmonary Diseases, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam.
Predictive value of neutrophil-to-lymphocyte ratio for adverse outcomes in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease: A retrospective study.
Studies have shown that the ideal dose of epidural dexmedetomidine is 0.4 μg mL-1 for epidural labor analgesia. However, the appropriate dose of ropivacaine when combined with 0.4 μg mL-1 of dexmedetomidine for epidural labor analgesia is still unknown. Therefore, we aimed to determine the dose-response of ropivacaine when using 0.4 μg mL-1 of dexmedetomidine as epidural adjuvant for labor analgesia.One hundred of nulliparous singleton pregnant patients were randomized allocated into 1 of 5 groups with epidural ropivacaine concentration of 0.05%, 0.0625%, 0.075%, 0.0875%, and 0.1%. Labor analgesia was initialed with 12 mL of the mixed study solution. Effective analgesia was defined as a visual analogue scale <10 mm 30 minutes after the initial epidural bolus. The EC50 and EC95 for epidural ropivacaine was calculated by probit regression.Ninety-three of parturients were involved into the final analysis. Totals of 63.2% (12/19), 73.7% (14/19), 88.9% (16/18), 94.7% (18/19), and 100% (18/18) of parturients in group 0.05, 0.0625, 0.075, 0.0875, and 0.1 received effective epidural labor analgesia. The calculated EC50 and EC95 of epidural ropivacaine were 0.046% (95% CI 0.028-0.054%) and 0.086% (95% CI 0.074-0.137%), respectively.Under the condition of the study, a bolus of 12 mL ropivacaine 0.086% and dexmedetomidine 0.4 μg mL-1 could afford 95% of nulliparous singleton pregnant patients without suffering labor pain after a test dose of lidocaine 45 mg.
Department of Anesthesia, Women and Children Hospital of Jiashan, Jiaxing, China.
Department of Anesthesia, The First People's Hospital of Jiashan, Jiaxing, China.
Department of Anesthesia, The First People's Hospital of Pinghu, Zhejiang, China.
Dose-response of epidural ropivacaine with 0.4 μg mL-1 of dexmedetomidine for labor analgesia: A prospective double-blinded study.
Portal vein thrombosis (PVT) is a common thrombotic complication of cirrhosis. It can lead to variceal bleeding and bowel ischemia and also complicate liver transplantation. Identifying the possible risk factors associated with PVT can aid in identifying patients at high risk, enabling their screening and potentially preventing PVT through the rational use of anticoagulants. This study focuses on examining the clinical characteristics of PVT in cirrhotic patients and identifying the clinical and biochemical factors that are linked to the development of PVT. Consecutive hospitalized cirrhotic patients between 2015 and 2023 were identified through the hospital's computerized medical records based on the Tenth Revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) coding system and retrospectively analyzed. 928 individuals were included in this study; 783 (84.3%) without PVT and 145 (15.7%) with benign PVT. Hepatitis B virus (HBV) was significantly more common in the PVT group (P-value = .02), while alcohol and primary sclerosing cholangitis (PSC) were less common in this group (P-value = .01 and .02, respectively). Hepatocellular carcinoma (HCC) (P-value < .01), ascites (P-value = .01), and spontaneous bacterial peritonitis (SBP) (P-value = .02) were more common in the PVT group. Patients with PVT had a higher international normalized ratio (INR) level (P-value = .042) and lower plasma albumin (P-value = .01). No differences were identified in white blood cell, hemoglobin, platelet, and bilirubin levels. However, patients with PVT had higher model for end-stage liver disease (MELD) (P-value = .01) and Child-Pugh scores (P-value = .03). This study demonstrated a higher likelihood of PVT presence in cirrhotic patients with advanced age, HBV, and HCC, along with ascites, SBP, splenomegaly, hypoalbuminemia, elevated INR, and a higher MELD score. Nevertheless, additional research endeavors are necessary to accurately ascertain and validate supplementary risk factors within a broader demographic.
Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Transplant and Hepatobiliary Surgery, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Health Information Technology and Management, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Medical-Surgical Nursing, School of Nursing and Midwifery, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Clinical characteristics and predictors of benign portal vein thrombosis in patients with liver cirrhosis: A retrospective single-center study.
The respiratory muscles in chronic obstructive pulmonary disease (COPD) patients have reduced strength and resistance, leading to loss of the functional ability of these muscles. Lung hyperinflation is one of the main alterations, and air trapping is the main factor limiting diaphragmatic mobility (DM) in these patients; however, its correlation with functional parameters, exercise capacity, and indicators of disease severity remains underexplored. This study aimed to assess DM in stable COPD patients and relate the findings with parameters such as the 6-minute walk test distance, forced expiratory volume in 1 second (FEV1) %predicted, residual volume (RV) %predicted, and dyspnea. An observational cohort study was conducted to measure DM using ultrasound both at rest (DMrest) and during deep inspiration (DMmax). Forty-nine patients with stable COPD were included in this study. There was a correlation between DMmax and FEV1 %predicted (R = 0.36; P = .012), RV %predicted (r = -0.42; P = .01), RV/total lung capacity (r = -0.61; P < .001), and distance reached in the 6MWT (R = 0.46; P = .001). Patients with a modified Medical Research Council score <2 exhibited greater DM than those with a score ≥2 (mean difference = 13.20 ± 4.6 mm; P = .0059). Similarly, patients with a Body Mass Index, Airflow Obstruction, Dyspnea and Exercise Capacity index ≤4 showed greater DM (61.95 mm) than those with a Body Mass Index, Airflow Obstruction, Dyspnea and Exercise Capacity index >4 (47.89 mm; mean difference = 14.05 ± 5.3 mm; 95% confidence interval = 25.09-3.01 mm). DM is correlated with bronchial obstruction (FEV1), lung hyperinflation (RV and RV/total lung capacity), exercise capacity, and dyspnea in patients with COPD, suggesting its utility as an evaluative tool in this population.
Rio de Janeiro State University, Rio de Janeiro, Brazil.
Ultrasonography as a way of evaluating the diaphragm muscle in patients with chronic obstructive pulmonary disease.
Cadmium (Cd) plays a key role in the occurrence of myocardial infarction (MI). We aimed to explore the association between blood Cd levels and all-cause mortality of MI on the basis of the National Health and Nutrition Examination Survey databases. This study included 800 adults with MI to obtain blood Cd concentrations and their follow-up information. The association between Cd concentrations and mortality was analyzed using Cox regression, restricted cubic spline (RCS) models, mediation analysis, receiver operating characteristic curve, and Kaplan-Meier curves. All the patients were divided into 4 groups according to the quartiles of blood Cd levels (Q1, Q2, Q3, and Q4). Cox regression analysis with adjustment for covariates indicated that Cd was the promoting factor of mortality, and patients with higher Cd had a higher death risk. The RCS model indicated an inverted checkmark shaped correlation between Cd levels and mortality, and a turning point of 1.06 μg/L was found. A significant positive correlation was observed on the left of the turning point. Grouped patients by turning point into 2 groups, Kaplan-Meier analysis showed that the low-concentration group had a lower death risk than the high-concentration group. Subgroup analysis revealed that the prognostic effect of Cd was more pronounced in patients with former smoking history, and receiver operating characteristic curve showed that blood Cd had a better-predicting function in patients with MI. Blood Cd levels were significantly related to all-cause mortality in patients with MI, especially in patients with Cd < 1.06 μg/L.
Emergency Department, Affiliated Hospital of Putian University, Putian, Fujian, China.
Emergency Department, The Second Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China.
A cross-sectional study of the association between blood cadmium and mortality among adults with myocardial infarction.
Major depressive disorder (MDD) is a common mental illness. The traditional Chinese medicine compound Xiaojian Zhongtang (XJZT) has a good therapeutic effect on MDD, but the specific mechanism is not clear. The aim of this study is to explore the molecular mechanism of XJZT in the treatment of MDD through network pharmacology and bioinformatics. The traditional Chinese medicine system pharmacology database was used to screen the chemical components and targets of XJZT, while the online Mendelian inheritance in man, DisGeNET, Genecards, and therapeutic target database databases were used to collect MDD targets and identify the intersection targets of XJZT and MDD. A drugs-components-targets network was constructed using the Cytoscape platform, and the STRING was used for protein-protein interaction analysis of intersecting targets. Gene Ontology and Kyoto encyclopedia of genes and genomes analysis of intersecting targets was performed using the DAVID database. Obtain serum and brain transcriptome datasets of MDD from the gene expression omnibus database, and perform differentially expressed genes, weighted gene co-expression network analysis, gene set enrichment analysis, and receiver operating characteristic analysis. A total of 127 chemical components and 767 targets were obtained from XJZT, among which quercetin, kaempferol, and maltose are the core chemical components, and 1728 MDD targets were screened out, with 77 intersecting targets between XJZT and MDD. These targets mainly involve AGE-RAGE signaling pathway in diabetic complexes, epidermal growth factor receptor tyrosine kinase inhibitor resistance, and HIF-1 signaling pathway, and these core targets have strong binding activity with core components. In addition, 1166 differentially expressed genes were identified in the MDD serum transcriptome dataset, and weighted gene co-expression network analysis identified the most relevant gene modules (1269 genes), among which RAC-alpha serine/threonine-protein kinase (AKT1), D(4) dopamine receptor (DRD4), and kynurenine 3-monooxygenase (KMO) were target genes for the treatment of MDD with XJZT, these 3 genes are mainly related to the ubiquitin-mediated proteolysis, arachidonic acid (AA) metabolism, and Huntington disease pathways, and the expression of AKT1, DRD4, and KMO was also found in the MDD brain transcriptome dataset, which is significantly correlated with the occurrence of MDD. We have identified 3 key targets for XJZT treatment of MDD, including AKT1, KMO, and DRD4, and they can be regulated by the key components of XJZT, including quercetin, maltose, and kaempferol. This provides valuable insights for the early clinical diagnosis and development of therapeutic drugs for MDD.
School of Basic Medicine, Heilongjiang University of Traditional Chinese Medicine, Harbin, China.
Integrating network pharmacology and bioinformatics to explore the mechanism of Xiaojian Zhongtang in treating major depressive disorder: An observational study.
To investigate the clinical significance of venous access nursing in modulating anxiety, depression, and adverse event incidence among patients undergoing painless colonoscopy. Sixty patients who underwent painless colonoscopy in our hospital from September 2021 to September 2022 were selected as the control group (CG, receiving routine perioperative nursing). Sixty patients who underwent painless colonoscopy in our hospital from October 2022 to August 2023 were taken as the study group (SG, receiving venous access nursing modulation). After nursing, patients in the SG exhibited lower scores of the Self-Rating Anxiety Scale and the Self-Rating Depression Scale than those in the CG (P < .05). The SG showed significantly lower mean Ottawa Bowel Preparation Score, but exhibited higher adequacy of bowel preparation compared with the CG (P < .05). The colonoscopy insertion time was (7.18 ± 1.02) minutes in the SG and (8.69 ± 1.00) minutes in the CG, and the colonoscopy withdrawal time was (4.66 ± 1.66) minutes in the SG and (5.64 ± 1.06) minutes in the CG, which showed statistically significant differences between the 2 groups (P < .05). The total incidence of adverse events did not have statistical significance between the 2 groups (P > .05). Application of venous access nursing in patients undergoing painless colonoscopy may help alleviate adverse emotions and shorten colonoscopy insertion time and colonoscopy withdrawal time, thus warranting recognition for its safety and efficacy.
Department of Nursing, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, China.
Central Health of Shangxi Town, Yiwu, Zhejiang, China.
Department of Digestive Medicine, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, China.
An observational study on the modulation of anxiety, depression, and adverse event incidence in painless colonoscopy patients through venous access nursing.
Although some studies have indicated that eating during hemodialysis may induce hypotension and cardiovascular events, some patients still consume food during their treatment. This prospective study was conducted to determine whether the need to eat during hemodialysis treatment was related to abnormal glucose metabolism and autonomic nerve dysfunction. Seventy patients were enrolled in this study, and their demographic features and various laboratory parameters were analyzed. At each routine hemodialysis visit, predialysis, intradialysis, and postdialysis blood pressure measurements were systematically conducted. A 24-hour ambulatory electrocardiogram (ECG) was performed during the hemodialysis interval, and heart rate variability (HRV) values were calculated. Additionally, whether the patients ate during the hemodialysis treatments was recorded. Another 20 people who underwent physical examinations during the same period and were matched for sex and age were included in the control group. The HRV values of the hemodialysis patients were generally lower than those of the control group. Univariate analysis revealed significant differences in sex, age, calcium antagonist use, blood calcium levels, insulin levels, diastolic blood pressure (DBP) measurements, and HRV indices between hemodialysis patients who ate and those who did not eat during hemodialysis (P < .05), whereas there were no significant differences in diabetes status or in the hemoglobin, albumin, blood glucose and C-peptide levels (P > .05). Multivariate analysis revealed that low values for very low frequency (VLF) and postdialysis DBP were risk factors for fasting intolerance during hemodialysis treatments. Autonomic dysfunction may affect whether hemodialysis patients tolerate fasting during dialysis. VLF evaluation may provide information that can be used to develop a more reasonable intradialytic nutritional supplementation method.
Department of Nephrology, General Hospital of Western Theater Command, Chengdu, PR China.
Department of Nephrology, General Hospital of Western Theater Command, Chengdu, PR China.College of Medicine, Southwest Jiaotong University, Chengdu, PR China.
Department of Information, Statistical Office, General Hospital of Western Theater Command, Chengdu, PR China.Department of Statistics, College of Mathematics, Southwest Jiaotong University, Chengdu, PR China.
Department of Information, Statistical Office, General Hospital of Western Theater Command, Chengdu, PR China.
Influence of autonomic nervous dysfunction on eating during hemodialysis sessions: An observational study.
Hepatolenticular degeneration is a rare treatable autosomal recessive inherited copper metabolism disorder with a diverse clinical phenotype and an exceptionally complex pathogenesis. Early definitive phenotypic diagnosis and targeted treatment are major challenges worldwide. In this study, we strictly followed the National Standards of the People's Republic of China - Terminology of Traditional Chinese Medicine Clinical Diagnosis and Treatment (Syndrome Part), Chinese Medicine Nomenclature, and the clinical investigation-determined traditional Chinese medicine syndrome differentiation standards at Anhui University of Chinese Medicine to select 6 of the most common traditional Chinese medicine syndrome differentiations. This study retrospectively analyzed 107 patients admitted between 2019 and 2023 with Wilson's disease based on real-world data. After testing for normal distribution and homogeneity of variance, corresponding analysis of variance was selected, followed by post hoc multiple comparisons. Of the selected 25 objective influencing factors, 22 exhibited normal distribution, while red blood cells, hemoglobin, and type IV collagen did not pass the homogeneity of variance test. After analysis of variance, the factors ceruloplasmin (CP) and copper oxidase (SCO) showed significant differences among patients with different traditional Chinese medicine syndromes (P < .05), with partial η2 for CP being 0.13 > 0.06 and for SCO being 0.143 > 0.14. Post hoc multiple comparison results indicated significant differences in CP and SCO among patients with certain traditional Chinese medicine syndromes (P < .05). There were significant differences in the factors CP and SCO among patients with different traditional Chinese medicine syndromes. Significant differences were observed in the copper blue protein factor between damp-heat syndrome and liver and kidney deficiency syndrome, liver and kidney deficiency syndrome and liver and kidney yin deficiency syndrome, liver and kidney deficiency syndrome and phlegm heat and wind syndrome, as well as liver and kidney deficiency syndrome and syndrome of phlegm and blood stasis (P < .05). Significant differences were also found in the SCO factor between damp-heat syndrome and liver and kidney deficiency syndrome, liver and kidney deficiency syndrome and liver and kidney yin deficiency syndrome, liver and kidney deficiency syndrome and phlegm heat and wind syndrome, and liver and kidney deficiency syndrome and syndrome of phlegm and blood stasis (P < .05).
Department of Brain Diseases, Geriatric Center, The First Affiliated Hospital of Anhui University of Chinese Medicine, Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM, Anhui University of Chinese Medicine, Hefei, China.
Department of Brain Diseases, Geriatric Center, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, China.
Discussion on the relationship between the distribution characteristics of TCM syndrome types and related objective indicators in hepatolenticular degeneration.
The aim of this study is to explore the traditional Chinese medicine (TCM) constitution among individuals suffering from dry eye disease. Following the diagnostic criteria outlined in TFO DEWS II, a total of 114 patients with dry eye were included in this study. Based on the classification criteria for dry eye, the patients were categorized into 3 distinct dry eye subtypes. Each participant underwent a thorough clinical assessment for dry eye, and their TCM pattern manifestations were assessed using the Traditional Chinese Medicine Questionnaire for Dry Eye. The Nine Constitutions Assessment Method was utilized for TCM pattern differentiation and classification. Spearman's correlation analysis was employed to investigate the associations between TCM constitution and dry eye subtypes, clinical indicators, and the relationships between TCM syndromes and dry eye subtypes. Among the 114 patients, the Qi-Stagnation constitution was the most common, with variations in constitution distribution among different dry eye subtypes. Significant correlations were observed between the Blood-Stasis, Yin-Deficiency, Qi-Deficiency, and Yang-Deficiency constitutions and 2, 4, 1, and 4 dry eye indicators, respectively. Spearman's analysis revealed that 5 out of 50 TCM syndromes were associated with mixed dry eye, 5 with evaporative dry eye, and 3 with aqueous tear deficiency dry eye. Further analysis, using lasso regression and binary unconditional logistic regression identified dizziness, lumbago, and weakness as influencing factors for both mixed-type and evaporative-type dry eye. In this study, we extensively examined the TCM constitution in individuals with dry eye, offering valuable insights and guiding future TCM-related research in the context of dry eye. Additionally, we established correlations between TCM syndrome patterns and dry eye indicators.
Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University; Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing, China.
Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University; Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing, China.Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University and Capital Medical University, Beijing, China.
Department of Ophthalmology, The Third Medical Center of Chinese People's Liberation Army General Hospital, Beijing, China.
Investigation of traditional Chinese medicine constitution in individuals afflicted by dry eye disease: A retrospective study.
To observe the clinical efficacy and safety of vancomycin intravenous drip combined with vancomycin intrathecal injection in the treatment of intracranial infection after severe brain injury surgery. From January 2020 to June 2022, 80 patients with intracranial infection after severe brain injury surgery were selected and randomly divided into 2 subgroups; there were 40 patients in each subgroup. All patients were treated with vancomycin. The control subgroup was medicated with intravenous drip, and the observation subgroup was treated through 2 channels (intravenous drip + intrathecal injection), with a course of 7 days. The clinical efficacy, intracranial pressure, infection control time, routine indexes of cerebrospinal fluid (white blood cell count [WBC], glucose content [Glu], and total protein content [Pro]) and the incidence of adverse reactions were contrasted between the 2 subgroups. Versus the control subgroup, the total effective rate in the observation subgroup was notably higher (95.00% vs 77.50%). After treatment, aiming at the intracranial pressure and infection control time, versus the control subgroup (146.20 ± 22.37) mmH2O and (9.86 ± 1.62) days, the observation subgroup were (125.43 ± 18.5) mmH2O and (7.35 ± 1.57) days respectively, which were notably lower. After treatment, versus the control subgroup, the concentrations of WBC and Pro in cerebrospinal fluid in the observation subgroup were lower, and the content of Glu was higher. There was no statistical distinction in the incidence of adverse reactions between the 2 subgroups (17.50% vs 10.00%). Two-channel administration of vancomycin can improve the clinical efficacy of internal infection after severe craniocerebral injury, reduce intracranial pressure, and cerebrospinal fluid WBC and Pro levels, and has high safety.
Medical College of Soochow University, Suzhou, Jiangsu, China.
Hulun Buir People's Hospital, Hulunbuir, China.
Safety and effectiveness of dual channels vancomycin administration in the treatment of intracranial infection after severe brain injury surgery.
Fundación Institut Guttmann, Institut Universitari de NeurorehabilitacióAdscrit a La UAB, 08916, Badalona, Spain.Faculty of Medicine, Pamukkale University, Denizli, Turkey.
Fundación Institut Guttmann, Institut Universitari de NeurorehabilitacióAdscrit a La UAB, 08916, Badalona, Spain.Universitat Autònoma de Barcelona, 08193, Barcelona, Spain.Fundació Institut d'Investigació en Ciències de La Salut Germans Trias I Pujol, 08916, Badalona, Spain.
Institut d'Investigació Biomèdic August Pi I Sunyer (IDIBAPS), Barcelona, Spain.
Fundación Institut Guttmann, Institut Universitari de NeurorehabilitacióAdscrit a La UAB, 08916, Badalona, Spain. hkumru@guttmann.com.Universitat Autònoma de Barcelona, 08193, Barcelona, Spain. hkumru@guttmann.com.Fundació Institut d'Investigació en Ciències de La Salut Germans Trias I Pujol, 08916, Badalona, Spain. hkumru@guttmann.com.
Frida Kahlo could have had cauda equina syndrome: a case report.
Hearing loss significantly affects communication, social interactions, and the overall quality of life. The bone-anchored hearing aid (BAHA) is an implantable system that bypasses the outer and middle ear to directly stimulate the cochlea through bone conduction. This study aimed to compare hearing performance and subjective auditory ability improvements between transcutaneous and percutaneous BAHA devices using audiological assessments and Speech, Spatial and Qualities of Hearing Scale. This cross-sectional prospective study included 29 participants aged 14 to 69 years who had used BAHA for at least 6 months. Both Cochlear Baha System's percutaneous (connect) and transcutaneous (attract) implants were evaluated. Audiological assessments involved pure-tone audiometry, speech recognition threshold, and free-field (FF) audiometry, while subjective auditory ability was measured using the Turkish Speech, Spatial and Qualities of Hearing scale (Tr-SSQ). Significant improvements in FF audiometry averages and speech recognition thresholds were observed with BAHA compared to without BAHA (P < .001). Both implant types provided similar FF averages, speech audiometry results, and Tr-SSQ outcomes, with no significant differences between them. Tr-SSQ scores showed substantial satisfaction, indicating significant improvements in speech perception, spatial perception, and hearing quality with BAHA (P < .001). The findings align with previous research, demonstrating that BAHA is a reliable and effective solution for hearing rehabilitation. The study also emphasized the importance of using both audiological test results and daily hearing function scales to comprehensively evaluate the benefits of hearing rehabilitation in real-world environments. In conclusion, BAHA, regardless of the implant type, can provide predictable and lasting improvements in hearing thresholds and daily hearing abilities, making it a valuable option for patients with conductive hearing loss.
Department of Audiology, Vocational School of Healthcare, Dokuz Eylül University, Izmir, Türkiye.Department of Otorhinolaryngology, Audiology, Dokuz Eylül University Hospital, Izmir, Türkiye.
Department of Otorhinolaryngology, School of Medicine, Dokuz Eylül University, Izmir, Türkiye.
Department of Otorhinolaryngology, Audiology, Institute of Health Sciences, Dokuz Eylül University, Izmir, Türkiye.
Department of Audiology, Faculty of Health Sciences, Ege University, Izmir, Türkiye.
The effect of percutaneous and transcutaneous BAHA on hearing and subjective auditory abilities: A comparative study.
This study aimed to investigate and compare the neurophysiological impacts of two widely used anesthetic agents, Fentanyl and Ketamine, on EEG power spectra during different stages of anesthesia in adult patients undergoing minimally invasive surgery. EEG data were collected from patients undergoing anesthesia with either Fentanyl or Ketamine. The data were analyzed for relative power spectrum and fast-to-slow wave power ratios, alongside Spectral Edge Frequency 95% (SEF95), at 3 key stages: pre-anesthesia, during stable anesthesia, and post-anesthesia. EEG Relative Power Spectrum: Initially, both groups exhibited similar EEG spectral profiles, establishing a uniform baseline (P > .05). Upon anesthesia induction, the Fentanyl group showed a substantial increase in delta band power (P < .05), suggesting deeper anesthesia, while the Ketamine group maintained higher alpha and beta band activity (P < .05), indicative of a lighter sedative effect. Fast and Slow Wave Power Ratios: The Fentanyl group exhibited a marked reduction in the fast-to-slow wave power ratio during anesthesia (P < .05), persisting post-anesthesia (P < .05) and indicating a lingering effect on brain activity. Conversely, the Ketamine group demonstrated a more stable ratio (P > .05), conducive to settings requiring rapid cognitive recovery. Spectral Edge Frequency 95% (SEF95): Analysis showed a significant decrease in SEF95 values for the Fentanyl group during anesthesia (P < .05), reflecting a shift towards lower frequency power. The Ketamine group experienced a less pronounced decrease (P > .05), maintaining a higher SEF95 value that suggested a lighter level of sedation. The study highlighted the distinct impacts of Fentanyl and Ketamine on EEG power spectra, with Fentanyl inducing deeper anesthesia as evidenced by shifts towards lower frequency activity and a significant decrease in SEF95 values. In contrast, Ketamine's preservation of higher frequency activity and more stable SEF95 values suggests a lighter, more dissociative anesthetic state. These findings emphasize the importance of EEG monitoring in anesthesia for tailoring anesthetic protocols to individual patient needs and optimizing postoperative outcomes.
Department of Anesthesiology and Perioperative Medicine, General Hospital of Ningxia Medical University, Yinchuan, China.
A study comparing brain wave patterns of fentanyl and ketamine in adult patients undergoing minimally invasive surgery.
Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Freiburg, Germany. marco.prinz@uniklinik-freiburg.de.Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany. marco.prinz@uniklinik-freiburg.de.
IRF8 as durable architect of the microglial chromatin landscape.
To explore the feasibility and application value of texture analysis based on computed tomography (CT) for predicting the differentiation of esophageal squamous cell carcinoma (ESCC). Patients diagnosed with ESCC who underwent chest contrast-enhanced CT before treatment were selected. Based on the pathological results, the patients were stratified into poorly differentiated and moderately well-differentiated groups. FireVoxel software was used to analyze the region of interest based on venous phase CT images. Texture parameters including the mean, median, standard deviation (SD), inhomogeneity, skewness, kurtosis, and entropy were obtained automatically. Differences in the texture parameters and their relationship with the degree of differentiation between the 2 groups were analyzed. The value of CT texture parameters in identifying poor differentiation and moderate-well differentiation of esophageal cancer was analyzed using the ROC curve. A total of 48 patients with ESCC were included, including 24 patients in the poorly differentiated group and 24 patients in the moderate-well-differentiated group. There were negative correlations between SD, inhomogeneity, entropy, and the degree of differentiation of esophageal cancer (P < .05). The correlation of inhomogeneity was the highest (r = -0.505, P < .001). SD, inhomogeneity, and entropy could effectively distinguish between the poorly and moderately well-differentiated groups, with statistically significant differences between the 2 groups (P < .05). The best critical values for SD, inhomogeneity, and entropy were 17.538, 0.017, and 3.917, respectively. The areas under the ROC curve were 0.793, 0.792, and 0.729, respectively, with the SD and inhomogeneity being the best. The application of texture analysis on venous phase CT images holds promise as a method for forecasting the degree of differentiation in esophageal cancers, which could significantly contribute to the preoperative noninvasive evaluation of tumor differentiation.
Department of Thoracic Surgery, The First Affiliated Hospital of Hebei North University, Zhangjiakou, China.
University College London, London, United Kingdom.
Department of Medicine, Hebei North University, Zhangjiakou, China.
Department of Nuclear medicine, The First Affiliated Hospital of Hebei North University, Zhangjiakou, China.
Department of Medical Imaging, Beijing Huairou Hospital, Beijing, China.
Department of Operating rooms, The First Affiliated Hospital of Hebei North University, Zhangjiakou, China.
Department of Medical Imaging, The First Affiliated Hospital of Hebei North University, Zhangjiakou, China.
Texture analysis based on CT for predicting the differentiation of esophageal squamous cancer: An observational study.
Low back pain (LBP) is a global musculoskeletal ailment. Over the past few years, dry needling (DN) has garnered interest from both physical therapists and patients. Physical therapy commonly employs spinal manipulation to alleviate persistent LBP and other musculoskeletal disorders. The aim of this study was to investigate the effects of spinal manipulation alone and in combination with DN on functional disability and endurance in individuals suffering from chronic nonspecific LBP.Patients of both genders who had chronic nonspecific LBP and who had not received physical therapy within the last 3 months were included in this single-blind, randomized controlled trial using purposive sampling. All participants were randomly assigned to either the experimental (SMT + DN) or control (SMT alone) group using computer-generated random numbers. The data were analyzed using the Statistical Package for Social Sciences (SPSS) version 23.0. For between-group comparisons, the Mann-Whitney U test was used. A P-value < .05 was considered to indicate statistical significance.The analysis of the difference between the 2 groups revealed that the mean ± standard deviation (SD) for the SMT alone group was 16.09 ± 3.963 at baseline and 12.66 ± 3.801 at 8 weeks, whereas for the DN + ST group, it was 13.67 ± 3.904 at baseline and 10.92 ± 3.534 at 8 weeks, with a P-value of .003. Thus, the RMDQ score improved gradually in both groups, and the mean endurance score reported for the ST group was 2.5 to 4.5, while that reported for the DN + ST group was 3.1 to 5.1.The results of this study showed that both therapies effectively reduced LBP. When comparing the effects of spinal manipulation alone to those of spinal manipulation combined with DN, the latter showed significantly greater benefits.
University Institute of Physical Therapy, Faculty of Allied Health Sciences, University of Lahore, Lahore, Pakistan.Department of Physiotherapy Sindh Institute of Physical Medicine and Rehabilitation, Karachi, Pakistan.
University Institute of Physical Therapy, Faculty of Allied Health Sciences, University of Lahore, Lahore, Pakistan.
University Institute of Physical Therapy, Faculty of Allied Health Sciences, University of Lahore, Lahore, Pakistan.Pediatric Neurorehabilitation Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
Riphah College of Rehabilitation and Allied Health Sciences, Riphah International University, Islamabad, Pakistan.
Comparison of the effects of dry needling and spinal manipulative therapy versus spinal manipulative therapy alone on functional disability and endurance in patients with nonspecific chronic low back pain: An experimental study.
School of Nursing, National Taipei University of Nursing and Health Sciences, Taipei City, Taiwan. 228455300teresa@gmail.com.Department of Research, Taipei Medical University Hospital, Taipei City, Taiwan. 228455300teresa@gmail.com.
Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Medical University Hospital, Taipei City, Taiwan.
Comment on: Premature Death in Bodybuilders: What Do We Know?
Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia. kkman@unimelb.edu.au.Department of Microbiology and Immunology, University of Melbourne, Melbourne, Victoria, Australia. kkman@unimelb.edu.au.
Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia. axel.kallies@unimelb.edu.au.Department of Microbiology and Immunology, University of Melbourne, Melbourne, Victoria, Australia. axel.kallies@unimelb.edu.au.
Recreating immune and epithelial interactions in organoids.
Gram-staining-negative, aerobic, white-cream-pearly colony, coccobacilli, and non-motile bacterial strain, PAMC 29798T was isolated from an Antarctic lichen. The strain was acidotolerant and psychrotolerant growing at pH 4.0-7.5 (optimally at pH 4.0-6.5) and 0-25 °C (optimally at 10-20 °C). The major fatty acids are Summed Feature 8, C18:1 2OH, and C19:0 cyclo ω8c. The major respiratory quinone was Q-10. Phylogenetic and phylogenomic analyses indicated that strain PAMC 29798T belonged to the genus Acidisoma and 16S rRNA gene sequences of PAMC 29798T were closely related to Acidisoma silvae (97.7% sequence similarity), Acidisoma cellulosilyticum (96.5%), Acidisoma tundrae (96.5%), and Acidisoma sibiricum (96.3%). Genomic relatedness analyses showed that strain PAMC 29798T was clearly distinguished from type strains of the genus Acidisoma based on values of average nucleotide identity (< 75%) and the digital DNA-DNA hybridization (< 19.6%). Genome analysis revealed that the genome size of PAMC 29798T is approximately 5.0 Mb with a G+C content of 63.4%. The complete genome comprises 5 contigs containing 4636 protein-coding genes, 46 tRNA genes, and 2 rRNA operons. The genome possesses genes for light-harvesting complexes, type-II photosynthetic reaction center, and C-P lyase to solubilize organic phosphates, while genes encoding nitrogenase iron protein involved in the nitrogen fixation were not present. Based on the results of phylogenetic, genome-based relatedness, and physiological and genomic analyses, strain PAMC 29798T is proposed to represent a novel species of the genus Acidisoma, with the name Acidisoma cladoniae. The type strain is PAMC 29798T (= KCTC 82159T = JCM 35634T).
Division of Life Sciences, Korea Polar Research Institute, 26 Songdomirae-ro, Yeonsu-gu, Incheon, 21990, Republic of Korea.
Division of Life Sciences, Korea Polar Research Institute, 26 Songdomirae-ro, Yeonsu-gu, Incheon, 21990, Republic of Korea. ymlee@kopri.re.kr.
Acidisoma cladoniae sp. nov., an acidotolerant bacterium isolated from an Antarctic lichen.
The proteins contactin (CNTN) 1-6 are synaptic proteins for which there is evidence that they are dysregulated in neurodegenerative dementias. Less is known about CNTN changes and differences in cerebrospinal fluid (CSF) of dementias, which can provide important information about alterations of the CNTN network and be of value for differential diagnosis.We developed a mass spectrometry-based multiple reaction monitoring (MRM) method to simultaneously determine all six CNTNs in CSF samples using stable isotope-labeled standard peptides. The analytical performance of the method was evaluated for peptide stability, dilution linearity and precision. CNTNs were measured in 82 CSF samples from patients with Alzheimer's disease (AD, n = 19), behavioural variant frontotemporal dementia (bvFTD, n = 18), Parkinson's disease dementia/dementia with Lewy bodies (PDD/DLB, n = 18) and non-neurodegenerative controls (n = 27) and compared with core AD biomarkers.The MRM analysis revealed down-regulation of CNTN2 (fold change (FC) = 0.77), CNTN4 (FC = 0.75) and CNTN5 (FC = 0.67) in bvFTD and CNTN3 (FC = 0.72), CNTN4 (FC = 0.75) and CNTN5 (FC = 0.73) in PDD/DLB compared to AD. CNTN levels strongly correlated with each other in controls (r = 0.73), bvFTD (r = 0.86) and PDD/DLB (r = 0.70), but the correlation was significantly lower in AD (r = 0.41). CNTNs in AD did not show correlation even with core AD biomarkers. Combined use of CNTN1-6 levels increased diagnostic performance of AD core biomarkers.Our data show CNTNs differentially altered in dementias and indicate CNTN homeostasis being selectively dysregulated in AD. The combined use of CNTNs with AD core biomarkers might help to improve differential diagnosis.
German Center for Neurodegenerative Diseases (DZNE E.V.), Helmholtzstr. 8/1, 89081, Ulm, Germany.
Department of Neurology, Ulm University Hospital, Helmholtzstr. 8/1, 89081, Ulm, Germany.
Department of Neurology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
Neurochemistry Laboratory, Department of Clinical Chemistry, Amsterdam University Medical Centers (UMC), Amsterdam, The Netherlands.
German Center for Neurodegenerative Diseases (DZNE E.V.), Helmholtzstr. 8/1, 89081, Ulm, Germany. patrick.oeckl@uni-ulm.de.Department of Neurology, Ulm University Hospital, Helmholtzstr. 8/1, 89081, Ulm, Germany. patrick.oeckl@uni-ulm.de.
Contactin proteins in cerebrospinal fluid show different alterations in dementias.
From the Department of Ophthalmology, Baylor College of Medicine, Houston, Texas.
Reply: Impact of spherical aberration on visual quality and depth of focus.
From the Anterior Segment and Refractive Surgery Department, Rothschild Foundation Hospital, Paris, France (Stern, Gatinel); Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel (Stern).
Comment on: Impact of spherical aberration on visual quality and depth of focus.
Preexercise caffeine intake has proven to exert ergogenic effects on cycling performance. However, whether these benefits are also observed under fatigue conditions remains largely unexplored. We aimed to assess the effect of caffeine ingested during prolonged cycling on subsequent time-trial performance in trained cyclists.The study followed a triple-blinded, randomized, placebo-controlled cross-over design. Eleven well-trained junior cyclists (17 ± 1 years) performed a field-based 8-min time trial under fresh conditions (i.e., after their usual warm-up) or after two work-matched steady-state cycling sessions (total energy expenditure∼20 kJ/kg and ∼100 min duration). During the latter sessions, participants consumed caffeine (3 mg/kg) or a placebo ∼60 min before the time trial. We assessed power output, heart rate, and rating of perceived exertion during the time trial and mood state (Brunel Mood Scale) before and after each session.No significant condition effect was found for the mean power output attained during the time trial (365 ± 25, 369 ± 31, and 364 32 W for fresh, caffeine, and placebo condition, respectively; p = .669). Similar results were found for the mean heart rate (p = .100) and rating of perceived exertion (p = 1.000) during the time trial and for the different mood domains (all p > .1).Caffeine intake during prolonged exercise seems to exert no ergogenic effects on subsequent time-trial performance in junior cyclists. Future studies should determine whether significant effects can be found with larger caffeine doses or after greater fatigue levels.
Faculty of Sport Sciences, Universidad Europea de Madrid, Madrid, Spain.
Faculty of Sport Sciences, Universidad Europea de Madrid, Madrid, Spain.Physical Activity and Health Research Group ( PaHerg ), Research Institute of Hospital 12 de Octubre ( imas12 ), Madrid, Spain.
Alimco-Campagnolo U19 team, Vitoria, Spain.
Facultad de Medicina y Ciencias de la Salud, Departamento de Ciencias Biomédicas, Área de Educación Física y Deportiva, Universidad de Alcalá, Madrid, Spain.
Physical Activity and Health Research Group ( PaHerg ), Research Institute of Hospital 12 de Octubre ( imas12 ), Madrid, Spain.Department of Systems Biology, University of Alcalá, Madrid, Spain.
Intrasession Caffeine Intake and Cycling Performance After Accumulated Work: A Field-Based Study.
Malnutrition is known to worsen the prognosis of chronic heart failure (HF). To gain information that may be helpful in establishing appropriate nutritional interventions for chronic HF, this study was performed to investigate the efficacy of nutritional management with 2 enteral formulas, EH, with a standard nutritional composition, and ER, fortified with omega-3 fatty acids, vitamin D, and carnitine. Experiments were performed in a Dahl rat HF model. After being fed a standard rodent feed (MF) containing 8% NaCl (high salt-MF [HS-MF]) from 6 to 11 weeks of age, rats were assigned to freeze-dried EH or ER diets with an NaCl concentration of 8% (HS-ER or HS-EH) until 18 weeks of age. Serum albumin was significantly higher at 14 and 17 weeks of age in rats fed the HS-ER and HS-EH diets compared with those remaining on the HS-MF diet. Body weight was also significantly higher at 14 and 17 weeks of age in animals fed the HS-ER diet, showing that nutritional deterioration was prevented. In addition, heart weight was significantly lower at 18 weeks of age in the HS-ER group than that in the HS-MF group, suggesting that cardiac hypertrophy was prevented. This study demonstrated improved nutritional status in a HF model in Dahl rats presumably owing to differences in nutritional composition in the diets. Future studies are needed to explore optimal nutritional management with enteral formulas in patients with chronic HF.
Research and Development Division, EN Otsuka Pharmaceutical Co., Ltd, Tokyo, Japan; and.
Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan .
Effect of an Enteral Formula Enriched With ω-3 Fatty Acids, Carnitine, and Vitamin D on Body Weight, Heart Weight, and Blood Biochemical Parameters in a Dahl Rat Heart Failure Model.
Department of Psychology, Division of Brain, Behavior and Cognition, Aristotelian University Faculty of Philosophy, Thessaloniki, Greece. triarhou@psy.auth.gr.
Department of Brain Repair and Rehabilitation, Institute of Neurology, University College London, London, UK.
Department of Psychology, Division of Brain, Behavior and Cognition, Aristotelian University Faculty of Philosophy, Thessaloniki, Greece. triarhou@auth.gr.Graduate Program in Neuroscience, Department of Neurosurgery, Aristotelian University School of Medicine, Thessaloniki, Greece. triarhou@auth.gr.
Little is known about the functional consequences of violence when directly assessed as a primary outcome, and even less about how consistently these consequences are evaluated in a judicial context. The World Health Organization (WHO) highlighted the importance of a functional approach to health in 2001 with the release of the International Classification of Functioning, Disability, and Health (ICF). In most European countries, forensic physicians assess individuals exposed to violence to evaluate the outcomes of violence, providing certified medical evidence for magistrates' sentencing decisions. This evaluation involves a mix of objective, subjective, and contextual elements, such as reported symptoms of fear, pain, and details of the assault. Quantifying these subjective elements with scales could enhance their interpretation and application in a judicial context.This study aims to (1) characterize and (2) assess 6 scales measuring subjective elements of functional impairment among individuals exposed to violence.We conducted a retrospective study that included individuals exposed to violence examined in a French department of forensic medicine over 12 months. A typology of violence encountered in medical settings was built based on the mining of electronic health records and the use of pattern recognition algorithms. The optimal number of violence types was determined using a robust and stable clustering approach, involving sample resampling and a multimetric scheme. Patients were then paired according to their homogeneous profiles, and the intra- and interrater reproducibility of the scales was evaluated.All pain, fear, and life threat scales were significantly associated with higher functional impairment, suggesting that these measures contribute to the overall assessment of functional impairment. The intra- and interrater reproducibility of scales among similar situations of violence was measured, ranging from mild to good, with coefficients of concordance between 0.46-0.66 and 0.43-0.66, respectively. Individuals reporting intimate partner violence showed higher scores in both fear and perception of a life threat during the assault and medical interview, while individuals reporting battery by multiple unknown assailants presented higher scores only in perception of a life threat during the assault. We identified 5 remarkably stable profiles of situations of violence, consistent with clinical practice.Pain, fear, and life threat scales were related to functional impairment according to expert knowledge and demonstrated fair reproducibility under real-life conditions for similar situations of violence. Subjective elements related to functional impairment in individuals exposed to violence can be quantified using Likert scales during medical interviews.
©Ivan Lerner, Patrick Chariot, Thomas Lefèvre. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 27.09.2024.
Department of Legal and Social Medicine, Hôpital Jean-Verdier, Assistance publique - Hôpitaux de Paris, Bondy, France.
Department of Legal and Social Medicine, Hôpital Jean-Verdier, Assistance publique - Hôpitaux de Paris, Bondy, France.Unité mixte de recherche 8156 Centre national pour la recherche scientifique - Unité 997 Institut national de la santé et de la recherche médicale - Ecole des hautes études en sciences sociales - Université Sorbonne Paris Nord, Institut de Recherche Interdisciplinaire Sur les Enjeux Sociaux, Aubervilliers, France.
JMIR Public Health Surveill. 2024-09-27;10():e43563.
Functional Impairment in Individuals Exposed to Violence Based on Electronical Forensic Medical Record Mining and Their Profile Identification: Controlled Observational Study.
Division of Brain, Behavior and Cognition, Department of Psychology, Aristotelian University Faculty of Philosophy, Thessaloníki, Greece. triarhou@auth.gr.Graduate Program in Neuroscience, Department of Neurosurgery, Aristotelian University School of Medicine, Thessaloníki, Greece. triarhou@auth.gr.
Nature Immunology, . paula.jauregui@nature.com.
Nature Immunology, . nick.bernard@nature.com.
Nature Immunology, . stephanie.houston@us.nature.com.
Nature Immunology, . ioana.staicu@us.nature.com.
The BioRobotics Institute and Centre for Excellence in AI and Robotics, Sant'Anna School of Advanced Studies, Via Rinaldo Piaggio, 34, 56025, Pontedera-Pisa, Italy. albertoarturo.vergani@santannapisa.it.
Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disorder characterized by relentless and progressive loss of motor neurons. A molecular diagnosis, supported by the identification of specific biomarkers, might promote the definition of multiple biological subtypes of ALS, improving patient stratification and providing prognostic information. Here, we investigated the levels of neurofilament light chain (NfL), chitotriosidase (CHIT1) and microRNA-181b (miR-181b) in the cerebrospinal fluid (CSF) of ALS subjects (N = 210) as well as neurologically healthy and neurological disease controls (N = 218, including N = 74 with other neurodegenerative diseases) from a large European multicentric cohort, evaluating their specific or combined utility as diagnostic and prognostic biomarkers. NfL, CHIT1 and miR-181b all showed significantly higher levels in ALS subjects compared to controls, with NfL showing the most effective diagnostic performance. Importantly, all three biomarkers were increased compared to neurodegenerative disease controls and, specifically, to patients with Alzheimer's disease (AD; N = 44), with NfL and CHIT1 being also higher in ALS than in alpha-synucleinopathies (N = 22). Notably, ALS patients displayed increased CHIT1 levels despite having, compared to controls, a higher prevalence of a polymorphism lowering CHIT1 expression. While no relationship was found between CSF miR-181b and clinical measures in ALS (disease duration, functional disability, and disease progression rate), CSF NfL was the best independent predictor of disease progression and survival. This study deepens our knowledge of ALS biomarkers, highlighting the relative specificity of CHIT1 for ALS among neurodegenerative diseases and appraising the potential diagnostic utility of CSF miR-181b.
Neurology Unit, Foundation IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy.
Department of Neurosciences, Laboratory of Neurobiology, University of Leuven (KU Leuven), Louvain, Belgium.Neurology Department, University Hospitals Leuven, Louvain, Belgium.
Department of Pathophysiology and Transplantation, Dino Ferrari Center, Università degli Studi di Milano, Milan, Italy.
Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy.
Neurology Department, University Hospitals Leuven, Louvain, Belgium.
Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy.Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Milan, Italy.
Department of Pathophysiology and Transplantation, Dino Ferrari Center, Università degli Studi di Milano, Milan, Italy.Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy.
Laboratory for Molecular Neurobiomarker Research, KU Leuven, Louvain, Belgium.Department of Laboratory Medicine, KU Leuven University Hospitals Leuven Gasthuisberg Campus, Louvain, Belgium.
Neurology Unit, Foundation IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy.Department of Pathophysiology and Transplantation, Dino Ferrari Center, Università degli Studi di Milano, Milan, Italy.
Department of Pathophysiology and Transplantation, Dino Ferrari Center, Università degli Studi di Milano, Milan, Italy.Neuromuscular and Rare Diseases Unit, Department of Neuroscience, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy.
Department of Pathophysiology and Transplantation, Dino Ferrari Center, Università degli Studi di Milano, Milan, Italy. f.verde@auxologico.it.Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, Milan, Italy. f.verde@auxologico.it.
Exploiting the role of CSF NfL, CHIT1, and miR-181b as potential diagnostic and prognostic biomarkers for ALS.
Biological development and genetic information transfer are governed by genetic, epigenetic, transcriptional, and posttranscriptional mechanisms. RNA methylation, the attachment of methyl (-CH 3) groups to RNA molecules, is a posttranscriptional modification that has gained increasing attention in recent years because of its role in RNA epitranscriptomics. RNA modifications (RMs) influence various aspects of RNA metabolism and are involved in the regulation of diverse biological processes and diseases. Neural cell types emerge at specific stages of brain development, and recent studies have revealed that neurodevelopment, aging, and disease are tightly linked to transcriptome dysregulation. In this review, we discuss the roles of N6-methyladenine (m6A) and 5-methylcytidine (m5C) RNA modifications in neurodevelopment, physiological functions, and related diseases.
State Key Laboratory of Reproductive Medicine and Offspring Health (Suzhou), Suzhou Affiliated Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou 215002, China.
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong 999077, China.
RNA methylation in neurodevelopment and related diseases.
Although researchers are committed to Indigenous data sovereignty in principle, they fall short in returning data and results to communities in which or with whom they conduct their research. This results in a misalignment in benefits of research toward researchers and settler institutions and away from Indigenous communities. To explore this, we conducted a case study analyzing the rate researchers returned data to Nunatsiavut, an autonomous area claimed by Inuit of Labrador, Canada. We assessed the data return rate for all research approved by the Nunatsiavut Government Research Advisory Committee between 2011 and 2021. In two-thirds of projects, researchers did not return the data they had collected. Based on our results and their contextualization with researchers and Nunatsiavut Research Centre staff members, we compiled recommendations for researchers, academia, government bodies, funding bodies, and Indigenous research governance boards. These recommendations aim to facilitate data return, thus putting data sovereignty into practice.
Mi'kma'ki, the unceded and unsurrendered territory of the Mi'kmaq People, Department of Biology, Dalhousie University, 1355 Oxford Street, PO Box 150000, Halifax, NS, B3H 4R2, Canada. ortenzi@dal.ca.
The Unceded and Unsurrendered Territory of the Algonquin Anishnaabeg People, 817-315 Holmwood Avenue, Ottawa, ON, K1S 2R2, Canada.
Nunatsiavut Research Centre, 12 Sandbanks Road, Nain, Nunatsiavut, NL, A0P 1L0, Canada.
WorldFish, Jalan Batu Maung, Batu Maung, 11900, Bayan Lepas, Penang, Malaysia.
Mikma'ki, the unceeded and unsurrendered territory of the Mi'kmaq People, Marine Affairs Program, Dalhousie University, 1355 Oxford Street, PO Box 150000, Halifax, NS, B3H 4R2, Canada.
Good data relations key to Indigenous research sovereignty: A case study from Nunatsiavut.
Prior analyses of the relationship between insurance status and receipt of tests and procedures have yielded conflicting findings and have focused on outpatient care. We sought to characterize the relationship between primary payer and diagnostic and procedural intensity, comparing rates of cardiac tests and procedures in matched hospitalized Medicaid and commercially insured patients.We created a propensity score-matched sample of Medicaid and commercially insured adults hospitalized at all acute care hospitals in Kentucky, Maryland, New Jersey, and North Carolina from 2016 to 2018. The main outcome was receipt of a cardiac test or procedure: echocardiogram, stress test, cardiac catheterization (elective, in acute coronary syndrome, in ST-segment-elevation myocardial infarction), and pacemaker and subcutaneous cardiac rhythm monitor implantation. Generalized linear models with a hospital-specific indicator variable were estimated to calculate the adjusted odds of a commercially insured patient receiving a given test or procedure relative to a Medicaid patient. Models controlled for race, ethnicity, and zip code income quartile. Commercially insured patients were more likely to receive each cardiac test or procedure, with adjusted odds ratios ranging from 1.16 (95% CI, 1.00-1.34) for cardiac catheterization in ST-segment-elevation myocardial infarction to 1.40 (95% CI, 1.27-1.54) for pacemaker implantation.Hospitalized commercially insured patients were more likely to undergo a range of cardiac tests and procedures, some of which may represent low-value care. This may be driven by a combination of physician and patient preference, financial incentives, and social determinants of health. Our findings support the need for hospital payment models focused on increasing value and reducing inequities.
Department of Medicine Johns Hopkins School of Medicine Baltimore MD USA.
Department of Biostatistics Johns Hopkins Bloomberg School of Public Health Baltimore MD USA.
Regulatory Finance and Clinical Analytics, Johns Hopkins Medicine Baltimore MD USA.
Relationship Between Insurance Status and Receipt of Cardiac Tests and Procedures During Hospitalization: A Cross-Sectional Study.
Inflammation is a feature of coronary heart disease (CHD), but the role of proinflammatory microbial infection in CHD remains understudied.CHD was defined in the MESA (Multi-Ethnic Study of Atherosclerosis) as myocardial infarction (251 participants), resuscitated arrest (2 participants), and CHD death (80 participants). We analyzed sequencing reads from 4421 MESA participants in the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine program using the PathSeq workflow of the Genome Analysis Tool Kit and a 65-gigabase microbial reference. Paired reads aligning to 840 microbes were detected in >1% of participants. The association of the presence of microbe reads with incident CHD (follow-up, ~18 years) was examined. First, important variables were ascertained using a single regularized Cox proportional hazard model, examining change of risk as a function of presence of microbe with age, sex, education level, Life's Simple 7, and inflammation. For variables of importance, the hazard ratio (HR) was estimated in separate (unregularized) Cox proportional hazard models including the same covariates (significance threshold Bonferroni corrected P<6×10-5, 0.05/840). Reads from 2 microbes were significantly associated with CHD: Gemella morbillorum (HR, 3.14 [95% CI, 1.92-5.12]; P=4.86×10-6) and Pseudomonas species NFACC19-2 (HR, 3.22 [95% CI, 2.03-5.41]; P=1.58×10-6).Metagenomics of whole-genome sequence reads opens a possible frontier for detection of pathogens for chronic diseases. The association of G morbillorum and Pseudomonas species reads with CHD raises the possibilities that microbes may drive atherosclerotic inflammation and that treatments for specific pathogens may provide clinical utility for CHD reduction.
Institute for Translational Genomics and Population Sciences The Lundquist Institute for Biomedical Innovation Torrance CA.Department of Pediatrics, David Geffen School of Medicine University of California at Los Angeles Los Angeles CA.
United States Department of Agriculture/Agricultural Research Service (USDA/ARS) Children's Nutrition Research Center Baylor College of Medicine Houston TX.
Department of Internal Medicine Wake Forest University Winston-Salem NC.
Department of Biostatistics, School of Public Health University of Washington Seattle WA.
Division of Cardiology, Department of Medicine Johns Hopkins University Baltimore MD.
Department of Pathology and Laboratory Medicine and Biochemistry Larner College of Medicine at the University of Vermont Colchester VT.
Center for Public Health Genomics University of Virginia Charlottesville VA.
Division of Cardiology, Department of Medicine University of California Irvine Irvine CA.Susan Samueli Integrative Health Institute Irvine CA.
Metagenomic Study of the MESA: Detection of Gemella Morbillorum and Association With Coronary Heart Disease.
Atrial fibrillation detected after stroke (AFDAS) is considered to be a distinct entity influenced by cardiogenic and neurogenic factors. We hypothesized that patients with AFDAS have larger stroke lesions than patients without atrial fibrillation (AF) and with known AF (KAF).Consecutive patients with magnetic resonance imaging-confirmed acute ischemic stroke admitted to a university hospital between October 2020 and January 2023 were prospectively registered. We categorized patients as AFDAS, no AF or KAF upon hospital discharge. We manually segmented diffusion-weighted imaging lesions to determine lesion volume. We analyzed 1420 patients (median age, 78; 47.2% women, median National Institutes of Health Stroke Scale score, 3; median hospital stay, 5 days). Of these, 81 had AFDAS (5.7%), 329 had KAF (23.2%) and 1010 had no AF (71.1%). Lesion volume was larger in patients with AFDAS (median, 5.4 mL [interquartile range, 1.0-21.6]) compared with patients with no AF and KAF (median, 0.7 [interquartile range,0.2-4.4] and 2.0 [interquartile range,0.3-11.1] mL, respectively; both P<0.001). Lesion volume was independently associated with AFDAS compared with no AF (adjusted odds ratio, 1.37 [95% CI, 1.20-1.58] per log mL) and KAF (adjusted odds ratio, 1.22 [95% CI, 1.07-1.41] per log mL). Patients in the highest lesion volume quartile (>6.5 mL) were more likely to be diagnosed with AFDAS compared with the lowest quartile (<0.22 mL, 13.6% versus 2.1%; adjusted odds ratio, 5.88 [95% CI, 2.30-17.40]). These associations were more pronounced when excluding 151 patients with nonembolic lesion pattern and similar when excluding 199 patients with KAF on oral anticoagulation.Larger stroke lesions were independently associated with AFDAS diagnosis during index stroke hospitalization highlighting a potential neurogenic contribution to AFDAS pathogenesis.
Center for Stroke Research Berlin (CSB) Berlin Germany.Department of Neurology with Experimental Neurology Charité Universitätsmedizin Berlin Berlin Germany.Exzellenzcluster NeuroCure Berlin Germany.
Center for Stroke Research Berlin (CSB) Berlin Germany.Department of Neurology with Experimental Neurology Charité Universitätsmedizin Berlin Berlin Germany.
Department of Neurology with Experimental Neurology Charité Universitätsmedizin Berlin Berlin Germany.Berlin Institute of Health Berlin Germany.
Center for Stroke Research Berlin (CSB) Berlin Germany.Department of Neurology with Experimental Neurology Charité Universitätsmedizin Berlin Berlin Germany.Berlin Institute of Health Berlin Germany.
Center for Stroke Research Berlin (CSB) Berlin Germany.
Center for Stroke Research Berlin (CSB) Berlin Germany.Department of Neurology with Experimental Neurology Charité Universitätsmedizin Berlin Berlin Germany.Exzellenzcluster NeuroCure Berlin Germany.Berlin Institute of Health Berlin Germany.
Center for Stroke Research Berlin (CSB) Berlin Germany.Department of Neurology with Experimental Neurology Charité Universitätsmedizin Berlin Berlin Germany.Berlin Institute of Health Berlin Germany.Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. (DZNE), partner site Berlin Berlin Germany.
Center for Stroke Research Berlin (CSB) Berlin Germany.Department of Neurology with Experimental Neurology Charité Universitätsmedizin Berlin Berlin Germany.Deutsches Zentrum für Herz-Kreislauf-Forschung e.V. (DZHK) Berlin Germany.Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. (DZNE), partner site Berlin Berlin Germany.Deutsches Zentrum für psychische Gesundheit (DZPG) Berlin Germany.
Center for Stroke Research Berlin (CSB) Berlin Germany.Department of Neurology with Experimental Neurology Charité Universitätsmedizin Berlin Berlin Germany.Berlin Institute of Health Berlin Germany.Deutsches Zentrum für Herz-Kreislauf-Forschung e.V. (DZHK) Berlin Germany.
Association Between Stroke Lesion Size and Atrial Fibrillation Detected After Stroke: An Observational Cohort Study.
Chronic Obstructive Pulmonary Disease (COPD) is a respiratory condition characterized by heterogeneous abnormalities of the airways and lung parenchyma that cause different clinical presentations. The assessment of the prevailing pathogenetic components underlying COPD is not usually pursued in daily practice, also due to technological limitations and cost.To assess non-invasively the lung emphysema component of COPD by the simultaneous measurement of DLNO and DLCO via a single-breath (sDLNO and sDLCO).COPD patients aged ≥40 years of both genders were recruited consecutively and labelled by computed tomography as with significant emphysema (>10% of CT lung volume) or with negligible emphysema otherwise. Current lung function tests such as sDLNO, sDLCO and Vc (the lung capillary blood volume) were measured. All possible subsets of independent spirometric and diffusive parameters were tested as predictors of emphysema, and their predicted power compared to each parameter alone by ROC analysis and area under the curve (AUC).Thirty-one patients with significant emphysema were compared to thirty-one with negligible emphysema . FEV1 and FEV1/FVC seemed to be the best spirometric predictors (AUC 0.80 and 0.81, respectively), while sDLCO and Vc had the highest predicted power among diffusive parameters (AUC 0.92 and 0.94, respectively). sDLCO and Vc values were the parameters most correlated to the extent of CT emphysema. Six subsets of independent predictors were identified and included at least one spirometric and one diffusive parameter. According to goodness-to-fit scores (AIC, BIC, log-likelihood and pseudo R2), RV coupled with sDLCO or Vc proved the best predictors of emphysema.When investigating the parenchymal destructive component due to emphysema occurring in COPD, sDLNO, sDLCO and Vc do enhance the predictive power of current spirometric measures substantially. sDLNO, sDLCO and Vc contribute to phenotype of the main pathogenetic components of COPD easily and with high sensitivity. Organizational problems, radiation exposure, time and costs could be reduced, while personalized and precision medicine could be noticeably implemented.
National Centre for Respiratory Pharmacoeconomics and Pharmacoepidemiology - CESFAR, Verona, Italy.
AdRes Health Economics and Outcomes Research, Turin, Italy.
International journal of chronic obstructive pulmonary disease
Int J Chron Obstruct Pulmon Dis. 2024;19():2123-2133.
Single-Breath Simultaneous Measurement of DLNO and DLCO as Predictor of the Emphysema Component in COPD - A Retrospective Observational Study.
The simplified Pulmonary Embolism Severity Index (sPESI) score could help identify low-risk patients with pulmonary embolism for home treatment. However, the application of the sPESI score and selection for home treatment have not been fully evaluated in the direct oral anticoagulants era.The COMMAND VTE (Contemporary Management and Outcomes in Patients With Venous Thromboembolism) Registry-2 is a multicenter registry enrolling consecutive patients with acute symptomatic venous thromboembolism. The current study population consists of 2496 patients with hemodynamically stable pulmonary embolism (2100 patients [84%] treated with direct oral anticoagulants), who were divided into 2 groups: sPESI scores of 0 and ≥1. We investigated the 30-day mortality, home treatment prevalence, and factors predisposing to home treatment using the Kaplan-Meier method and logistic regression model. Patients with an sPESI score of 0 accounted for 612 (25%) patients, and only 17% among 532 patients with out-of-hospital pulmonary embolism were treated at home. The cumulative 30-day mortality was lower in patients with an sPESI score of 0 than the score of ≥1 (0% and 4.8%, log-rank P<0.001). There was no patient with 30-day mortality with an sPESI score of 0. Independent factors for home treatment among out-of-hospital pulmonary embolism patients with an sPESI score of 0 were no transient risk factors for venous thromboembolism, no cardiac biomarker elevation, and direct oral anticoagulants use in the acute phase.The 30-day mortality rate was notably low in an sPESI score of 0. Nevertheless, only a minority of patients with an sPESI score of 0 were treated at home between 2015 and 2020 after the introduction of direct oral anticoagulants for venous thromboembolismin Japan.
Department of Cardiovascular Medicine, Graduate School of Medicine Kyoto University Kyoto Japan.
Department of Clinical Epidemiology Hyogo College of Medicine Nishinomiya Japan.
Department of Cardiovascular Medicine Kurashiki Central Hospital Kurashiki Japan.
Department of Cardiology Hyogo Prefectural Amagasaki General Medical Center Amagasaki Japan.
Division of Cardiovascular Medicine Toho University Ohashi Medical Center Tokyo Japan.
Department of Cardiovascular Center Osaka Red Cross Hospital Osaka Japan.
Department of Cardiovascular Medicine Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan.
Department of Cardiovascular Medicine Kobe City Medical Center General Hospital Kobe Japan.
Cardiovascular Center Tazuke Kofukai Medical Research Institute, Kitano Hospital Osaka Japan.
Department of Cardiology Kinki University Hospital Osaka Japan.
Department of Cardiology Japanese Red Cross Wakayama Medical Center Wakayama Japan.
Department of Cardiology Japanese Red Cross Otsu Hospital Otsu Japan.
Department of Cardiology Tokyo Women's Medical University Tokyo Japan.
Department of General Internal Medicine Kobe University Hospital Kobe Japan.
Department of Cardiology Tenri Hospital Tenri Japan.
Department of Cardiology and Nephrology Mie University Graduate School of Medicine Tsu Japan.
Department of Cardiology Shiga General Hospital Moriyama Japan.
Department of Cardiology Kansai Electric Power Hospital Osaka Japan.
Department of Cardiology Osaka Saiseikai Noe Hospital Osaka Japan.
Division of Cardiology, Nara Hospital Kinki University Faculty of Medicine Ikoma Japan.
Department of Cardiovascular Medicine Gunma University Graduate School of Medicine Maebashi Japan.
Department of Cardiology Kokura Memorial Hospital Kokura Japan.
Department of Cardiology National Hospital Organization Kyoto Medical Center Kyoto Japan.
Department of Cardiology Koto Memorial Hospital Higashiomi Japan.
Division of Cardiology Shimada General Medical Center Shimada Japan.
Department of Cardiology Shizuoka City Shizuoka Hospital Shizuoka Japan.
Department of Cardiology Hirakata Kohsai Hospital Hirakata Japan.
Department of Cardiovascular Medicine Sugita Genpaku Memorial Obama Municipal Hospital Obama Japan.
Department of Cardiovascular Medicine, Graduate School of Medical Sciences Kumamoto University Kumamoto Japan.
Department of Cardiovascular Medicine Shiga University of Medical Science Otsu Japan.
Division of Cardiology Kohka Public Hospital Koka Japan.
Selection of Home Treatment and Identification of Low-Risk Patients With Pulmonary Embolism Based on Simplified Pulmonary Embolism Severity Index Score in the Era of Direct Oral Anticoagulants.
Cardiac surgery with cardiopulmonary bypass (CPB) triggers pulmonary injury. In this trial we assessed the feasibility, safety, and efficacy of low frequency ventilation (LFV) during CPB in patients undergoing valvular surgery.Patients with severe mitral or aortic valve disease were randomized to either LFV or usual care. Primary outcomes included release of generic inflammatory and vascular biomarkers and the lung-specific biomarker sRAGE (soluble receptor for advance glycation end products) up to 24 hours postsurgery. Secondary outcomes included pulmonary function tests and 6-minute walking test up to 8 weeks postdischarge. Sixty-three patients were randomized (33 LFV versus 30 usual care). Mean age was 66.8 years and 30% were female. LFV was associated with changes of sRAGE (soluble receptor for advance glycation end products) levels (geometric mean ratio, 3.05; [95% CI, 1.13-8.24] 10 minutes post CPB, and 1.07 [95% CI, 0.64-1.79], 0.84 [95% CI, 0.55-1.27], 0.67 [95% CI, 0.42-1.07], and 0.62 [95% CI, 0.45-0.85] at 2, 6, 12, and 24 hours post CPB respectively). No changes were observed for any of the generic biomarkers. Respiratory index soon after surgery (mean difference, -0.61 [95% CI, -1.24 to 0.015] 10 minutes post end of CPB), forced expiratory volume after 1 second/forced vital capacity ratio (0.050 [95% CI, 0.007-0.093] at 6 to 8 weeks pos-surgery), Forced vital capacity alone (95% CI, -0.191 L [-0.394 to 0.012]) and 6-minute walking test score at discharge (63.2 m [95% CI, 12.9-113.6]) were better preserved in the LFV group. No other differences were noted.The use of LFV during CPB in patients undergoing valvular surgery was feasible and safe and was associated with changes in sRAGE levels along with better preserved lung function and walking performance. These observations warrant further investigation in larger future studies.URL: https://www.isrctn.com; Unique Identifier: ISRCTN75795633.
Bristol Trials Centre, Bristol Medical School University of Bristol UK.
Faculty of Life and Health Sciences, Bristol Heart Institute University of Bristol UK.
Respiratory Medicine Southmead Hospital Bristol UK.
Department of Respiratory Medicine University Hospital Bristol and Weston NHS Foundation Trust Bristol UK.
Low Frequency Ventilation During Cardiopulmonary Bypass to Protect Postoperative Lung Function in Cardiac Valvular Surgery: The PROTECTION Phase II Randomized Trial.
Gastroesophageal reflux disease (GERD) is a common disease worldwide with varying clinical presentations and risk factors. Prevalence data for Africa is lacking, but an increasing trend is expected due to demographic and epidemiological transitions. Although endoscopic studies for general gastrointestinal disorders have shown some patients with erosive esophagitis (EE), no studies in Ethiopia have investigated the clinical characteristics, risk factors, and severity of GERD using esophagogastroduodenoscopy (EGD).To assess the clinical features of GERD in Ethiopian patients who underwent EGD and determine the severity and risk factors of EE.We conducted a multicenter, retrospective cross-sectional study of 221 patients diagnosed with GERD and endoscopic findings of EE at Trauma Associated Severe Hemorrhage and Amniotic Membrane Stem Cell between January 2019 and August 2022. Data were collected from electronic medical records and phone call interviews. We used descriptive statistics and binary logistic regression analysis with SPSS version 26 to identify the association between variables with a statistical significance set at P value < 0.05.The mean ± SD age of the patients was 44.8 (± 15.9) years, with a male-to-female ratio of 1.6:1. The most commonly reported symptom was epigastric pain (80.5%), followed by heartburn (43%). Los Angeles (LA)-A EE was diagnosed in 71.1% of patients, followed by LA-B (14.9%), LA-C (7.7%), and LA-D (5.9%). Multivariate analysis showed that age 50 or above, presence of bleeding, and endoscopic findings of duodenitis/duodenopathy were significantly associated with severe EE (P < 0.05). Stricture and Barrett's esophagus were observed in 4.5% and 1.36% of patients with EE, respectively.Most of the patients had milder EE with fewer complications. However, severe EE was more prevalent in older patients and those with duodenitis/duodenopathy.
©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
Department of Internal Medicine, Addis Ababa University, Addis Ababa 1176, Addis Ababa, Ethiopia.Department of Internal Medicine, Rheum Rheumatology and Internal Medicine Specialty Clinic, Addis Ababa 1000, Addis Ababa, Ethiopia. firehiwotabebe671@gmail.com.
Department of Internal Medicine, Addis Ababa University, Addis Ababa 1176, Addis Ababa, Ethiopia.Division of Gastroenterology and Hepatology, Department of Internal Medicine, Adera Medical and Surgical Center, Addis Ababa 1000, Addis Ababa, Ethiopia.
Department of Internal Medicine, Addis Ababa University, Addis Ababa 1176, Addis Ababa, Ethiopia.
Clinical features of gastroesophageal reflux disease and erosive esophagitis: Insights from patients undergoing esophagogastroduodenoscopy in resource-limited Ethiopia.
This double-blind, placebo-controlled, randomized (1:1) clinical trial was conducted at the West China Hospital, Sichuan University, from March to September 2017.Eligible participants included adults aged 18 years and older, living in the community, diagnosed with type 2 Diabetes Mellitus according to ADA guidelines, capable of self-managing their diabetes, and able to visit the study site for follow-up. The intervention group received 25 ml of a probiotic beverage containing with over 10^8 CFU/mL of Lactobacillus, administered four times daily. An equal volume of inactivated Lactobacillus was administered to the control group and the control group was administered the same volume of inactivated Lactobacillus. This study aimed to evaluate the effectiveness of probiotics on glycemic control and other diabetes-related outcomes in patients with type 2 diabetes patients. The primary outcomes were changes in HbA1c and FBG levels post-intervention. Investigators, participants, and study site personnel were blinded to the treatment allocation until the conclusion of the study. This double-blind, randomized, placebo-controlled clinical trial was registered in the Chinese Clinical Trial Registry (ChiCTR-POR-17010850).Of the 490 participants screened, 213 were randomized to either the probiotics group (n = 103) or the placebo group (n = 110). After 16 weeks of follow-up, the probiotic group showed reductions in HbA1c [-0.44 (-0.66 to -0.22)] and FBG [-0.97 (-1.49 to 0.46)] post-intervention, similar to the placebo group with reductions in HbA1c [-0.33 (-0.52 to -0.15)] and FBG [-0.90 (-1.32 to -0.47)], but these changes were not statistically significant in PP and ITT analyses (P>0.05). Adverse events were similarly distributed among groups, indicating comparable safety profiles.Overall, 16-week probiotic supplementation showed no beneficial effects on glycemic control, lipid profiles, or weight.https://www.chictr.org.cn/showproj.html?proj=18421, identifier ChiCTR-POR-17010850.
Copyright © 2024 Peng, Xian, Ge, Hou, Tang, Xie, Gao and Yue.
Department of Geriatrics and National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, China.
Front Endocrinol (Lausanne). 2024;15():1440286.
Effect of probiotics on glycemic control and lipid profiles in patients with type 2 diabetes mellitus: a randomized, double blind, controlled trial.
For treating patients with refractory chronic spontaneous urticaria (CSU) resistant to standard doses of 2nd generation H1-antihistamines (H1AH) the International and Japanese guidelines recommend increasing H1AH dose. The latter also recommends switching to a different H1AH. This study explored if the efficacy of the standard dose of bilastine 20 mg is non-inferior to that of double-dose of H1AH in patients with refractory CSU.This phase IV, multicenter, open-label, randomized, parallel-group trial evaluated the efficacy and safety of switching treatment to bilastine compared to treatment with a 2-fold dose of H1AH in patients with CSU refractory to standard dose H1AH. The primary endpoint was the mean total symptom score (TSS) at Day 5-7 after the start of administration.Treatment efficacy and safety were evaluated in 128 patients (bilastine, n=64; 2-fold dose of H1AH, n=64). The mean TSS at Day 5-7 after the start of administration was smaller than the non-inferiority margin of 0.8, demonstrating non-inferiority of the bilastine switching group to the double-dose H1AH group (0.17 (95% CI -0.32, 0.67)). No difference in Japanese version of Epworth Sleepiness Scale (JESS), DLQI, and urticaria activity score over 7 consecutive days (UAS7) was observed between the two groups. There were no serious adverse events in either group. H1AH-related adverse events occurred in 5 subjects (8 cases) and 2 subjects (3 cases) in the double-dose H1AH and bilastine groups, respectively.Switching treatment to bilastine demonstrated non-inferiority to a double-dose of H1AH in terms of efficacy in patients with CSU refractory to standard dose H1AH with a favorable safety profile.https://jrct.niph.go.jp/latest-detail/jRCTs051180105, identifier jRCTs051180105.
Copyright © 2024 Fukunaga, Kakei, Murakami, Kan, Masuda, Jinnin, Washio, Amano, Nagano, Yamamoto, Otsuka, Takahagi, Takenaka, Ishiguro, Hayama, Inomata, Nakagawa, Sugiyama and Hide.
Department of Dermatology, Division of Medicine for Function and Morphology of Sensory Organs, Faculty of Medicine, Osaka Medical and Pharmaceutical University, Takatsuki, Japan.Department of Dermatology, Kobe University Graduate School of Medicine, Kobe, Japan.
Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.Clinical and Translational Research Center, Kobe University Hospital, Kobe, Japan.
Clinical and Translational Research Center, Kobe University Hospital, Kobe, Japan.
Department of Dermatology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan.
Department of Dermatology, Wakayama Medical University, Wakayama, Japan.
Department of Dermatology, Kobe City Nishi-Kobe Medical Center, Kobe, Japan.
Department of Dermatology, Iwate Medical University School of Medicine, Shiwa-gun, Japan.
Department of Dermatology, Kobe City Medical Center General Hospital, Kobe, Japan.
Department of Dermatology, Takarazuka City Hospital, Takarazuka, Japan.
Department of Dermatology, Division of Medicine for Function and Morphology of Sensory Organs, Faculty of Medicine, Osaka Medical and Pharmaceutical University, Takatsuki, Japan.
Department of Dermatology, School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Department of Dermatology, Nagasaki University School of Biomedical Sciences, Nagasaki, Japan.
Department of Dermatology, Tokyo Women's Medical University, Shinjuku-ku, Japan.
Division of Cutaneous Science, Department of Dermatology, Nihon University School of Medicine, Tokyo, Japan.
Department of Environmental Immuno-Dermatology, Yokohama City University School of Medicine, Yokohama, Japan.
Department of Dermatology, Course of Integrated Medicine, Graduate School of Medicine, Osaka University, Suita, Japan.
Department of Allergology, National Hospital Organization (NHO), Fukuoka National Hospital, Fukuoka, Japan.
Department of Dermatology, School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.Department of Dermatology, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan.
Efficacy and safety of switching to bilastine, an H1-antihistamine, in patients with refractory chronic spontaneous urticaria (H1-SWITCH): a multicenter, open-label, randomized, parallel-group comparative study.
Inspiratory muscle dysfunction is prevalent in chronic obstructive pulmonary disease (COPD). This study aimed to compare the benefits of adding volume incentive spirometry (VIS) to active-cycle-breathing technique (ACBT) and ground-based walking (GBW) training in patients hospitalised for COPD exacerbations. The objectives were to evaluate the impact of early initiation of VIS on respiratory muscle strength, measured by maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP) and the 6-minute walk test (6-MWT), as well as on symptoms, as assessed by the COPD assessment test (CAT) score.This randomised, prospective study was conducted among COPD subjects admitted with exacerbation between June 2021 and August 2022. Subjects were randomly assigned to either the VIS (interventional group) or the control group. Baseline assessments, including spirometry, MIP, CAT score, and the 6-minute walk test (6MWT), were performed. Both groups commenced active cycle of breathing techniques (ACBT) and groundbased walking (GBW) training within 72 hours of admission, with daily sessions involving three repetitions of each phase to complete one cycle, repeated three times daily. The intervention group received VIS. Upon discharge, subjects were provided with a diary and instructed to continue a home-based pulmonary exercise regimen, performed for at least 15 minutes per day, 3 days a week, with compliance monitored through weekly phone calls. At the 4-week followup, repeat assessments of spirometry, MIP, maximal expiratory pressure (MEP), CAT score and 6MWT were conducted to evaluate the outcomes.A total of 34 subjects with a median age of 68 years (interquartile range [IQR] 65-74.3 years). The cohort predominantly males (32 subjects, 94%). The distribution of disease severity was as follows: GOLD 2 in 15 subjects (44%) and GOLD 3 in 14 subjects (41%). Additionally, 17 subjects (50%) had experienced three or more exacerbations in the preceding year. The majority of patients (29 out of 34, 85%) had a length of stay of less than 7 days. In the interventional group, the median MIP improved from 50 cm H2O (IQR 40.5-70.5) to 59 cm H2O (IQR 39-76.5), though this was not statistically significant (p = 0.407). The control group saw an improvement from 58 cm H2O (IQR 36.5-85) to 60 cm H2O (IQR 33-88), also not statistically significant (p = 0.112). The 6MWT distance improved in the interventional group from 220 meters (IQR 118-275) to 260 meters (IQR 195-327) (p = 0.002) and in the control group from 250 meters (IQR 144-294) to 280 meters (IQR 213-359.5) (p = 0.001). The median CAT score decreased significantly in the interventional group from 22 (IQR 16-28) to 11 (IQR 7.5-13) (p < 0.001) and in the control group from 21 (IQR 14-24.5) to 10 (IQR 8-12.5) (p < 0.001).Early initiation of pulmonary rehabilitation in patients with acute exacerbations, characterised by poor muscle strength and a history of exacerbations, resulted in significant improvements in patient-reported symptoms and 6MWT outcomes. Although there was only a numerical improvement in MIP and MEP, the intervention did not extend the length of hospital stay, highlighting its safety and efficacy in the acute care setting.
Universiti Kebangsaan Malaysia, Hospital Canselor Tuanku Muhriz, Faculty of Medicine, Department of Medicine, Respiratory Unit, Kuala Lumpur, Malaysia.
Universiti Kebangsaan Malaysia, Hospital Canselor Tuanku Muhriz, Faculty of Medicine, Department of Medicine, Respiratory Unit, Kuala Lumpur, Malaysia. niknuratiqah1984@gmail.com.
Universiti Kebangsaan Malaysia, Faculty of Medicine, Department of Community Health, Kuala Lumpur, Malaysia.
Universiti Kebangsaan Malaysia, Hospital Canselor Tuanku Muhriz, Faculty of Medicine, Department of Paediatrics, Kuala Lumpur, Malaysia.
The benefits of early pulmonary rehabilitation with incentive spirometer among chronic obstructive pulmonary disease patients with exacerbation of chronic obstructive pulmonary disease.
A growing body of research indicates significant differences between left-sided colon cancers (LCC) and right-sided colon cancers (RCC). Pan-immune-inflammation value (PIV) is a systemic immune response marker that can predict the prognosis of patients with colon cancer. However, the specific distinction between PIV of LCC and RCC remains unclear.To investigate the prognostic and clinical significance of PIV in LCC and RCC patients.This multicenter retrospective cohort study included 1510 patients with colon cancer, comprising 801 with LCC and 709 with RCC. We used generalized lifting regression analysis to evaluate the relative impact of PIV on disease-free survival (DFS) in these patients. Kaplan-Meier analysis, as well as univariate and multivariate analyses, were used to examine the risk factors for DFS. The correlation between PIV and the clinical characteristics was statistically analyzed in these patients.A total of 1510 patients {872 female patients (58%); median age 63 years [interquartile ranges (IQR): 54-71]; patients with LCC 801 (53%); median follow-up 44.17 months (IQR 29.67-62.32)} were identified. PIV was significantly higher in patients with RCC [median (IQR): 214.34 (121.78-386.72) vs 175.87 (111.92-286.84), P < 0.001]. After propensity score matching, no difference in PIV was observed between patients with LCC and RCC [median (IQR): 182.42 (111.88-297.65) vs 189.45 (109.44-316.02); P = 0.987]. PIV thresholds for DFS were 227.84 in LCC and 145.99 in RCC. High PIV (> 227.84) was associated with worse DFS in LCC [PIV-high: Adjusted hazard ratio (aHR) = 2.39; 95% confidence interval: 1.70-3.38; P < 0.001] but not in RCC (PIV-high: aHR = 0.72; 95% confidence interval: 0.48-1.08; P = 0.114).These findings suggest that PIV may predict recurrence in patients with LCC but not RCC, underscoring the importance of tumor location when using PIV as a colon cancer biomarker.
Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Medical Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China.
Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China. wubin@pumch.cn.
Pan-immune-inflammation value as a prognostic biomarker for colon cancer and its variation by primary tumor location.
This paper aims to investigate the impact of conventional rehabilitation training and neuromuscular electrical stimulation (NMES) on the recovery of motor abilities in patients following ligament injury reconstruction. Forty postoperative patients who underwent surgery for anterior cruciate ligament reconstruction (ACLR) were randomly allocated to either the conventional rehabilitation group or the NMES group. The NMES group received NMES treatment in addition to the conventional rehabilitation program starting from eight weeks postoperatively. Various parameters, including knee joint function, stability, and balance, were compared between the two groups at eight weeks and 12 weeks postoperatively. Compared to the data at eight weeks postoperatively, both groups exhibited significant improvements in all measured indicators at 12 weeks postoperatively (p < 0.05). In the 12th week after the surgery, the NMES group demonstrated a Lysholm score of 93.18 ± 3.67 points, an IKDC score of 84.65 ± 2.33 points, a KT-2000 measurement of 0.88 ± 0.45 mm, a thigh circumference difference of -1.33 ± 0.55 cm, a knee flexion angle of 130.12 ± 4.21°, a single-leg standing time of 60.12 ± 9.33 s, a YBT score of 70.26 ± 2.68 points, and a Bulgarian split squat 1RM size of 58.07 ± 6.85 kg; all of these results were significantly superior to those observed in the conventional group (p < 0.05). NMES significantly enhances the recovery of athletic ability in patients following postoperative ACLR and can be effectively applied in clinical practice.
Nanchang Institute of Technology, Nanchang, Jiangxi, China.
Journal of medical engineering & technology
Effects of combining rehabilitation training on the recovery of athletic ability after reconstruction of injured ligament.
Community acquired bloodstream infection (CA-BSI) is positive blood culture obtained within 48 hours of hospital admission. Bloodstream infections need to be treated with antibiotics. Inappropriate choice of antibiotics will lead to antimicrobial resistance. This is an observational retrospective study to look at the antimicrobial resistance of organisms causing bloodstream infections in patients admitted to the medical wards in our centre. The aim of the study is to determine the appropriate choice of empirical antibiotics for suspected CA-BSI in our hospital.All patients admitted to medical wards with blood stream infection during the period January 2021 to June 2021 were enrolled. Identification of organisms and antimicrobial susceptibility testing were obtained. Information regarding the severity of the bacteremia was collected by assessing if the patient needed inotropes, mechanical ventilation or renal replacement therapy. Data on comorbidities which were the presence of end-stage renal failure, diabetic mellitus and immunosuppression were collected.Total of 269 cases were screened. Out of these 104 communities acquired cases were included. The pathogens frequently isolated were gram negative organisms most commonly Escherichia coli (43%) and Klebsiella species (30%). Staphylococcus aureus accounts for the majority of gram-positive organisms. Only two out of 20 Staphylococcus aureus were methicillin resistant. Bulkholderia pseudomallei accounts for 7.8% cases. All Burkholderia pseudomallei isolates were sensitive to cotrimoxazole. Escherichia coli (46%) isolates demonstrated a higher resistance pattern to Augmentin compared to klebsiella species (17.4%). The overall mortality rate was 22%, with higher rates for those critically ill (39%). Patients with Enterobacteriaceae infection showed no difference in outcome between the groups of patients according to sensitivity to Augmentin and cefotaxime. These groups of patients who were critically ill did not demonstrate any significant difference in terms of resistance pattern to Augmentin (p = 0.3) and cefotaxime (p = 0.7). Patients who are aged 65 or older have a significantly more resistant pattern to Augmentin and cefotaxime.Antibiogram serves as a guide for clinicians to choose appropriate choices of antibiotics based on local data. Empirical antibiotics of choice for patients with sepsis should be narrow-spectrum beta lactam/beta lactamase inhibitors. Broad spectrum beta lactam/beta lactamase inhibitors such as piperacillin tazobactam should be reserved for patients who are critically ill and elderly patients over 65 years. The antibiotics should be deescalated once the organisms and sensitivity of the antibiotics are known.
Hospital Tuanku Ja'afar, Department of Medicine, Seremban, Malaysia. suganthini2411@gmail.com.
Hospital Tuanku Ja'afar, Department of Medicine, Seremban, Malaysia.
Hospital Tuanku Ja'afar, Department of Microbiology, Seremban, Malaysia.
Organisms causing community-acquired bloodstream infection in medical department: A single centre retrospective observational study.
Patients with epistaxis typically visit the emergency department for initial treatment. According to recent studies, tranexamic acid (TXA) is effective in the treatment of epistaxis. This study compared the therapeutic superiority of saline to that of 500 and 1000 mg doses of topical TXA for the treatment of anterior epistaxis. Materials and methods: This phase 4 clinical trial was a randomized, controlled, and double-blind trial. A total of 152 patients were divided into three groups. Group 1 was treated with 1000 mg TXA, Group 2 with 500 mg TXA, and Group 3 with saline. Results: Based on multinomial logistic regression analysis, the bleeding frequency at the 5th minute was 2.9 times and rebleeding status was 4.3 times less in Group 1 (1000 mg TXA) than in Group 3 (saline). There were no differences between the three groups in terms of side effects or salvage therapy. Conclusion: In addition to its superiority in treatment, 1000 mg of TXA is recommended because of the decreased rate of recurrent bleeding and low incidence of side effects.
Department of Emergency Medicine, İzmir Ataturk Training and Research Hospital, Izmir, Turkey.Department of Emergency Medicine, Soma State Hospital, Manisa, Turkey.
Department of Emergency Medicine, İzmir Ataturk Training and Research Hospital, Izmir, Turkey.
Appropriate dose of tranexamic acid in the topical treatment of anterior epistaxis, 500 mg vs 1000 mg: A double-blind randomized controlled trial.
Tuberculosis (TB) is a serious global health problem in Indonesia, which is the country with the secondhighest TB burden after India. Accuracy in TB diagnosis is the key to effective treatment and decreased transmission rate. One of the latest diagnostic methods is interferon gamma release assay (IGRA), which measures the interferon-γ release associated with Mycobacterium tuberculosis (MTB) infection. This study aims to determine the diagnostic value of IGRA-TB using IchromaTM IGRA-TB diagnostic kit (sensitivity, specificity, positive predictive value [PPV], and negative predictive value [NPV]), compared to Ziehl-Neelsen (AFB) staining, nucleic acid amplificationbased test (Xpert-MTB) and chest-X Ray as the gold standard in TB diagnosis.A cross-sectional observational study design was used. Patients were recruited through purposive sampling from pulmonology outpatient clinic and inpatient ward at Jemursari Islamic Hospital (RSI Jemursari), Surabaya from July 2023 to December 2023. All enrolled patients should have been previously tested positive or negative for pulmonary TB using AFB staining, Xpert MTB and chest x-ray. Blood samples of the patients were collected and processed using the IchromaTM IGRA-TB diagnostic kit. The results were then compared with gold standard methods for calculating the IGRA-TB diagnostic value.A total of 56 adult patients were enrolled in this study. The sensitivity, specificity, PPV, NPV and accuracy rate of IGRA-TB using IchromaTM IGRA-TB diagnostic kit were 80.56%, 85%, 90.62%, 70.83% and 82.14%, respectively.IchromaTM IGRA-TB showed reasonably high diagnostic sensitivity and specificity, indicating that this method can be further utilised as a diagnostic and screening tool for pulmonary TB.
Universitas Nahdlatul Ulama, Faculty of Medicine, Department of Clinical Pathology, Surabaya, Indonesia. dr.bastiana@unusa.ac.id.
Universitas Nahdlatul Ulama, Faculty of Medicine, Department of Clinical Pathology, Surabaya, Indonesia.
Jemursari Islamic Hospital, Department of Clinical Pathology, Surabaya, Indonesia.
Universitas Nahdlatul Ulama, Faculty of Medicine, Research and Community Service Unit, Surabaya, Indonesia.
Pulmonary tuberculosis diagnostic test using fluorescence immunoassay-based interferon gamma release assay with IchromaTM IGRA-TB.
The period after psychiatric hospital discharge is one of elevated risk for suicide-related behaviors (SRBs). Post-discharge clinical outreach, although potentially effective in preventing SRBs, would be more cost-effective if targeted at high-risk patients. To this end, a machine learning model was developed to predict post-discharge suicides among Veterans Health Administration (VHA) psychiatric inpatients and target a high-risk preventive intervention.The Veterans Coordinated Community Care (3C) Study is a multicenter randomized controlled trial using this model to identify high-risk VHA psychiatric inpatients (n = 850) randomized with equal allocation to either the Coping Long Term with Active Suicide Program (CLASP) post-discharge clinical outreach intervention or treatment-as-usual (TAU). The primary outcome is SRBs over a 6-month follow-up. We will estimate average treatment effects adjusted for loss to follow-up and investigate the possibility of heterogeneity of treatment effects.Recruitment is underway and will end September 2024. Six-month follow-up will end and analysis will begin in Summer 2025.Results will provide information about the effectiveness of CLASP versus TAU in reducing post-discharge SRBs and provide guidance to VHA clinicians and policymakers about the implications of targeted use of CLASP among high-risk psychiatric inpatients in the months after hospital discharge.ClinicalTrials.Gov identifier: NCT05272176 (https://www.gov/ct2/show/NCT05272176).
© 2024 The Author(s). International Journal of Methods in Psychiatric Research published by John Wiley & Sons Ltd.
Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, Rhode Island, USA.
Center of Excellence for Suicide Prevention, Canandaigua VA Medical Center, Canandaigua, New York, USA.Department of Psychiatry, University of Rochester Medical Center, Rochester, New York, USA.
Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA.
VA St. Louis Healthcare System, St. Louis, Missouri, USA.
Center of Excellence for Suicide Prevention, Canandaigua VA Medical Center, Canandaigua, New York, USA.Department of Psychiatry and Behavioral Neurosciences, University of South Florida, Tampa, Florida, USA.
Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA.VA Boston Healthcare System, Boston, Massachusetts, USA.
VA Center to Improve Veteran Involvement in Care (CIVIC), Portland, Oregon, USA.
Tennessee Valley Healthcare System, Nashville, Tennessee, USA.
Department of Health Care Policy, Harvard Medical School, Boston, Massachusetts, USA.
VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, USA.Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Department of Psychiatry, Baptist Health-UAMS Medical Education Program, North Little Rock, Arkansas, USA.Psychiatric Research Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA.Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA.
Behavioral Health Quality Enhancement Research Initiative (QUERI), Central Arkansas Veterans Healthcare System, North Little Rock, Arkansas, USA.Department of Psychiatry, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Center of Excellence for Suicide Prevention, Canandaigua VA Medical Center, Canandaigua, New York, USA.Department of Health Care Policy, Harvard Medical School, Boston, Massachusetts, USA.
Department of Statistics, University of Washington, Seattle, Washington, USA.Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
National Center for PTSD, VA Boston Healthcare System, Boston, Massachusetts, USA.Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts, USA.
VA North Texas Healthcare System, Dallas, Texas, USA.
Department of Psychology, Harvard University, Cambridge, Massachusetts, USA.
Psychiatric Research Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.Central Arkansas Veterans Healthcare System, Little Rock, AR, USA.
VA North Texas Healthcare System, Dallas, Texas, USA.Department of Psychiatry, UT Southwestern Medical Center, Dallas, Texas, USA.
Minneapolis VA Healthcare System, Minneapolis, Minnesota, USA.Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, Minnesota, USA.
International journal of methods in psychiatric research
Int J Methods Psychiatr Res. 2024-12;33(4):e70003.
Design of a multicenter randomized controlled trial of a post-discharge suicide prevention intervention for high-risk psychiatric inpatients: The Veterans Coordinated Community Care Study.
The COVID-19 pandemic in Argentina has challenged health professionals to implement teleconsultation to maintain continuity of care.Describe the implementation of new technologies in teleconsultation by Nutrition professionals from Entre Ríos, from the beginning of the ASPO to the new normal.Methodology: Observational, descriptive, quantitative, and cross-sectional study, in which 72 Nutrition professionals from Entre Ríos, Argentina participated through a self-administered online questionnaire. The descriptive analysis of the data was carried out in the IBM® SPSS Statistics program.84.7% of professionals began to implement new technologies in teleconsultation since the beginning of the ASPO. Although the majority did not experience significant changes in their income, relationships with patients, or time spent in teleconsultation compared to in-person care, 78% did not receive specific training for the implementation of these technologies in remote care. Despite this challenge, 80% expressed their intention to continue with this type of care in the new normal, allocating hours of their workload for this purpose.The implementation of new technologies in teleconsultation has proven to be an ally in maintaining the continuity of nutritional care since the beginning of ASPO. However, to provide a quality service, it is necessary to select the most appropriate technologies and dedicate sufficient time to planning and implementation.
Facultad de Bromatología, Universidad Nacional de Entre Ríos (UNER).
UNER - Facultad de Bromatología e ICTAER CONICET-UNER.
Revista de la Facultad de Ciencias Medicas (Cordoba, Argentina)
La pandemia de COVID-19 en Argentina ha desafiado a los profesionales de la salud a implementar la teleconsulta para mantener la continuidad de la atención. Describir la implementación de nuevas tecnologías en la teleconsulta por profesionales en Nutrición de Entre Ríos, desde el inicio del ASPO hasta la nueva normalidad. Metodología: Estudio observacional, descriptivo, cuantitativo y transversal, en el que participaron 72 profesionales en Nutrición de Entre Ríos, Argentina a través de un cuestionario en línea autoadministrado. El análisis descriptivo de los datos se realizó en el programa IBM® SPSS Statistics. El 84,7% de los profesionales comenzó a implementar nuevas tecnologías en la teleconsulta desde el inicio del ASPO. Aunque la mayoría no experimentó cambios significativos en sus ingresos, la relación con los pacientes ni en el tiempo dedicado a la teleconsulta en comparación con la atención presencial, el 78% no recibió capacitación específica para la implementación de estas tecnologías en la atención remota. A pesar de este desafío, el 80% expresó su intención de continuar con esta modalidad de atención en la nueva normalidad, asignando horas de su carga horaria para este propósito. La implementación de nuevas tecnologías en la teleconsulta ha demostrado ser un aliado para mantener la continuidad de la atención nutricional desde el inicio del ASPO. Sin embargo, para brindar un servicio de calidad, es necesario seleccionar las tecnologías más apropiadas y de dedicar suficiente tiempo a la planificación e implementación.
Rev Fac Cien Med Univ Nac Cordoba. 2024-09-27;81(3):570-586.
[Implementation of new technologies in nutritional teleconsultation by Nutrition Graduates from Entre Ríos, Argentina]
This study investigated symptoms of anxiety and depression, feelings of loneliness, and life satisfaction among low-to-middle income Peruvian adolescents during 2 years of remote schooling due to the COVID-19 lockdown.We used a four-wave longitudinal observational approach. Data were collected in April 2020, October 2020, June 2021, and November 2021 in Perú. A total of 2,392 adolescents (ages 10-15; 57% female) participated in the study. We described longitudinal changes in symptoms of anxiety and depression, feelings of loneliness, and life satisfaction across the four time points and investigated sex and school grade differences.Symptoms of anxiety, depression, and loneliness increased, and life satisfaction decreased over the course of 2 years of remote education. The rate of change was different for each outcome of well-being. We found robust sex differences for all outcomes. In addition, we found school grade differences for anxiety and depression.The mental health and well-being of Peruvian adolescents, particularly female adolescents, declined during 2 years of remote education, despite loosening of other pandemic restrictions. Depression appears to have the earliest impacts, with anxiety levels showing even some improvement for male adolescents. School grade differences in levels of anxiety and depression for seventh and eighth graders in 2020 and 2021 provide initial evidence to disentangle pandemic from developmental effects.
Copyright © 2024 Society for Adolescent Health and Medicine. All rights reserved.
Department of Psychology, University of Washington, Seattle, Washington.
School of Public Health, University of California, Berkeley, California.
Department of Psychology, Pontificia Universidad Católica del Perú, Lima, Peru.
Department of Psychology, University of Washington, Seattle, Washington. Electronic address: luciamw@uw.edu.
The Journal of adolescent health : official publication of the Society for Adolescent Medicine
Peruvian Adolescent Mental Health Across Two Years of the COVID-19 Pandemic: A Four Time-Point Longitudinal Study.
Department of Neurology and Neurosurgery, Universidade Federal de São Paulo, São Paulo, Brazil.
Department of Neurology and Neurosurgery, Universidade Federal de São Paulo, São Paulo, Brazil marianna.m.moraes@gmail.com.
Departament of Pathology, UNIFESP, Sao Paulo, Brazil.
Acute spinal cord compression due to extramedullary haematopoiesis.
This study aimed to examine the effect of a commercially available multi-ingredient powder (AG1Ⓡ) on the gut microbiome and assess the impact of AG1Ⓡ on GI tolerability and other clinical safety markers in healthy men and women.Using a double-blind, randomized, two-arm, placebo-controlled, parallel design, we examined a 4-week daily supplementation regimen of AG1Ⓡ vs. placebo (PL). Fifteen men and 15 women provided stool samples for microbiome analysis, questionnaires for digestive quality of life (DQLQ), and completed visual analog scales (VAS) and Bristol stool charts to assess stool consistency and bowel frequency before and after the 4-week intervention. Participant's blood work (CBC, CMP, and lipid panel) was also assessed before and after the 4-week intervention. Alpha diversity was determined by Shannon and Chao1 index scores and evaluated by a two-way ANOVA, beta diversity in taxonomic abundances and functional pathways was visualized using partial least squares-discriminant analyses and statistically evaluated by PERMANOVA. To identify key biomarkers, specific feature differences in taxonomic relative abundance and normalized functional pathway counts were analyzed by linear discriminant analysis (LDA) effect size (LEfSe). Questionnaires, clinical safety markers, and hemodynamics were evaluated by mixed factorial ANOVAs with repeated measures. This study was registered on clinicaltrials.gov (NCT06181214).AG1Ⓡ supplementation enriched two probiotic taxa (Lactobacillus acidophilus and Bifidobacterium bifidum) that likely stem from the probiotics species that exist in the product, as well as L. lactis CH_LC01 and Acetatifactor sp900066565 ASM1486575v1 while reducing Clostridium sp000435835. Regarding community function, AG1Ⓡ showed an enrichment of two functional pathways while diminishing none. Alternatively, the PL enriched six, but diminished five functional pathways. Neither treatment negatively impacted the digestive quality of life via DQLQ, bowel frequency via VAS, or stool consistency via VAS and Bristol. However, there may have been a greater improvement in the DQLQ score (+62.5%, p = 0.058, d = 0.73) after four weeks of AG1Ⓡ supplementation compared to a reduction (-50%) in PL. Furthermore, AG1Ⓡ did not significantly alter clinical safety markers following supplementation providing evidence for its safety profile.AG1Ⓡ can be consumed safely by healthy adults over four weeks with a potential beneficial impact in their digestive symptom quality of life.
The Center for Applied Health Sciences, Canfield, OH, USA.
AG1, Research, Nutrition, and Innovation, Carson City, NV, USA.
AG1, Research, Nutrition, and Innovation, Carson City, NV, USA.Concordia University Chicago, Health & Human Performance, River Forest, IL, USA.
Journal of the International Society of Sports Nutrition
The effects of AG1® supplementation on the gut microbiome of healthy adults: a randomized, double-blind, placebo-controlled clinical trial.
An aerobic, Gram-stain negative bacterium was isolated from sediment samples of Barkol salt lake in Hami City, Xinjiang Uygur Autonomous Region, China, with the number EGI_FJ10229T. The strain is ellipse-shaped, oxidase-negative, catalase-positive, and has white, round, smooth, opaque colonies on marine 2216 E agar plate. Growth occurs at 4.0-37.0 ℃ (optimal:30.0 ℃), pH 7.0-9.0 (optimal: pH 8.0) and NaCl concentration of 0-8.0% (optimal: 3.0%). Phylogenetic analysis based on 16S rRNA gene and genome sequences indicated that the isolated strain should be assigned to the genus Aquibaculum and was most closely related to Aquibaculum arenosum CAU 1616 T. Average nucleotide identity (ANI) and Average amino-acid identity (AAI) values between the type species of the genus Aquibaculum and other related type species were lower than the threshold values recommended for bacterial species. The genomic DNA G + C content of EGI_FJ10229T was 65.41%. The major polar lipids were diphosphatidylglycerol, phosphatidylmethylethanolamine, phosphatidylcholine, phosphatidylethanolamine and unidentified phospholipid. The major fatty acids (> 5%) were C19:0 cyclo ω8c (42.0%) and C18:1 ω7c (33.78%). The respiratory quinone identified was Q-10. Differential phenotypic and genotypic characteristics of this strain and species of genus Aquibaculum showed that the strain should be classified as representing a new species belonging to this genus, for which the name Aquibaculum sediminis sp. nov. is proposed. The type strain of the proposed novel species is EGI_FJ10229T (= KCTC 8570 T = GDMCC 1.4598 T).
Key Laboratory of Ecological Safety and Sustainable Development in Arid Lands, Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, Urumqi, 830011, People's Republic of China.University of Chinese Academy of Sciences, Beijing, 100049, People's Republic of China.
State Key Laboratory of Biocontrol, Guangdong Provincial Key Laboratory of Plant Stress Biology and Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), School of Life Sciences, Sun Yat-Sen University, Guangzhou, 510275, People's Republic of China.
Key Laboratory of Ecological Safety and Sustainable Development in Arid Lands, Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, Urumqi, 830011, People's Republic of China.Xinjiang Key Laboratory of Biodiversity Conservation and Application in Arid Lands, Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, Urumqi, 830011, People's Republic of China.
Guangdong University of Education, Guangzhou, 510275, Guangdong, People's Republic of China.
Key Laboratory of Ecological Safety and Sustainable Development in Arid Lands, Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, Urumqi, 830011, People's Republic of China. fangbaozhu2009@126.com.Xinjiang Key Laboratory of Biodiversity Conservation and Application in Arid Lands, Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, Urumqi, 830011, People's Republic of China. fangbaozhu2009@126.com.
Key Laboratory of Ecological Safety and Sustainable Development in Arid Lands, Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, Urumqi, 830011, People's Republic of China. liwenjun3@mail.sysu.edu.cn.Xinjiang Key Laboratory of Biodiversity Conservation and Application in Arid Lands, Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, Urumqi, 830011, People's Republic of China. liwenjun3@mail.sysu.edu.cn.State Key Laboratory of Biocontrol, Guangdong Provincial Key Laboratory of Plant Stress Biology and Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), School of Life Sciences, Sun Yat-Sen University, Guangzhou, 510275, People's Republic of China. liwenjun3@mail.sysu.edu.cn.
Aquibaculum sediminis sp. nov., a halotolerant bacteria isolated from salt lake sediment.
To evaluate the hemodynamic effects and the safety profile of fluid bolus resuscitation with hypertonic saline albumin (HSA) in critically ill children, we performed a prospective observational pilot study between October 2018 and May 2021 in the pediatric intensive care unit (PICU) in a tertiary hospital in Madrid, Spain. Sixty-four HSA boluses were analyzed in 23 patients. A mean volume of 5.7 ml/kg (Standard Deviation, SD 2.3 ml/kg) per bolus was infused. Acute hypotension was the main indication. 91% of the patients had a cardiac disease, 56% of them had undergone cardiac surgery in the previous 72 h, and 47.8% associated right ventricular dysfunction. A significant increase in systolic, mean, and diastolic blood pressure and a decrease in the vasoactive index was observed after the infusion of HSA. This effect lasted for twenty-four hours (p < 0.05). Moreover, the amount of fluid requirements decreased significantly in the 6 h following HSA infusion [8.7 ml/kg (SD 9.6) vs. 15.1 ml/kg (SD 13.6) in the previous 6 h (p < 0.05)]. Serum levels of sodium and chloride increased after the infusion, reaching their peak concentration after one hour (143 mEq/L (SD 3.5) and 109.7 mEq/L (SD 6) respectively). HSA-related metabolic acidosis or acute kidney injury were not observed in this study. Hypertonic saline albumin is safe and effective when infused at a dose of 5 ml/kg in critically ill children. However, further research is required to confirm our findings.
Pediatric Intensive Care Department, Hospital General Universitario Gregorio Marañón, Dr Castelo 47, 28009, Madrid, Spain.Gregorio Marañón Health Research Institute, Madrid, Spain.Primary Care Interventions to Prevent Maternal and Child Chronic Diseases of Perinatal and Development Origin Network (RICORS) RD21/0012/0011, Carlos III Health Institute, Madrid, Spain.
Pediatric Intensive Care Department, Hospital General Universitario Gregorio Marañón, Dr Castelo 47, 28009, Madrid, Spain.
Gregorio Marañón Health Research Institute, Madrid, Spain.
Pediatric Intensive Care Department, Hospital General Universitario Gregorio Marañón, Dr Castelo 47, 28009, Madrid, Spain. pielvi@hotmail.com.Gregorio Marañón Health Research Institute, Madrid, Spain. pielvi@hotmail.com.Primary Care Interventions to Prevent Maternal and Child Chronic Diseases of Perinatal and Development Origin Network (RICORS) RD21/0012/0011, Carlos III Health Institute, Madrid, Spain. pielvi@hotmail.com.Maternal and Child Public Health Department, School of Medicine, Complutense University of Madrid, Madrid, Spain. pielvi@hotmail.com.
Fluid bolus resuscitation with hypertonic saline albumin solution in critically ill children: a prospective observational pilot study.
Medication use during pregnancy is a critical concern due to potential risks to both the mother and fetus. To the extent of our knowledge, there has been no prior research to assess medication use and identify the specific factors of pregnant women within the Yemeni community. This study aimed to investigate the knowledge, beliefs, and practices of Yemeni pregnant women regarding medication use and assess the factors associated with the knowledge during pregnancy.A cross-sectional multi-center study was conducted through face-to-face interviews using a validated structured questionnaire. The study was conducted on pregnant women receiving antenatal care at tertiary care hospitals in four governorates in Yemen. Univariable and multivariate logistic regressions were employed to examine the relationship between participant variables and their knowledge. A P-value of less than .05 was considered statistically significant.Out of the 1003 pregnant women, 35.4% (n = 355) were aged 21-25 years, 33.9% (n = 340) had primary education, 73.6% (n = 738) lived in urban areas, 12.2% (n = 122) were smokers, 38.3% (n = 384) reported chewing khat, and the majority (90.2%, n = 905) were unemployed. Also, 65.5% (n = 657) of the participants reported taking folic acid in their current pregnancy. A total of 2,623 medications were utilized during pregnancy, with 17.8% during the first trimester (n = 468). Around 39.3% (n = 1,037) of medications used fell under the blood and blood-forming organs category. Education level (AOR: 4.00, P < .001), insurance status (AOR: 1.71, P = .026), information about medication risks to the fetus (AOR: 1.96, P = .023), the use of folic acid either in a previous pregnancy (AOR: 1.65, P < .008) or in the current pregnancy (AOR: 4.26, P < .001), and checking the medication leaflet (AOR: 5.67, P < .001) were predictors of higher knowledge.The findings underscore the pressing need for educational interventions aimed at pregnant women. By bridging knowledge gaps and promoting informed decision-making, such initiatives can contribute to a safer and healthier pregnancy journey, reducing the inclination towards self-medication.
Copyright: © 2024 Al-khawlani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Department of Pharmacy, College of Medical Sciences, AL-Saeeda University, Dhamar, Yemen.Institute of Pharmaceutical Chemistry, Philipps University of Marburg, Marburg, Germany.
Department of Clinical Pharmacy, College of Pharmacy, Al-Ayen Iraqi University, Thi-Qar, Iraq.
Department of Clinical Pharmacy and Pharmacy Practice, University of Science and Technology, Sana'a, Yemen.Discipline of Clinical Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia.
Faculty of Pharmacy, Applied Science Private University, Amman, Jordan.
Department of Clinical Practice, College of Pharmacy, Northern Border University, Rafha, Saudi Arabia.
Department of Clinical Pharmacy, College of Pharmacy, Al-Ayen Iraqi University, Thi-Qar, Iraq.Department of Clinical Pharmacy and Pharmacy Practice, University of Science and Technology, Sana'a, Yemen.
Insights and perceptions: Investigating pregnant women's attitudes, understanding, and factors influencing knowledge regarding medication usage during pregnancy-A cross-sectional study.
Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
Department of Radiology, Addenbrooke's Hospital, Cambridge, UK.
Mental Health and Clinical Neuroscience, University of Nottingham, Nottingham, UK.
Radiological Sciences, Division of Clinical Neuroscience, University of Nottingham, Nottingham, UK.
Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK ahensiek@nhs.net.
J Neurol Neurosurg Psychiatry. 2025-01-16;96(2):202-204.
Novel observation for adult ataxia-telangiectasia: evaluating the lack of hypointensity of the dentate nuclei.
The United States' current Seafood Import Monitoring Program (SIMP) and a potential extension are undergoing review, yet quantitative evaluation of the current program is lacking. The SIMP is a traceability program aimed at reducing imports of seafood products that are of illegal, unreported, and unregulated (IUU) origin or associated with seafood fraud. We conducted a quantitative examination of the SIMP's current scope and design by synthesizing publicly available trade data along with measures of IUU fishing and seafood mislabeling. We found prioritized shipments amounted to 33% of 2016 imported tonnage. The SIMP species groups had higher IUU scores and mislabeling rates relative to non-SIMP groups, but the difference was consistent with random prioritization suggesting potential benefits from program expansion. Furthermore, two-thirds of imported volume lacked a mislabeling rate and 5% lacked species information, underlining the urgent need for improved open-access data on globalized seafood supply chains.
Resources for the Future, 1616 P St NW, Washington, DC, 20036, USA.
Resources for the Future, 1616 P St NW, Washington, DC, 20036, USA. kkroetz@asu.edu.School of Sustainability, Arizona State University, 777 E University Dr, Tempe, AZ, 85281, USA. kkroetz@asu.edu.
School of Sustainability, Arizona State University, 777 E University Dr, Tempe, AZ, 85281, USA.
School of Aquatic and Fishery Sciences, University of Washington, 1122 NE Boat St Box 355020, Seattle, WA, 98195, USA.
Advanced Conservation Strategies, PO Box 413, Midway, UT, 84049, USA.
Advanced Conservation Strategies, PO Box 413, Midway, UT, 84049, USA.Cornell Lab of Ornithology, Cornell University, 159 Sapsucker Woods Road, Ithaca, NY, 14850, USA.
Seafood traceability program design: Examination of the United States' Seafood Import Monitoring Program.
The urban development of Rome (Italy) has been intertwined with the dynamics of the Tiber River since its foundation. In this review paper, we analyse more than 2500 years of flood history and urban development to untangle the dynamics of flood risk and assess the resulting socio-hydrological phenomena. Until the 1800s, urban dwellers living in the riparian areas of the Tiber River were accustomed to frequent flooding. From the 1900s, the construction of flood walls reshaped the co-evolution of hydrological, economic, political, technological, and social processes. As a result, while the probability of flooding is currently very low, its potential adverse consequences would be catastrophic. From the analysis of the long-term feedback between urban development of Rome and flood events from ancient times to present days, it emerges the crucial need for an effective flood risk mitigation strategy that combines structural and non-structural measures. In particular, heightened flood risk awareness and preparedness to cope with rare but potentially devastating events is key to alleviate flood risk.
Dipartimento di Ingegneria Civile, Edile e Ambientale, Università Degli Studi di Roma La Sapienza, 00184, Rome, Italy. elena.ridolfi@uniroma1.it.
Dipartimento di Ingegneria Civile, Edile e Ambientale, Università Degli Studi di Roma La Sapienza, 00184, Rome, Italy.
Department of Earth Sciences, Uppsala University, Uppsala, Sweden.Centre of Natural Hazards and Disaster Science, Uppsala, Sweden.
The interplay between the urban development of Rome (Italy) and the Tiber River floods: A review of two millennia of socio-hydrological history.
Encephalitis originates from diverse autoimmune and infectious etiologies. Diagnostic challenges arise due to the spectrum of presentation and the frequent absence of specific biomarkers. This study aimed to comprehensively characterize and differentiate autoimmune encephalitis (AE) from infectious encephalitis (IE) in adults, and disentangle clinical, paraclinical, and therapeutic differences.A cohort study spanning 10 years was conducted across three Austrian tertiary care hospitals. Inclusion criteria comprised adults with probable or definite encephalitis. Demographics, clinical features, technical findings, treatment modalities, and outcomes were collected from the electronic patient files. A follow-up was performed via telephone interviews and clinical visits.Of 149 patients, 17% had AE, 73% IE, and 10% encephalitis of unknown etiology. Significant differences between AE and IE included the prevalence of acute symptomatic seizures (AE: 85% vs. IE: 20%, p < 0.001), fever (8% vs. 72%, p < 0.001), headache (15% vs. 61%, p < 0.001), and focal neurological deficits (56% vs. 23%, p = 0.004), respectively. Paraclinical differences comprised lower CSF pleocytosis in AE compared to IE (median 6 cells/µl vs. 125 cells/µl, p < 0.001). Epileptic discharges on EEG and MRI lesions were more prevalent in AE than IE (50% vs. 14%, p < 0.001; 50% vs. 28%, p = 0.037). The modified Rankin Scale scores at discharge and last follow-up (median duration 2304 days, IQR 1433-3274) indicated favorable outcomes in both groups.This comprehensive analysis provides insights into the epidemiology, clinical, paraclinical, and therapeutic aspects and the outcomes of AE and IE in adults. We developed a diagnostic tool that facilitates early differentiation between AE and IE, aiding in timely therapeutic decision-making.
Department of Neurology, Neurocritical Care, and Neurorehabilitation, Christian Doppler University Hospital, Paracelsus Medical University and Centre for Cognitive Neuroscience, European Reference Network EpiCARE, Salzburg, Austria.
Department of Neurology, Kepler University Hospital, Johannes Kepler University, Linz, Austria.
Department of Neurology, Neurocritical Care, and Neurorehabilitation, Christian Doppler University Hospital, Paracelsus Medical University and Centre for Cognitive Neuroscience, European Reference Network EpiCARE, Salzburg, Austria.Neuroscience Institute, Christian Doppler University Hospital, Paracelsus Medical University and Centre for Cognitive Neuroscience, Salzburg, Austria.
Medical Directorate, University Hospital Würzburg, Würzburg, Germany.
Department of Neurology, Evangelisches Klinikum Gelsenkirchen, Teaching Hospital University Duisburg-Essen, Gelsenkirchen, Germany. judith.wagner@evk-ge.de.
Autoimmune and infectious encephalitis: development of a discriminative tool for early diagnosis and initiation of therapy.
During extensive field explorations of the Lateritic area in West Bengal, one remarkable wild Russuloid macrofungus, ethnically termed Kend Patra, was collected. The species was known to enrich the diet of the local people, being considered as income source for some tribal groups. Using morphological characters and molecular analysis of this collection, provide a unique placement of the taxon in the Russula subgenus Compactae (Fr.) Bon. Further in order to find functional constituents for biopharma applications, methanolic extract was prepared that shows the existence of a substantial amounts of phenol, flavonoid, ascorbic acid and carotenoids. Antioxidant activity was determined where the fraction demonstrated strong DPPH, ABTS, and nitric oxide radical scavenging activities, high Fe2+ ion chelating ability, and a reducing power with EC50 values ranging from 538.69 to 891.75 µg/ml. The extract was found to be effective against Listeria monocytogenes, Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli, Salmonella typhi and Staphylococcus aureus. In addition, the extract exhibited potent anticancer activities as it inhibited A549 cell proliferation, caused morphological changes, elevated ROS levels, hindered the clonogenic ability and migratory potential of cancerous cells, arrested cell cycle progression at S phase, and induced apoptosis by modulating the intrinsic mitochondrial pathway. Overall, this study contributes a new species to the world's myco-diversity and presents an exciting opportunity for future researchers to conduct comprehensive investigations on this unique species in order to uncover potential new medications for human use.
Molecular and Applied Mycology and Plant Pathology Laboratory, Department of Botany, Centre of Advanced Study, University of Calcutta, 35, Ballygunge Circular Road, Kolkata, West Bengal, 700019, India.
Molecular and Applied Mycology and Plant Pathology Laboratory, Department of Botany, Centre of Advanced Study, University of Calcutta, 35, Ballygunge Circular Road, Kolkata, West Bengal, 700019, India.Food Technology & Science Institute (FTSI), TCG Centres for Research & Education in Science and Technology, ARDC building, 54/A/1, Block-DN, Sector-5, Salt Lake, Kolkata, West Bengal, 700091, India.
School of Biological and Environmental Sciences, Shoolini University of Biotechnology and Management Sciences, Solan, 173229, India.
Molecular and Applied Mycology and Plant Pathology Laboratory, Department of Botany, Centre of Advanced Study, University of Calcutta, 35, Ballygunge Circular Road, Kolkata, West Bengal, 700019, India. krish_paper@yahoo.com.
Unveiling tribal treasures: myco-chemical characterization and pharmacological evaluation of an unexplored Russula pers. species.
Acta Biochim Biophys Sin (Shanghai). 2024-12-25;56(12):1895.
Corrigendum to: TIPE1 suppresses the invasion and migration of breast cancer cells and inhibits epithelial-to-mesenchymal transition primarily via the ERK signaling pathway.
Streptococcus pneumoniae is a major cause of meningitis in under developed countries with low vaccination rates and high antibiotic resistance. This study aimed to analyze 83 suspected meningitis patients in Karachi for the detection of S. pneumoniae followed by its whole genome sequencing and Pan Genome analysis. Out of the 83 samples collected, 33 samples with altered physical (turbidity), cytological (white blood cell count) and biochemical (total protein and total glucose concentrations) parameters indicated potential meningitis cases, while these parameters were within normal healthy ranges in remaining 50 samples. Latex particle agglutination (LPA) was performed on the 33 samples, revealing 20 positive cases of bacterial meningitis. The PCR and culturing methods revealed 5 S. pneumoniae isolates. Antibiotic susceptibility tests showed that one S. pneumoniae strain was resistant to erythromycin, levofloxacin, and tetracycline. Whole-genome sequencing of this resistant strain was performed and S. pneumoniae was confirmed with MLST analysis, while it had > 2.3 Mb genome and a single repUS43 plasmid. In CARD analysis, the strain had tet(M), ermB, RlmA(II), patB, pmrA, and patA ARGs, which could provide resistance against tetracycline, macrolide, fluoroquinolone, and glycopeptide antibiotics. Phylogenetic analysis revealed that the isolate was closely related to strains from Hungary and the USA. Pan-genome analysis with 144 genome assemblies from NCBI database showed that 1101 non-redundant core genes were shared between all strains. This study gives valuable understanding into the prevalence and characterization of meningitis-causing bacteria in Karachi, Pakistan with prime focus on multi-drug resistant S. pneumoniae.
Department of Biosciences, Faculty of Life Sciences, Shaheed Zulfikar Ali Bhutto Institute of Science and Technology (SZABIST), Karachi, 75600, Pakistan.
Faculty of Engineering Sciences and Technology (FEST), Department of Applied Sciences, Hamdard University, Karachi, 74600, Pakistan. aurangzebku@gmail.com.
Department of Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan.
Jamil-Ur-Rahman Center for Genome Research, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, ICCBS, University of Karachi, Karachi, 75270, Pakistan.
Department of Biochemistry, University of Karachi, Karachi, 75270, Pakistan.
College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
Department of Biosciences, COMSATS University Islamabad (CUI), Islamabad, 45550, Pakistan. Kaleem.imdad@comsats.edu.pk.
Neuroscience Center, King Fahad Specialist Hospital, Dammam, Saudi Arabia.
Characterization of meningitis-causing bacteria, with focus on genomic and pangenomic study of multi-drug resistant Streptococcus pneumoniae from cerebrospinal fluid.
Obesity is a major public health concern and burden on individuals and healthcare systems. Due to the challenges and limitations of lifestyle adjustments, it is advisable to consider pharmacological treatment for people affected by obesity. However, the side effects and limited efficacy of available drugs make the obesity drug market far from sufficient. Drug repurposing involves identifying new applications for existing drugs and offers some advantages over traditional drug development approaches including lower costs and shorter development timelines. This review aims to provide an overview of drug repurposing for anti-obesity medications, including the rationale for repurposing, the challenges and approaches, and the potential drugs that are being investigated for repurposing. Through advanced computational techniques, researchers can unlock the potential of repurposed drugs to tackle the global obesity epidemic. Further research, clinical trials, and collaborative efforts are essential to fully explore and leverage the potential of drug repurposing in the fight against obesity.
Department of Clinical Pharmacy, School of Pharmacy, Naval Medical University, Shanghai, China.
Department of Clinical Pharmacy, School of Pharmacy, Naval Medical University, Shanghai, China.Department of Nutrition and Food Hygiene, Faculty of Naval Medicine, Naval Medical University, Shanghai, China.
Obesity reviews : an official journal of the International Association for the Study of Obesity
A review on drug repurposing applicable to obesity.
To assess implementation outcomes and potential efficacy of a user-informed, theory-based digital health intervention developed to improve adolescent and young adult (AYA) male sexual health.We conducted a pilot randomized controlled trial of sexually active male emergency department (ED) patients aged 14-21 years. Participants were randomized to the intervention (Dr. Eric, Emergency Room Interventions to improve Care) or usual care. Dr. Eric consists of an ED-based sexual health app followed by 3 months of interactive text messages. We assessed the feasibility, adoption, and fidelity among users. Condom use, defined as the number of sexual encounters with condoms divided by the total number of sexual encounters over the past 4 weeks, was the primary efficacy outcome.We enrolled 119 patients; mean age was 17.9 years, 87% were Hispanic, and half used condoms at last intercourse. Dr. Eric demonstrated feasibility, with high rates of consent (86.2%) and follow-up (81.5%). Intervention participants found Dr. Eric acceptable, liking (86.2%) and recommending (87.9%) the program. 98% of intervention participants interacted with all five app modules; one-quarter opted out of text messaging. At 6-week follow-up, the intervention group more often used a condom compared to the control group [OR 3.57, 95% confidence interval (1.93, 6.60)], p < .001]; however, this significant difference did not sustain at 13 weeks.Dr. Eric was feasible to deliver and acceptable to male AYA patients. To our knowledge, Dr. Eric is the first intervention to demonstrate evidence of short-term efficacy for improving condom use among male AYA in the ED.
Copyright © 2024 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.
Division of Pediatric Emergency Medicine, Department of Emergency Medicine, Columbia University Medical Center, New York, New York; Department of Population and Family Health, Mailman School of Public Health, Columbia University Medical Center, New York, New York. Electronic address: Lc2243@columbia.edu.
Division of Pediatric Emergency Medicine, Department of Emergency Medicine, Columbia University Medical Center, New York, New York.
Department of Biostatistics, Mailman School of Public Health, Columbia University Medical Center, New York, New York.
Department of Nursing and Bioinformatics, Columbia University Medical Center, New York, New York.
Department of Population and Family Health, Mailman School of Public Health, Columbia University Medical Center, New York, New York; Department of Pediatrics, Columbia University Medical Center, New York, New York.
A Randomized Controlled Trial of a Digital Intervention to Improve the Sexual Health of Adolescent and Young Adult Male Emergency Department Patients.
There is an extensive amount of evidence that links changes in the intestinal microbiota structure to the progression and pathophysiology of many liver diseases. However, comprehensive analysis of gut flora dysbiosis in arsenic-induced hepatotoxicity is lacking. Herein, C57BL/6 mice are exposed to arsenic (1, 2, or 4 mg/kg) for 12 weeks, after which fecal microbiota transplantation (FMT) study is conducted to confirm the roles of the intestinal microbiome in pathology. Treatment with arsenic results in pathological and histological changes in the liver, such as inflammatory cell infiltration and decreased levels of TP and CHE but increased levels of ALP, GGT, TBA, AST, and ALT. Arsenic causes an increase in the relative abundance of Escherichia-Shigella, Klebsiella and Blautia, but a decrease in the relative abundance of Muribaculum and Lactobacillus. In arsenic-exposed mice, protein expressions of Occludin, ZO-1, and MUC2 are significantly decreased, but the level of FITC in serum is increased, and FITC fluorescence is extensively dispersed in the intestinal tract. Importantly, FMT experiments show that mice gavaged with stool from arsenic-treated mice exhibit severe inflammatory cell infiltration in liver tissues. Arsenic-manipulated gut microbiota transplantation markedly facilitates gut flora dysbiosis in the recipient mice, including an up-regulation in Escherichia-Shigella and Bacteroides, and a down-regulation in Lactobacillus and Desulfovibrio. In parallel with the intestinal microbiota wreck, protein expressions of Occludin, ZO-1, and MUC2 are decreased. Our findings suggest that subchronic exposure to arsenic can affect the homeostasis of the intestinal microbiota, induce intestinal barrier dysfunction, increase intestinal permeability, and cause damage to liver tissues in mice.
Intestinal microbiota dysbiosis contributes to the liver damage in subchronic arsenic-exposed mice.
Patients with atrial fibrillation (AF) taking antithrombotic (AT) therapy are at an increased risk of gastrointestinal bleeding (GIB). The comparative effect of a combination of anticoagulant (AC) and antiplatelet (AP) versus AC monotherapy on clinical outcomes in patients with AF presenting with GIB is not well characterized. This study compares outcomes in AF patients with GIB on AC alone with those on combination AP and AC therapy, as part of a larger prospective study from 2013 to 2023. One hundred and thirty-seven patients diagnosed with AF who presented with overt GIB were evaluated during their hospitalization, at 1 month and 1 year postdischarge and then annually. The median follow-up of patients was 57 months. Patients in the combination AP + AC therapy group had a higher prevalence of coronary artery disease, myocardial infarction, and coronary/vascular stent placement compared with the AC monotherapy group. No statistically significant differences were noted between the 2 groups in terms of end-of-follow-up mortality, in-hospital mortality, major bleeding, rebleeding, and length of hospital stay. Cox regression analysis revealed chronic kidney disease [hazard ratio (HR) 2.05, 95% confidence interval (1.04-4.05) ( P = 0.038)] and warfarin use [HR 4.94, 95% confidence interval (1.11-22.09) ( P = 0.037)] to be independent predictors of mortality at 12 months. Antithrombotic therapy in patients with AF who experience GIB should be mainly directed by their cardiovascular needs. Health care providers may explore non-vitamin K antagonist oral anticoagulants as alternatives to warfarin for AF patients at risk of GIB, and efforts must be maximized to prevent bleeding in patients with chronic kidney disease.
Department of Cardiovascular Medicine, Faculty of Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX; and.
Division of Gastroenterology and Hepatology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon .
Comparative Analysis of Anticoagulation Versus Combination Anticoagulation and Antiplatelet Therapy in Atrial Fibrillation Patients Presenting With Gastrointestinal Bleeding.
Two Gram-stain-negative, facultatively anaerobic, motile, and rod-shaped marine bacteria, designated strains ZSDZ35T and ZSDZ42T, were isolated from surface seawater of Qingdao offshore. Phylogenetic analysis of the 16S rRNA genes and whole genome data placed ZSDZ35T and ZSDZ42T within the genus Enterovibrio. Strain ZSDZ35T was most closely related to Enterovibrio nigricans DSM 22720T with 97.55% sequence similarity, whereas ZSDZ42T was most closely related to Enterovibrio calviensis DSM 14347T with 98.97% sequence similarity. Strain ZSDZ35T grew with 0-8% (w/v) NaCl (optimum 4%), at 16-37 °C (optimum 28 °C) and pH 6.0-9.0 (optimum pH 8.0); whereas strain ZSDZ42T grew with 1-7% (w/v) NaCl (5%), at 4-28 °C (8 °C) and pH 6.0-9.0 (pH 7.0). Both strains shared the same major fatty acid components of summed feature 3 (C16:1ω7c or/and C16:1ω6c), summed feature 8 (C18:1ω7c and C18:1ω6c) and C16:0, with different proportions. The DNA G + C contents of strains ZSDZ35T and ZSDZ42T were 47.2% and 46.7%, respectively. Based on the results of polyphasic analyses, ZSDZ35T and ZSDZ42T are considered to represent novel species, for which the names Enterovibrio qingdaonensis sp. nov. (type strain, ZSDZ35T = MCCC 1K06293T = KCTC 82887T) and Enterovibrio gelatinilyticus sp. nov. (type strain, ZSDZ42T = MCCC 1K06294T = KCTC 82886T) are proposed, respectively.
College of Marine Life Sciences, and Frontiers Science Center for Deep Ocean Multispheres and Earth System, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China.Laboratory for Marine Ecology and Environmental Science, Qingdao Marine Science and Technology Center, Qingdao, 266071, China.Institute of Evolution & Marine Biodiversity, Ocean University of China, Qingdao, 266003, China.
College of Marine Life Sciences, and Frontiers Science Center for Deep Ocean Multispheres and Earth System, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China. xhzhang@ouc.edu.cn.Laboratory for Marine Ecology and Environmental Science, Qingdao Marine Science and Technology Center, Qingdao, 266071, China. xhzhang@ouc.edu.cn.Institute of Evolution & Marine Biodiversity, Ocean University of China, Qingdao, 266003, China. xhzhang@ouc.edu.cn.
Enterovibrio qingdaonensis sp. nov. and Enterovibrio gelatinilyticus sp. nov., two marine bacteria isolated from surface seawater of Qingdao offshore.
Apraxia has been identified in all clinical forms of frontotemporal lobar degeneration (FTLD). The characteristics of apraxia symptoms and their underlying cognitive/motor basis are not fully understood. This study investigated apraxia in pathological subtypes of FTLD.The study constituted a retrospective review of 115 pathologically confirmed cases of FTLD from a single cognitive neurology centre. Patients in whom apraxia had been documented as a notable clinical characteristic were identified. Apraxia features, demographic, cognitive, neurological, and imaging findings were recorded.Eighteen patients were identified: 12 with FTLD-tau pathology (7 corticobasal degeneration (CBD), four Pick type and one progressive supranuclear palsy (PSP)) and six with FTLD-TDP pathology, all type A and four linked to progranulin gene mutations. Apraxia as a dominant presenting feature was typically associated with tau pathologies, whereas it emerged in the context of aphasia in TDP pathology. Apraxia typically predominated in one body part (face or limb) in tau but not TDP pathology. Relatively preserved activities in daily life were associated with TDP. Apraxia of speech was associated with tau pathology. Pick-type pathology was linked to symmetrical atrophy and late development of limb rigidity.Apraxia in FTLD subtypes has variable characteristics. Apraxia associated with CBD pathology conformed to criteria for probable corticobasal syndrome (CBS), whereas apraxia with Pick-type pathology did not. Apraxia in patients with TDP-A pathology was interpreted as one manifestation of their generalised communication disorder. Apraxia in FTLD may have distinct cognitive and motor substrates that require prospective investigation.
Cerebral Function Unit, Manchester Centre for Clinical Neurosciences, Northern Care AllianceNHS Foundation Trust, Salford, UK. tobias.langheinrich@nca.nhs.uk.Division of Psychology, Communication & Human Neuroscience, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK. tobias.langheinrich@nca.nhs.uk.
Cerebral Function Unit, Manchester Centre for Clinical Neurosciences, Northern Care AllianceNHS Foundation Trust, Salford, UK.Division of Psychology, Communication & Human Neuroscience, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Cerebral Function Unit, Manchester Centre for Clinical Neurosciences, Northern Care AllianceNHS Foundation Trust, Salford, UK.Division of Medical Education, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Division of Neuroscience, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Cerebral Function Unit, Manchester Centre for Clinical Neurosciences, Northern Care AllianceNHS Foundation Trust, Salford, UK.Division of Neuroscience, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Apraxia phenotypes and frontotemporal lobar degeneration.
There are three isoforms of human collagen prolyl 4-hydroxylases (C-P4Hs), each of which has been reported to play an important role in regulating the progression of a variety of human cancers. By analyzing TGCA datasets on human head and neck squamous cell carcinoma (HNSC), we find that a higher expression of all three C-P4HAs (the α subunit of C-P4Hs) is a superior prognostic indicator than a higher expression of two or a single C-P4HA. Unexpectedly, some patients with higher levels of three C-P4HAs survive longer than patients whose tumors have lower expression of C-P4HAs. Therefore, there may be molecule(s) that can negate the deleterious effects of overexpressing C-P4HAs during cancer progression. By constructing a functional protein interaction network of C-P4HAs and analyzing molecules whose expressions are correlated significantly with that of C-P4HAs, we identify scribble cell polarity complex component 2 (LLGL2) as a factor that antagonizes the effects of overexpressed C-P4HAs on HNSC. Silencing of LLGL2 in the human oral squamous cell line Cal-27 upregulates the expression of occludin and increases cancer cell invasion and migration. In contrast, knocking down C-P4HA alone inhibits cell migration and invasion. Furthermore, simultaneously downregulating three C-P4HAs has more pronounced effects on inhibiting cell migration and invasion. Accordingly, high LLGL2 expression is also a marker indicating improved prognosis in patients with HNSC. These results suggest that the interplay between LLGL2 and C-P4HAs may be targeted to mitigate HNSC tumorigenesis and progression.
Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Cancer Research Institute, School of Basic Medical Sciences, University of South China, Hengyang 421001, China.Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, China.
School of Medicine, Pingdingshan University, Pingdingshan 467000, China.
Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, China.
Guangzhou Institute of Cancer Research, the Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou 510095, China.
Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Department of Interventional Radiology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou 510095, China.
Department of Human Anatomy, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Hunan Province Key Laboratory of Tumor Cellular & Molecular Pathology, Cancer Research Institute, School of Basic Medical Sciences, University of South China, Hengyang 421001, China.Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, China.Guangzhou Institute of Cancer Research, the Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou 510095, China.
Collagen prolyl 4-hydroxylase subunit α member-induced head and neck squamous cell carcinoma aggressiveness is antagonized by LLGL2 via reduced expression of occludin.
Seth Gordhandhas Sunderdas Medical College and King Edwards Memorial Hospital, Mumbai, Maharashtra, India.
Medical College, Aga Khan University, Karachi, Pakistan.
Maulana Azad Medical College, 2-Bahadurshah Zafar Marg, New Delhi, Delhi, 110002, India.
Mymensingh Medical College, Mymensingh, Bangladesh.
Rheumatology Department, Saint-Joseph University, Beirut, Lebanon.Rheumatology Department, Hotel-Dieu de France Hospital, Beirut, Lebanon.
Department of Rheumatology, Royal Melbourne Hospital, Parkville, VIC, 3050, Australia.Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia.Department of Medical Biology, University of Melbourne, Parkville, VIC, 3052, Australia.
Department of Rheumatology, King's College Hospital, London, UK.
Rheumatology and Clinical Immunology Unit, ASST Spedali, Civili and University of Brescia, 25123, Brescia, Italy.Department of Clinical and Experimental Sciences, University of Brescia, 25123, Brescia, Italy.
Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.Department of Rheumatology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals Trust, Leeds, UK.Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
Division of Rheumatology, Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo, SP, Brazil.
Department of Medicine and Therapeutics, School of Medicine and Dentistry, University of Ghana, College of Health Sciences, Korle-Bu, Accra, Ghana.
Rheumatology Unit, Dipartimento Di Medicine Interna E Terapia Medica, Università Degli Studi Di Pavia, Pavia, Lombardy, Italy.
Department of Internal Medicine, University of Illinois College of Medicine at Peoria, Peoria, IL, USA.
Medizinische Klinik 3, Rheumatologie Und Immunologie, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Ulmenweg 18, 91054, Erlangen, Deutschland.
Department of Rheumatology, China-Japan Friendship Hospital, Yinghua East Road, Chaoyang District, Beijing, 100029, China.
Department of Medicine, University of Auckland, Auckland, New Zealand.
Medical Faculty, Sofia University, St. Kliment Ohridski, 1 Kozyak Str., 1407, Sofia, Bulgaria.
Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Campus of Savona, University of Genova, Savona, Italy.
Associate Board Member, International Myositis Society, Göttingen, Germany.Patient Advisor, MIHRA Foundation, New Orleans, USA.Patient Research Partner, Myositis Support and Understanding, Lincoln, USA.
Services Support Ofcer, Arthritis Ireland, Dublin, Ireland.EULAR PARE Committee, Kilchberg, Switzerland.
Research and Communications Specialist, The Myositis Association, Columbia, MD, USA.
Department of Internal Medicine, National Medical Center La Raza , Instituto Mexicano del Seguro Social, General Hospital, Av. Jacaranda S/N, Col. La Raza, Del. Azcapotzalco, C.P. 02990, Mexico City, Mexico.
Division of Rheumatology, Mayo Clinic, Rochester, MN, USA.
Reference Center for Osteoporosis, Rheumatology and Dermatology, Pontifcia Universidad Javeriana Cali, Cali, Colombia.
Department of Medicine, Hospital Universidad del Norte, Barranquilla, Atlantico, Colombia.
Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, 1-1-5 Sendagi, Bunkyo-Ku, Tokyo, 113-8602, Japan.
Department of Rheumatology and Clinical Immunology, Charité, University Medicine Berlin, Free University and Humboldt University Berlin, Berlin, Germany.
EA 4360 Apemac, Université de Lorraine, Nancy, France.Inserm, CHRU Nancy, CIC-1433 Epidémiologie Clinique, Université de Lorraine, Nancy, France.
Centre for Rheumatic Diseases, King's College London, London, UK.Rheumatology Department, King's College Hospital, London, UK.
Division of Musculoskeletal and Dermatological Sciences, Centre for Musculoskeletal Research, School of Biological Sciences, The University of Manchester, Manchester, UK.National Institute for Health Research Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, The University of Manchester, Manchester, UK.Department of Rheumatology, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, Salford, UK.
Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
Division of Musculoskeletal and Dermatological Sciences, Centre for Musculoskeletal Research, School of Biological Sciences, The University of Manchester, Manchester, UK. drlatikagupta@gmail.com.Department of Rheumatology, Royal Wolverhampton Hospitals NHS Trust, Wolverhampton, UK. drlatikagupta@gmail.com.
Correction to: Collating the voice of people with autoimmune diseases: Methodology for the third phase of the COVAD studies.
Department of Neuropathology (the Brain Bank for Aging Research), Tokyo Metropolitan Institute for Geriatrics and Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan.Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Department of Neuropathology (the Brain Bank for Aging Research), Tokyo Metropolitan Institute for Geriatrics and Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan.The Brain Bank for Neurodevelopmental, Neurological and Psychiatric Disorders, United Graduate School of Child Development, Graduate School of Medicine, Osaka University, Osaka, Japan.
Department of Neuropathology (the Brain Bank for Aging Research), Tokyo Metropolitan Institute for Geriatrics and Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan.Department of Neurology (the Brain Bank for Aging Research), Tokyo Metropolitan Institute for Geriatrics and Gerontology, Tokyo, Japan.
Department of Neuropathology (the Brain Bank for Aging Research), Tokyo Metropolitan Institute for Geriatrics and Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan.
Research Team for Neuroimaging, Tokyo Metropolitan Institute for Geriatrics and Gerontology, Tokyo, Japan.
Department of Diagnostic Radiology, Tokyo Metropolitan Institute for Geriatrics and Gerontology, Tokyo, Japan.
Department of Dementia and Higher Brain Function, Metropolitan Institute of Medical Science, Tokyo, Japan.
Department of Neurology (the Brain Bank for Aging Research), Tokyo Metropolitan Institute for Geriatrics and Gerontology, Tokyo, Japan.
Department of Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Department of Neuropathology (the Brain Bank for Aging Research), Tokyo Metropolitan Institute for Geriatrics and Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan. yukosm@bbarjp.net.
A case of argyrophilic grain disease with an initial clinical diagnosis of Parkinson's disease.
An earlier observational study described selected patients with acute neck pain syndrome, who experienced short bursts of cervical vertigo elicited by rapid head movements. The current study on a larger cohort of 20 patients with chronic or frequently recurring neck pain syndrome and age-matched controls focused on two major questions: (1) Can head movements in subjects with exacerbations of neck pain and restrictions of neck mobility also elicit bursts of vertigo? (2) What is the impact on postural balance measured by analysis of body sway and locomotion? A detailed questionnaire was applied, posture and gait were evaluated by use of instrumented posturography-and gait analysis with and without slow or rapid horizontal head rotations in the yaw plane with and without sight/visual input. All patients reported some or frequent episodes of dizziness in the range of seconds only elicited by rapid, not by slow head movements. Postural sway in patients was unremarkable in undisturbed conditions without head movements, but specifically increased by rapid but not slow head turns. The latter is best explained by the lack of continuous control of velocity and amplitude of saccadic head movements. Gait analysis revealed a slowed and cautious gait pattern already at undisturbed condition that was even exaggerated during rapid head turns. These observations demonstrate that chronic or recurrent neck pain is associated with episodic experiences of dizziness and above results in both chronic and episodic alterations of stance and gait that resemble those described for patients with phobic postural vertigo/persistent postural perceptual dizziness, a functional gait disorder.
German Center for Vertigo and Balance Disorders, University Hospital, LMU University Hospital, Ludwig-Maximilians-Universität München, Marchioninistrasse 15, 81377, Munich, Germany. doreen.huppert@med.uni-muenchen.de.Department of Neurology, University Hospital, LMU University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany. doreen.huppert@med.uni-muenchen.de.
German Center for Vertigo and Balance Disorders, University Hospital, LMU University Hospital, Ludwig-Maximilians-Universität München, Marchioninistrasse 15, 81377, Munich, Germany.
German Center for Vertigo and Balance Disorders, University Hospital, LMU University Hospital, Ludwig-Maximilians-Universität München, Marchioninistrasse 15, 81377, Munich, Germany.Department of Neurology, University Hospital, LMU University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.
Musculoskeletal University Center Munich, University Hospital, LMU University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.
Department of Neurology, University Hospital, LMU University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.Interdisciplinary Pain Center, University Hospital, LMU University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.
Impact of proprioceptive cervical dizziness in chronic neck pain syndromes on gait and stance during active head-turn challenges.
The kinetics of interfacial ion insertion govern the uniformity of electrochemical reactions, playing a crucial role in lithium-ion battery performance. In two-dimensional lithium-conducting layered-oxide battery particles, variation in insertion rates across insertion channels remains unclear due to poorly defined crystal orientation at the solid-liquid interface and solid-state-lithium-diffusion length. This ambiguity complicates understanding inhomogeneous lithium-insertion channels activation. A systematic study requires crystallographically predefined interfaces and in situ lithium-concentration mapping. Here, we fabricated a freestanding, (104)-oriented-LiNi1/3Mn1/3Co1/3O2 single-crystal thin film using dissolution-induced release and performed in situ scanning-transmission-X-ray-microscopy to spatially resolve lithium-insertion at well-defined-interfaces. We observed heterogeneous lithium-concentration evolution due to channel-by-channel insertion rate variation, despite the potential for homogeneous lithium distribution via a solid-solution-phase at equilibrium in NMC111. Increasing current density exacerbates this heterogeneity, highlighting channel-by-channel variation. Our findings provide critical insights into battery electrode utilization and lifetime management, potentially guiding the design of more efficient and durable lithium-ion batteries.
Department of Chemistry, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.
Department of Materials Science and Engineering, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.
Department of Chemistry, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.Pohang Accelerator Laboratory, Pohang University of Science and Technology, Pohang 37673, Republic of Korea.
Department of Chemistry, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.Graphene Research Center, Advanced Institute of Convergence Technology, Suwon 16629, Republic of Korea.
Pohang Accelerator Laboratory, Pohang University of Science and Technology, Pohang 37673, Republic of Korea.
Advanced Light Source, Lawrence Berkeley National Laboratory, Berkeley, California 94720, United States.
Department of Materials Science and Engineering, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.Advance Institute of Convergence Technology, Seoul National University, Suwon 16229, Republic of Korea.
Department of Chemistry, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.Institute of Applied Physics, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.Institute for Battery Research Innovation, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.
Elucidating Heterogeneous Li Insertion Using Single-Crystalline and Freestanding Layered Oxide Thin Film.
Correction to: P-516 working in the time of covid-19: how covid-19 public health policies affect the experience of bullying and harassment among restaurant workers.
This study examined whether reductions in the severity of personality disorders (PD) mainly reflect changes in personality traits or rather an alleviation of a demoralized state involving nonspecific unpleasant affect. We used 4 years of longitudinal data from the Collaborative Longitudinal Personality Disorders Study, in which patients (N = 419) completed the Neuroticism-Extraversion-Openness Personality Inventory-Revised (NEO-PI-R) three times over 4 years (at baseline and at 6-month and 4-year follow-up assessments). We compared the NEO Demoralization scale with NEO-PI-R domain scales adjusted for demoralization-related items to determine whether changes in demoralization are more pronounced than changes in adjusted personality traits. Results showed that adjusted Neuroticism and Demoralization changed at similar rates and both changed more than other traits. These changes were most pronounced in the first 6 months and tapered thereafter. Rank-order correlations were somewhat lower for Demoralization than adjusted traits. Our findings suggest that decreases in PD symptoms over time have to do with reductions in negative affect and that Demoralization as assessed via a subset of NEO-PI-R items is limited in its ability to distinguish negative affect from trait Neuroticism. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
Centre for Care Research and Consultancy, Katholieke Universiteit Leuven.
Department of Psychology, University of Amsterdam.
Department of Psychology, Texas A&M University.
Department of Psychology, University of Arizona.
Department of Psychology, University of Zurich.
The impact of demoralization on the stability of personality traits in a clinical sample.
Rashba states have been actively revisited as a platform for advanced applications such as spintronics and topological quantum computation. Yet, access to the Rashba state is restricted to the specific material sets, and the methodology to control the Rashba state is not established. Here, we report the Rashba states on the (001) surface of KZnBi, a 3D Dirac semimetal. Using angle-resolved photoemission spectroscopy and first-principles calculations, we investigated the evolution of Rashba states under different surface conditions controlled by alkali metal deposition. We observed that restoring surface ordering enables a Rashba state, which is absent in freshly cleaved surfaces. Interestingly, we were able to modify the dispersion of the Rashba state from an ordinary parabolic dispersion to a linearly dispersing Dirac-like state by additional alkali-metal deposition. Our findings provide a methodology for engineering the properties of Rashba states for advanced applications and redefine topological systems as generic hosts of Rashba states.
Department of Physics, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.
Quantum Technology Institute, Korea Research Institute of Standards and Science, Daejeon 34113, Republic of Korea.
Donostia International Physics Center, San Sebastían 20018, Spain.
Department of Physics, Ajou University, Suwon 16499, Republic of Korea.
Department of Energy Science, Sungkyunkwan University, Suwon 16419, Republic of Korea.
Progressive Control of Rashba State on Topological Dirac Semimetal KZnBi.
Microalgae are significantly influenced by light quality and quantity, whether in their natural habitats or under laboratory and industrial culture conditions. The present study examines the adaptive responses of the marine microalga Tetraselmis chuii to different light regimes, using a cost-effective filtering method and a multi-omics approach. Microalgal growth rates were negatively affected by all filtered light regimes. After six days of cultivation, growth rate for cultures exposed to blue and green filtered light was 67%, while for red filter was 83%, compared to control cultures. Transcriptomic analysis revealed that the usage of green filters resulted in upregulation of transcripts involved in ribosome biogenesis or coding for elongation factors, exemplified by a 2.3-fold increase of TEF3. On the other hand, a 2.7-fold downregulation was observed in photosynthesis-related petJ. Exposure to blue filtered light led to the upregulation of transcripts associated with pyruvate metabolism, while photosynthesis was negatively impacted. In contrast, application of red filter induced minor transcriptomic alterations. Regarding metabolomic analysis, sugars, amino acids, and organic acids exhibited significant changes under different light regimes. For instance, under blue filtered light sucrose accumulated over 6-fold, while aspartic acid content decreased by 4.3-fold. Lipidomics analysis showed significant accumulation of heptadecanoic and linoleic acids under green and red light filters. Together, our findings indicate that filter light can be used for targeted metabolic manipulation.
Department of Biotechnology, School of Applied Biology and Biotechnology, Agricultural University of Athens, 11855, Athens, Greece.
Fitoplancton Marino, S.L., Dársena Comercial S/N (Muelle Pesquero), El Puerto de Santa María, 11500, Cádiz, Spain.
Department of Marine Sciences, University of the Aegean, University Hill, 81100, Mytilene, Greece.
Department of Nutritional Physiology and Feeding, Agricultural University of Athens, Iera Odos 75, 11855, Athens, Greece.
Department of Biotechnology, School of Applied Biology and Biotechnology, Agricultural University of Athens, 11855, Athens, Greece. mflem@aua.gr.
Omics exploration of Tetraselmis chuii adaptations to diverse light regimes.
An extraordinary resolution down to 50 microns is demonstrated for the first time for bulk ultrasonics, using novel micro-fabricated metamaterial lenses. The development and performance of the silicon-based Fabry-Perot type metalenses with an array of 10 micrometre square holes are discussed. Challenges in wave reception are addressed by a custom-developed micro-focal laser with a sub-micron spot size and an innovative experimental set-up together with physics based signal processing. The results provide a pathway for material diagnostics at greater depths with high resolution using micro-metalens-enhanced ultrasound as an alternative to expensive and radiation prone electromagnetic techniques.
Centre for Nondestructive Evaluation (CNDE), Indian Institute of Technology Madras, Chennai, 600036, India.
Intelligent Optical Systems, Inc, 19601 Mariner Avenue, Torrance, CA, 90503, USA.
Centre for NEMS and Nanophotonics (CNNP), Indian Institute of Technology Madras, Chennai, 600036, India.
Centre for Nondestructive Evaluation (CNDE), Indian Institute of Technology Madras, Chennai, 600036, India. prajagopal@iitm.ac.in.Centre for NEMS and Nanophotonics (CNNP), Indian Institute of Technology Madras, Chennai, 600036, India. prajagopal@iitm.ac.in.
Micron-scale imaging using bulk ultrasonics.
Geodesign supports collaborative urban planning by managing 'boundaries' between diverse knowledge holders. However, there is a paucity of empirical evidence of its contribution to 'boundary work'. This paper aims to evaluate how a geodesign process facilitates knowledge co-production through boundary work and to assess the scientific credibility, political saliency, and procedural legitimacy of its outputs in urban planning. We propose a replicable geodesign framework to assess boundary work, and test it in a case study on urban transformations with nature-based solutions in the Skarpnäck district of Stockholm, Sweden. Findings indicate that all geodesign steps facilitated communication by promoting collective reasoning. Participants acknowledged contributions to knowledge co-production and decision-making by mediating between different perspectives. However, data quality and modeling simplicity were identified as critical factors affecting the outputs' perceived credibility. Future applications should include co-designing the geodesign process, improving capacity and skills, and facilitating more integrated planning.
Institute of Geography, Ruhr University Bochum, Universitätsstr. 150, 44805, Bochum, Germany. blal.ademesmail@ruhr-uni-bochum.de.GLOMOS - Centre for Global Mountain Safeguard Research & Institute for Alpine Environment, Eurac Research, Bolzano, Italy. blal.ademesmail@ruhr-uni-bochum.de.
Institute of Geography, Ruhr University Bochum, Universitätsstr. 150, 44805, Bochum, Germany.Institute of Environmental Planning, Leibniz Universität Hanover, Herrenhäuser Str. 2, 30419, Hanover, Germany.
Department of Sustainable Development, Environmental Science and Engineering, KTH Royal Institute of Technology, Teknikringen 10B, SE-10044, Stockholm, Sweden.
Department of Civil, Environmental and Mechanical Engineering, University of Trento, 38123, Trento, Italy.
Department of Urban Planning and Environment, KTH Royal Institute of Technology, 10044, Stockholm, Sweden.
Geo-Col GIS and Collaborative Planning, 2612 BB, Delft, The Netherlands.
Geodesign to advance boundary work in urban planning: A study in Stockholm focused on nature-based solutions.
Pre-hospital emergency nurses, frequently exposed to high-stress situations, are at risk for burnout and stress-related issues, affecting their overall well-being. The Professional Quality of Life (ProQoL) scale, widely used among hospital nurses, remains untested in pre-hospital emergency settings.To adapt and validate the ProQoL scale for pre-hospital emergency contexts and explore the protective role of emotional intelligence in professional well-being.A mixed-method study was conducted. The qualitative approach involved semi-structured interviews to inform the modification of items for adapting the ProQoL to the pre-hospital emergency setting. A quantitative method was applied to assess the relationship between emotional intelligence and professional well-being through content and face validity measures.Qualitative interviews suggested refining the ProQoL for pre-hospital emergency settings, emphasising factors such as job satisfaction and professional conduct. The revised 21-item Pre-Hospital Emergency-Professional Quality of Life (PHE-ProQoL) scale demonstrated strong content validity (I-CVI: 0.86-1, S-CVI: 0.9) and face validity. Significant correlations were observed between emotional intelligence and professional well-being, with negative correlations between emotional intelligence and both burnout (Pearson's r = -0.859) and post-traumatic stress (Pearson's r = -0.792), and a positive correlation with compassion satisfaction (Pearson's r = +0.917). Pre-hospital nurses displayed moderate levels of compassion satisfaction (27.3 ± 9.81), high emotional intelligence (28.0 ± 9.58), especially in empathy, and substantial levels of burnout (22.5 ± 6.09) and stress (21.2 ± 4.3).The study found that pre-hospital emergency nurses exhibit moderate compassion satisfaction and above-average emotional intelligence, particularly in perceiving and managing others' emotions. However, they also experience significant levels of burnout and post-traumatic stress.Burnout and post-traumatic stress significantly affect pre-hospital emergency nurses. Enhancing emotional intelligence is crucial for their well-being. Nursing managers now have access to a validated and reliable tool to assess this.
Department of Health Sciences, University of Genoa, Genoa, Italy.
School of Nursing, Midwifery & Health Systems, University College Dublin, Dublin, Ireland.
Faculty of Health and Education, Manchester Metropolitan University, Manchester, UK.
The Impact of Emotional Intelligence on Nurses' Professional Quality of Life in Pre-Hospital Emergency Settings: A Multicentre Mixed-Method Study.
Department of Coronary Disease and Heart Failure, Jagiellonian University Medical College, The St. John Paul II Hospital, Kraków, Poland. pawel.rostoff@uj.edu.pl.
Department of Thromboembolic Diseases, Jagiellonian University Medical College, The St. John Paul II Hospital, Kraków, Poland.Krakow Center for Medical Research and Technologies, The St. John Paul II Hospital, Kraków, Poland.
Enhanced complement consumption and histone H3 citrullination predict disease severity and early mortality risk in non-high-risk pulmonary embolism.
Glassy organic dots (g-Odots) are an emerging class of luminescent nanoparticles that offer enhanced photostability, superior brightness, and modular tunability compared to other commonly employed nanoparticles. In the last several years, they have been used as bioimaging probes for single- and multi-photon cellular imaging, exhibiting low cytotoxicity even after several days. While they are emerging as promising materials for use in biological applications, g-Odots face several key challenges before their use can become widespread. In this concept, we outline the state of the literature on g-Odots and highlight a few ways in which their design and use can be improved upon.
Department of Chemistry, The University of British Columbia, 2036 Main Mall, Vancouver, British Columbia, V6T 1Z1, Canada.
Chemistry (Weinheim an der Bergstrasse, Germany)
The Future is Bright: The Emergence of Glassy Organic Dots for Biological Applications.
Department of Rehabilitation Sciences, Tufts University School of Medicine, 145 Harrison Avenue, Boston, MA, 02111, USA. james.smoliga@tufts.edu.
Renewed Performance, West Palm Beach, FL, 33407, USA.
The Supplement Stop, Palm Beach Gardens, FL, 33403, USA.
Response to Comment on Premature Death in Bodybuilders: What Do We Know?
Tim-1 (T-cell immunoglobulin and mucin domain 1), also known as Kim-1 (kidney injury molecule 1) or hepatitis A virus cellular receptor 1 (HAVCR1), is a transmembrane protein expressed on various immune and epithelial cells. It plays a role in modulating inflammatory and immune responses. In this study, we find that Tim-1 is overexpressed in hepatocellular carcinoma (HCC) samples and that its expression is significantly correlated with postoperative survival. Bulk RNA sequencing reveals a general upregulation of extracellular matrix-related genes in HCC tissues with Tim-1 overexpression. The results of the cell and in vivo experiments reveal that Tim-1 in HCC not only affects biological processes such as the proliferation, migration, and invasion of HCC cells but also broadly promotes extracellular matrix processes by influencing cytokine secretion. Further studies demonstrate that Tim-1 mediates the activation of hepatic stellate cells and upregulates Th1 and Th2 cytokines, thereby promoting HCC progression. Thus, Tim-1 may represent a novel target for future interventions in HCC and liver fibrosis.
Department of General Surgery, the First Affiliated Hospital of Soochow University, Suzhou 215006, China.Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Nantong 226001, China.
Affiliated Huishan Hospital of Xinglin College, Nantong University, Wuxi Huishan District People's Hospital, Wuxi 214100, China.
Department of General Surgery, the First Affiliated Hospital of Soochow University, Suzhou 215006, China.Research Institute of General Surgery, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210095, China.
Department of General Surgery, the First Affiliated Hospital of Soochow University, Suzhou 215006, China.
Tim-1-mediated extracellular matrix promotes the development of hepatocellular carcinoma.
Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany.
Decoding complement: Novel disease insights and therapeutic horizons.
Mitochondria Research Group, Newcastle University, Newcastle upon Tyne, UK.Department of Neurology, Royal Victoria Infirmary, Newcastle upon Tyne, UK.
Department of Neuroradiology, Royal Victoria Infirmary, Newcastle upon Tyne, UK.
Department of Histopathology, Royal Victoria Infirmary, Newcastle upon Tyne, UK.
Department of Neurology, Royal Victoria Infirmary, Newcastle upon Tyne, UK.
Massachusetts General Hospital, Boston, MA, USA.
Department of Rheumatology, Royal Victoria Infirmary, Newcastle upon Tyne, UK.
Department of Neurology, Royal Victoria Infirmary, Newcastle upon Tyne, UK tim.griffiths@newcastle.ac.uk.
Bright ears on MRI: an imaging clue to relapsing polychondritis-associated encephalopathy.
Pastoralism is gaining in recognition for its provision of a broad range of ecosystem services. However, in Western countries, especially in Europe, it has been in decline for decades and its future is uncertain. Professional satisfaction, social appreciation and community integration are key factors for the sustainability of any activity. Using information from 167 traditional Spanish herders, we assessed their perceived degree of satisfaction with their profession and the reasons behind their perceptions. Herders were extremely satisfied with their profession, but they perceived medium and low levels of appreciation by the rural and urban sectors of society, respectively. Herders had negative feelings about the sustainability of their profession, as they felt more appreciated by society in the past than they do today, half of them did not want their offspring to make a living as herders. Improving communication between herders and society could help to enhance herders' appreciation of their profession.
Biodiversity Research Institute (CSIC, University of Oviedo, Principality of Asturias), University of Oviedo, Campus de Mieres, 33600, Mieres, Spain. j.perez.barberia@csic.es.Department of Agroforestry Science and Technology and Genetics, IDR, IREC, University of Castilla-La Mancha, 02071, Albacete, Spain. j.perez.barberia@csic.es.
Biomathematics and Statistics Scotland (BioSS), James Hutton Institute, Craigiebuckler, Aberdeen, AB15 8QH, Scotland, UK.
Fenner School of Environment and Society, The Australian National University, Canberra, Australian Capital Territory, Australia.
Traditional herders' perception of job satisfaction and integration into society: Another obstacle to the survival of pastoralism?
Strain WL0113T was isolated from surface seawater of the coast of Lianyungang, Jiangsu province, PR China. Strain WL0113T shared highest 16S rRNA gene sequence similarity with Roseobacter insulae YSTF-M11T (98.8%), followed by R. cerasinus AI77T (98.8%), R. ponti MM-7 T (98.0%). Strain WL0113T was Gram-stain-negative, cream, aerobic, non-motile and coccoid- to oval-shaped, and able to grow at pH 6.5-9.0 (optimum, pH 7.0-8.0), at 10-37 °C (optimum, 28 °C) and in the presence of 1-5% (w/v; optimum, 2.5%) NaCl. Ubiquinone-10 was detected as dominant. The main fatty acids (> 5%) of the strain WL0113T were C16:0, iso-C17:0 3OH, C20:4ω6,9,12,15c (arachidonic acid), and summed feature 8 (C18:1ω7c and/or C18:1ω6c). The major polar lipids include phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine, glycophospholipid, unknown aminolipid, unknown phospholipid, and two unknown polar lipids. The ANI and dDDH values between strain WL0113T and Roseobacter cerasinus were 80.4% and 23.0%, respectively. The genomic DNA G + C content of strain WL0113T was 63.1%. Based on these data, it is proposed that strain WL0113T represent novel species of the genus Roseobacter, for which the name Roseobacter sinensis sp. nov. is proposed. The type strain is WL0113T (= GDMCC 1.3082T = JCM 35567T).
Jiangsu Province Engineering Research Center for Marine Bio-Resources Sustainable Utilization and College of Oceanography, Hohai University, Nanjing, People's Republic of China.Guangdong Provincial Key Laboratory of Plant Stress Biology and Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), School of Life Sciences, Sun Yat-Sen University, Guangzhou, People's Republic of China.
Jiangsu Province Engineering Research Center for Marine Bio-Resources Sustainable Utilization and College of Oceanography, Hohai University, Nanjing, People's Republic of China.
Guangdong Provincial Key Laboratory of Plant Stress Biology and Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), School of Life Sciences, Sun Yat-Sen University, Guangzhou, People's Republic of China.
Guangdong Provincial Key Laboratory of Plant Stress Biology and Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), School of Life Sciences, Sun Yat-Sen University, Guangzhou, People's Republic of China.College of Life Sciences, Henan Normal University, Xinxiang, People's Republic of China.
Jiangsu Province Engineering Research Center for Marine Bio-Resources Sustainable Utilization and College of Oceanography, Hohai University, Nanjing, People's Republic of China. zdf@hhu.edu.cn.
Jiangsu Province Engineering Research Center for Marine Bio-Resources Sustainable Utilization and College of Oceanography, Hohai University, Nanjing, People's Republic of China. liwenjun3@mail.sysu.edu.cn.Guangdong Provincial Key Laboratory of Plant Stress Biology and Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), School of Life Sciences, Sun Yat-Sen University, Guangzhou, People's Republic of China. liwenjun3@mail.sysu.edu.cn.
Roseobacter sinensis sp. nov., a marine bacterium capable to synthesize arachidonic acid.
This study constitutes one of the first investigations aiming to examine the association between traumatic experiences within religious settings and symptoms of post-traumatic stress among religious lesbians, gays, and bisexuals. Furthermore, the study tested whether the anticipated positive link between those traumatic experiences and post-traumtic stress is influenced by a positive perception of God's image. The sample consisted of 146 Israeli Jewish lesbians, gays, and bisexuals who professed a belief in God or demonstrated religious inclinations either presently or in the past. They completed self-report measures via an online questionnaire, assessing traumatic experiences within religious settings, post-traumtic stress symptoms, and positive perceptions of God's image. The findings revealed a significant and robust positive connection between traumatic experiences within religious settings and post-traumtic stress. A positive perception of God's image exhibited a negative correlation with post-traumtic stress but did not moderate the relationship traumatic experiences within religious settings and symptoms of post-traumatic stress. These findings highlight the significance of traumatic experiences within religious settings as a distinct potential risk factor of post-traumtic stress among lesbians, gays, and bisexuals and underscore the necessity of enhancing awareness among mental health professionals, religious leaders, and legal entities regarding the detrimental effects of those expereinces.
Bob Shapell School of Social Work, Tel-Aviv University, Tel Aviv, Israel.
On the Links Between Exposure to Traumatic Events in Religious Contexts, Post-Traumatic Stress Symptoms, and a Positive Perception of God's Image Among Jewish Lesbians, Gays and Bisexuals in Israel.
Department of Pediatrics, University of Perugia, Perugia, Italy.
Department of Pediatrics, University of Perugia, Perugia, Italy. antonella.fattorusso@ospedale.perugia.it.
Child Neurology and Psychiatry Unit, Department of Human Neurosciences, Sapienza University of Rome, 00185, Rome, Italy.
Department of Women/Child Health and Urological Science, Sapienza University of Rome, Rome, Italy.
UOC Neuropsychiatry of the Pediatric Age, IRCCS Institute of Neurological Sciences of Bologna, Bologna, Italy.
Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.
Pediatrics Unit, Neuroscience, Mental Health and Sense Organs (NESMOS) Department, Faculty of Medicine and Psychology, Sapienza University of Rome, 00189, Rome, Italy.
Child and Adolescent Neuropsychiatry Unit, Department of Medicine, Surgery and Dentistry, University of Salerno, Salerno, Italy.Department of Science of Health, School of Medicine, University Magna Graecia of Catanzaro, Catanzaro, Italy.
Unit of Neurology and Clinical Neurophysiopathology, Oasi Research Institute-IRCCS, Troina, Italy.
Clinic of Child and Adolescent Neuropsychiatry, Department of Mental Health, Physical and Preventive Medicine, Università degli studi della Campania 'Luigi Vanvitelli', Naples, Italy.
Child Neurology and Epileptology Unit, Paediatric Department, ARNAS Brotzu, Cagliari, Italy.
Department of Pediatrics, University of Chieti, Chieti, Italy.
Pediatric Neurology, Azienda Policlinico Modena, Modena, Italy.
Department of Pediatrics, Sapienza University of Rome, Rome, Italy.
Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
Pediatric Clinic and Rare Diseases, Microcythemic Pediatric Hospital A. Cao , University of Cagliari, Cagliari, Italy.
Medical Genetics Unit, Hospital Santa Maria Della Misericordia, Perugia, Italy.
Department of Medicine and Surgery, University of Perugia, Perugia, Italy.
Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.Department of Neuromuscular Diseases, Queen Square Institute of Neurology, University College London, London, UK.
Giannina Gaslini Institute, Scientific Institute for Research and Health Care, Genoa, Italy.Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy.
Correction to: CDKL5 deficiency-related neurodevelopmental disorders: a multi-center cohort study in Italy.
The consumption of ethanol has frequently been seen as largely restricted to humans. Here, we take a broad eco-evolutionary approach to understanding ethanol's potential impact on the natural world. There is growing evidence that ethanol is present in many wild fruits, saps, and nectars and that ethanol ingestion offers benefits that favour adaptations for its use in multiple taxa. Explanations for ethanol consumption span both the nutritional and non-nutritional, with potential medicinal value or cognitive effects (with social-behavioural benefits) explored. We conclude that ethanol is ecologically relevant and that it has shaped the evolution of many species and structured symbiotic relationships among organisms, including plants, yeast, bacteria, insects, and mammals.
Centre for Ecology and Conservation, Faculty of Environment, Science and Economy, University of Exeter, Penryn Campus, Cornwall, UK.
Department of Anthropology and Archaeology, University of Calgary, Calgary, Alberta, Canada.
Centre for Ecology and Conservation, Faculty of Environment, Science and Economy, University of Exeter, Penryn Campus, Cornwall, UK. Electronic address: k.hockings@exeter.ac.uk.
Science Department, College of Central Florida, Ocala, FL, USA.
Degenerative musculoskeletal diseases are a class of diseases related to the gradual structural and functional deterioration of muscles, joints, and bones, including osteoarthritis (OA), osteoporosis (OP), sarcopenia (SP), and intervertebral disc degeneration (IDD). As the proportion of aging people around the world increases, degenerative musculoskeletal diseases not only have a multifaceted impact on patients, but also impose a huge burden on the medical industry in various countries. Therefore, it is crucial to find key regulatory factors and potential therapeutic targets. Recent studies have shown that irisin plays an important role in degenerative musculoskeletal diseases, suggesting that it may become a key molecule in the prevention and treatment of degenerative diseases of the musculoskeletal system. Therefore, this review provides a comprehensive description of the release and basic functions of irisin, and summarizes the role of irisin in OA, OP, SP, and IDD from a cellular and tissue perspective, providing comprehensive basis for clinical application. In addition, we summarized the many roles of irisin as a key information molecule in bone-muscle-adipose crosstalk and a regulatory molecule involved in inflammation, senescence, and cell death, and proposed the interesting possibility of irisin in degenerative musculoskeletal diseases.
Copyright © 2024. Published by Elsevier Ltd.
Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China; Department of Clinical Medicine, Xiangya Medicine School, Central South University, Changsha, Hunan, China.
Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
The Central Hospital of Yongzhou, Yongzhou 425000, China.
School of Kinesiology, Jianghan University, Wuhan, Hubei, China.
Department of chemistry, School of Arts and Sciences, National University of Mongolia, Ulaanbaatar 14201, Mongolia.
Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address: liyusheng@csu.edu.cn.
Department of Joint Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China. Electronic address: Orth_shuguang@163.com.
Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address: xiaowenfeng@csu.edu.cn.
Irisin in degenerative musculoskeletal diseases: Functions in system and potential in therapy.
Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Fondazione Stella Maris, via dei Giacinti 2, Calambrone, 56128, Pisa, Italy.
Department of Neurosciences, Università Cattolica del Sacro Cuore, Rome, Italy.
Department of Brain and Behavioral Sciences, University of Pavia, 27100, Pavia, Italy.IRCCS Mondino Foundation, 27100, Pavia, Italy.
Department of Neurology and Neurosurgery, Montreal Neurological Hospital and Institute, McGill University, Montreal, Canada.
Department of Clinical and Experimental Medicine, Department of Mathematics, University of Pisa, Pisa, Italy.
Department of Medicine, Surgery and Neurosciences, Unit of Neurology and Neurometabolic Disorders, Azienda Ospedaliera Universitaria Senese, Università Di Siena, Siena, Italy.
Department of Neurosciences, Division of Pediatric Neurology, Santobono-Pausilipon Children's Hospital, Naples, Italy.
Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy.
Department of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy.
Department of Clinical and Experimental Medicine, Center for Neurodegenerative Diseases-Parkinson's Disease and Movement Disorders, University of Pisa, Pisa, Italy.
Department of Advanced Biomedical Sciences, University of Naples Federico II , Naples, Italy.
Department of Clinical and Experimental Sciences, NeMO-Brescia Clinical Center for Neuromuscular Diseases, University of Brescia, Brescia, Italy.
Department of Neurosciences, Reproductive Sciences and Odontostomatology, University Federico II of Naples, Naples, Italy.CDCD Neurology, Federico II University Hospital, Naples, Italy.
Macdonald Foundation, Department of Human Genetics, Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA.
Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli , Naples, Italy.
Department of Neurosciences, Reproductive Sciences and Odontostomatology, University Federico II of Naples, Naples, Italy.
Unit of Neurology and Neuromuscular Disorders, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
UO Neurologia, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
Department of Neurosciences, Neurology Unit, Azienda Ospedaliero Universitaria Di Modena, Modena, Italy.
Neuromuscular-Skeletal and Sensory Organs Department, AOU Careggi, Florence, Italy.
UOC Genetica Medica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168, Rome, Italy.
Institute of Biostructure and Bioimaging, National Research Council, Via T. De Amicis 95, 80145, Naples, Italy.
Department of Medicine, Surgery and Dentistry Scuola Medica Salernitana , Neuroscience Section, University of Salerno, Salerno, Italy.
Center for Neuromuscular and Neurological Rare Diseases, San Camillo Forlanini Hospital, Rome, Italy.
Unità Operativa Complessa Di Neurologia E Neuroriabilitazione, Presidio Ospedaliero Di Abano Terme - Azienda ULSS, 6 Euganea, Padua, Italy.
Dipartimento Universitario Scienze Della Vita E Sanità Pubblica, Sezione Di Medicina Genomica, Università Cattolica del Sacro Cuore, 00168, Rome, Italy.Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168, Rome, Italy.
Department of Neurosciences, Università Cattolica del Sacro Cuore, Rome, Italy.UOC Neurologia Dipartimento Neuroscienze, Organi Di Senso E Torace, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy.
Department of Brain and Behavioral Sciences, University of Pavia, 27100, Pavia, Italy.Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK.
Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Fondazione Stella Maris, via dei Giacinti 2, Calambrone, 56128, Pisa, Italy. filippo3364@gmail.com.
Correction to: Spinocerebellar ataxia 27B: a frequent and slowly progressive autosomal-dominant cerebellar ataxia-experience from an Italian cohort.
Rumen ciliates constitute a highly diverse group within the subclass Trichostomatia. They are known for their symbiotic relationship with ruminant hosts and their pivotal role in digestive metabolism. This review presents a historical analysis of research on rumen ciliate metabolism, since the earliest studies, based on in vitro and in situ experiments, as well as molecular studies, initially relying on Sanger sequencing, and more recently, next-generation sequencing techniques. Finally, the paper discusses future approaches that may be useful for elucidating the metabolic profile of various taxa of rumen ciliates.
Copyright © 2024 Elsevier GmbH. All rights reserved.
Laboratório de Diversidade Genética, Departamento de Genética, Evolução, Microbiologia e Imunologia, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil.
Laboratório de Diversidade Genética, Departamento de Genética, Evolução, Microbiologia e Imunologia, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, São Paulo, Brazil. Electronic address: cedrolaf@unicamp.br.
Disentangling the metabolic profile of rumen ciliates: A historical perspective and future directions.
Motor neuron disease (MND), also referred to as amyotrophic lateral sclerosis (ALS), is a monogenic disease in a minority of cases, with autosomal dominant inheritance. Increasing numbers of people with MND are requesting genetic testing, and indeed receiving a genetic diagnosis. Consequently, requests for genetic counselling and predictive testing (i.e. of unaffected family members) are similarly expected to rise, alongside pre-symptomatic clinical trials. Despite this, there is no evidence-based guideline for predictive genetic testing in MND. This paper provides an overview of the genomic basis of MND, focusing specifically on the most common monogenic causes of MND. It then lays out the complexities of MND predictive testing, including the genetic landscape characterised by incomplete penetrance, clinical and genetic heterogeneity, and an oligogenic mechanism of pathogenesis in some cases. Additionally, there is limited research on the psychosocial impact of predictive genetic testing for MND, with studies suggesting potential difficulty in adjusting to the news, in part due to a lack of support and follow-up. This underscores a case for evidence-based, disease-specific guidance for predictive testing in MND.
Division of Neuroscience and Neuroscience Institute, The University of Sheffield, Sheffield, UK.
Manchester Centre for Clinical Neuroscience, Salford Royal NHS Foundation Trust, Northern Care Alliance, Stott Lane, M6 8HD, UK.
Oxford Centre for Genomic Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Division of Evolution, Infection and Genomics, School of Biological Sciences, The University of Manchester, Manchester, UK.Manchester Centre for Genomic Medicine, Manchester University NHS Foundation Trust, Manchester, UK.
Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, USA.
Division of Neuroscience and Neuroscience Institute, The University of Sheffield, Sheffield, UK. a.mcneill@sheffield.ac.uk.Sheffield Clinical Genetics Service, Sheffield Children's Hospital NHS Foundation Trust, Sheffield, UK. a.mcneill@sheffield.ac.uk.
European journal of human genetics : EJHG
Genetic testing for monogenic forms of motor neuron disease/amyotrophic lateral sclerosis in unaffected family members.
Department of Otolaryngology-Head and Neck Surgery, the First Affiliated Hospital of Hainan Medical University, Haikou 571199, China.
Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China.
Cancer Centre, Faculty of Health Sciences, University of Macau, Macao 999078, China.
Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China.College of Animal Science and Technology, Shihezi University, Shihezi 832003, China.
SMG-1 serves as a prognostic indicator for the radiotherapy response in head and neck squamous cell carcinoma xenografts and patients.
Photobiomodulation (PBM) and transcutaneous electrical nerve stimulation (TENS) are used to reduce neck pain.To investigate the immediate and 1-month post-treatment effects of 10 treatment sessions of PBM and TENS delivered over 2 weeks on pain intensity in individuals with neck pain.Individuals with neck pain were randomized into four groups: PBM+TENS, PBM, TENS, and Sham.pain intensity at rest.pain intensity during movement, pressure pain threshold (PPT), temporal summation (TS), conditioned pain modulation (CPM), cervical range of motion (ROM), psychosocial factors, drug intake for neck pain, and global perceived effect (GPE). All outcome assessments were made pre- and post-treatment. Mean differences and 95 % confidence intervals were calculated for between-group comparisons.A total of 144 participants were recruited. No significant between-group difference was observed for pain intensity at rest, TS, CPM, ROM, psychosocial factors, and drug intake. The PBM+TENS showed a reduction in pain intensity during movement and GPE compared to the PBM (MD: 1.0 points; 95 % CI: 0.0, 2.0; MD: 2.0 points; 95 % CI: 1.0, 3.0) and Sham (MD: 2.0 points; 95 % CI: 1.0, 3.0; MD: 2.0 points; 95 % CI: 1.0, 3.0) groups. PBM+TENS presented a medium effect size to increase local PPT compared to PBM and Sham groups. TENS presented a medium effect size to increase local PPT compared to PBM and Sham groups. TENS presented a medium effect size to increase distant PPT compared to other groups.The use of PBM or TENS was not effective for reducing pain intensity at rest. The combination of PBM and TENS was effective in improving pain intensity during movement, local hyperalgesia, and the GPE. TENS reduced local and distant hyperalgesia.
Copyright © 2024. Publicado por Elsevier España, S.L.U.
Physical Therapeutic Resources Research Laboratory, Department of Physical Therapy, Federal University of São Carlos (UFSCar), São Carlos SP, Brazil. Electronic address: erika.rampazo@gmail.com.
Physical Therapeutic Resources Research Laboratory, Department of Physical Therapy, Federal University of São Carlos (UFSCar), São Carlos SP, Brazil.
Sport Sciences - Performance and Technology, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.
Physical Therapeutic Resources Research Laboratory, Department of Physical Therapy, Federal University of São Carlos (UFSCar), São Carlos SP, Brazil; Department of Rehabilitation Sciences, University of Hartford, West Hartford, CT, USA.
The effects of photobiomodulation and transcutaneous electrical nerve stimulation on chronic neck pain: A double-blind, randomized, sham-controlled trial.
To address climate change and global biodiversity loss, the world must hit three important international conservation targets by 2030: protect 30% of terrestrial and marine areas, halt and reverse forest loss, and restore 350 Mha of degraded and deforested landscapes. Here, we (1) provide estimates of the gaps between these globally agreed targets and business-as-usual trends; (2) identify examples of rapid past trend-shifts towards achieving the targets; and (3) link these past trend-shifts to different levers. Our results suggest that under a business-as-usual scenario, the world will fail to achieve all three targets. However, trend-shifts that rapidly bend the curve have happened in the past and these should therefore be fostered. These trend-shifts are linked to transformative change levers that include environmental governance, economic factors, values, and knowledge. Further research on trend-shifts, as well as bold action on underlying levers, is urgently needed to meet 2030 global conservation targets.
Univ. Grenoble-Alpes, IRD, CNRS, Grenoble INP, INRAE, IGE, 38000, Grenoble, France. ignacio.palomo@univ-grenoble-alpes.fr.
Univ. Grenoble-Alpes, IRD, CNRS, Grenoble INP, INRAE, IGE, 38000, Grenoble, France.
Carey Business School and Department of Environmental Health and Engineering, Johns Hopkins University, Baltimore, MD, USA.
Faculty of Economics, Universidade Federal Fluminense, Niterói, Rio de Janeiro, Brazil.
Centre for Environment and Development, University of Bern, 3012, Bern, Switzerland.Basque Centre for Climate Change, BC3, 48940, Leioa, Bizkaia, Spain.Ikerbasque, Basque Foundation for Science, 48009, Bilbao, Bizkaia, Spain.
UK Centre for Ecology & Hydrology (UKCEH), Wallingford, UK.
Department of International Environment and Development Studies (Noragric), Faculty of Landscape and Society, Norwegian University of Life Sciences (NMBU), PO Box 5003, 1432, Ås, Norway.Norwegian Institute for Nature Research (NINA), Gaustadalléen 21, 0349, Oslo, Norway.
Laboratoire d'Ecologie Alpine, UMR 5553, CNRS-UGA-USMB, CS 40700, 38058, Grenoble Cedex 9, France.
Business-as-usual trends will largely miss 2030 global conservation targets.
Department of Imaging Neuroscience, Institute of Neurology, University College London, London, UK.
King's College London, Institute of Psychiatry, Psychology and Neuroscience, London, UK South London and Maudsley NHS Foundation Trust, London, UK Institute of Cognitive Neuroscience, University College London, London, UK.
Institute of Cognitive Neuroscience, Institute of Neurology, University College London, London, UK.
How disrupted interoception could lead to disturbances in perceptual reality monitoring.
Department of Neurorehabilitation, National Hospital for Neurology and Neurosurgery, London, UK siobhanleary@nhs.net.
Department of Neurorehabilitation, National Hospital for Neurology and Neurosurgery, London, UK.
We evaluated and compared early postprocedural and midterm incidence and evolution of atrioventricular and intraventricular conduction disorders following rapid deployment aortic valve replacement (RDAVR) and conventional aortic valve replacement (AVR). One hundred and forty-seven patients who underwent isolated rapid deployment AVR between 2017 and 2021 as well as 128 patients after conventional biological AVR in the same period were included in this study. ECGs recorded at baseline, discharge, and 12 months were retrospectively analyzed. Intrinsic rhythm, PQ interval, QRS duration, and atrioventricular and intraventricular conduction were evaluated and compared between both groups. Patients in both groups had comparable Society of Thoracic surgeons risc (STS) scores (2.9 ± 1.6 vs. 3.1 ± 2.2, p = 0.32) and comparable baseline characteristics. The mean age was 73.4 ± 5.7 years in the RDAVR group and 74.2 ± 5.9 years in the AVR group, respectively. At baseline, the mean QRS width was 95.7 ± 25.5 ms in the RDAVR group, and 97.3 ± 23.5 ms in the AVR group, respectively (p = 0.590). At discharge, the mean QRS width in the RDAVR group was significantly increased with 117.4 ± 28.6 ms and a mean ΔQRS width of 21.7 ± 26.3 ms (p < 0.001) compared with baseline. No significant changes in QRS width were found in the AVR group with a mean value of 101.2 ± 24.1 ms and a mean ΔQRS width of 3.9 ± 23.9 ms at discharge (p = 0.193). The left bundle branch block (LBBB) was increased in the RDAVR group after 12 months (19.3% vs. 5.1%, p < 0.001). Permanent pacemaker implantation (PPI) rates were significantly higher in the RDAVR group after 12 months (hazard ratio (HR): 4.68; 95% CI: 2.23-7.43, p < 0.001). Mortality did not differ between both groups after 12 months (HR: 1.09; 95% CI: 0.46-1.83, p = 0.835) CONCLUSION: Patients after RDAVR showed significantly higher rates of LBBB and PPI after 12 months. However, higher mortality was not observed in the RDAVR group.
Department of Cardiothoracic Surgery, Ruhr University Hospital Bergmannsheil Bochum, Bochum, Nordrhine Westphalia, Germany.
Department of Anesthesiology, Ruhr-University Bochum, Bochum, Nordrhin-Westphalia, Germany.
Conduction Disorders after Rapid Deployment Aortic Valve Replacement Compared to Conventional Aortic Valve Replacement.
National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China.Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
Successful combined venetoclax to PD-1 blockade and ruxolitinib for refractory Epstein-Barr virus-associated haemophagocytic lymphohistiocytosis.
Department of Neurology, University Hospital of Wales, Heath Park, Cardiff, CF14 4XN, UK.
Department of Neurology, University Hospital of Wales, Heath Park, Cardiff, CF14 4XN, UK. marc.edwards@wales.nhs.uk.
Evolving management of Alzheimer's disease.
Asian Seabass (Lates calcarifer) is widely farmed as a sustainable source of protein for countries in the tropical Indo-West Pacific region. However, microbial species of the gut microbiome of healthy Asian Seabass remain largely uncharacterized and uncultured. Here, we analysed the microbial composition along the gastrointestinal tract of a farmed healthy Asian Seabass. We used different cultivation approaches to obtain isolates from the seabass intestinal tract and describe the isolation and characterization of a novel strain, TLL-SE01T. Analysis of the strain's 16S rRNA gene indicates that the strain belongs to the family Vibrionaceae with Photobacterium damselae as its closest relative, albeit sharing only 94.8% (aligned region 1553 bp) nucleotide identity. Comparative genomic analysis with all validly published Vibrionaceae species with available genomes revealed average nucleotide identity (ANI) and DNA-DNA hybridisation (DDH) values of around 70% and 24% respectively to strain TLL-SE01T, which are well below proposed thresholds for species delineation (ANI, 95-96%; DDH, 70%). The alignment fraction and ANI genus demarcation boundaries for all genera in the Vibrionaceae family were determined for which strain TLL-SE01T is well below the calculated values, indicating that it belongs to a novel genus. Single- and core-gene phylogenetic analysis places strain TLL-SE01T in a monophyletic clade, further supporting its designation to a novel genus. Phenotypic comparison between strain TLL-SE01T and its close relatives indicated additional differences, such as growth response at different salt concentrations and different metabolic capabilities. Based on genotypic, phylogenetic and phenotypic differences to other Vibrionaceae species, we propose a novel species in a new genus, Parasalinivibrio latis gen. nov. sp. nov. and strain TLL-SE01T (= BCRC 81435T = JCM 36283T) as the type strain.
Temasek Life Sciences Laboratory, 1 Research Link, Singapore, 117604, Singapore.
Temasek Life Sciences Laboratory, 1 Research Link, Singapore, 117604, Singapore.Department of Medicine, MD6-Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 14 Medical Drive, Singapore, 117599, Singapore.
Temasek Life Sciences Laboratory, 1 Research Link, Singapore, 117604, Singapore. henning@tll.org.sg.Department of Biological Sciences, National University of Singapore, Singapore, 117558, Singapore. henning@tll.org.sg.
Parasalinivibrio latis gen. nov., sp. nov., isolated from the distal gut of healthy farmed Asian Seabass (Lates calcarifer).
Cancer continues to be a leading cause of death worldwide, highlighting the urgent need for the development of new therapeutic strategies. Chrysophanol, a naturally occurring anthraquinone compound, has demonstrated significant potential in cancer treatment due to its diverse biological activities. This review delves into the mechanisms through which chrysophanol exerts its anti-cancer effects, including the induction of cell cycle arrest, promotion of apoptosis, regulation of autophagy, and initiation of necrosis across various cancer cell lines. Additionally, the review discusses chrysophanol's impact on inhibiting cancer cell invasion and metastasis and its role in modulating chemotherapy sensitivity. Despite the promising therapeutic potential of chrysophanol, challenges such as poor water solubility, low bioavailability, and safety concerns remain. Comprehensive clinical trials are essential to validate its efficacy and safety. This review emphasizes chrysophanol as a promising candidate for cancer therapy and underscores the necessity for further research to fully harness its therapeutic potential.
Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China.
Chengdu Fifth People's Hospital, The Fifth People's Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 611130, China.
Hospital of Chengdu University of Traditional Chinese Medicine, TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Chengdu 610072, China. Electronic address: 624440310@qq.com.
Hospital of Chengdu University of Traditional Chinese Medicine, TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Chengdu 610072, China. Electronic address: yuxujun@cdutcm.edu.cn.
Chrysophanol: A promising natural compound in cancer therapy - Mechanistic insights and future perspectives.
Nursing, University of West Florida, Pensacola, FL, USA.
Social Work, University of West Florida, Pensacola, FL, USA.
The Impact of a Mental Health Community Symposium on Nursing Students' Knowledge and Attitudes Toward Mental Illness.
Marine-derived proteins, such as blue whiting-derived protein hydrolysates (BWPH), represent high-quality sources of dietary protein, but their ability to support postexercise anabolism is not established. The impact of BWPH on whole-body anabolism was compared with an isonitrogenous whey protein isolate (WPI) and nonessential amino acid (NEAA) control in 10 trained young males (31 ± 4 years) who, on three separate visits, performed a session of whole-body resistance exercise and then consumed, in randomized crossover fashion, BWPH, WPI, or NEAA (0.33 g/kg; 19, 33, and 0 mg/kg leucine, respectively) with L-[1-13C]leucine. Breath, blood, and urine samples were collected for 6-hr postprandial to assess dietary leucine oxidation, amino acid (AA) concentrations, and 3-methylhistidine: creatinine ratio. Peak and area under the curve concentrations for leucine, branched-chain amino acids, and essential amino acids were greater in WPI compared with BWPH (all p < .05) but with no differences in time to peak concentration. Total oxidation reflected leucine intake (WPI > BWPH > NEAA; p < .01), whereas relative oxidation was greater (p < .01) in WPI (28.6 ± 3.6%) compared with NEAA (21.3 ± 4.2%), but not BWPH (28.6 ± 8.8%). Leucine retention, a proxy for whole-body protein synthesis, was greater in WPI (185.6 ± 9.5 μmol/kg) compared with BWPH (109.3 ± 14.1 μmol/kg) and NEAA (5.74 ± 0.30 μmol/kg; both p < .01), with BWPH being greater than NEAA (p < .01). Urinary 3-methylhistidine: creatinine ratio did not differ between conditions. Both WPI and BWPH produced essential aminoacidemia and supported whole-body anabolism after resistance exercise, but a higher intake of BWPH to better approximate the leucine and EAA content of WPI may be needed to produce an equivalent anabolic response.
School of Health and Human Performance, Dublin City University, Dublin, Ireland.
Faculty of Kinesiology and Physical Education, University of Toronto, Toronto, ON, Canada.
Department of Physical Education and Sports Sciences, University of Limerick, Limerick, Ireland.
Department of Physical Education and Sports Sciences, University of Limerick, Limerick, Ireland.Physical Activity for Health, Health Research Institute, University of Limerick, Limerick, Ireland.
School of Health and Human Performance, Dublin City University, Dublin, Ireland.Florida Institute for Human and Machine Cognition, Pensacola, FL, USA.
Postexercise Dietary Leucine Retention for Whole-Body Anabolism Is Greater With Whey Protein Isolate and Fish-Derived Protein Hydrolysate Than Nonessential Amino Acids in Trained Young Men.
John F. Hardesty, MD, Department of Ophthalmology and Visual Science, Washington University in St Louis, St Louis, Missouri.
Surgical Services, University of Miami, Miami, Florida.Bascom Palmer Eye Institute, University of Miami, Miami, Florida.
PharmaLogic Development, Inc, San Rafael, California.Department of Ophthalmology and Vision Science, University of California, Davis School of Medicine, Sacramento.
This Viewpoint addresses the high rate of incorrect ophthalmological diagnoses and harm experienced by patients and examines causes.
Implications of Diagnostic Error in Ocular Surface Disease: The Role of Anchoring and Ambiguous Diagnostic Terminology.
Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Henan Province Eye Hospital, Henan International Joint Research Laboratory for Ocular Immunology and Retinal Injury Repair, Zhengzhou, People's Republic of China.The Academy of Medical Sciences, Zhengzhou University, Zhengzhou, People's Republic of China.
Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Henan Province Eye Hospital, Henan International Joint Research Laboratory for Ocular Immunology and Retinal Injury Repair, Zhengzhou, People's Republic of China.Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.
Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Henan Province Eye Hospital, Henan International Joint Research Laboratory for Ocular Immunology and Retinal Injury Repair, Zhengzhou, People's Republic of China.
A 20-year-old Chinese woman was experiencing fever, malaise, headache, nausea, vomiting, and neck stiffness for 2 weeks. Further examination revealed inflammation, vitritis and cystoid macular edema, tortuous dilatation of retinal venous vessels with fluorescence leakage, and hyperfluorescence in the optic disc. What would you do next?
Viral Meningoencephalitis and Bilateral Blurry Vision.
This review describes the first steps necessary to apply any reproductive biotechnology in South American camelids (SAC) semen or sperm: sample collection, evaluation and handling. In camelids, the length and position adopted for mating and the site of semen deposition have conditioned semen collection methods. The advantages and disadvantages of available collection methods are summarized. The two main drawbacks for applying assisted reproductive techniques in SAC: sperm concentration and rheological characteristics are discussed. Techniques currently available to reliably evaluate diverse sperm characteristics are described, as are different methods to improve semen handling. Finally, advances made regarding the role of seminal plasma in SAC spermatozoon physiology are addressed. Part II of the review will cover the subsequent steps of dilution and cryopreservation of samples. Current results obtained using artificial insemination (AI) in SAC will also be covered in Part II.
Copyright © 2024 Elsevier B.V. All rights reserved.
Universidad de Buenos Aires, Facultad de Ciencias Veterinarias, Instituto de Investigación y Tecnología en Reproducción Animal (INITRA), Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina. Electronic address: ignaciacarretero@fvet.uba.ar.
Universidad de Buenos Aires, Facultad de Ciencias Veterinarias, Instituto de Investigación y Tecnología en Reproducción Animal (INITRA), Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.
Male reproductive biotechnologies in South American Camelids Part I: Semen collection, evaluation and handling.
Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Retina-Vitreous Surgeons of Central New York, Liverpool.Department of Ophthalmology & Visual Sciences, State University of New York Upstate Medical University, Syracuse.Flaum Eye Institute, University of Rochester Medical Center, Rochester, New York.
Southeastern Retina Associates, Chattanooga, Tennessee.
This case report describes an HIV-positive patient with bilateral syphilitic panuveitis, for whom diagnosis was initially delayed by negative treponemal testing.
Negative Treponemal Serologies in Syphilitic Panuveitis.
ALDH1A3-acetaldehyde metabolism potentiates transcriptional heterogeneity in melanoma.
Diabetic retinopathy (DR) continues to be the leading cause of preventable vision loss among working-aged adults, marked by immune dysregulation within the retinal microenvironment. Typically, the retina is considered as an immune-privileged organ, where circulating immune cells are restricted from entry under normal conditions. However, during the progression of DR, this immune privilege is compromised as circulating immune cells breach the barrier and infiltrate the retina. Increasing evidence suggests that vascular and neuronal degeneration in DR is largely driven by the infiltration of immune cells, particularly neutrophils, monocyte-derived macrophages, and lymphocytes. This review delves into the mechanisms and therapeutic targets associated with these immune cell populations in DR, offering a promising and innovative approach to managing the disease.
Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: zhaoyin85@hust.edu.cn.
Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: sunxufang2016@163.com.
Mechanism and therapeutic targets of circulating immune cells in diabetic retinopathy.
In many transdisciplinary research settings, a lack of attention to the values underpinning project aims can inhibit stakeholder engagement and ultimately slow or undermine project outcomes. As a research collective (The Careoperative), we have developed a set of four shared values through a facilitated visioning process, as central to the way we work together: care, reflexivity, inclusivity, and collectivity. In this paper, we explore the implications of a values-centered approach to collaboration in food system transformation research. The paper presents two cases that illustrate how researchers might approach centering values in practice. Where much research on food system transformation focuses on values of food system stakeholders, we contribute insights into the values of researchers in such transdisciplinary endeavors. Specifically, we argue that researchers working on sustainability transformations need to be better prepared to engage in such reflections and aspire to embody values aligned with the transformations they seek to research.
Stockholm Resilience Centre, Stockholm University, Albanovägen 28, 106 91, Stockholm, Sweden.
Wyss Academy for Nature, Kochergasse 4, 3012, Bern, Switzerland.Centre for Development and Environment, University of Bern, Mittelstrasse 43, 3012, Bern, Switzerland.Institute of Geography, University of Bern, Hallerstrasse 12, 3012, Bern, Switzerland.
AIT, Austrian Institute of Technology, Gieffengasse 4, 1210, Vienna, Austria.
Transdisciplinarity Lab, Department of Environmental Systems Science, ETH Zurich, Universitaetstrasse 22, 8092, Zurich, Switzerland.
Department of Geosciences and Natural Resource Management, University of Copenhagen, Øster Voldgade 10, 1350, Copenhagen, Denmark.
Australian Centre for Culture, Environment, Society and Space, University of Wollongong, Northfields Ave, Wollongong, NSW, 2220, Australia.
Stockholm Resilience Centre, Stockholm University, Albanovägen 28, 106 91, Stockholm, Sweden. jamila.haider@su.se.
University for Sustainable Development, Alfred-Möller-Str. 1-Haus 11, 16225, Eberswalde, Germany.
TMG Research gGmbH, EUREF Campus 6-9, 10829, Berlin, Germany.
ZALF, Eberswalder Str. 84, 15374, Müncheberg, Germany.
Cardiff University, Glamorgan Building, King Edward VII Avenue, Cardiff, CF10 3WA, Wales, UK.
Institute of Social Sciences in Agriculture, Department Sustainable Use of Natural Resources (430C), University of Hohenheim, Stuttgart, Germany.Centre for Development and Environment, University of Bern, Mittelstrasse 43, 3012, Bern, Switzerland.Institute of Geography, University of Bern, Hallerstrasse 12, 3012, Bern, Switzerland.
Reaping what we sow: Centering values in food systems transformations research.
We present a minimally invasive technique for deep brain hematoma evacuation that combines 3-dimensional visualization through 3DSlicer and laser-guided navigation, providing a practical and cost-effective alternative to traditional navigation in resource-limited settings.
Department of Emergency Medicine, Affiliated Kunshan Hospital of Jiangsu University, Suzhou, P.R. China.
Department of Neurosurgery, Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine, Suzhou, P.R. China.
Department of Neurosurgery, Affiliated Kunshan Hospital of Jiangsu University, Suzhou, P.R. China.
Department of Child and Adolescent Healthcare, Children's Hospital of Soochow University, Suzhou, P.R. China.
Three-dimensional Visualization Technology With 3DSlicer and Laser Guidance for Deep Brain Hematoma Evacuation in Primary Hospitals: A Technical Note.
To determine the dimension of the dorsum sellae (DS) in fetuses.Skull bases of 32 fetuses aged from 17 to 32 weeks were included in the work. The length of the DS at its superior border (DSL-SB) and the thickness of DS at its middle part (DST-ML) were measured. In addition, DS's height at its right lateral margin (DSH-RLB), at its left lateral margin (DSH-LLB), and at its middle part (DSH-ML) were measured.DSL-SB, DSH-RLB, DSH-LLB, DSH-ML, and DST-ML were measured as 8.42±1.89, 2.67±0.68, 2.73±0.68, 2.48±0.75, and 2.00±0.50 mm, respectively. All parameters were statistically similar for both sexes ( P >0.05). All parameters increased with advancing gestational weeks ( P <0.001). Linear functions were calculated for DSL-SB (y=- 1.756 + 0.426 × age), DSH-RLB (y=- 1.072 + 0.156 × age), DSH-LLB (y=- 0.851 + 0.150 × age), DSH-ML (y=- 1.687 + 0.174 × age), and DST-ML (y=- 0.473 + 0.103 × age).In fetuses, DS size grows with age. The linear functions regarding DS-related parameters may be used to estimate its size.
Department of Anatomy, Faculty of Medicine, Gaziantep University, Gaziantep.
Department of Medical Imaging Techniques, Health Services Vocational School, Osmaniye Korkut Ata University, Osmaniye.
Department of Anatomy, Faculty of Medicine, Gaziantep Islam Science and Technology University, Gaziantep, Türkiye.
Growth Dynamic of the Dorsum Sellae in Fetuses.
Department of Neurology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany.
Department of Neurosurgery, Hannover Medical School, Hannover, Germany.
Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover, Germany.
Institute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany.
Department of Neuropathology, Institute of Pathology, Hannover Medical School, Hannover, Germany.
Department of Neurology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany. skripuletz.thomas@mh-hannover.de.
Correction: Metabolomic profile of cerebrospinal fluid from patients with diffuse gliomas.
Department of Microbiology, Pondicherry University, Puducherry, 605014, India. prathaban_micro@pondiuni.ac.in.
Department of Microbiology, Pondicherry University, Puducherry, 605014, India.
Department of Microbiology, Vivekanandha Arts and Science College for Women, Sankagiri, Tamil Nadu, India.
School of Biosciences, Mar Athanasios College for Advanced Studies, Thiruvalla, Kerala, India.
Department of Microbiology, Altum Agro Technologies, Coimbatore, Tamil Nadu, India.
Correction: Isoptericola haloaureus sp. nov., a dimorphic actinobacterium isolated from mangrove sediments of southeast India, implicating biosaline agricultural significance through nitrogen fixation and salt tolerance genes.
Nasoethmoidal dermoid cysts are rare congenital ectodermal malformations. Unlike other dermoid cysts, those located in the midline can exhibit intracranial extension. Clinically, they may manifest with sebaceous discharge through a fistulous orifice and other morphologic alterations, occasionally presenting with complications at the onset. The authors present a clinical case of a nasoethmoidal dermoid cyst with an intracranial extension, treated with combined interdisciplinary surgical intervention. An adequate imaging evaluation before the surgical planning and complete lesion resection are crucial, considering their high recurrence rates.
Department of Plastic Surgery, Gantz Foundation.Department of Plastic Surgery, Surgery Service, Clínica Alemana.
Faculty of Medicine, Universidad del Desarrollo.Universidad del Desarrollo, Santiago, Chile.
Universidad del Desarrollo, Santiago, Chile.
Medical University of Vienna, Vienna, Austria.
Nasoethmoidal Dermoid Cyst With Intracranial Extension. Case Presentation and Surgical Management.
Department of Otolaryngology, University of Health Sciences, Umraniye Training and Research Hospital.
Ear Nose and Throat Specialist, Private Practice, Istanbul, Turkiye.
The Struggle to Allocate Time for Academic Studies Amidst Clinical Workloads.
To investigate the immune reconstitution after total parathyroidectomy and forearm transplantation in chronic renal failure.Forty-three patients, accompanied with chronic renal failure and secondary hyperparathyroidism (SHPT) that hospitalized during January 2019 to 2021 and underwent total thyroidectomy and forearm transplantation were enrolled as observation group. Forty hemodialysis patients with chronic renal failure but without SHPT were selected as the hemodialysis group. In addition, fifty volunteers who underwent physical examination within the same period were chosen as a control group. The parathyroid hormone (iPTH), blood phosphorus, blood calcium, th22, Treg cells, and inflammatory factors were detected in the three groups.The preoperative iPHT, serum phosphorus, and calcium levels in the observation group were higher than those in the control group and hemodialysis group ( P<0.05 ), and the index values of the observation group at each time point after surgery were remarkably lower than those in pre-surgery ( P<0.05 ). The preoperative Th22 and Th22/Treg in the observation group were higher, and Treg was lower than those in the control group and hemodialysis group ( P<0.05 ); The levels of Th22 and Th22/Treg in the observation group at each time point in post-operation were lower than those in pre-operation ( P<0.05 ), whereas Treg cells in observation group at each time point postoperatively were higher than those prior-operation ( P<0.05 ). The preoperative serum TNF-α, IL-6, TGF-β, and IL-22 in the observation group were notably higher than those in the control group and hemodialysis group ( P<0.05 ); And TNF-α, IL-6, TGF-β, and IL-22 in observation group at each time point in post-operation were lower than those in pre-surgery( P<0.05 ).For chronic renal failure patients complicated with SHPT, total parathyroidectomy and forearm transplantation can effectively improve their clinical symptoms, reduce the inflammatory state of the body, and beneficial for immune reconstruction.
Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of Mutaz B. Habal, MD.
Department of Nephrology, The Sixth People's Hospital of Chengdu.
Department of General Surgery, The Sixth People's Hospital of Chengdu.
Department of Cardiology, The Sixth People's Hospital of Chengdu, Chengdu, China.
Immune Reconstitution After Total Parathyroidectomy and Forearm Transplantation in Chronic Renal Failure.
I read The Pilgrim's Progress, by John Bunyan, and this book echoes the journey I have taken from medical school to the present. Christian's journey symbolizes the spiritual path of a believer in the pursuit of salvation. This narrative serves as an allegory for the Christian life, highlighting themes such as faith, redemption, and perseverance through trials. It includes twelve key stage. Comparing the life of a surgeon, from medical student to master surgeon approaching retirement, to Christian's journey in The Pilgrim's Progress makes for a fascinating allegory. Both paths involve growth, challenges, and perseverance toward a final goal: (1) Medical Student (City of Destruction), (2) Basic Training (Slough of Despond), (3) Residency (Wicket Gate and Hill of Difficulty), (4) Becoming a Junior Surgeon (Interpreter's House), (5) First Independent Operations (The Cross and the Burden Lifted), (6) Early Career (Palace Beautiful), (7) Facing Major Challenges (Valley of Humiliation and Shadow of Death), (8) Mid-Career Success and Worldly Temptations (Vanity Fair), (9) Crisis of Confidence (Doubting Castle and Giant Despair), (10) Mastery and Maturity (Delectable Mountains), (11) Facing Retirement (Enchanted Ground), and (12) Retirement and Legacy (Celestial City). In this allegory, the life of a surgeon mirrors Christian's spiritual journey-a path marked by challenges, doubts, triumphs, and ultimately, the fulfillment of a calling. Both are in pursuit of a final rest in their respective fields, whether it be spiritual salvation or the surgeon's sense of a lasting contribution to humanity. The journey of the surgeon is similar to that of the pilgrim.
Department of Plastic Surgery, Armed Forces Capital Hospital, Bundang-gu, Seongnam-City, Gyeonggi-do, and Department of Anatomy, College of Medicine, Ewha Womans University, Seoul, Republic of Korea.
Surgeon's Journey and Pilgrim's Progress.
Surgery is performed for craniosynostosis to enlarge intracranial volume and improve cranial morphology. Endoscope-assisted suturectomy is one of the effective treatments. Compared with other techniques, it is reported to be low invasive and enables improvement of cranial volume and morphology at an early age. At the National Center for Child Health and Development (Tokyo, Japan), endoscope-assisted suturectomy is performed for all patients with craniosynostosis under the age of 3 months. Bone defects are sometimes observed several years after endoscope-assisted suturectomy. In syndromic bilateral coronal craniosynostosis patients in whom fused coronal sutures are removed, bone defects often remain in the temporal region. These may cause difficulty in setting the osteotomy line and placing distraction device for later monobloc advancement. In the present study, syndromic bilateral coronal craniosynostosis patients who underwent endoscope-assisted suturectomy between 2017 and 2022 at our hospital were retrospectively reviewed to investigate residual bone defects after the operation. As monobloc advancement, tongue-in-groove technique and placing internal distractors were assumed, and cranial bone defects between the ages of 3 and 5 years were evaluated in 3D by using image processing software. Five patients were included, and in 2 patients, the bone defects in the temporal regions were deemed large enough to interfere with making the bandeau or restrict the use of internal distractors for monobloc advancement. When performing suturectomy for syndromic craniosynostosis patients with midfacial concavity, careful surgical strategies that take into account future monobloc advancement should be considered.
Division of Plastic Surgery, National Center for Child Health and Development, Setagaya-ku.
Division of Neurosurgery, National Center for Child Health and Development, Setagaya-ku, Tokyo.
Division of Neurosurgery, Saitama Prefectural Hospital, Chuo-ku, Saitama-shi, Saitama, Japan.
Influence of Bone Defects After Endoscope-Assisted Suturectomy on Monobloc Advancement in Syndromic Bilateral Coronal Craniosynostosis Patients.
Neurogenic orthostatic hypotension (nOH) causes pathological falls in standing blood pressure that may or may not be symptomatic. nOH also raises the risk of poor neurological outcomes irrespective of symptom presence, possibly reflecting subclinical cerebral hypoperfusion. Dynamic changes in cerebral blood flow velocity (CBFv) help infer how blood pressure fluctuations influence CBFv and cerebral autoregulation. Whether CBFv is impacted in nOH relative to related conditions without nOH and healthy controls (HC) remains unresolved. Whether nOH symptoms reflect greater CBFv falls is also unclear. This review aimed to compare CBFv between nOH and HC, nOH and disease-matched controls (eg, Parkinson disease±nOH), and between symptomatic and asymptomatic nOH.Embase and MEDLINE were searched up to April 2024. Means, SDs, and sample sizes for supine and upright CBFv were extracted to generate standardized effect sizes (Hedge g). Random-effects modeling compared postintervention between-group effect sizes.Seventeen studies were included for review. Thirteen studies were suitable for meta-analysis comparing nOH to HC, 2 comparing disease-matched controls to nOH and to HC, and 3 for symptomatic comparisons. Compared with HC, nOH had larger drops in CBFv (Hedge g, -0.64 [95% CI, -0.85 to -0.44]; P<0.001). CBFv falls between nOH and disease-matched controls were similar (P=0.17). Symptomatic nOH had larger CBFv drops (Hedge g, 0.84 [95% CI, 0.212-1.461]; P=0.009) than asymptomatic nOH.nOH causes significant orthostatic reductions in CBFv compared with HC, and symptomatic patients experience greater falls in CBFv than asymptomatic patients. Recognizing the clinical implications of CBFv in nOH is crucial for mitigating adverse outcomes.
Department of Cardiac Sciences, Cumming School of Medicine, University of Calgary, Alberta, Canada (J.R.B., S.I.R., A.P., S.R.R.).Libin Cardiovascular Institute, University of Calgary, Alberta, Canada (J.R.B., S.I.R,. A.P., S.R.R).
Department of Neurology, Emory University School of Medicine, Atlanta, GA (P.A.B.).
Department of Anesthesiology and Perioperative Medicine, University of Rochester School of Medicine, NY (J.G.).
Department of Electrical Engineering, Mathematics, and Computer Science, University of Twente, the Netherlands (C.O.T).
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (R.F.).
Cerebral Blood Flow Dynamics in Neurogenic Orthostatic Hypotension: A Systematic Review and Meta-Analysis.
In this paper, the authors aim to explore the reasons behind human makeup from both medical and literary perspectives. In a PubMed search for makeup and cosmetics, 509 titles were identified. Of these, 64 abstracts were reviewed, and ultimately, 8 full texts were referenced. The poem A Woman Young and Old written by William Butler Yeats was analyzed. In Research Information Sharing Service ( https://www.riss.kr ), 4 full texts about the poem A Woman Young and Old were found and referenced. Common motivations for using makeup include enhancing natural features, boosting confidence, expressing creativity, covering imperfections, fulfilling cultural and social expectations, and meeting professional requirements. Makeup can make women appear younger. Makeup enhances the reward value of human facial appearance. Makeup can conceal blemishes, scars, dark circles, and other skin imperfections, resulting in a more even and flawless complexion. In a poem by Yeats A Woman Young and Old, he describes a young woman applying makeup and captures a moment in which she engages in the ritual of enhancing her beauty. The line I'm looking for the face I had before the world was made speaks to a longing for something beyond the mundane, a yearning for a deeper connection with existence. Before this world was made is a typical poetic turn of phrase that compares women to eternal beauty. The reasons why women use makeup are diverse and multifaceted, reflecting a combination of personal preferences, societal influences, and individual motivations. Makeup can be a powerful tool for expressing oneself, boosting one's confidence, and enhancing one's natural beauty.
Department of Plastic, Reconstructive Microsurgery, and Hand Surgery, Kyrgyz State Medical Academy, and National Hospital of Kyrgyzstan.
Department of Plastic, Reconstructive Microsurgery, and Hand Surgery, National Hospital of Kyrgyzstan, Bishkek, Kyrgyzstan.
Department of Plastic Surgery, Armed Forces Capital Hospital, Bundang-gu, Seongnam, Gyeonggi-do.Department of Anatomy, College of Medicine, Ewha Womans University, Seoul, Republic of Korea.
Makeup, An Attempt to Reach Eternal Beauty; Plastic Surgeon's View.
Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland.
Division of Oculoplastic Surgery, Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland.
Ocular Immunology Division, Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland.
A 63-year-old woman with a history of type 1 diabetes presents with gradually progressive vision loss in the right eye for the past year. What would you do next?
Looking Beyond and Behind a Retinal Detachment.
Publisher Correction: The interplay between the urban development of Rome (Italy) and the Tiber River floods: A review of two millennia of socio-hydrological history.
Mobilization with movement (MWM) is commonly used to treat patients with rotator cuff-related shoulder pain (RCRSP). However, the evidence supporting MWM efficacy for improving range of motion (ROM) and pain in patients with RCRSP is limited.To assess the immediate effects of MWM on the angular onset of pain in patients with RCRSP.Sixty-three participants with RCRSP were randomized to receive 3 sets of 10 repetitions of MWM or sham MWM with a minute rest between each set. The angular onset of pain (primary outcome), and pain intensity at rest and during shoulder abduction to the onset of pain were measured at baseline, and after receiving the 1st and 3rd sets of 10 repetitions of interventions. Other secondary outcomes were measured at baseline and after receiving 3 sets of 10 repetitions of interventions or 1, 2, 3, 5, and 7 days after interventions.Compared with the sham MWM group, the MWM group had an additional improvement of 6.5° (95% CI -0.9, 13.9) and 13.7° (95% CI 6.3, 21.1) (from baseline) after receiving the 1st and 3rd sets of 10 repetitions of interventions, respectively.MWM improves the angular onset of pain after 3 sets of 10 repetitions of MWM in patients with RCRSP. This study provides preliminary support for the use of MWM in treating patients with RCRSP and provides some guidance for clinicians to decide the MWM dosage to be used in clinical practice.
Copyright © 2024 The Author(s). Publicado por Elsevier España, S.L.U. All rights reserved.
Centre for Health, Activity and Rehabilitation Research (CHARR), School of Physiotherapy, University of Otago, Dunedin, Otago, New Zealand; Division of Physiotherapy, Department of Health Sciences, College of Health, Medicine and Life Sciences, Brunel University London, Uxbridge, London, United Kingdom; Centre for Physical Activity in Health and Disease (CPAHD), Brunel University London, Uxbridge, London, United Kingdom. Electronic address: sizhong.wang@brunel.ac.uk.
Department of Preventive and Social Medicine, Dunedin School of Medicine, Division of Health Sciences, University of Otago, Dunedin, Otago, New Zealand.
Centre for Health, Activity and Rehabilitation Research (CHARR), School of Physiotherapy, University of Otago, Dunedin, Otago, New Zealand.
Centre for Health, Activity and Rehabilitation Research (CHARR), School of Physiotherapy, University of Otago, Dunedin, Otago, New Zealand; Curtin School of Allied Health, Faculty of Health Sciences, Curtin University, Perth, WA, Australia. Electronic address: daniel.curyribeiro@curtin.edu.au.
The immediate effects of mobilization with movement on shoulder range of motion and pain in patients with rotator cuff-related shoulder pain: A randomized controlled trial (Evolution Trial).
The pioneers of next-generation sequencing technology and bioinformatic analyses initiated a new era in microbiology research by offering profound insights into bacterial microbiome communities. In the pig farming sector, while considerable attention has been devoted to the gut microbiome and the microbiome of the female reproductive tract, research on the microbiome of boar semen remains limited. Nonetheless, published studies have provided valuable insights, serving as important references and sparking ideas for further investigations into the seminal microbiome. Factors such as breed, seasons, feed additives, hygiene management, and antibiotic use are believed to exert a notable influence on the diversity and richness of bacterial genera in the boar seminal microbiome, potentially affecting semen quality. Moreover, current shifts towards sustainability in the swine industry, coupled with global guidelines concerning the prudent use of antibiotics in stored boar semen for artificial insemination, underscore the need for insights into factors influencing seminal bacteria. The objective of this review is to elucidate the current understanding of boar bacterial contents using conventional culture methods, as well as the boar seminal microbiome through metagenomics and bioinformatics. It also aims to review specific microbiome communities, such as those in the reproductive tract and gut, and their connections to semen quality. In addition, strategic enhancements for processing boar semen doses through alternative methods to improve seminal quality are proposed.
Department of Obstetrics, Gynaecology and Reproduction, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand.
Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala SE-75007, Sweden.
Department of Obstetrics, Gynaecology and Reproduction, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand; Center of Excellence in Swine Reproduction, Chulalongkorn University, Bangkok 10330, Thailand. Electronic address: Padet.t@chula.ac.th.
Boar semen microbiome: Insights and potential implications.
Metabolic syndrome, as a complex pathological condition, is caused by a series of pathogenic factors and has become a global public health challenge. Anthocyanins, a natural water-soluble flavonoid pigment, have attracted much attention due to their antioxidant, anti-inflammatory, and anticancer biological activities. After ingestion, a majority of anthocyanins is not directly absorbed but rather reaches the colon. Hence, the exertion of their biological benefits is closely intertwined with the role played by gut microbiota. In this review, we introduce the pathogenesis and intervention methods of metabolic syndrome, as well as the interaction between anthocyanins and gut microbiota. We also discuss the therapeutic potential of anthocyanins through gut microbiota in addressing a range of metabolic syndrome conditions, including obesity, type 2 diabetes mellitus, cardiovascular diseases, non-alcoholic fatty liver disease, inflammatory bowel disease, polycystic ovary syndrome, osteoporosis, and cancer.
State Key Laboratory of Tree Genetics and Breeding, Co-Innovation Center for Sustainable Forestry in Southern China, College of Forestry and Grassland, Nanjing Forestry University, Nanjing 210037, China.
Jiangsu Key Laboratory for the Research and Utilization of Plant Resources, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China.
Jiangsu Key Laboratory for the Research and Utilization of Plant Resources, Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China. Electronic address: chenjian80@aliyun.com.
State Key Laboratory of Tree Genetics and Breeding, Co-Innovation Center for Sustainable Forestry in Southern China, College of Forestry and Grassland, Nanjing Forestry University, Nanjing 210037, China. Electronic address: lwlcnbg@cnbg.net.
Effect of anthocyanins on metabolic syndrome through interacting with gut microbiota.
Efficient and sustainable reproduction and production of cattle and goats are vitally important for ensuring global food security. There is a need for potent biomarkers to accurately evaluate semen quality and predict male fertility. Although there is a reasonable set of biomarkers identified in bull sperm, there is a significant lack of such information in buck sperm along with a lack of transfer of proven technologies in goat reproductive biotechnology. These gaps are important problems because they are preventing advances in fundamental andrology and applied science of goat production. Both cattle and goats are ruminants, and they share significant similarities in their genetics and physiology although subtle differences do exist. This review harnesses the power of utilizing the knowledge developed in bull sperm to generate information on buck sperm fertility markers. These include genomic, functional genomic, epigenomic fertility markers. Revealing molecular underpinnings of such similarity and diversity using systems biology is expected to advance both fundamental and applied andrology of livestock and endangered species.
College of Agriculture, Food and Natural Resources, Cooperative Agricultural Research Center, Prairie View A&M University, Prairie View, TX, United States; Department of Reproduction and Artificial Insemination, Faculty of Veterinary Medicine, Selcuk University, Konya, Türkiye. Electronic address: mbodu@selcuk.edu.tr.
College of Agriculture, Food and Natural Resources, Cooperative Agricultural Research Center, Prairie View A&M University, Prairie View, TX, United States. Electronic address: muhitit@pvamu.edu.
College of Agriculture, Food and Natural Resources, Cooperative Agricultural Research Center, Prairie View A&M University, Prairie View, TX, United States. Electronic address: ermemili@pvamu.edu.
Harnessing the value of fertility biomarkers in bull sperm for buck sperm.
Mycobacteroides abscessus is a non-tuberculous mycobacteria implicated in causing lung infections. It is difficult to control owing to resistance to antibiotics and disinfectants. This work was aimed at comprehending: the pan-genome architecture, evolutionary dynamics, and functionalities of pan-genome components linked to COGs and KEGG. Around 2802 core genes were present in each strain of the M. abscessus genome. The number of accessory genes ranged from 1615 to 2481. The open pan-genome of M. abscessus was attributed to the accessory genes underlining its adaptability in the host. Phylogenetic analysis revealed cluster-based relationships and highlighted factors shaping variability and adaptive capabilities. Transcription, metabolism, and pathogenic genes were vital for M. abscessus lifestyle. The accessory genes contributed to the diverse metabolic capability. The incidence of a significant portion of secondary metabolite biosynthesis genes provided insights for investigating their biosynthetic gene clusters. Additionally, a high proportion of xenobiotic biodegradation genes highlighted potential metabolic capabilities. In silico screening identified a potential vaccine candidate among hypothetical proteins in COGs. Functional analysis of M. abscessus pan-genome components unveiled factors associated with virulence, pathogenicity, infection establishment, persistence, and resistance. Notable amongst them were: MMPL family transporters, PE-PPE domain-containing proteins, TetR family transcriptional regulators, ABC transporters, Type-I, II, III, VII secretion proteins, DUF domain-containing proteins, cytochrome P450, VapC family toxin, virulence factor Mce family protein, type II toxin-antitoxin system. Overall, these results enhanced understanding of the metabolism, host-pathogen dynamics, pathogenic lifestyle, and adaptations. This will facilitate further investigations for combating infections and designing suitable therapies.
Department of Botany, Ramananda College, Life Sciences Block, Bishnupur, West Bengal, 722122, India.
Department of Botany, Ramananda College, Life Sciences Block, Bishnupur, West Bengal, 722122, India. saubashya@gmail.com.
Unlocking the Mycobacteroides abscessus pan-genome using computational tools: insights into evolutionary dynamics and lifestyle.
A Gram-positive, moderately halophilic, rod-shaped and facultatively anaerobic strain T66T, was isolated from the rhizosphere soil of mangrove Acanthus ebracteatus in Guangxi, China. Strain T66T was observed to grow at 15-40 ℃ (optimum 30 ℃), pH 5-8 (optimum 6-7) and with 2-20% (w/v) NaCl (optimum 6%). The phylogenetic tree of the 16S rRNA gene sequences depicted a cluster of strain T66T to be closely related to Halobacillus litoralis SL-4 T (98.72%), Halobacillus dabanensis D-8 T (98.70%) and Halobacillus campisalis ASL-17 T (98.66%). The phylogenetic analysis based on the 16S rRNA gene sequence showed that strain T66T belonged to the genus Halobacillus and formed a separate branch. The digital DNA-DNA hybridisation and average nucleotide identify values between strain T66T and its related species were 17.80-19.80% and 70.78-73.22%, respectively, which were lower than the threshold recommended for species delineation. The genomic DNA G + C content was 40.9%. The predominant isoprenoid quinone was MK-7, the cell-wall peptidoglycan contained meso-diaminopimelic acid, and the major fatty acids that accounted for more than 10.0% were anteiso-C15:0 (68.4%) and anteiso-C17:0 (13.4%). Phosphatidylglycerol, diphosphatidylglycerol, three unidentified phospholipids and an unidentified glycolipid were found in the polar lipid extraction. Strain T66T could hydrolyse casein and contains several genes (e. g. vanY, vpr, pbpG and elpC) involved in protease. Therefore, strain T66T is salt-tolerant and produces protease, and it may have development and utilisation value in flavouring agents and food curing. Based on phenotypic, chemotaxonomic data and genotypic characteristics, strain T66T represents a novel species of the genus Halobacillus, for which the name Halobacillus rhizosphaerae sp. nov. is proposed. The type strain is T66T (= JCM 36534 T = MCCC 1K08701T).
Guangxi Key Laboratory for Polysaccharide Materials and Modifications, School of Marine Sciences and Biotechnology, Guangxi Minzu University, Nanning, 530006, China.
Guangxi Key Laboratory of Mangrove Conservation and Utilization, Guangxi Mangrove Research Center, Guangxi Academy of Sciences, Beihai, 536007, China.
Guangxi Key Laboratory for Polysaccharide Materials and Modifications, School of Marine Sciences and Biotechnology, Guangxi Minzu University, Nanning, 530006, China. hongyanzhang2008@163.com.
Halobacillus rhizosphaerae sp. nov., a moderately halophilic bacterium with protease activities isolated from the rhizosphere soil of the mangrove Acanthus ebracteatus.
Gallbladder cancer (GBC) is an aggressive disease with limited treatment options but high prevention potential. GBC tumours take 10-20 years to develop, a timeframe that holds potential for early detection. MicroRNAs (miRNAs) play a central role in abnormal cell processes, and circulating miRNAs may constitute valuable biomarkers of early disease. We used microarray data to pre-select differentially expressed miRNAs in formalin-fixed paraffin-embedded (FFPE) gallbladder tissue samples (GBC n = 40, normal n = 8). We then applied small-RNA sequencing to screen for miRNA expression differences in serum samples from three European prospective cohorts (n = 37 GBC case-control pairs), and validated the most promising candidates in three independent cohorts (n = 36 GBC case- control pairs). Statistical analyses included robust linear regression, pathway and meta-analysis, and examination of expression correlation between miRNAs and target genes. MiR-4533 and miR-671-5p were overexpressed in GBC tissue and serum samples, and meta-analysis confirmed the overexpression of miR-4533 in GBC serum samples from the prospective cohorts (p-value = 4.1×10-4), especially in individuals of female sex, under 63.5 years, or with a BMI below 26.2 kg/m2. Pathway and correlation analyses revealed that miR-4533 targets SIPA1L2 in the Rap1 signalling pathway, and SIPA1L2 was downregulated in GBC serum samples. Our study highlights the advantage of integrating small-RNA sequencing results from different types of samples and independent datasets, and the need for international research collaborations to identify and validate biomarkers for secondary prevention of rare tumours such as GBC. The function of miR-4533 and its interaction with SIPA1L2 in GBC development need to be further investigated.
Statistical Genetics Research Group, Institute of Medical Biometry, Heidelberg University, Heidelberg, Germany.
Department of Research, Cancer Registry of Norway, Norwegian Institute of Public Health, Oslo, Norway; Center for Bioinformatics, Department of Pharmacy, University of Oslo, Oslo, Norway.
Department of Research, Cancer Registry of Norway, Norwegian Institute of Public Health, Oslo, Norway; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany; Institute of Pathology, Heidelberg University Hospital, Heidelberg University, Heidelberg, Germany.
HUNT Research Centre, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway; HUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology), Trondheim, Norway; Department of Research, St Olav's Hospital, Trondheim, Norway.
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany; German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany.
Institute for Asthma and Allergy Prevention, Helmoltz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Research Unit Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Statistical Genetics Research Group, Institute of Medical Biometry, Heidelberg University, Heidelberg, Germany; Laboratory of Biostatistics for Precision Oncology, Institut de Cancérologie Strasbourg Europe, France. Electronic address: lorenzo@imbi.uni.heidelberg.de.
European journal of cancer (Oxford, England : 1990)
Small-RNA sequencing reveals potential serum biomarkers for gallbladder cancer: Results from a three-stage collaborative study of large European prospective cohorts.
Forests' ability to provide opportunities for recreation is an important ecosystem service. This has prompted attempts to create indicators to assess forests' suitability for recreation, although hitherto with limited success. This study introduces a novel framework for indicators of potential and realised recreational values of forests, with a primary focus on Sweden and Fennoscandia. We divided forest attributes into intrinsic qualities (i.e. the structure and composition of the forest), extrinsic qualities (i.e. the location of the forest in relation to other components of the landscape), and facilitation qualities (i.e. the presence of recreational infrastructure). Using Fennoscandia as a case study, we performed a literature review to find specific indicators of recreational values, as well as evaluate the current availability of spatial data suitable to map the forest qualities on a national scale. The most important intrinsic quality we identified was tree size/age, whereas for extrinsic quality it was proximity to water. Systematic monitoring of recreational use is essential to estimate realised recreational values. The conceptual framework proved to be a valuable tool for identifying potential indicators, and applying it in other regions is likely to yield useful outcomes.
Department of Ecology, Swedish University of Agricultural Sciences, Box 7044, 750 07, Uppsala, Sweden. Carl.lehto@slu.se.
Universidad Intercultural de las Nacionalidades y Pueblos Indígenas Amawtay Wasi, Av. Colón E5-56 y Juan León Mera, Edif. Ave María, Torre B, Quito, Ecuador.
Department of Urban and Rural Development, Swedish University of Agricultural Sciences, Box 7012, 750 07, Uppsala, Sweden.
Department of Economy, Geography, Law and Tourism (EJT), Mid Sweden University, 831 25, Östersund, Sweden.
A conceptual framework of indicators for the suitability of forests for outdoor recreation.
Recently, the microbiome has been gaining significant attention in the healthcare sector as a next-generation factor. However, there remains a substantial gap in our understanding of the fundamental mechanisms of microbes, particularly regarding the effector microbial products exchanged between the microbiota and the host. Consequently, research on microbial extracellular vesicles (MEVs) has increased. MEVs, which are nano-sized, can circulate throughout the body and penetrate the bloodstream, carrying diverse information. Consequently, they are increasingly being utilized in medical applications. Additionally, AI technologies are being utilized in medicine. The combination of MEVs and AI technology is being explored for the development of algorithm-based in vitro diagnostics (IVD). Therefore, this study aims to review the integration of MEVs and AI technology as diagnostic tools for personalized medicine. This paper reviewed the MEV-based algorithms developed by a variety of human samples and AI technology. Additionally, most of MEV-based diagnostic models showed higher clinical performance. Several important factors are crucial for accurate diagnosis. First, optimizing sample types according to specific diseases is essential. Second, AI technology with higher diagnostic power yields more accurate results. Finally, incorporating additional markers can enhance diagnostic power. However, applying this tool in situ faces several limitations, including method standardization, sample size, and analysis techniques. In the future, we anticipate that research on MEVs will advance our understanding of their role in disease and establish the foundation for precision medicine strategies.
Copyright © 2024 The Author. Published by Elsevier Ltd.. All rights reserved.
Department of Occupational Health and Safety, Semyung University, Jecheon, Chungcheongbuk-do, Republic of Korea. Electronic address: iamjinho@semyung.ac.kr.
Insight into the potential of algorithms using AI technology as in vitro diagnostics utilizing microbial extracellular vesicles.
Two novel strains, SYSU D00514T and SYSU D00778, were isolated from desert soil in the Gurbantunggut Desert, Xinjiang Uygur Autonomous Regions, PR China. SYSU D00514T and SYSU D00778 were aerobic, Gram-stain-positive, rod-shaped, catalase-positive and oxidase-negative. SYSU D00514T grew at temperatures ranging from 4 to 37 °C (optimum, 28-30 °C), at pH 6.0-8.0 (optimum, 7.0), and tolerated NaCl concentrations from 0 to 7.5% (optimum, 0.5% w/v). Phylogenetic analysis based on 16S rRNA gene sequences revealed that strains SYSU D00514T and SYSU D00778 were closely related to the members of the genus Nocardioides. Two isolates were most closely related to Nocardioides alpinus Cr7-14 T (98.05% and 98.19%). The G + C content of the genomic DNA of strains SYSU D00514T and SYSU D00778 were both 72.8%. Strain SYSU D00514T and the type strains of the genus Nocardioides in the analysis had average nucleotide identity values of 76.8-85.8% as well as digital DNA-DNA hybridization values between 19.5% and 28.0%. The predominant cellular fatty acids of strain SYSU D00514T were C17:1 ω8c, C18:1 ω9c and iso-C16:0. For strain SYSU D00514T, the major polar lipids encompassed diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, phosphatidylinositol, an unidentified aminophospholipid and two unidentified aminolipids. The main respiratory quinone of strain SYSU D00514T was MK-8 (H4). Based on the results of polyphasic taxonomic experiments, we propose that strains SYSU D00514T and SYSU D00778 represent a novel species of the genus Nocardioides, with the name Nocardioides xinjiangensis. The type strain is SYSU D00514T (= CGMCC 1.18622 T = MCCC 1K05001T = KCTC 49488 T).
State Key Laboratory of Biocontrol, Guangdong Provincial Key Laboratory of Plant Stress Biology and Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), School of Life Sciences, Sun Yat‑Sen University, Guangzhou, 510275, People's Republic of China.
State Key Laboratory of Desert and Oasis Ecology, Key Laboratory of Ecological Safety and Sustainable Development in Arid Lands, Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, Urumqi, 830011, People's Republic of China.
State Key Laboratory of Biocontrol, Guangdong Provincial Key Laboratory of Plant Stress Biology and Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), School of Life Sciences, Sun Yat‑Sen University, Guangzhou, 510275, People's Republic of China. donglei6@mail.sysu.edu.cn.
State Key Laboratory of Biocontrol, Guangdong Provincial Key Laboratory of Plant Stress Biology and Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), School of Life Sciences, Sun Yat‑Sen University, Guangzhou, 510275, People's Republic of China. liwenjun3@mail.sysu.edu.cn.State Key Laboratory of Desert and Oasis Ecology, Key Laboratory of Ecological Safety and Sustainable Development in Arid Lands, Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, Urumqi, 830011, People's Republic of China. liwenjun3@mail.sysu.edu.cn.
Nocardioides xinjiangensis sp. nov., a novel species isolated from desert soil.
Lower eyelid blepharoplasty is a procedure to address issues arising from age-related anatomic changes of the lower eyelid. These include excess skin, fat herniation, tear trough hollowing, and midface descent. Unlike the well-defined structures of the upper eyelid, the lower eyelid's anatomy, including the retractors and surrounding ligaments, is less distinct and understudied. In addition, lower eyelid blepharoplasty has an unfavorable complication profile compared with that of the upper eyelid. This review examines relevant studies on lower eyelid anatomy, focusing on age-related structural changes and the variability of key structures involved in blepharoplasty surgery to minimize the risk of complications and achieve desirable outcomes. A literature search for relevant publications on the topic was performed through Medline and PubMed, with the appropriate data extracted, identifying 54 relevant studies. These studies demonstrate how degenerative changes to the supporting structures of the lower eyelid contribute to prolapse of the orbital fat pads, and highlight the relevant ligamentous structures, blood supply, and innervation to avoid complications during transcutaneous or transconjunctival orbital fat repositioning. With detailed knowledge of the anatomy of the lower eyelid as outlined in our review, surgeons can improve and optimize outcomes whilst minimizing complications.
UCL Medical School, University College London, Bloomsbury.
Moorfields Eye Hospital NHS Trust.The Ezra Clinic, London, UK.
Lower Eyelid Surgical Anatomy and the Implications for Blepharoplasty Surgery: A Systematic Review of Anatomic Studies in the Literature.
Fulzerasib (Dupert®; Innovent Biologics/GenFleet Therapeutics) is an orally active small molecule inhibitor of the KRAS G12C mutant protein being developed for the treatment of solid tumors harboring the KRAS G12C oncogenic driver mutation, including non-small cell lung cancer (NSCLC) and colorectal cancer. Fulzerasib received its first approval on 21 August 2024 in China, for the treatment of adults with KRAS G12C-mutated advanced NSCLC who have received at least one line of systemic therapy. This conditional approval was based on the positive results of a single-arm, phase II study. This article summarizes the milestones in the development of fulzerasib leading to this first approval for KRAS G12C-mutated advanced NSCLC.
Springer Nature, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand. dru@adis.com.
Older patients with cutaneous cancer often have comorbidities. Tumor resection and defect reconstruction in these patients are challenging.To evaluate the safety and feasibility of cervicofacial (CFF) and cervicothoracic (CTF) flaps in the reconstruction of large oncosurgical defects in the lateral facial region of older patients.The study enrolled 36 patients with facial cutaneous cancers (age range, 65-94 years). They were divided into CFF and CTF groups in the facial region and in the neck. The clinical stages were I, II, and III in 6, 21, and 9 patients, respectively. The lateral face was divided into 3 aesthetic units: forehead, cheeks, and neck. Postoperative complications were scored using the Clavien-Dindo classification.The CFF was used to reconstruct oncosurgical defects in 8 foreheads and 16 cheeks; the CFF was used to reconstruct defects in 4 cheeks and 8 necks. The median sizes of skin defects in the CFF and CTF groups were 3.9×4.4 and 6.8×7.7 cm, respectively. There were no full flap failures. The Clavien-Dindo grades were I, II, and IIIa in 20, 9, and 2 patients, respectively, in the CFF and 0, 2, and 3 in the CTF group. Twenty-nine patients were alive without disease, 5 patients were alive with disease, and 2 patients had died of local recurrence or distant metastases.The CFF and CTF are simple, reliable, and excellent methods for reconstructing large oncosurgical defects in the lateral face of older patients with cutaneous cancer.
Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou.
Stomatological Center, Foshan Hospital of Traditional Chinese Medicine, Foshan, China.
Outcomes of Reconstructing Large Oncosurgical Defects of the Lateral Face in Older Cutaneous Cancer Patients Using Cervicofacial and Cervicothoracic Flaps.
Increasing the thermodynamic stability of metal complexes in water is a key challenge for various applications of coordination chemistry. In this study, a calix[6]arene macrocycle functionalized with three imidazole units on the narrow rim and three primary amino legs on the wide rim was synthesized and studied. This ligand coordinates a Zn2+ cation in water, within a pH window centered around 7, through the three imidazole units and one self-included amino leg occupying the coordination site within the macrocycle cavity. The coordination process benefits from a favourable entropic effect, conferring greater thermodynamic stability to the resulting ouroboros-like complex compared to the one stabilized by an exogenous amine. Additionally, the intramolecular coordination ensures a supramolecular protection, which can be exploited for the site-selective functionalization of two out of the three amino groups. These findings demonstrate that the use of macrocyclic ligands capable of forming ouroboros-like molecular complexes represents a valuable strategy for stabilizing metal ions in water.
Université libre de Bruxelles (ULB), Ecole polytechnique de Bruxelles, Engineering of Molecular NanoSystems, Avenue F.D. Roosevelt 50, CP165/64, B-1050 Brussels, Belgium. Kristin.Bartik@ulb.be.Université libre de Bruxelles (ULB), Laboratoire de Chimie Organique, Avenue F.D. Roosevelt 50, CP160/06, B-1050 Brussels, Belgium. Ivan.Jabin@ulb.be.
Université libre de Bruxelles (ULB), Laboratoire de Chimie Organique, Avenue F.D. Roosevelt 50, CP160/06, B-1050 Brussels, Belgium. Ivan.Jabin@ulb.be.Université libre de Bruxelles (ULB), Laboratoire de Résonance Magnétique Nucléaire Haute Résolution, Avenue F.D. Roosevelt 50, CP160/08, B-1050 Brussels, Belgium.
Université Paris Cité, CNRS, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques, F-75006 Paris, France.
Université libre de Bruxelles (ULB), Ecole polytechnique de Bruxelles, Engineering of Molecular NanoSystems, Avenue F.D. Roosevelt 50, CP165/64, B-1050 Brussels, Belgium. Kristin.Bartik@ulb.be.
Université libre de Bruxelles (ULB), Laboratoire de Chimie Organique, Avenue F.D. Roosevelt 50, CP160/06, B-1050 Brussels, Belgium. Ivan.Jabin@ulb.be.
Development of a water-soluble ouroboros-like calix[6]arene-trisimidazole-based ligand for enhanced binding of zinc.
We aim to characterize the clinical, pathological, laboratory and imaging features of various antibody defined IIM subgroups in Indian population.103 patients who satisfied 2017 ACR/ EULAR Classification criteria for IIM, and tested seropositive for myositis antibodies using Immunoblot technique were retrospectively identified. Patients were classified into following subgroups - Mi2B group, SRP group, Anti RNA Synthetase antibody group (Jo 1, PL 7, PL 12, OJ), multiple MSA, only MAA group (U1RNP, Ro 52, SS-A, SS-B, PM Scl 75, PM Scl 100). Clinical, laboratory, histopathology and imaging parameters were compared among different groups.Ro52 (n = 31; 22.46%) was the most common autoantibody seen in our cohort followed by Mi2B (n = 26; 18.84%) and SRP (n = 20; 14.49%). Skin manifestations (p = 0.053) and joint involvement (p = 0.023) were seen more frequently among Mi2B and MAA sub groups. Three out of 4 patients with persisting antibody positivity on serial measurements developed clinical relapse between 2 and 3 years after the initial episode. Remaining 2 patients showed declining titres of antibodies and developed no clinical relapses during follow up period of 5 and 6 years. Among histopathology features, perifascicular atrophy was found to be more prevalent among Mi2B (55.6%) and MAA subgroups (31.3%) (p value = 0.037). In thigh muscle MRI, Mi2B group showed a pattern of diffuse involvement of affected muscles without regional preference, with sparing of hamstring group. SRP group showed characteristic pattern of edema involving peripheral regions of Quadriceps femoris and central regions of Adductor group along with severe atrophy involving hamstring and adductor compartment muscles. ILD was seen in 27.5% of patients who underwent CT Chest. 3 patients were found to have underlying malignancy at the time of diagnosis of myositis (Mi2B = 2 and PM Scl = 1).Classification of IIM patients based on myositis antibodies yields subgroups with certain differences in clinical, laboratory, histopathological and imaging features.
Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bengaluru, India.
Journal of clinical neuromuscular disease
Autoantibody-Based Clinicoradiopathologic Phenotyping of Idiopathic Inflammatory Myopathies: An Indian Cohort.
The authors retrospectively analyzed the reported rate of added diplopia and associated factors in patients with thyroid-associated ophthalmopathy (TAO) after transnasal endoscopic inferomedial wall decompression, to illuminate the issue and look for ways to improve prognosis.Retrospective analysis was done on the medical records of patients with moderate-to-severe TAO between 2023-01 and 2024-01. Under general anesthesia, transnasal endoscopic inferomedial wall decompression was carried out on each subject. Clinical outcomes included postoperative added diplopia (including new-onset and aggravated), strabismus, and alterations in the extraocular muscles.Sixty-five eyes in 65 patients received treatment. Nineteen patients (29.3%) had new-onset horizontal diplopia at 1 month and 10 patients (15.4%) at 6 months postoperatively; 9 patients (13.8%) experienced aggravated horizontal diplopia at 1 month and 6 patients (9.2%) at 6 months (C2=4.947, P <0.05). The average volume of the medial rectus muscle was the only one to increase in the extraocular muscles (F=34.131, P <0.001), and the preoperative medial rectus muscle volume was higher in the added diplopia patients than in the no-added diplopia patients (F=267.405, P <0.001).Postoperative diplopia (both new-onset and aggravated) increased in TAO with transnasal endoscopic inferomedial wall decompression. Most added diplopia was horizontal and most added strabismus was esotropia. They were closely associated with changes in the medial rectus's thickness, displacement, and structural alterations. The preoperative medial rectus volume is one of the possible markers of further postoperative diplopia.
Southwest Medical University, Luzhou City.Department of Ophthalmology, Mianyang City Central Hospital, Mianyang City.
Department of Ophthalmology, Mianyang City Central Hospital, Mianyang City.North Sichuan Medical College, Nanchong City, Sichuan Province, China.
Department of Ophthalmology, Mianyang City Central Hospital, Mianyang City.
Analysis of Added Postoperative Diplopia After Transnasal Endoscopic Inferomedial Wall Decompression for Thyroid-Associated Ophthalmopathy.
Spinal muscular atrophy is an incurable inherited disease caused by lower motor neuron death from mutations of the survival motor neuron genes. Intrathecal therapy with the antisense oligonucleotide, nusinersen, has been demonstrated to be beneficial in children with this disease, but the experience in adults, particularly ambulatory patients, is limited. We present a prospective observational case series from a single center using nusinersen therapy where we categorize 6 adult patients with spinal muscular atrophy into 2 functional categories: ambulatory (n = 3) or nonambulatory (n = 3). All received therapy that was administered intrathecally every 4 months. We monitored the course and laboratory data for 1 year and observed for side effects. There was no significant deterioration for 1 year. There was some minor improvement particularly in subjective changes. The benefit seems to decrease after 3 months. No significant complications were observed.
College of Medicine, Department of Neurology, University of Tennesee Health Science Center, Memphis, TN; and.
Methodist Le Bonheru Healthcare, Memphis, TN.
A Case Series Examining Clinic, Laboratory, and Physical Function After Administration of Nusinersen in Adults With Spinal Muscular Atrophy, a Single-Center Study.
A systematic review conducted in 2017 found that Musculoskeletal (MSK) injuries were prevalent among surgeons. Few studies have assessed the role that poor surgical ergonomic practices have had in the development of MSK injuries in plastic and reconstructive surgery (PRS), and fewer specifically in craniofacial surgeons. The impact that MSK injuries have on the emotional well-being of craniofacial surgeons is also not well understood.A branched logic survey with a maximum of 35 questions pertaining to surgical practices, MSK injuries, and emotional well-being was distributed to all active attending physicians who were members of the American Society of Maxillofacial Surgeons (ASMS). The responses were divided into 2 groups, surgeons who reported developing MSK injuries or physical discomfort and those who denied developing MSK injuries or physical discomfort. Data analysis was performed to determine which factors contributed to the incidence of MSK injury and the emotional impact that these injuries had on craniofacial surgeons.A total of 82 active craniofacial surgeons completed responses to the survey for an overall response rate of 16.6%. Of these respondents, 65.9% (n=54) suffered MSK injuries or physical discomfort, and 53.7% (29/54) reported difficulty with either falling asleep or staying asleep because of these symptoms within the last year. Both male and female respondents reported experiencing some level of anxiety or depression because of their MSK injuries.The impact of a MSK injury may impact both physical and emotional wellness of craniofacial surgeons. This study found that a high percentage of craniofacial surgeons have MSK-injuries whereas some have reported a negative impact on their sleep and emotional well-being.
Brody School of Medicine, East Carolina University, Greenville, NC.
Department of Surgery, Central Michigan University, Saginaw.
College of Medicine, Central Michigan University, Mount Pleasant, MI.
Department of Plastic and Reconstructive Surgery, The Ohio State University Wexner Medical Center, Columbus, OH.
Understanding the Impact of Ergonomic Practices on Musculoskeletal-Related Symptoms and Emotional Wellness in Craniofacial Surgeons.
This update starts with an interesting series of children and adults with congenital myasthenic syndrome with a DOK7 variant. The next section is on autoimmune myasthenia gravis (MG) epidemiology, cost of care, and hospitalizations. A number of studies on the newer treatments are discussed including a phase 2 trial of nipocalimab and recommendations for using some of these drugs. A large trial emphasizing the negative effects of pyridostigmine in muscle-specific kinase MG is covered. A study on the incidence of taste disorders and alopecia in MG follows. The update ends with the topic of the burden of disease in MG and Lambert-Eaton myasthenic syndrome.
Departments of Neurology and Pathology (Neuropathology), University of Pittsburgh School of Medicine, Pittsburgh, PA.
What Is in the Neuromuscular Junction Literature?
In a world that is globalizing and centered on rapid communication, hearing impairment is one of the most common disabilities. The most effective and successful neural prosthesis in humans for treating the dysfunction of a sensory organ is cochlear implantation. The minimally invasive placement of the array in the cochlea should warrant the rehabilitation of profound hearing loss over all frequencies. Some key factors for structure and hearing preservation consist of minimal invasive drilling in the temporal bone and tailored inner ear access. Next-generation Robotically Assisted Cochlear Implantation Surgery (RACIS) focuses on robotic inner ear access. The purpose of this cadaveric preclinical study was to assess the viability and precision of a novel technology (the HEARO method) for RACIS, or more particularly, personalized robotic inner ear access.The external auditory canal, chorda tympani, ossicles, facial nerve, and other pertinent anatomical components were all 3-dimensional (3D)-reconstructed by the surgeon. The mean intended distance and drilling trajectory to the chorda tympani and facial nerve were, respectively, 0.44±0.13 and 0.35±0.27 mm.With a mean insertion percentage of 94%, the surgeon was able to complete the HEARO method in 9 out of 10 procedures. There was no evidence of a collision or damage to vital structures.Future iterations of RACIS will prioritize haptic feedback, automated segmentation and trajectory, robotic insertion with adjustable speed, and imaging mobile cone beam computed tomography.
Department of Otorhinolaryngology Head and Neck surgery, Vrije Universiteit Brussel, Brussels Health Campus.Department of Otorhinolaryngology Head and Neck surgery, University Hospital UZ Brussel, Vrije Universiteit Brussel, Brussels Health Campus, Brussels, Belgium.
Department of Anatomy, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
Department of Otorhinolaryngology Head and Neck surgery, Vrije Universiteit Brussel, Brussels Health Campus.
MED-EL Medical Electronics, Innsbruck, Austria.
Department of Otorhinolaryngology Head and neck surgery, Antwerp University Hospital, Edegem, Belgium.Department of Translational Neurosciences, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp.
Department of Anatomy, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey.
Department of Otorhinolaryngology Head and Neck surgery, University Hospital UZ Brussel, Vrije Universiteit Brussel, Brussels Health Campus, Brussels, Belgium.
Next-generation Robotics in Otology: The HEARO Procedure.
From the Department of Medical Ethics & Health Policy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Ethics in Psychedelic Science: Promises and Responsibilities.
DNA replication stress is a significant contributor to spontaneous DNA damage and genome instability. While the impact of p53 deficiency on increasing DNA replication stress is known, the specific molecular mechanism underlying this phenomenon remains poorly understood. This study explores how p53 deficiency induces DNA replication stress by activating mTORC1 through R-loop formation, which is facilitated by the upregulation of RNR. Research has shown that p53 deficiency results in increased γH2AX expression and a higher mutation rate in the HPRT gene. Interestingly, these effects can be alleviated by rapamycin, an mTORC1 inhibitor. Additionally, rapamycin reduces the abundance of R-loop structures in p53KO cells, which is linked to mTORC1's regulation of ribonucleotide reductase (RNR) level. These findings suggest that p53 deficiency-induced DNA replication stress relies on mTORC1 activation, with the upregulation of RNR expression and R-loop formation. Overall, this study underscores the importance of R-loops in mTORC1 activation-dependent DNA replication stress triggered by p53 deficiency.
Jiangxi Provincial Key Laboratory of Respiratory Diseases, Jiangxi Institute of Respiratory Disease, Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China.China-Japan Friendship Jiangxi Hospital, National Regional Center for Respiratory Medicine, Nanchang 330200, China.
Jiangxi Provincial Key Laboratory of Respiratory Diseases, Jiangxi Institute of Respiratory Disease, Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China.Jiangxi Medical College, First Clinical Medical College, Nanchang University, Nanchang 330006, China.
Jiangxi Provincial Key Laboratory of Respiratory Diseases, Jiangxi Institute of Respiratory Disease, Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China.Department of Respiratory and Critical Care Medicine, Renmin Hospital of Shangrao, Shangrao 334000, China.
Jiangxi Medical College, First Clinical Medical College, Nanchang University, Nanchang 330006, China.
R-loop formation contributes to mTORC1 activation-dependent DNA replication stress induced by p53 deficiency.
New surgical techniques that access the orbit and intracranial cavity have been developed in recent years called transorbital neuroendoscopic surgery. The superior eyelid route, as a transorbital corridor, is a clinically feasible route to access selected anterior and middle skull base pathologies. However, studies regarding the suitability of this approach in vascular surgery are lacking. In this study, transorbital endoscopic dissections were performed bilaterally in 4 cadavers through the superior eyelid approach. The authors aimed to define the arterial vascular structures that can be accessed through this approach. In this study, the M1 and M2 segments of the middle cerebral artery and the branches originating from it were accessible with a 0 degree endoscope after an appropriate dissection. Thus, the endoscopic superior eyelid approach may be a novel alternative approach for some cranial pathologies.
Department of Neurosurgery, School of Medicine, Dokuz Eylul University.
Department of Neurosurgery, School of Medicine, Usak University, Usak.
Department of Anatomy, School of Medicine, Dokuz Eylul University, Izmir, Turkey.
Elucidation of the Cranial Arterial Anatomy Using the Transorbital Endoscopic Approach.
Auricular reconstruction is one of the most challenging procedures in plastic surgery. However, traumatic auricular defects present more uncertainty and complexity than congenital microtia with various surgical options in auricular reconstruction. The purpose of this article is to review advances in the use of microsurgical techniques for the treatment of traumatic ear defects.Three databases, PubMed, Web of Science, and Google Scholar, have been used to gather the most relevant papers discussing the topic. This paper searched for studies from 1980 to 2023: searching for a range of keywords such as post-traumatic ear deformities, free flap, and free facial flap. Using this method, studies related to free flaps in posttraumatic ear reconstruction were reviewed and discussed.Fifty-four studies related to auricular reconstruction using different free flaps were obtained through screening.The microsurgical technique for auricular reconstruction requires both exceptional auricular reconstruction skills and microsurgical expertise due to its intricate nature. Nevertheless, microsurgical techniques remain a valuable avenue of investigation and can provide satisfactory surgical outcomes in appropriately selected patients.Level V.
Department of Plastic and Reconstructive Surgery, Xijing Hospital of Fourth Military Medical University, Xi'an, Shaanxi, China.
Advances in the Application of Microsurgical Techniques in Repairing Traumatic Auricular Defects.
Adverse alcohol consumption is a major public health concern, which might have been further increased by the COVID-19 pandemic. In this study we investigated the impact of a lockdown stage on the association between alcohol consumption, loneliness, and COVID-19-related worries. We used smartphone-based Ecological Momentary Assessment (EMA) conducted during the COVID-19 pandemic in Germany. We recruited 280 participants from the general population, who experienced at least mild loneliness and distress due to the COVID-19 pandemic. We assessed daily alcohol intake, loneliness, and COVID-19-related worries every evening for 7 consecutive days across a no-lockdown [8th August 2020-1st November 2020] and lockdown stage [2nd November 2020-11th March 2021]. We did not find that a lockdown stage, compared to a no-lockdown stage, is associated with increased alcohol consumption. We found that loneliness, previous day drinking, and COVID-19-related worries were not associated with increased, but with decreased alcohol consumption. Moreover, COVID-19-related worries were more negatively associated with alcohol consumption during a no-lockdown stage compared to a lockdown stage. We found that the effect of COVID-19 related worries on alcohol consumption is mediated by loneliness. Our study suggests that heightened levels of worry can decrease alcohol intake. This association can be explained by loneliness: individuals who worry more are lonelier and thus less likely to engage in social drinking. However, during a lockdown stage, the negative association between worrying and drinking diminishes.
Department of Psychiatry and Psychotherapy, Charité- Universitätsmedizin Berlin (Campus Charité Mitte), Charitéplatz 1, 10117, Berlin, Germany. matthias.haucke@gmx.de.Clinical Psychology and Psychotherapy, Department of Education and Psychology, Freie Universität Berlin, Berlin, Germany. matthias.haucke@gmx.de.
Department of Psychiatry and Psychotherapy, Charité- Universitätsmedizin Berlin (Campus Charité Mitte), Charitéplatz 1, 10117, Berlin, Germany.German Center for Mental Health (DZPG), Berlin, Germany.
Clinical Psychology and Psychotherapy, Department of Education and Psychology, Freie Universität Berlin, Berlin, Germany.Departement of Educational Sciences and Psychology, Clinical and Biological Psychology, Technische Universität Dortmund, Dortmund, Germany.
Department of Psychiatry and Psychotherapy, Charité- Universitätsmedizin Berlin (Campus Charité Mitte), Charitéplatz 1, 10117, Berlin, Germany. shuyan.liu@charite.de.German Center for Mental Health (DZPG), Berlin, Germany. shuyan.liu@charite.de.
European archives of psychiatry and clinical neuroscience
Eur Arch Psychiatry Clin Neurosci. 2024-11-27;():.
Investigating the impact of COVID-19 related worries and loneliness on alcohol consumption: an ecological momentary assessment.
Even though South American Camelids (SAC) are a rustic species, adapted to harsh environments, their ability to reproduce is low in their natural habitat. Conception and birth rates in camelids vary from 50 % to 90 %. This depends on the mating system used, sire and dam fertility, postpartum interval, environmental conditions, and nutrition. Reproductive biotechnology can reduce generation intervals and quickly spread high-quality genetics, addressing the growing need for genetically superior animals. The advantages of using artificial insemination (AI) and semen preservation are widely known. However, no cryopreservation protocol providing an acceptable sperm survival and pregnancy rate after thawing is currently available for SAC. Not having an effective semen cryopreservation protocol has hindered rapid genetic improvement and efficient use of males. For all these reasons, this biotechnology is currently only used for research purposes but not commercially in SAC. In Part I of this review on reproductive biotechnology, the initial steps of semen and/or sperm collection, evaluation and handling were discussed. The objective of Part II of the review is to describe the progress achieved in semen or sperm dilution, cooling and freezing. Current results obtained using AI in SAC will also be covered.
Universidad de Buenos Aires, Facultad de Ciencias Veterinarias, Instituto de Investigación y Tecnología en Reproducción Animal (INITRA), Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.
Male reproductive biotechnologies in South American Camelids Part II: Semen dilution, cryopreservation and artificial insemination.
Ischemic Priapism With Therapeutic Serum Concentrations of Psychotropic Medications.
Simultaneous reconstruction after removal of nasal silicone implants was published as diced, autologous rib and ear auricular cartilages, and each had their shortcomings. Temporoparietal fascial grafts were used for facial and nasal contouring, vascularized tissue coverage, and augmentation the nose, lip. The temporoparietal fascia graft may be considered for in-time replacement of allografts and remaining bulkiness. From 2006 until 2008, the temporoparietal fascial graft was used in 20 referred patients with nasal allografts in a medical center. The female-to-male ratio is 17:3. The mean age is around 32.6 years old. All the patients refused disfigurement after the removal of the implants for at least 3 months. All the patients were followed up for 5 years. All patients recovered within 1 to 2 weeks. The nasal skin envelop was preserved or healed. There was neither graft exposure, nor recurred infection. The procedure is a useful method of eliminating inflammatory squeals. The temporoparietal fascial graft used, was able to bridge the 3-month gap without the implant. The smooth nasal dorsum skin was regained with adequate nasal projection. All patients were followed up in plastic surgery clinics without recurrence. There are no reports in the English literature of the use of temporoparietal fascial grafts to treat nasal implant infection. The temporoparietal fascial graft is a simple and reliable method to provide thin, broad, pliable, easy neovascularized, adequate coverage, contour, and bulk on the cartilage dorsum of the nose, an inconspicuous donor site, consistency, and minimal resorption.
Department of Plastic Surgery, Nanjing BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
Department of Plastic Surgery, Nanjing BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.Department of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
Immediate Reconstruction With Autologous Temporoparietal Fascia After Enucleation of Infected or Extruded Alloplastic Nasal Implants.
A novel gram-stain-indeterminate, rod-shaped, endospore-forming, motile, aerobic bacterium, designated JETA1-E2T, was isolated from aircraft fuel Jet A1 sample. The strain showed high pairwise similarity values of partial 16S rRNA gene sequences to Sphingomonas paucimobilis (MT367853) (99.42%), Sphingomonas sanguinis (MF319771) (99.34%), and Sphingomonas pseudosanguinis (HE716953) (99.27%) within the family Sphingomonadaceae. However, API test results revealed that the strain JETA1-E2T differed from these type strains. The phylogenetic tree based on the whole genome and the phylogenomic tree generated with the UBCG tool showed that the strain JETA1-E2T formed a distinct monophyletic clade within the family Sphingomonadaceae, and clustered distantly with the genera Sphingomonas and Sphingobium. The predominant respiratory quinone is Q-10. The major fatty acids are C16:0 and summed feature 8 (C18:1ω7c and/or C18:1ω6c). C19:0 is present in small amounts. The polar lipids are diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, aminophospholipid, unidentified glycolipid, and two unidentified sphingoglycolipids. The only polyamine is putrescine in minor amounts. The DNA G + C content of the type strain is 66.5 mol%. Several unique genes in the strain JETA1-E2T may contribute to fight against various stressors, virulence and pathogenicity, as well as survival in challenging conditions. The strain JETA1-E2T contains 100 of the characterised proteins available in the HADEG database of which 58% of these are involved in metabolic process of aromatics degradation. The findings indicate that the strain JETA1-E2T has the potential to metabolise hydrocarbons such as fuel, especially aromatic compounds. Based on the results of polyphasic taxonomic analyses, the strain JETA1-E2T represents a novel species in a new genus in the family Sphingomonadaceae for which the name Facivitalis istanbulensis gen. nov., sp. nov. is proposed. The type strain of Facivitalis istanbulensis is JETA1-E2T (DSM 117971T = LMG 33634T = KUEN 1206 (B) F3-1-1T).
Department of Biology, Institute of Graduate Studies in Sciences, Istanbul University, 34134, Vezneciler, Istanbul, Türkiye.Department of Pathology Laboratory Techniques, Vocational School of Health Services, Uskudar University, 34664, Uskudar, Istanbul, Türkiye.
Department of Biology, Faculty of Science, Istanbul University, 34134, Vezneciler, Istanbul, Türkiye.
Department of Biology, Faculty of Science, Istanbul University, 34134, Vezneciler, Istanbul, Türkiye. esungur@istanbul.edu.tr.
Facivitalis istanbulensis gen. nov., sp. nov., a novel member of the family Sphingomonadaceae with the potential for aromatic-degradation isolated from Jet A1 fuel.
A mandible fracture is a common traumatic craniofacial injury for which surgery is sometimes indicated. Post-fracture and postoperative pain are often controlled through prescribed narcotics, which have received increased attention for potential abuse. The current work identified 90-day opioid prescribing patterns following surgically treated mandible fractures. Patients who underwent open reduction and internal fixation to treat a closed mandible fracture between 2011 and 2021 were identified in the PearlDiver Mariner165 database. Exclusion criteria included: (1) patients with records active for fewer than 180 days before the injury and 90 days post-fracture, (2) age younger than 18, and (3) those with long bone fracture within 30 days of mandible fracture. Variables associated with filling an opioid prescription and utilizing excess morphine milligram equivalents (MMEs) were identified through multivariate regression. Prescribing patterns between 2011 and 2021 were analyzed using simple linear regression. A total of 15,049 patients were identified. Of these patients, opioid prescriptions were filled by 10,389 (69.0%). Greater MMEs were filled for those with greater age, prior opioid use, and history of chronic pain ( P < 0.01 for all). The proportion of patients who received opioids decreased from 2011 to 2021 (73.3% versus 61.9%) during which declines were also seen for median MMEs (225.0 versus 128.4) and mean number of filled prescriptions (4.1 versus 2.8). The present work identified age and preexisting risk factors as significantly associated with excess MMEs following open reduction and internal fixation-treated mandible fracture. The decreasing proportion of patients receiving opioids along with decreasing MMEs suggests more refined practice with regard to their use.
Division of Plastic and Reconstructive Surgery, Department of Surgery, Yale School of Medicine.
Department of Orthopaedics and Rehabilitation, Yale School of Medicine, New Haven, CT.
Opioid Use Following Open Reduction and Internal Fixation of Mandibular Fractures.
Campbell University Jerry M. Wallace School of Osteopathic Medicine, Lillington, North Carolina.
Campbell University Jerry M. Wallace School of Osteopathic Medicine, Lillington, North Carolina.Departments of Pathology and Ophthalmology, Duke University Medical Center, Durham, North Carolina.
This case report describes a patient whose autopsy revealed that the posterior choroid of the right eye had a focal eosinophil-rich inflammatory infiltrate with a cross-section of a possible degenerating Strongyloides stercoralis larva and a coiled, incompletely sectioned, filariform larva in a medium-caliber choroidal artery.
Pathologic response following neoadjuvant immune checkpoint blockade (ICB) in stage III melanoma serves as a surrogate marker for long-term outcomes. This may support more personalized, response-directed treatment strategies.The OpACIN-neo and PRADO trials were phase 2 studies evaluating neoadjuvant treatment with ipilimumab and nivolumab in stage III melanoma. In OpACIN-neo, all patients underwent therapeutic lymph node dissection (TLND) without subsequent adjuvant therapy. In contrast, PRADO explored a response- directed strategy, where patients achieving a major pathologic response (MPR) omitted TLND and adjuvant therapy, while those without a pathologic response (pNR) received TLND and adjuvant therapy. Here, we provide a descriptive post-hoc comparison of 3-year survival outcomes between the non-personalized approach in OpACIN-neo and the response-directed approach in PRADO.For patients who achieved an MPR, the 3-year recurrence-free survival (RFS) was 93 % for those without TLND versus 96 % for those with TLND (log-rank p = 0.47), and distant metastasis-free survival (DMFS) was 98 % compared to 96 % (log-rank p = 0.49), respectively. For patients with pNR, 3-year RFS rates were 64 % for those receiving adjuvant systemic therapy and 35 % for patients without (log-rank p = 0.10). DMFS rates were 70 % versus 52 % (log-rank p = 0.24), respectively.These data suggest that TLND and adjuvant therapy may be safely omitted in most patients achieving an MPR, while adjuvant systemic therapy following TLND appears to improve RFS and DMFS in patients with pNR. Although these results are hypothesis-generating and require further validation, they offer a potential foundation for developing personalized neoadjuvant immunotherapy approaches.
Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
Melanoma Institute of Australia, The University of Sydney, Sydney, NSW, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia; Department of Medical Oncology, Royal North Shore and Mater Hospitals, Sydney, NSW, Australia.
Department of Biometrics, Netherlands Cancer Institute, Amsterdam, the Netherlands.
Melanoma Institute of Australia, The University of Sydney, Sydney, NSW, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia; Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
Department of Surgical Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands.
Departments of Medical Oncology and Radiology & Nuclear Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden; Department of Oncology/Skin Cancer Center, Theme Cancer, Karolinska University Hospital, Stockholm, Sweden.
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Department of Head and Neck Surgery, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
Melanoma Institute of Australia, The University of Sydney, Sydney, NSW, Australia.
Department of Radiotherapy, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
Melanoma Institute of Australia, The University of Sydney, Sydney, NSW, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia; Department of Breast and Melanoma Surgery, Royal North Shore and Mater Hospitals, Sydney, NSW, Australia.
Melanoma Institute of Australia, The University of Sydney, Sydney, NSW, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia; Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital and NSW Health Pathology, Sydney, NSW, Australia; Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
Department of Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
Melanoma Institute of Australia, The University of Sydney, Sydney, NSW, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia; Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Sydney, NSW, Australia; Department of Surgical Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
Melanoma Institute of Australia, The University of Sydney, Sydney, NSW, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia; Department of Medical Oncology, Royal North Shore and Mater Hospitals, Sydney, NSW, Australia; Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands; Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands; Molecular Oncology and Immunology, Netherlands Cancer Institute, Amsterdam, the Netherlands; University Clinic Regensburg, Dept. Hematology and Medical Oncology, Regensburg, Germany. Electronic address: c.blank@nki.nl.
Impact of personalized response-directed surgery and adjuvant therapy on survival after neoadjuvant immunotherapy in stage III melanoma: Comparison of 3-year data from PRADO and OpACIN-neo.
The immune system plays a major role in ovarian physiology by regulating the ovarian follicle pool through complex signaling of different growth factors, cytokines, and chemokines. These may promote follicle activation and further growth but could also trigger follicle atresia and clearance of aging or damaged cells within the ovarian cortex. Moreover, extraglandular steroidogenesis potentially occurring in different immune cells like macrophages and natural killer cells might be another way of modulating follicle growth. Ovarian macrophages have recently been found to contain two different populations, namely resident macrophages and monocyte-derived cells, with potentially different roles. The immune system also plays a role in the development of pathological conditions, including premature ovarian insufficiency (POI). Indeed, autoimmune activation against various ovarian antigen targets results in lymphocytic oophoritis mainly targeting early growing follicles, but later leading to complete follicle pool depletion. Immune-mediated ovarian damage may also be caused by viral infection or be the consequence of iatrogenic damage. Certain novel cancer immunotherapies like checkpoint inhibitors have recently been shown to induce ovarian reserve damage in a murine model. Studies are needed to corroborate these findings and further investigate the potential of newly developed immunotherapies to treat POI. Technological advances such as single-cell analyses of less represented cell populations like immune cells inside the ovary are now contributing to valuable new information, which will hopefully lead to the development of new therapeutic strategies for women with fertility issues.
© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Gynecology Research Unit, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium.
Gynecology Research Unit, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium.Department of Anatomopathology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
Gynecology Research Unit, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium.Gynecology Department, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
Immune system regulation of physiological and pathological aspects of the ovarian follicle pool throughout the female reproductive lifespan.
Ischemic stroke (IS), primarily caused by cerebrovascular occlusion, poses a significant public health challenge with limited effective therapeutic options. Evidence suggests that salvianolic acids (SAs), mainly from Salvia miltiorrhiza Bunge, have been formulated into injections and are widely used in clinical treatments for cardiovascular and cerebrovascular diseases, including stroke. The pharmacological properties of SAs include reducing neuroinflammation, alleviating oxidative stress injury, inhibiting cellular apoptosis, preserving endothelial function, maintaining blood-brain barrier integrity, and promoting angiogenesis. Salvianolic acids for injection (SAFI) serve as a safe and effective treatment option for cardiovascular and cerebrovascular conditions by influencing various signaling pathways and molecular targets associated with these diseases. In this review, we first discuss the pathogenesis of IS, then summarize the classification of SAs, elaborate detailed molecular mechanisms of their efficacy, and the related clinical applications of SAFI. We also emphasize the recent pharmacological advancements and therapeutic possibilities of this promising drug preparation derived from herbs for cerebrovascular conditions.
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi'an 710021, China.
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. Electronic address: wangjingwen8021@163.com.
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. Electronic address: dingyi.007@163.com.
The therapeutic effects of salvianolic acids on ischemic stroke: From molecular mechanisms to clinical applications.
Male fertility potential depends on physical, endocrine, and genetic factors responsible for producing functional male gametes. Although the main function of the male gamete, the spermatozoon, is to deliver its genetic material to the oocyte, this premise has been modified over the past few years. It is believed that the spermatozoon provides essential factors for fertilization and pre-implantation embryo development. A viable/healthy spermatozoon has functional subcellular compartments (nucleus, acrosome, midpiece, and flagellum) due to the actions of proteins, transcripts, and epigenetic marks in the organelles present in them that have important roles in reproductive biology. Male fertility potential reflects viable spermatozoa with proper function. Therefore, new approaches to functional sperm analysis are essential. Additionally, intrinsic factors and sperm molecules constitute potential biomarkers of viable spermatozoa and male fertility. Among these factors are proteins, the genome, and coding and non-coding RNAs, such as microRNAs, that act during fertilization and early embryo development. Research has been seeking increasingly efficient tools to predict fertility and functional studies of these molecules through gene and protein expression. Thus, analytical tools are essential to identify and classify viable and functional spermatozoa, to evaluate assisted reproductive male potential.
Department of Animal Reproduction, School of Veterinary Medicine and Animal Science, University of Sao Paulo (USP), SP, Brazil. Electronic address: meoaa@usp.br.
Department of Animal Morphology and Physiology, School of Agriculture and Veterinary Sciences, Sao Paulo State University (UNESP), SP, Brazil.
New approaches in bovine spermatozoa evaluation and their relationship with male fertility.
Strahlenklinik, Universitätsklinikum Erlangen, Universitätsstr. 27, 91054, Erlangen, Deutschland. Felix.Grabenbauer@uk-erlangen.de.
Strahlenklinik, Universitätsklinikum Erlangen, Universitätsstr. 27, 91054, Erlangen, Deutschland.
Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al]
[Through the labyrinth towards the goal: doxorubicin/trabectedin in metastatic and initially unresectable leiomyosarcoma].
A Gram-stain-negative, non-motile, aerobic, pale-yellow coloured and oval-shaped bacterium designated GRR-S6-38T was isolated from a tidal flat sediment that collected from Garorim Bay of the Yellow Sea, Republic of Korea. Strain GRR-S6-38T grew at 15-40 °C (optimum, 30 °C) at pH 6-9 (optimum, pH 7) and at 2-6% (w/v) NaCl (optimum, 2% NaCl). Phylogenetic analysis based on the 16S rRNA gene sequence indicated that strain GRR-S6-38T was closely related to those of J. seosinensis CL-SP26T (98.1%), J. helgolandensis DSM 14858T (97.4%), J. rubra CECT 5088T (97.4%), J. faecimaris DSM 100420T (97.4%), J. marina SHC163T (97.3%), J. donghaensis CECT 7802T (97.2%) and J. pohangensis DSM 19073T (97.1%). The average nucleotide identity and digital DNA-DNA hybridization value between GRR-S6-38T and related type strains were 71.47-78.59% and 17.80-21.40%. Strain GRR-S6-38T was characterized as having Q-10 as the predominant respiratory quinone and the major principle fatty acids (> 10%) were SF 8 (C18:1 ω7c/C18:1 ω6c, 39.3%), C19:0 ω8c cyclo (13.2%) and C18:1 ω7c 11-methyl (10.6%). The polar lipids consisted of diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, an unidentified lipid, two unidentified aminolipids and two unidentified phospholipids. The assembled genome of strain GRR-S6-38T has a total length of 3.32 Mbp, and a G + C content is 69.98%. Based on the polyphasic taxonomic evidence presented in this study, GRR-S6-38T is regarded to represent a novel species within the genus Jannaschia, for which name Jannaschia ovalis sp. nov. is proposed. The type strain is GRR-S6-38T (= KCTC 82518 = KACC 22240 = JCM 36187).
Division of Environmental Science and Ecological Engineering, College of Life Science and Biotechnology, Korea University, Seoul, 02841, Republic of Korea.
School of Earth and Environmental Science and Research Institute of Oceanography, Seoul National University, Seoul, Republic of Korea.
Department of Biotechnology, School of Life Science and Biotechnology, Korea University, Seoul, 02841, Republic of Korea.
Division of Environmental Science and Ecological Engineering, College of Life Science and Biotechnology, Korea University, Seoul, 02841, Republic of Korea. yeonjaeu@korea.ac.kr.
Division of Environmental Science and Ecological Engineering, College of Life Science and Biotechnology, Korea University, Seoul, 02841, Republic of Korea. jae-jinkim@korea.ac.kr.
Jannaschia ovalis sp. nov., a marine bacterium isolated from a tidal flat sediment in the Republic of Korea.
Liver cancer represents a multifactorial, multistage, and intricately progressive malignancy. Over the past decade, artesunate (ART), initially renowned for its anti-malarial efficacy, has been the focus of over 3000 studies uncovering its diverse pharmacological actions, including anti-inflammatory, immunoregulatory, metabolic regulatory, anti-fibrotic, and anti-cancer properties. This review highlights ART's role in the multistep progression from hepatitis to cancer and its underlying regulatory mechanisms, revealing signal transducer and activator of transcription 3 (STAT3) and ferroptosis (a novel form of programmed cell death) as promising therapeutic targets. ART demonstrates efficacy in inhibiting hepatitis virus infections, modulating inflammation, and facilitating recovery from inflammatory processes. During stages of hepatic fibrosis or cirrhosis, ART reverses fibrotic and cirrhotic changes by suppressing hepatic stellate cell activity, regulating inflammatory pathways, inhibiting hematopoietic stem cell proliferation, and inducing ferroptosis. Additionally, ART hinders hepatocellular carcinoma (HCC) cell proliferation, invasion, and metastasis, induces apoptosis and autophagy, combats drug resistance, and enhances chemosensitivity. Collectively, ART exhibits multi-step actions across multiple targets and signaling pathways, highlighting its potential as a clinical candidate for the prevention and treatment of liver cancer, from hepatitis and hepatic fibrosis to advanced HCC.
School of Clinical Medicine, Chengdu University of Chinese Medicine, Chengdu 610075, China; Department of Oncology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China.
School of Clinical Medicine, Chengdu University of Chinese Medicine, Chengdu 610075, China.
State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China. Electronic address: tobymaxiao@cdutcm.edu.cn.
School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China. Electronic address: wenyueqiang@cdutcm.edu.cn.
Department of Oncology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China. Electronic address: 735405661@qq.com.
TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China; Department of Gastroenterology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China. Electronic address: zengjinhao@cdutcm.edu.cn.
Artesunate: A potential drug for the prevention and treatment from hepatitis to hepatocellular carcinoma.
Heart disease is a common human disease with high morbidity and mortality. Timely and effective prevention and treatment is an urgent clinical problem. The pathogenesis of heart disease is complex and diverse, involving hypertension, diabetes, atherosclerosis, drug toxicity, thrombosis, infection and other aspects. LL-37, an endogenous peptide, is well known for its antimicrobial properties. In recent years, LL-37 has been found to have a variety of biological functions, including its role in the regulation of atherosclerosis, thrombosis, inflammatory responses, and cardiac hypertrophy. Engineered LL-37-related peptides were developed and proved to regulate the development of disease, which revealed its potential clinical application. A comprehensive review and summary of LL-37 is presented to clarify its role in heart disease and to provide a reference and direction for future research.
Department of Urology, Affiliated Hospital of Qingdao University, Qingdao, China; School of Basic Medicine, Qingdao University, Qingdao, China.
School of Basic Medicine, Qingdao University, Qingdao, China.
Department of Urology, Affiliated Hospital of Qingdao University, Qingdao, China.
Department of Urology, Affiliated Hospital of Qingdao University, Qingdao, China; Qingdao Ruipule Medical Technology Co., Ltd, China.
School of Basic Medicine, Guizhou University of Traditional Chinese, China.
Department of Urology, Affiliated Hospital of Qingdao University, Qingdao, China. Electronic address: XMsubmit@163.com.
Department of Urology, Affiliated Hospital of Qingdao University, Qingdao, China. Electronic address: Qingsong3333@163.com.
Cathelicidin peptide LL-37: A multifunctional peptide involved in heart disease.
Klinik für Strahlentherapie - Radioonkologie, Universitätsklinikum Münster (UKM), Albert-Schweitzer-Campus 1, Gebäude A1, 48149, Münster, Deutschland. Michael.oertel@ukmuenster.de.
Klinik für Strahlentherapie - Radioonkologie, Universitätsklinikum Münster (UKM), Albert-Schweitzer-Campus 1, Gebäude A1, 48149, Münster, Deutschland.
[Improved prognosis with radiotherapy in early-stage Hodgkin lymphoma: a critical analysis of the long-term data from the EORTC/LYSA/FIL H10 trial].
Regulatory T cells (Tregs) have emerged as crucial players in maintaining maternal-fetal tolerance and promoting successful pregnancy outcomes. This review examines the importance of these cells in pregnancy, drawing on human and animal-based studies, with a focus on their role in bovine fertility. Tregs employ various mechanisms to mediate maternal-fetal tolerance, including regulation of effector T-cell responses, interactions with innate immune cells in the uterine microenvironment, and modulation of trophoblast function. In humans, Treg dynamics during normal pregnancy and alterations in pregnancy complications provide compelling evidence for their involvement in maintaining fetal-maternal harmony. Animal models, particularly mouse studies, have further elucidated the importance of Tregs in preventing fetal rejection and promoting successful pregnancy outcomes. The review also explores the characterization of bovine Tregs, highlighting their similarities and unique features compared to human and rodent counterparts. Recent studies have indicated the presence and potential significance of Tregs in the bovine uterine environment during early pregnancy. Translational applications of Treg research in livestock fertility are discussed, with a focus on immunomodulatory strategies for enhancing Treg function, such as antigen-specific tolerance induction, pharmacological targeting of Treg pathways, and cell-based therapies using autologous or allogeneic Tregs. The review concludes by emphasizing the potential impact of Treg-based strategies on the livestock industry and the broader implications for human reproductive health. Future research directions are outlined, underscoring the need for further investigations into the role of Tregs in bovine reproductive tissues and their relationship with fertility outcomes.
Center of Excellence in Animal Reproductive Biotechnology, Mountain Livestock Research Institute, Sher E Kashmir University of Agricultural Sciences and Technology of Kashmir, Srinagar, Jammu and Kashmir, India. Electronic address: arif.pandit@skuastkashmir.ac.in.
Center of Excellence in Animal Reproductive Biotechnology, Mountain Livestock Research Institute, Sher E Kashmir University of Agricultural Sciences and Technology of Kashmir, Srinagar, Jammu and Kashmir, India.
Division of Veterinary Microbiology and Immunology, Faculty of Veterinary Sciences, Sher E Kashmir University of Agricultural Sciences and Technology of Kashmir, Srinagar, Jammu and Kashmir, India.
College of Dairy Sciences, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana, Punjab, India.
Directorate of Research, Sher E Kashmir University of Agricultural Sciences and Technology of Kashmir, Srinagar, Jammu and Kashmir, India. Electronic address: masoodmir1@skuastkashmir.ac.in.
Regulatory T cells in bovine fertility: Current understanding and future prospects.
The surfaces of various immune cells are rich in glycan chains, including the sialic-acid-binding immunoglobulin-like lectins (Siglecs) family. As an emerging glyco-immune checkpoint, Siglecs have the ability to bind and interact with various glycoproteins, thereby eliciting a series of downstream reactions to modulate the immune response. The impact of Siglecs has been extensively studied in tumor immunotherapy. However, research in neurological disorders and neurological diseases is very limited, and therapeutic options involving Siglecs need further exploration. Siglecs play a crucial role in the development, homeostasis, and repair processes of the nervous system, especially in degenerative diseases. This review summarizes studies on the immunomodulatory role mediated by Siglecs expressed on different immune cells in various neurological disorders, elucidates how dysregulated sialic acid contributes to several psychiatric disorders, and discusses the progress and limitations of research on the treatment of neurological disorders.
Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China.
Department of Neurology, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin 300190, China. Electronic address: 13752451956@163.com.
Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China. Electronic address: kywang@tmu.edu.cn.
Siglecs-mediated immune regulation in neurological disorders.
Two modular systems were synthesized composed of triphenylamine (ZnTPAP) and pyrene (ZnPyP) covalently linked at meso position of the Zn(II) porphyrins. Both compounds behaved as energy transfer antenna and orthogonal units to enhance the electron donating ability of Zn(II) porphyrins. Detailed photophysical and aggregation studies reveal that an appreciable electronic interaction exists between peripheral units to the porphyrin π-system so that they behave like strong donor materials. The electrochemical and computational studies demonstrate delocalization of the frontier highest occupied molecular orbital (-5.08 eV) over the triphenylamine entities (ZnTPAP) in addition to the porphyrin macrocycle. Fluorescence experiments with ZnTPAP and ZnPyP in the presence of different nitro analytes at various concentrations show turn-off fluorescence behaviour and exhibit superior selectivity towards 2,4-dinitrophenol (DNP) with limit of detection (LOD) of ~ 2.3 and 9.2 ppm for ZnTPAP and ZnPyP. Photoinduced electron transfer process is involved in the static and dynamic fluorescence quenching process. A Stern-Volmer quenching association constant (Ksv) determination revealed that ZnTPAP is more sensitive than the ZnPyP. This is attributed to the strong donating behaviour of TPA units caused by intermolecular interaction through metal center and strong π-π interactions with nitro analytes. The present study provides new insights into the ability to tune the affinity and selectivity of porphyrin-based sensors utilising electronic factors associated with the central Zn(II) ion. Furthermore, a smartphone-interfaced portable fluorimetric method by recognising colour variations in RGB and the luminance (L) values facilitate sensitive and real-time sensing at low concentration levels will have a significant impact on development of a new class of chemosensors.
© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.
Functional Materials Laboratory, Department of Chemistry, College of Engineering and Technology, SRM Institute of Science and Technology (SRMIST), Kattankulathur, Tamil, Nadu- 603203, India.
Department of Life Sciences, Yeungnam University, Gyeongsanbuk-Do, Gyeongsan, 38541, Republic of Korea.
Functional Materials Laboratory, Department of Chemistry, College of Engineering and Technology, SRM Institute of Science and Technology (SRMIST), Kattankulathur, Tamil, Nadu- 603203, India. nvenkat83@gmail.com.
Antenna effect on Zn(II) porphyrin-based molecular ensembles for the detection of 2,4-dinitrophenol through energy and electron transfer process.
Myelin damage is frequently associated with central nervous system (CNS) diseases and is a critical factor influencing neurological function and disease prognosis. Nevertheless, the majority of current treatments for the CNS concentrate on gray matter injury and repair strategies, while clinical interventions specifically targeting myelin repair remain unavailable. In recent years, natural products and herbal medicine have achieved considerable progress in the domain of myelin repair, given their remarkable curative effect and low toxic side effects, demonstrating significant therapeutic potential. In this review, we present a rather comprehensive account of the mechanisms underlying myelin formation, injury, and repair, with a particular emphasis on the interactions between oligodendrocytes and other glial cells. Furthermore, we summarize the natural products and herbal medicine currently employed in remyelination along with their mechanisms of action, highlighting the potential and challenges of certain natural compounds to enhance myelin repair. This review aims to facilitate the expedited development of innovative therapeutics derived from natural products and herbal medicine and furnish novel insights into myelin repair in the CNS.
Institute of Integrative Chinese Medicine, Department of Integrated Chinese Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China; Hunan Key Laboratory of TCM Gan, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China.
Institute of Integrative Chinese Medicine, Department of Integrated Chinese Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China; Hunan Key Laboratory of TCM Gan, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China; Department of Neurology of Integrated Chinese Medicine, Xiangya Jiangxi Hospital, Central South University, Nanchang 330006, PR China.
The College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, PR China.
Institute of Integrative Chinese Medicine, Department of Integrated Chinese Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China; Hunan Key Laboratory of TCM Gan, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China; Department of Neurology of Integrated Chinese Medicine, Xiangya Jiangxi Hospital, Central South University, Nanchang 330006, PR China. Electronic address: litengxiangya@csu.edu.cn.
Promoting remyelination in central nervous system diseases: Potentials and prospects of natural products and herbal medicine.
An ultra-sensitive photoelectrochemical (PEC) biosensor for amyloid-beta 40 (Aβ40), a biomarker for Alzheimer's disease (AD), was developed using g-C₃N₄ modified with gold nanoparticles (Au NPs) to form Au-C₃N₄. This was further combined with TiO₂ to create a tightly bonded TiO₂/Au-C₃N₄ heterojunction, leading to a highly responsive photocatalytic process. Furthermore, the incorporation of noble metal Au NPs not only enhances photocurrent generation but also securely immobilizes the aptamer through Au-S bonds, providing additional surface binding sites. This significantly increases the sensor's capture efficiency. The sensor exhibited excellent performance, featuring a linear detection range from 10-15 to 10-11 g/mL and a remarkably low detection limit (LOD) of 0.33 fg/mL. Moreover, the validation in clinical settings demonstrated the successful detection in real cerebrospinal fluid (CSF) and plasma, from AD patients and non-AD controls. These results strongly suggest that PEC biosensors possess significant potential as cost-effective and highly sensitive tools for detecting ultra-trace substances in human body fluids, which offers promising opportunities for the early screening of high-risk populations for AD.
Department of Neurology, Northwest University First Hospital, Xi'an, 710043, China.The College of Life Sciences, Northwest University, Xi'an, 710068, China.
The College of Life Sciences, Northwest University, Xi'an, 710068, China.
Key Laboratory of Wide Band-Gap Semiconductor Materials and Devices, School of Microelectronics, Xidian University, Xi'an, 710071, China.
Department of Neurology, Northwestern University School of Medicine, Xi'an, 710068, China.
Department of Neurology, Northwest University First Hospital, Xi'an, 710043, China. zhaogang@nwu.edu.cn.Department of Neurology, Northwestern University School of Medicine, Xi'an, 710068, China. zhaogang@nwu.edu.cn.
Key Laboratory of Wide Band-Gap Semiconductor Materials and Devices, School of Microelectronics, Xidian University, Xi'an, 710071, China. yybu@xidian.edu.cn.
Department of Neurology, Northwest University First Hospital, Xi'an, 710043, China. zhoelfu@nwu.edu.cn.Department of Neurology, Northwestern University School of Medicine, Xi'an, 710068, China. zhoelfu@nwu.edu.cn.
Detection of Aβ40 in cerebrospinal fluid and plasma of Alzheimer's disease patients using photoelectrochemical biosensors.
Department of Diagnostic Ultrasound and Echocardiography, Sir Run Run Shaw Hospital, Zhejiang University College of Medicine, Hangzhou, China.
Pathology Department, Sir Run Run Shaw Hospital, Zhejiang University College of Medicine, Hangzhou, China.
Warning from heart: An unusual case report of isolated Rosai-Dorfman disease in an Asian.
Academy of Scientific and Innovative Research (AcSIR), CSIR-Human Resource Development Centre, (CSIR-HRDC) Campus, Postal Staff College Area, Sector 19, Kamla Nehru Nagar, Ghaziabad, Uttar Pradesh, 201002, India.CSIR-National Physical Laboratory, Dr. K. S. Krishnan Marg, New Delhi, 110012, India.
Amity University, Sector 125, Noida, Uttar Pradesh, 201301, India.
Academy of Scientific and Innovative Research (AcSIR), CSIR-Human Resource Development Centre, (CSIR-HRDC) Campus, Postal Staff College Area, Sector 19, Kamla Nehru Nagar, Ghaziabad, Uttar Pradesh, 201002, India. vedvarun@nplindia.res.in.CSIR-National Physical Laboratory, Dr. K. S. Krishnan Marg, New Delhi, 110012, India. vedvarun@nplindia.res.in.
Correction: Molecularly imprinted electrochemical sensor based on APTES-functionalized indium tin oxide electrode for the determination of sulfadiazine.
Publisher Correction: Business-as-usual trends will largely miss 2030 global conservation targets.
The first dual immunosensor is reported for the determination of IL-12 and IL-23, two relevant biomarkers of Crohn's disease (CD). The strategy relies on the selective capture of the targets by the respective antibodies which were covalently immobilized onto SPCEs modified with crystalline nanocellulose (CNC) and multi-walled carbon nanotubes (MWCNTs) followed by conjugation with a detector antibody labelled with poly-HRP-Strept and amperometric transduction using the H2O2/HQ system. The combination of CNC, a nanomaterial scarcely exploited in immunosensing, with MWCNTs enables the preparation of a novel dual immunosensor for the determination of CD biomarkers in clinical samples, including faeces. The developed bioplatform exhibits a high reproducibility and selectivity allowing the simultaneous determination of IL-12 and IL-23 using a smaller sample volume and in a much shorter assay time than those reported for each target with commercial ELISA kits. The dual immunosensor was successfully applied to the analysis of raw serum and faeces spiked with IL-12 and IL-23 at the expected levels in patients with severe CD.
Department of Analytical Chemistry, Faculty of Chemistry, University Complutense of Madrid, 28040, Madrid, Spain.
Department of Analytical Chemistry, Faculty of Chemistry, University Complutense of Madrid, 28040, Madrid, Spain. aracelig@ucm.es.
Department of Analytical Chemistry, Faculty of Chemistry, University Complutense of Madrid, 28040, Madrid, Spain. yseo@quim.ucm.es.
Electrochemical immunosensing of Crohn's disease biomarkers using diazonium salt-grafted crystalline nanocellulose/carbon nanotube-modified electrodes.
Importance of a reference ladder in analytical testing of CRISPR HDR donor ssDNA templates.
In 2014, the Advisory Committee on Immunization Practices recommended routine use of the 13-valent pneumococcal conjugate vaccine (PCV13) in adults age ≥ 65 years. Incidence of most PCV13-serotype cases declined, however serotype 3 cases have persisted. We estimated PCV13 vaccine effectiveness (VE) against PCV13-serotypes and serotype 3 invasive pneumococcal disease (IPD) among Kaiser Permanente Northern California (KPNC) adults.This observational study included adults ≥65 years between September 1, 2014-December 31, 2020. We used active laboratory-based surveillance to identify and serotype all Streptococcus pneumoniae isolates obtained from normally-sterile sites. We estimated the odds ratio (OR) of vaccine-type IPD using conditional logistic regression stratified by age and calendar day, adjusting for sex, age, race, ethnicity, influenza vaccine receipt, 23-valent pneumococcal polysaccharide vaccine receipt since age 65, pneumonia risk factors, healthcare utilization, and KPNC service area. We estimated VEAdjusted as (1-ORAdjusted) × 100 %.There were 610,576 adults ≥65 years in the study population. By the end of the study period, PCV13 coverage was nearly 80 %. There were 307 IPD cases during the study period, of which 98 (31.9 %) were serotype 3. PCV13 was associated with a VEAdjusted of 61.5 % (95 % CI: 36.2, 76.7; p < 0.001) against PCV13-serotype IPD and 46.3 % (95 % CI: -2.4, 77.9; p = 0.06) against serotype 3 IPD.PCV13 vaccination protected adults ≥65 years against IPD due to PCV13 serotypes. Continued surveillance will be critical in the ≥65-year-old population to assess the impact of higher valent PCVs on IPD serotype distribution, including individual serotypes such as serotype 3.
Kaiser Permanente Vaccine Study Center, Oakland, CA, USA. Electronic address: Amber.Hyman@kp.org.
Kaiser Permanente Vaccine Study Center, Oakland, CA, USA.
Heller School, Brandeis University, Waltham, MA, USA.
Pfizer Vaccine Medicines Development & Scientific Clinical Affairs, Collegeville, PA, USA.
Effectiveness of 13-valent pneumococcal conjugate vaccine against vaccine-type invasive pneumococcal disease in older adults.
An advanced biochemical assay named modified Carba PBP test was innovated to identify and differentiate distinct categories of clinically significant carbapenemases (Ambler classes A, B, and D) within the Enterobacterales. The mechanism of mCarba PBP hinges on two core attributes: (i) the hydrolysis of the meropenem substrate by various carbapenemases, (ii) the immobilized penicillin and free meropenem in their affinity to interact with a limited quantity of penicillin-binding protein (PBP). Specific inhibitors for class A (phenylboronic acid, PBA) and class B (ethylenediaminetetraacetic acid, EDTA) were employed to inhibit the hydrolysis activity of carbapenemase and facilitate the classification of carbapenemase classes within 25 min. A comprehensive evaluation was undertaken using 94 clinical Enterobacterales isolates, comprising 75 carbapenemase-producing strains and 19 non-carbapenemase-producing strains. Its overall specificity and sensitivity were 100% and 97.3%, respectively, including detection of all types of OXA-48-like carbapenemases. For precise carbapenemase type identification, the assay exhibited remarkable sensitivities for class A, class B, and class D detection at 94.7%, 100%, and 100%, respectively. This user-friendly test presents a promising tool for carbapenemase identification, refining the selection of β-lactam/β-endoenzyme inhibitor combinations for effectively treating infections due to carbapenemase-producing organisms.
National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Yuanmingyuan West Road 2#, Haidian District, Beijing, 100193, People's Republic of China.
National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Yuanmingyuan West Road 2#, Haidian District, Beijing, 100193, People's Republic of China.College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, Shaanxi, People's Republic of China.
Beijing WDWK Biotechnology Co. Ltd, Beijing, 100095, People's Republic of China.
National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Yuanmingyuan West Road 2#, Haidian District, Beijing, 100193, People's Republic of China. wenkai@cau.edu.cn.
Modified Carba PBP test for rapid detection and differentiation between different classes of carbapenemases in Enterobacterales.
This review explores the impact of transport-related stresses on the quality of liquid-preserved artificial insemination (AI) doses in pig reproduction. Transport of boar semen from AI centers to sow farms, the place of application, is an essential part of the production chain with increasing international demand, especially against the background of growing export demand. Understanding how factors such as: a) transport-related vibration emissions; b) temperature fluctuations during transport; c) transport duration; d) duration of storage after transport; and e) the method used for preserving AI doses, affect their quality is, therefore, essential for optimizing fertility outcomes. We provide a review of existing literature on the biological responses of liquid-preserved boar sperm to transport conditions. In addition, we discuss their impact on sperm quality and summarize potential mitigation strategies.
Institute for Reproduction of Farm Animals Schönow, Bernauer Allee 10, Bernau D-16321, Germany.
Institute for Reproduction of Farm Animals Schönow, Bernauer Allee 10, Bernau D-16321, Germany. Electronic address: m.schulze@ifn-schoenow.de.
Transport-related influences on the quality of liquid-preserved boar sperm: A review.
Department Medicine and Biological Sciences, Brown University, Providence, Rhode Island; and University of Maryland School of Medicine, Baltimore, Maryland.
The Maryland Infertility Mandates: Firsts Across the Board.
Reactogenicity, the occurrence of vaccine side effects, can impact vaccine acceptance. There is limited data comparing the reactogenicity of COVID-19 vaccines to other routinely used vaccines, such as the meningococcal conjugate vaccine (MenACWY). In a trial of UK adults, participants received a third COVID-19 vaccine dose (NVX-CoV2373, BNT162b2, or mRNA1273) alongside MenACWY as an active control. Compared to MenACWY, we found that mRNA vaccines, particularly mRNA1273, showed the greatest relative increase in side effects, while protein-based NVX-CoV2373 generally elicited similar reactogenicity to MenACWY. These findings suggest that platform type can influence vaccine reactogenicity, and further research is needed to compare COVID-19 vaccines with other routinely administered vaccines.
Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Novavax, Inc., Gaithersburg, MD, USA. Electronic address: stoback@novavax.com.
NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton, UK.
Local and systemic reactogenicity after mRNA and protein-based COVID-19 vaccines compared to meningococcal vaccine (MenACWY) in a UK blinded, randomized phase 2 trial (COV-BOOST).
Cancer immunotherapy has revolutionized melanoma treatment, but the high number of non-responders still emphasizes the need for improvement of therapy. One potential avenue for enhancing anti-tumor treatment is through the modulation of coagulation and platelet activity. Both have been found to play an important role in the tumor microenvironment, tumor growth and metastasis. Preclinical studies indicate a beneficial effect, clinical data has been inconsistent.We examined a cohort of advanced, non-resectable melanoma patients (n = 2419) derived from the German prospective multicenter skin cancer registry ADOReg, who were treated with immune checkpoint inhibitors (ICI). The patients were classified based on whether it was documented that they received platelet aggregation inhibition (PAI) (n = 137) (acetylsalicylic acid (ASA) or clopidogrel), anticoagulation (AC) (n = 185) (direct oral anticoagulation (DOAC), phenprocoumon, heparins) at the start of ICI or no antithrombotic medication (n = 2097) at any point during ICI treatment. The study endpoints were best overall response (BOR), progression-free survival (PFS) and overall survival (OS).A significantly improved PFS was observed in patients documented to receive ASA (15.1 vs 6.4 months, HR 0.67, 95 % CI: 0.5 to 0.88, p = 0.0047) as well as in patients to receive AC (15.1 vs. 6.4 months, HR 0.7, 95 % CI: 0.53 to 0.91, p = 0.01) compared to patients for whom no antithrombotic medication was documented. Multivariate analysis of OS showed significant risk reduction in patients who received DOAC (HR 0.68, 95 % CI: 0.49 to 0.92, p = 0.0170) or phenprocoumon (HR: 0.44, 95 % CI: 0.19 to 0.85, p = 0.0301).Our study indicates a positive prognostic effect of anticoagulant and antiplatelet concomitant medication in melanoma patients receiving ICI. Further studies are needed to confrim the cancer-related benefit of adding anticoagulation or platelet inhibition to ICI treatment.
Department of Dermatology and Venereology, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany; Fleur Hiege Center for Skin Cancer Research, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany. Electronic address: j.koett@uke.de.
Department of Dermatology and Venereology, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany; Fleur Hiege Center for Skin Cancer Research, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany.
Fleur Hiege Center for Skin Cancer Research, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany; Institute of Tumor Biology, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany.
Department of Dermatology and Venereology, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany.
Department of Dermatology and Venereology, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany; Fleur Hiege Center for Skin Cancer Research, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany; Institute of Tumor Biology, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany.
Department of Dermatology, University Hospital of Schleswig-Holstein, Kiel, Germany.
Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany and German Cancer Consortium (DKTK), partner site Essen/Düsseldorf, Germany.
Division of Dermatooncology, Department of Dermatology, University Medical Center, Tuebingen, Germany.
Department of Dermatology, Uniklinikum Erlangen, Deutsches Zentrum Immuntherapie (DZI), Comprehensive Cancer Center Erlangen - EMN, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Germany.
Department of Dermatology, Johannes Wesling Medical Center, Ruhr University Bochum, Minden, Germany.
Skin Cancer Center Hannover, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany.
Elbe Clinic Buxtehude, Buxtehude, Germany.
Department of Dermatology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Skin Cancer Center at the University Cancer Centre Dresden and National Center for Tumor Diseases, Dresden, Germany.
Department of Dermatology, University Hospital Regensburg, Regensburg, Germany.
Helios Skin Cancer Center, Helios Klinikum Erfurt, Germany.
Heidelberg University, Medical Faculty Mannheim, Department of Dermatology and National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and University Hospital Heidelberg, Heidelberg, Germany.
Saarland University Medical School, Department of Dermatology, Homburg, Saar, Germany.
Department of Dermatology, University of Lübeck, Lübeck, Germany.
Department of Dermatology and Skin Cancer Center, Harzklinikum Dorothea Christiane Erxleben, Quedlinburg, Germany.
Department of Dermatology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Department of Dermatology, University Hospital Augsburg, Germany.
Department of Dermatology, University Hospital Würzburg, Würzburg, Germany.
Department of Dermatology, DRK Krankenhaus Rabenstein, Chemnitz, Germany.
Department of Dermatology, Venereology, and Allergology, Helios St. Elisabeth Hospital Oberhausen, University Witten-Herdecke, Oberhausen, Germany; Department of Dermatology, Venereology, and Allergology, Helios St. Johannes Hospital Duisburg, Germany.
Department of Dermatology, University Hospital Ulm, Germany.
Department of Dermatology, Ludwigshafen Medical Center, Ludwigshafen, Germany.
Skin Cancer Center, Department of Dermatology, Allergology and Phlebology, Bremerhaven Reinkenheide Medical Center, Bremerhaven, Germany.
Department for Dermatology and Venereology, University Clinic Münster, Münster, Germany.
Department of Dermatology, Hospital of Dortmund, Dortmund, Germany.
Department of Dermatology, Uniklinikum Erlangen, Deutsches Zentrum Immuntherapie (DZI), Comprehensive Cancer Center Erlangen - EMN, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Germany; Department of Dermatology, LMU University Hospital, LMU Munich, Munich, Germany.
Department of Dermatology and Allergology, Klinik Bremen-Mitte, Bremen, Germany.
Department of Dermatology, Helios Kliniken Schwerin, Schwerin, Germany.
Skin Cancer Center, Department of Dermatology, Ruhr-University Bochum, Bochum, Germany.
Department of Dermatology, SLK-Kliniken Heilbronn, Heilbronn, Germany.
Department of Dermatology, University of Mainz Medical Center, Mainz, Germany.
Department of Dermatology, Nürnberg General Hospital, Paracelsus Medical Center, Nürnberg, Germany.
Skin Cancer Center Hamburg, Department of Dermatosurgery Tabea/HOPA, Hamburg, Germany.
Department of Dermatology and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany.
Department of Dermatology, Venerology and Allergology, Skin Cancer Center, Leipzig University Medical Center, Leipzig, Germany.
University Clinics of Dermatology and Allergy, University of Oldenburg, Oldenburg, Germany.
Department of Dermatology, Helios Klinikum Krefeld, Krefeld, Germany.
Department of Dermatology and Skin Cancer Center, Hospital Karlsruhe, Karlsruhe, Germany.
Department of Dermatology and Venereology, University Hospital Halle, Martin-Luther-University Halle-Wittenberg, Halle, Germany.
Center for Dermatology, Allergy and Dermatosurgery, HELIOS University Hospital Wuppertal, University Witten/Herdecke, Germany.
Department of Dermatology, Klinikum Darmstadt, Darmstadt, Germany.
Department of Dermatology, Helios Klinikum Hildesheim, Hildesheim, Germany.
Department of Dermatology, Asklepios Klinikum Uckermark, Schwedt/Oder, Germany.
Comprehensive Cancer Center Munich of the Technical University Munich and the Ludwig Maximilians University, Munich, Germany.
Department of Dermatology, Fachklinik Hornheide, Münster, Germany.
Departments of Dermatology, Venereology, Allergology and Immunology, Staedtisches Klinikum Dessau, Brandenburg Medical School Theodor Fontane and Faculty of Health Sciences Brandenburg, Dessau, Germany.
Department of Dermatology, University Hospital Magdeburg, Magdeburg, Germany.
Department of Dermatology and Venereology, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany; Fleur Hiege Center for Skin Cancer Research, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany. Electronic address: st.schneider@uke.de.
Department of Dermatology and Venereology, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany; Fleur Hiege Center for Skin Cancer Research, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany. Electronic address: ch.gebhardt@uke.de.
Improved survival of advanced melanoma patients receiving immunotherapy with concomitant antithrombotic therapy - A multicenter study on 2419 patients from the prospective skin cancer registry ADOReg.
Creutzfeldt-Jakob disease (CJD) is a rare, neurodegenerative disorder that is incurable, always fatal, and transmissible. EEG is an integral part of the diagnostic workup with typical periodic sharp wave complexes indicative of CJD, but early in the disease EEG is often unaltered. Accordingly, we aimed at evaluating disruption of brain network functional connectivity (FC) in regions belonging to the default mode network (DMN) as a potential early marker in CJD when EEG is considered visually normal.EEGs considered visually normal obtained from 7 CJD patients were compared to EEGs of 7 patients with subjective cognitive impairment (SCI) using Brainstorm application for MATLAB. FC was calculated using the phase locking value separately for the delta-, theta-, alpha-, and beta-frequency band. The global efficacy of the DMN was calculated as the inverse characteristic path length with brain regions belonging to the DMN as nodes.CJD versus SCI had significantly lower global efficacy of the DMN in the gamma band. FC was decreased between bilateral orbitofrontal regions and the right parahippocampal gyrus and between bilateral orbitofrontal gyrus and the right anterior cingulate gyrus in CJD.Our findings provide evidence of disruption of the DMN in the gamma band and alterations of FC between specific brain regions in early CJD patients with visually normal EEGs. EEG brain network properties bear potential as a diagnostic tool for CJD early in the disease course in addition to established criteria. These findings call for further studies evaluating the diagnostic value of FC in early CJD.
Department of Neurology, Clinic Hietzing with Neurological Center Rosenhuegel, Vienna, Austria.Karl Landsteiner Institute for Cognitive Neurology and Epileptology, Vienna, Austria.
Department of Neurology, Clinic Hietzing with Neurological Center Rosenhuegel, Vienna, Austria.
Department of Neurology, Clinic Hietzing with Neurological Center Rosenhuegel, Vienna, Austria.Karl Landsteiner Institute for Cognitive Neurology and Epileptology, Vienna, Austria.Institut für Klinische Epilepsieforschung und Kognitive Neurologie, Sigmund Freud University, Vienna, Austria.
Dementia and geriatric cognitive disorders
Dement Geriatr Cogn Disord. 2024-12-06;():1-11.
Reduced Functional Connectivity in the Default Mode Network in EEGs without Other Abnormalities in Early Creutzfeldt-Jacob Disease.
Hepatic artery infusion (HAI) chemotherapy, particularly with floxuridine (FUDR), has previously shown effectiveness in improving recurrence-free survival (RFS) in colorectal cancer (CRC) patients with colorectal liver metastases (CRLM). Nonetheless, its adjuvant use alongside modern systemic chemotherapy remains unevaluated.The HARVEST trial is an open-label, randomized, controlled study conducted from May 2018 to August 2021. CRC patients with resectable primary tumors and CRLM were recruited and randomized to receive standard systemic chemotherapy only (non-HAI group) or in combination with HAI-FUDR (HAI group). However, due to a FUDR manufacturing shortage, the study was terminated early after enrolling 92 patients. The primary endpoint was the 3-year RFS rate, with secondary endpoints including overall survival (OS), liver-specific RFS, and adverse events.Of the 92 randomized patients, 77 were included in the modified intention-to-treat analysis. Three-year RFS rates were comparable between the HAI (N = 38) and non-HAI (N = 39) groups (31.4 % vs. 34.4 %; P = 0.28). However, improved 1-year RFS and a longer expected five-year OS were observed in the HAI group. While exploratory subgroup analysis suggested potential RFS benefits for patients with multiple liver metastases, RAS/BRAF mutations, and positive postoperative ctDNA methylation, multivariable analysis did not identify these as independent factors. Safety analysis showed comparable chemotherapy-related adverse events, except for a higher occurrence of ALT elevation in the HAI group.While our study showed no significant difference in three-year RFS, adjuvant chemotherapy intensification with HAI-FUDR is feasible and may offer early benefits in RFS and long-term OS. Nonetheless, a larger sample size is needed for validation and identifying which patient subgroup might benefit from this regimen.ClinicalTrials.gov: NCT03500874.
Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
Department of Radiation Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
Department of Minimally Invasive & Interventional Therapy, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
Department of Hepatobiliary Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
Department of Hepatobiliary Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China. Electronic address: yuanyf@sysucc.org.cn.
Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China. Electronic address: panzhzh@sysucc.org.cn.
Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China. Electronic address: liyh@sysucc.org.cn.
Safety and efficacy of adjuvant FOLFOX/FOLFIRI with versus without hepatic arterial infusion of floxuridine in patients following colorectal cancer liver metastasectomy (HARVEST trial): A randomized controlled trial.
Extranodal natural killer/T-cell lymphoma (ENKTCL) is almost always fatal after the failure of asparaginase. This phase II study aimed to investigate the efficacy and safety of tislelizumab combined with gemcitabine and oxaliplatin (Tisle-GemOx) in patients with ENKTCL failing asparaginase.Eligible patients received Tisle-GemOx as initial induction for 6-8 cycles at 21-day intervals. Responders continued tislelizumab maintenance every two months for two years. The primary endpoint was the best complete response rate (CRR).As of September 2023, 32 patients were enrolled in our study. Among the 30 efficacy-evaluable patients, the best CRR was 60 %, meeting the primary efficacy endpoint. With a median follow-up of 22.6 months, the median progression-free survival (PFS) was 7.4 months and the 1-year PFS rate was 46.4 %. Subgroup analyses showed that shorter PFS was associated with previous lines of chemotherapy ≥ 2 (P = 0.034) and concomitant hemophagocytic lymphohistiocytosis (P = 0.040). Pseudo-progression was observed in three patients (10 %). The most common grade ≥ 3 toxicities were lymphopenia (25 %) and anemia (15.6 %).Tisle-GemOx exhibits promising anti-tumor activity and manageable toxicities as a salvage therapy for ENKTCL failing asparaginase. Further long-term follow-up is necessary to evaluate the durability of the response with tislelizumab maintenance in this patient population.
Department of Hematology, Anhui Provincial Hospital, the First Affiliated Hospital of USTC, Hefei 230002, Anhui, China.
Department of Hematology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing 210029, Jiangsu, China.
Department of Hematology, the First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, China.
Department of Hematology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
Department of Hematology, the Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu, China.
Department of Hematology, the Affiliated Hospital of Nantong University, Nantong 226006, Jiangsu, China.
Department of Hematology, the Friendship Hospital of Ili Kazakh Autonomous Prefecture, Yining 835000, Xinjiang, China.
Department of Hematology, the Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China.
Department of Hematology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing 210029, Jiangsu, China. Electronic address: lijianyonglm@126.com.
Department of Hematology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, Nanjing Medical University, Nanjing 210029, Jiangsu, China. Electronic address: fanlei@jsph.org.cn.
Anti-PD-1 antibody (Tislelizumab) combined with gemcitabine and oxaliplatin for extranodal NK/T-cell lymphoma failing asparaginase: A multicenter phase II trial.
This review aims to compile sparse information on the ecology of freshwater heterotrophic euglenoids and synthesize the main phenomena and hypotheses from published results. Apparently, heterotrophic euglenoids play a very important role in the nutrient flow of water ecosystems and are irreplaceable heterotrophic contributors in benthic communities, as their total biomass is by far the largest among heterotrophic flagellates. Even though they are obviously a very crucial part of the diversity of freshwater heterotrophic protists, and likely the most represented (in terms of biovolume) group of heterotrophic flagellates, there have been only a few attempts to elucidate their ecological preferences, roles, niches, and importance. They exhibit three nutrition modes-bacterivory, eukaryovory, and osmotrophy-which are strategies closely related to their taxonomical groupings and phylogenetic positions. Unfortunately, the phylogeny of the majority of the species remains unknown, similar to their autecology. There are major problems with the quantitative research methodologies, which is a big challenge for future research to improve.
Copyright © 2024. Published by Elsevier GmbH.
Department of Botany, Faculty of Science, University of South Bohemia in České Budějovice, České Budějovice, Czech Republic. Electronic address: kubinj05@prf.jcu.cz.
Department of Botany, Faculty of Science, University of South Bohemia in České Budějovice, České Budějovice, Czech Republic; Třeboň Experimental Garden and Gene Pool Collections, Institute of Botany of the CAS, Třeboň, Czech Republic.
Ecology of free-living freshwater heterotrophic euglenoids: A summarizing review.
The capacity of recipients to support transferred embryos is a challenge for dairy cattle production systems. This review explores methods for increasing P4 to improve early pregnancy establishment in dairy cattle. A key aspect of P4 supplementation during the critical first weeks of pregnancy is its correlation with successful embryo elongation. Moreover, P4 was correlated to an increased chance of embryo survival after maternal recognition of pregnancy. Internal releasing devices increase circulating P4 concentrations but may negatively impact fertility possibly due to unwanted health pathologies such as vaginitis and the still undefined mechanism of haste luteolysis. The accessory corpus luteum (CL) induction in recipient dairy cattle increases endogenous P4 output increasing circulating P4 concentrations. Two ovulatory inducers are commonly used: gonadotropin-releasing hormone (GnRH) and human chorionic gonadotropin (hCG). Despite their distinct structures, GnRH and hCG are equally capable of inducing ovulation in cattle. The P4 supplementation by an accessory CL formation was widely used in fixed-time artificial insemination breeding programs, but still not exhaustively studied in embryo transfer (ET) programs. The induction of an accessory CL in ET programs has yielded inconsistent results depending on parity, embryo type production, embryo stage of development, and type of hormone used. Although maternal physiological mechanisms support the idea of increasing P4 for higher fertility and better embryo development, the actual results in creating a high-P4 maternal environment are still uncertain.
Department of Animal and Dairy Sciences, University of Wisconsin-Madison, Madison, WI, USA; Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA; Faculdade de Zootecnia e Medicina Veterinária, Universidade Federal de Lavras, Lavras, Minas Gerais, Brazil. Electronic address: marceloelazzi@gmail.com.
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.
Faculdade de Zootecnia e Medicina Veterinária, Universidade Federal de Lavras, Lavras, Minas Gerais, Brazil.
Strategies to increase circulating progesterone in late metestrus and early diestrus in recipient dairy heifers and cows: A focus on induction of accessory corpus luteum formation.
Division of Rheumatology, Department of Medicine, Queen's University, Kingston, ON, Canada.Faculty of Health Sciences, School of Medicine, Queen's University, Kingston, ON, Canada.
Division of Rheumatology, Department of Medicine, Queen's University, Kingston, ON, Canada.Faculty of Health Sciences, School of Medicine, Queen's University, Kingston, ON, Canada.Department of Medicine, Translational Institute of Medicine, Queen's University, Kingston, ON, Canada.Rheumatology Clinic, Kingston Health Science Centre, Kingston, ON, Canada.
Macrophage migration inhibitory factor as a potential 'missing important factor' driving inflammatory arthritis in adrenocorticotropic hormone deficiency.
Various metabolic abnormalities, including obesity, insulin resistance, hypertension, dyslipidemia, hyperthyroidism and low vitamin D levels, have been linked to both osteopenia and sarcopenia. Osteosarcopenia is also commonly observed in older age groups, notably in postmenopausal women. Glucagon-like peptide-1 (GLP-1), a labile incretin secreted from the intestinal L-cells, stimulates insulin secretion and sensitivity, making it an effective anti-diabetic medication. GLP-1 binds to its receptor, the GLP-1 receptor, a G-protein-coupled receptor, and leads to the stimulation of adenylate cyclase, increasing the levels of cyclic AMP (cAMP). Elevated cAMP then activates protein kinase A and other downstream signaling pathways. These signaling cascades result in various cellular responses, such as enhanced insulin secretion from pancreatic beta cells, improved insulin sensitivity and modulation of appetite and gastric emptying. In addition, GLP-1 signaling can promote cell growth and survival, contributing to its effects on muscle and bone health. Its role as an anti-diabetic medication has been enhanced through various modifications to extend its half-life, thereby improving its effectiveness and druggability. GLP-1 analogs, initially developed for diabetes management, have also been harnessed for obesity treatment due to the effect of GLP-1 to induce satiety and slow gastric emptying. Beyond their well-known anti-diabetic and anti-obesity effects, GLP-1 agonists can enhance muscle mass and bone density, making them valuable in addressing conditions such as sarcopenia and osteoporosis. This review focuses on the effects of GLP-1 analogs on musculoskeletal health by critically assessing the underlying signaling mechanisms in order to understand their translational potential for the treatment of osteosarcopenia.
The role of glucagon-like peptides in osteosarcopenia.
In the poultry industry, every chick or poult produced has high economic value; therefore, selection of male breeders capable of transmitting desirable traits to their offspring has an important role in fertility and hatching success. Following either natural mating or artificial insemination, sperm must go through a sequence of steps to fertilize the egg: 1. Go from the site of deposition (vagina) to the Sperm Storage Tubules (SST); 2. Enter and stay inside the SST; 3. Reacquire motility; and 4. Bind to and penetrate the egg. To perform these tasks successfully, sperm must be alive, motile, and have structural integrity (membrane, glycocalyx, acrosome, and DNA). To evaluate sperm fitness, several in vitro tests can be performed; however, it is often necessary to combine several assays to have a more reliable fertility estimation, as each procedure evaluates specific and distinct sperm features. In this article, we briefly review in vitro tests that can be used to evaluate poultry sperm, associating them with each step for fertilization. The sperm-egg interaction assay using the inner perivitelline layer of chicken eggs is highlighted, since it is a single test that evaluates multiple sperm characteristics and is highly correlated with fertility.
Federal University of Pelotas, Pelotas, RS, Brazil. Electronic address: denisecb@ufpel.edu.br.
Sperm fitness assessment in poultry: Brief review of in vitro methods.
Efficient transformation systems are highly desirable for plant genetic research and biotechnology product development efforts. Tissue culture-free transformation (TCFT) and minimal tissue culture transformation (MTCT) systems have great potential in addressing genotype-dependency challenge, shortening transformation timeline, and improving operational efficiency by greatly reducing personnel and supply costs. The development of Arabidopsis floral dip transformation method almost 3 decades ago has greatly expedited plant genomic research. However, development of efficient TCFT or MTCT systems in non-Brassica species had limited success until recently despite the demonstration of successful in planta transformation in many plant species. In the last few years, there have been some major advances in the development of such systems in several crops using novel approaches. This article will review these new advances and discuss potential areas for further development.
© 2024 The Author(s). The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.
Seeds Research, Syngenta Crop Protection, LLC, 9 Davis Drive, Research Triangle Park, North Carolina, 27709, USA.
The Plant journal : for cell and molecular biology
Development of high-throughput tissue culture-free plant transformation systems.
Overbiopsy is a serious health issue in prostate cancer (PCa) diagnostics. We have developed a urine tumor DNA multidimensional bioinformatic algorithm, utLIFE, to avoid unnecessary biopsy. The objective is to recognize all or clinically significant PCa. Of the 801 participants recruited in our study, 630 are selected for subsequent analysis. In the training cohort (n = 237), utLIFE-PC gets an area under the receiver operating characteristic curve (AUC) of 0.967 and a sensitivity of 85.57% at 95% specificity. In the independent prospective validation cohort (n = 343), utLIFE-PC has an AUC of 0.929, sensitivity of 84.24%, and specificity of 93.26%. Notably, in patients with ≥grade group (GG)2 and ≥GG3, the assay's sensitivity is still excellent (85.33% and 87.10%, respectively). The model shows better performance than prostate-specific antigen (PSA) (p < 0.001) or the single-dimensional biomarkers (methylation, p < 0.001; copy-number variations [CNVs], p < 0.001; mutation, p < 0.001). The utLIFE-PC model can potentially optimize the PCa diagnostic process and avoid unnecessary biopsies. This study was registered at Chinese Clinical Trial Registry: ChiCTR2300071837.
Department of Urology and State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Urology, The Second Affiliated Hospital of Tianjin Medical University, Tianjin, China.
Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Research and Development, Acornmed Biotechnology Co., Ltd., Beijing, China.
Department of Urology, Guangdong Second Provincial General Hospital, Guangzhou, China.
Department of Urology, Cancer Hospital of HuanXing, Chaoyang District Beijing, Beijing, China.
Department of Urology, China Medical University, The First Hospital of China Medical University, Shenyang, Liaoning, China.
Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
Department of Urology, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, China.
Department of Urology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
Department of Research and Development, Acornmed Biotechnology Co., Ltd., Beijing, China. Electronic address: fenglou@acornmed.com.
Department of Research and Development, Acornmed Biotechnology Co., Ltd., Beijing, China. Electronic address: shanbocao@acornmed.com.
Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China. Electronic address: dwyeli@163.com.
Department of Urology, The Second Affiliated Hospital of Tianjin Medical University, Tianjin, China. Electronic address: niuyuanjie9317@163.com.
Department of Urology and State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Department of Urology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China. Electronic address: nianzeng2006@vip.sina.com.
Development and validation of the utLIFE-PC algorithm for noninvasive detection of prostate cancer in urine: A prospective, observational study.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major public health threat globally. Management of patients afflicted with MASLD and research in this domain are limited by the lack of robust well-established non-invasive biomarkers for diagnosis, prognostication, and monitoring. The circulating metabolome reflects both the systemic metabo-inflammatory milieu and changes in the liver in affected individuals. In this review we summarize the available literature on changes in the different components of the metabolome in MASLD with a focus on changes that are linked to the presence of underlying steatohepatitis, severity of disease activity, and fibrosis stage. We further summarize the existing literature around biomarker panels that are derived from interrogation of the metabolome. Their relevance to disease biology and utility in practice are also discussed. We further highlight potential direction for future studies particularly to ensure they are fit for purpose and suitable for widespread use.
Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore. Electronic address: enying.tan@mohh.com.sg.
Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, Virginia Commonwealth University School of Medicine, Richmond, VA, USA. Electronic address: arun.sanyal@vcuhealth.org.
Metabolomics at the cutting edge of risk prediction of MASLD.
Socioemotional selectivity theory (SST) maintains that perceived constraints on time horizons motivate people to optimize emotionally meaningful experiences in the present, whereas expansive time horizons lead people to pursue goals that hold future utility. Theoretically, the prioritizing of goals about emotional meaning contributes to the relatively high levels of emotional well-being and mental health observed in older people. The present article provides an overview of SST and places it in historical context, noting the differences and similarities it shares with contemporaneous approaches. We briefly review support for core theoretical postulates and consider a recent set of empirical findings that speak against the role of perceived time on emotional well-being. We argue that existing survey measures of time horizons do not capture the increasing value and appreciation of remaining time posited in SST and describe the development of and evidence for a new Appreciation of Remaining Time scale. We conclude with a discussion about the need for theoretical precision in research and, more broadly, the need to consider explanations for age differences that extend beyond compensation for loss to fully understand socioemotional development in adulthood. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
Department of Psychology, Stanford University.
What's time got to do with it? Appreciation of time influences social goals and emotional well-being.
Thickened liquids are frequently recommended for individuals with swallowing disorders who are at risk of aspiration. However, thickened liquids may be poorly tolerated and result in reduced fluid intake, which may impact performance in a number of areas. The purpose of this study was to examine the possible impact of a thickened liquid regimen on visuospatial skills in young healthy adults.Twenty young adults, aged 19-26 years, were included as participants. Baseline data consisting of urine specific gravity (USG) measurements as a marker of hydration status and completion of a visuospatial task were obtained prior to initiation of the experimental protocol. Participants in the experimental group followed a thickened liquid protocol, which consisted of drinking nectar-thick liquids for 48 h. Data collection procedures were repeated.Participants in the experimental group exhibited significantly higher USG levels and required more time to complete the visuospatial task post-thickened liquids. No significant change in performance accuracy was found. Participants in the experimental group reported a decrease in fluid intake.Performance accuracy on a visuospatial task was not significantly impacted by a 48-h period of thickened liquid intake, but time required to complete the task increased and was associated with mild dehydration as indicated by higher USG levels.
Department of Communication Sciences and Disorders, Valdosta State University, Valdosta, Georgia, USA.
Folia phoniatrica et logopaedica : official organ of the International Association of Logopedics and Phoniatrics (IALP)
Effect of a 48-Hour Thickened Liquid Protocol on Visuospatial Skills in Young Adults.
A 23-year-old woman was referred for low visual acuity in the left eye after a corneal ulcer associated with contact lens use 2 years previously. The patient had a history of contact lens use, reported use of antibiotic eye drops with improvement of infection, and subsequent scarring. There were no comorbidities. The manifest refraction was -3.25 -2.25 × 180 (20/20) in the right eye and was -2.00 esf -2.00 × 165 (20/80) in the left eye. The patient demands a solution in a reasonable time because of the need for functional vision and possible restoration of her binocular functions. The slitlamp examination revealed a corneal scar partially affecting the visual axis (Figure 1JOURNAL/jcrs/04.03/02158034-202412000-00016/figure1/v/2024-12-12T192825Z/r/image-tiff). Corneal topography revealed an irregular pattern and spectral-domain optical coherence tomography (OCT) examinations revealed scarring in the anterior stroma (Figures 2 and 3JOURNAL/jcrs/04.03/02158034-202412000-00016/figure2/v/2024-12-12T192825Z/r/image-tiffJOURNAL/jcrs/04.03/02158034-202412000-00016/figure3/v/2024-12-12T192825Z/r/image-tiff). Given the patient's refraction, corneal scar, and visual demands, would you perform photorefractive keratectomy (PRK) treatment to correct ametropia and partially remove the anterior stroma? Would you perform excimer laser treatment for therapeutic purposes guided by topography? Would you opt for a 2-stage treatment, regularizing the cornea with neutral phototherapeutic keratectomy (PTK) or PRK treatment guided by topography and then correcting the ametropia? Considering the OTC maps, would you perform a femtosecond laser-assisted anterior lamellar keratoplasty (FALK), deep anterior lamellar keratoplasty (DALK), or even penetrating keratoplasty? Would you consider any other surgical step to prevent delayed cornea healing-persistent epithelial defect?
Corneal scar after ulcer in a young patient demanding visual restoration in a timely fashion treated with PTK + topo-guided PRK.
How a biochemistry department used redacted job applications to achieve gender parity.
A novel molecular-imprinted electrochemical sensor for 3,4-benzopyrene (3, 4-BaP) in food samples, with high sensitivity and selective detection, is introduced. Firstly, graphene oxide was modified onto a glassy carbon electrode (GCE) by electroreduction deposition to form an RGO/GCE sensing platform, thereby enhancing the sensitivity and stability of the sensor. Then, magnetic molecularly imprinted polymer-zeolite imidazole framework-8 (MMIP-ZIF-8) was synthesized in one step using the crystal growth method and modified onto RGO/GCE, endowing the sensor with good adsorption capacity and selectivity. The performance of the sensor for 3, 4-BaP was studied using differential pulse voltammetry (DPV), and the detection conditions of the constructed sensor were optimized. The results showed that under the optimal conditions, the constructed sensor exhibited a wide linear range (0.5 ~ 1000 nmol L-1), a low limit of detection (0.16 nmol L-1), and good selectivity and stability for the detection of 3, 4-BaP. It also showed a good recovery (99.74 ~ 102.58%) for the detection of 3, 4-BaP in actual corn meal samples. The MMIP-ZIF-8/RGO/GCE sensor developed has potential application prospects in the precise detection of 3, 4-BaP in food.
College of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang, 414006, Hunan, China.
College of Chemistry and Chemical Engineering, Hunan Institute of Science and Technology, Yueyang, 414006, Hunan, China. zhongming2613@163.com.
Construction of an electrochemical sensor based on magnetic molecularly imprinted polymer-zeolite imidazole framework-8 for detection of 3,4-benzopyrene.
Klinik für Strahlentherapie und Radioonkologie, UKE, Hamburg, Deutschland.
Klinik für Strahlentherapie, UKSH Kiel, Arnold-Heller-Str. 3, 24105, Kiel, Deutschland.
Klinik für Strahlentherapie, UKSH Kiel, Arnold-Heller-Str. 3, 24105, Kiel, Deutschland. juergen.dunst@uksh.de.
[Stereotactic radiotherapy with five fractions vs. robot-assisted prostatectomy: first results of the PACE-A study].
Parkinson's disease (PD) is primarily driven by the protein Alpha Synuclein (A-Syn) accumulation. Synphilin-1 protein, encoded by the SNCAIP gene, which co-localizes with A-Syn is a known risk factor for PD. Retinitis pigmentosa (RP), is a cluster of retinal degenerative disorders, and Cyclic Nucleotide Gated channel subunit Alpha 1 (CNGA1) is one of the initial genes associated with RP. Patients with PD can have various kinds of visual dysfunction as a non-motor manifestation, but to date, CNGA1 mutation and RP as a PD associated visual symptom has not been reported. We report a mutation in the SNCAIP gene in a PD patient, not reported earlier, and its co-occurrence with RP-associated CNGA1 gene mutation.Whole exome sequencing (WES) of the patient DNA sample and in-silico protein-protein interaction (PPI) analysis performed to find out proteins interacting with SNCAIP relevant concerning reported mutation of SNCAIP and further, CNGA1 interaction with SNCAIP.We are reporting, a missense mutation (p.Thr64Ser) at the SNCAIP gene, co-occurring with a missense variation (p.Gly509Arg) in the CNGA1 gene. In silico PPI analysis suggests SIAH1 as an important protein affected by SNCAIP mutation. LGALS4 and SNCA (gene encoding A-Syn) are common interactors between SNCAIP and CNGA1.The current study has determined the co-occurrence of RP and PD, whole exome sequencing ascertains the mutations in SNCAIP and CNGA1 genes, which could be the cause of PD and RP co-occurrence.
Copyright © 2024 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.
Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
CSIR-Institute of Genomic and Integrative Biology, Mall Road, Delhi, India.
Department of Community Medicine, NDMC Medical College and Hindu Rao Hospital, Delhi, India.
Dr. B. R. Ambedkar Institute Rotary Cancer Hospital, AIIMS Delhi, India.
Kalinga Institute of Medical Sciences, Bhuvaneshwar, Odisha 751024, India.
Department of Neurology, AIIMS, Bibinagar, Telangana, India.
Institute of Medical Sciences, Banaras Hindu University, Varanasi, India. Electronic address: drdeepikajoshi73@gmail.com.
Co-occurrence of Parkinson's disease and Retinitis Pigmentosa: A genetic and in silico analysis.
Most individuals in recovery are likely to attempt discontinuing their prescribed medication at least once. The collection of articles in this special issue uses research with quantitative and qualitative methods, reviews of the literature, conceptualization of theory, and first-person accounts from various perspectives to begin to shift the field of psychiatric rehabilitation from a narrow focus on symptom reduction and a fear-driven emphasis on medication adherence to a new perspective in which dilemmas and strong feelings about medication use are commonplace. We issue a call to action for training psychiatric rehabilitation practitioners, who often have the most direct and frequent interactions with people in recovery, to explore their clients' experiences with using medication and its impact on a range of life domains. Rehabilitation, recovery, and medication have ongoing mutual influences and require an inclusive, multidimensional framework that integrates complex ongoing interactions between personal, societal, and biological processes and assures that treatment decisions are in alignment with recovery goals. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
Mental Health Center Copenhagen, Copenhagen University Hospital, Copenhagen.
Broadening understanding of individual choices about psychiatric medication use in psychiatric rehabilitation.
Maharishi Markandeshwar Institute of Physiotherapy and Rehabilitation, Maharishi Markandeshwar (Deemed to be University) Mullana - Ambala, Haryana, India.
On Effectiveness of Cognitive Functional Therapy Versus Core Exercises and Manual Therapy in Patients With Chronic Low Back Pain After Spinal Surgery: Randomized Controlled Trial. Avila L, da Silva M, Neves M, et al. Phys Ther. 2024;104:pzad105. https://doi.org/10.1093/ptj/pzad105.
Chronic subdural hematoma (CSDH) is characterized by the collection of blood beneath the dura mater. Traditional treatments involve surgical drainage of the hematoma, but recurrence rates can be high. A highly vascularized neo-membrane irrigated by the middle meningeal artery (MMA) may be involved in CSDH re-accumulation. We conducted a systematic review and meta-analysis of studies that compared the efficacy and safety of MMA embolization to conventional treatment alone for CSDH.A systematic search of PubMed, Embase Ovid, and ClinicalTrials.gov identified observational and randomized clinical studies comparing MMA embolization to conventional treatment for CSDH. The efficacy outcomes were hematoma recurrence and good functional outcome (as defined by a modified Rankin Scale Score [mRS] of 0-2). Safety outcomes were the rate of major complication and mortality. Heterogeneity among studies were evaluated using the I2 statistic. Analyses were conducted using Cochrane Review Manager Software, with risk ratios (RRs) and 95% confidence intervals (95% CI) presented for key outcomes. Absolute risk reduction (95% CI) of 1,000 patients was also calculated using GRADEpro software.The analysis included data from 13 studies (4 randomized clinical trials [RCTs] and 9 observational studies) with a total number of 2,960 patients (35.3% in the MMA group and 64.7% in the conventional treatment group). Compared to conventional treatment, MMA embolization decreased risk of hematoma recurrence by 59% (13 studies, RR = 0.41, 95% CI: 0.26-0.65; I2 = 49%), for an absolute effect of 116 fewer events/1,000 patients (95% CI: 69-145), with similar risk of major complications (13 studies, RR = 0.88, 95% CI: 0.67-1.15; I2 = 43%) and mortality risk (13 studies, RR = 1.05, 95% CI: 0.67-1.65). In subgroup analyses by study type, pooled results from RCTs showed similar direction effects as those from observational studies for both efficacy and safety outcomes.MMA embolization in CSDH management is a safe and effective approach for CSDH.
University of Illinois at Chicago, Department of Neurology and Rehabilitation, Chicago, Illinois, USA.
Cerebrovascular diseases (Basel, Switzerland)
Efficacy and Safety of Middle Meningeal Artery Embolization for Patients with Chronic Subdural Hematoma: A Systematic Review and Meta-Analysis.
A biosensor is reported for electrochemical detection of ampicillin based on Au5Pt and DNA cycle dual-signal amplification strategy. Firstly, Au5Pt is prepared by reduction of chloroauric acid and chloroplatinic acid with serine-functionalized graphene quantum dot (SGQD). The resulting Au5Pt shows an excellent catalytic activity because of the synergy of Au and Pt. Then, Au5Pt is covalently combined with hairpin DNA and thionine molecule to form a redox probe. The probe was used for construction of the ampicillin biosensor coupling with DNA cycling. In the presence of ampicillin, the DNA cycle was triggered and leads to many redox probes being carried to the biosensor. This produces a significant signal amplification by oxidation and reduction of thionine molecules in these probes. The combination of Au5Pt catalysis with DNA cycle achieve ultrahigh sensitivity, selectivity, and stability for the electrochemical detection of ampicillin. Differential pulse voltammetry current linearly increases with the increase of ampicillin concentration in the range 1 × 10-18-1 × 10-12 M with a detection limit of 3.2 × 10-19 M (S/N = 3). The proposed analytical method has been satisfactorily used for electrochemical detection of ampicillin in milk.
School of Life Sciences and Health Engineering, School of Chemical and Material Engineering, Jiangnan University, Wuxi, 214122, China.
School of Life Sciences and Health Engineering, School of Chemical and Material Engineering, Jiangnan University, Wuxi, 214122, China. ruiyili@jiangnan.edu.cn.
School of Life Sciences and Health Engineering, School of Chemical and Material Engineering, Jiangnan University, Wuxi, 214122, China. zaijunli@jiangnan.edu.cn.
Electrochemical biosensor for detection of ampicillin in milk based on Au5Pt and DNA cycle dual-signal amplification strategy.
The aim of the study was to investigate the caries-preventive effect of fluoride-free toothpastes, containing either herbal agents or (nano-)hydroxyapatite.Bovine dentin specimens each having a sound (ST) and a demineralized area (DT) were prepared and randomly allocated to eleven groups (n = 187). Treatments during pH cycling (28 days; 6 × 120 min demineralization/day) were brushing 2×/day with 0 ppm F- [NaF0], 500 ppm F- [NaF500], 1,100 ppm F- [NaF1100], grape seed extract [GSE], (nano-)hydroxyapatite, melaleuca oil [MO1, MO2, MO-CU], and propolis + myrrh [PM1, PM2] containing dentifrices. Dentifrice slurries were prepared with deionized water (1:3 w/w). Differences in integrated mineral loss (∆∆Z) and lesion depth (∆LD) were evaluated before and after pH cycling using transversal microradiography.The correlation between ΔΔZ/ΔLD and F- concentration (NaF0, NaF500, NaF1100) was strong for the DT (rΔΔZ, DT = 0.681; p < 0.001) and very strong for ST (rΔΔZ, ST = 0.861; p < 0.001), indicating a fluoride dose-response for both baseline substrate conditions. For ΔΔZDT and ΔLDDT, only NaF1100 and GSE revealed significant differences compared with NaF0 (p < 0.001; ANOVA). For ΔΔZST and ΔLDST, significant differences could be found for NaF1100 and NaF500 compared to all fluoride-free groups (p ≤ 0.002; ANOVA), without significant difference between fluoride-free groups (p = 1.000; ANOVA). For DT and ST, a hypermineralized surface layer and no surface loss could only be observed when fluoride was present.A dose-response for fluoride concentrations was observed in this mild demineralization pH-cycling model. Fluoride-free dentifrices containing GSE or melaleuca oil showed certain preventive effect against further progression of root caries lesions. However, surface loss was observed for all fluoride-free dentifrices.
© 2024 The Author(s). Published by S. Karger AG, Basel.
Department of Restorative, Preventive and Pediatric Dentistry, ZMK Bern, University of Bern, Bern, Switzerland.
Fluoride Dose-Response and Anticaries Effect of Herbal Antibacterial Agents and (Nano-)Hydroxyapatite on Dentin Caries: An in vitro Study.
Headaches are a common reason for pediatric visits to the emergency department. Emergency clinicians must distinguish between common and dangerous secondary causes of headache and primary headache disorders such as migraine and tension-type headaches. This issue discusses the diagnosis of primary headaches by history and physical examination, the options for first-line treatment of primary headache and for severe or refractory migraines, and procedural interventions that may be considered when other therapies have failed. Guidance is provided for patient and family education regarding triggers, lifestyle modifications, and nutraceutical prophylaxis.
Pediatric Emergency Medicine Fellow, University of British Columbia, Pediatric Emergency Medicine, BC Children's Hospital, Vancouver, BC, Canada.
Emergency Medicine Resident Physician, University of British Columbia; Provisional Fellow, Pain Medicine, Royal North Shore Hospital, University of Sydney, Sydney, Australia.
Associate Professor of Pediatrics and Emergency Medicine, University of British Columbia; Division Head, Pediatric Emergency Medicine, BC Children's Hospital, BC, Canada.
Pediatr Emerg Med Pract. 2025-01;22(1):1-28.
Emergency department management of primary headache disorders in pediatric patients.
Institute for Innovations in Medical Education, NYU Grossman School of Medicine, New York, New York.Division of Hospital Medicine, Department of Medicine, NYU Langone Health, New York, New York.
Division of Hospital Medicine, Department of Medicine, NYU Langone Health, New York, New York.Internal Medicine Residency Program, NYU Grossman School of Medicine, New York, New York.
Characterizing Residents' Clinical Experiences-A Step Toward Precision Education.
New evidence convincingly shows that metformin, a drug that reduces circulating glucose, acts by inhibiting mitochondrial complex I.
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38139, USA.
Meeting metformin again for the first time.
Artificial haptics has the potential to revolutionize the way we integrate physical and virtual technologies in our daily lives, with implications for teleoperation, motor skill acquisition, rehabilitation, gaming, interpersonal communication, and beyond. Here, we delve into the intricate interplay between the somatosensory system and engineered haptic inputs for perception and action. We critically examine the sensory feedback's fidelity and the cognitive demands of interfacing with these systems. We examine how artificial touch interfaces could be redesigned to better align with human sensory, motor, and cognitive systems, emphasizing the dynamic and context-dependent nature of sensory integration. We consider the various learning processes involved in adapting to artificial haptics, highlighting the need for interfaces that support both explicit and implicit learning mechanisms. We emphasize the need for technologies that are not only physiologically biomimetic but also behaviorally and cognitively congruent with the user, affording a range of alternative solutions to users' needs.
Department of Biomedical Engineering, Ben-Gurion University of the Negev, Beer Sheva, Israel.The School of Brain Sciences and Cognition, Ben-Gurion University of the Negev, Israel.
MRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, UK.
A neurocognitive pathway for engineering artificial touch.
During the past decade (and beyond), neurologists have become aware of the emergence, persistence, and consequences of some familiar and new infections affecting the nervous system. Even among the familiar CNS infections, such as herpes virus, polyoma virus/JC, influenza, arbovirus, and hepatitis, challenges remain in developing effective antiviral treatments and treatments of postinfection sequelae. With the changing environment and increased global travel, arthropod vectors that mediate zoonotic disease transmission have spread unfamiliar viruses such as West Nile virus, dengue, chikungunya, equine encephalitis, and Zika, among others. Although the global health impact of these diseases has not risen to that of COVID-19 and HIV, it is likely to dramatically increase with continued spread of transmission vectors and the emergence of new zoonotic animal-to-human diseases mediated by those transmission vectors. Furthermore, specific virus-targeting treatments or effective vaccines for arboviral infections are not yet available, and this represents a major challenge in limiting the morbidity of these infections. By contrast, HIV-1, a disease that originated by direct transmission from nonhuman primates to humans (as early as the 1930s), after many years of intense study, is now targeted by highly specific and effective antiviral drugs that can limit the spread of infection and extend human life and health in all populations. Even with these dramatic therapeutic effects of suppressing HIV replication, neurologic dysfunction (primarily cognitive impairment) affects significant numbers of persons living with HIV. This emphasizes not only the importance of treating the underlying infection but also developing treatments for legacy effects of the initial infection even after antiviral therapy. Notably, the rapid emergence of SARS-CoV-2 infection was met with rapid implementation of highly effective and specific antiviral therapies. This resulted in early and dramatic lowering of the morbidity and mortality of SARS-CoV-2 infection. Nonetheless, the postinfectious complications of SARS-CoV-2 infection (long COVID) are now among the more costly consequences of emerging zoonotic infections worldwide. Developing new antiviral therapies that can penetrate the CNS, vaccines, and therapies that target host immune responses and metabolic dysfunction will be necessary for management of infectious and postinfectious complications of established and emerging infections.
Section of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD; and.
Department of Neurology, University of Pennsylvania, Philadelphia.
Neurology(R) neuroimmunology & neuroinflammation
Neurol Neuroimmunol Neuroinflamm. 2025-01;12(1):e200356.
Reemerging Infectious Diseases and Neuroimmunologic Complications.
Pulsed-field ablation (PFA) is a novel modality for pulmonary vein isolation in patients with atrial fibrillation (AF). We describe the initial uptake and experience of PFA using a pentaspline catheter across selected National Health Service England (NHSE) centres.Data collected by NHSE Specialised Services Development Programme regarding AF ablation procedures using a single-shot, pentaspline, multielectrode PFA catheter (FARAWAVE, Boston Scientific) between June 2022 and August 2024 were aggregated and analysed to examine procedural metrics, acute efficacy and safety outcomes over 3-month follow-up.1034 procedures were submitted. The patients were 32.1% female, mean age 63.8±10.7 years, 53.1% paroxysmal AF and 89.7% first-time AF ablation. Procedures were performed by 48 consultant operators at nine NHSE centres, with a mean of 115 procedures per centre (range 25-264). 93.7% of procedures were performed under general anaesthesia. Median skin-to-skin procedure time was 74 min (IQR 55-96 min) and fluoroscopy time 20 min (IQR 15-27 min). Electroanatomical mapping was used in 15.3%. In first-time ablation cases, acute isolation of all pulmonary veins was achieved in 99.5% of patients. Left atrial (LA) posterior wall ablation using the PFA catheter was performed in 11.0% of cases; additional LA radiofrequency ablation was performed in 0.6%. The major and minor acute procedural complication rates were, respectively, 1.3% and 3.1%, with no reports of periprocedural death or atrio-oesophageal fistula. 63.8% of patients were discharged on the day of procedure. Follow-up data were available for 870 procedures (84.1%). In the 3 months following ablation, hospitalisation for arrhythmia occurred in 3.2%, with 0.9% rehospitalised for procedural-related complications.In this real-world, nationwide registry of a pentaspline PFA catheter, efficacy, safety and efficiency outcomes were comparable to those from previous PFA studies in patients with AF.
© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ Group.
Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart and Chest Hospital, Liverpool, UK mark.mills@lhch.nhs.uk.Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, UK.NHS England Cardiac Rhythm Management Device Working Group, London, UK.
NHS England Cardiac Rhythm Management Device Working Group, London, UK.
NHS England Cardiac Rhythm Management Device Working Group, London, UK.Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK.
NHS England Cardiac Rhythm Management Device Working Group, London, UK.King's College Hospital NHS Foundation Trust, London, UK.
Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart and Chest Hospital, Liverpool, UK.Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, UK.
Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, UK.
Royal Papworth Hospital NHS Foundation Trust, Cambridge, UK.
University Hospitals Dorset NHS Foundation Trust, Bournemouth, UK.
Lancashire Cardiac Centre, Victoria Hospital, Blackpool Teaching Hospitals NHS Trust Foundation, Blackpool, UK.Biomedical Engineering and Imaging Sciences Department, King's College London, London, UK.
Lancashire Cardiac Centre, Victoria Hospital, Blackpool Teaching Hospitals NHS Trust Foundation, Blackpool, UK.
Royal Brompton and Harefield Hospitals, London, UK.
St George's University Hospitals NHS Foundation Trust, London, UK.
Guy's and St Thomas' NHS Foundation Trust, London, UK.St Vincent's Private Hospital, Dublin, Ireland.
University Hospitals of Leicester NHS Trust, Leicester, UK.
Guy's and St Thomas' NHS Foundation Trust, London, UK.
Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, UK.NHS England Cardiac Rhythm Management Device Working Group, London, UK.
Pulsed-field ablation of atrial fibrillation with a pentaspline catheter across National Health Service England centres.
Pharmaceutical product development relies on thorough and costly clinical trials. Participant recruitment and monitoring can be challenging. The incorporation of cutting-edge technologies such as blockchain and artificial intelligence has revolutionized clinical research (particularly in the recruitment stage), enhanced secure data storage and analysis, and facilitated participant monitoring while protecting their personal information.This study aims to investigate the use of novel digital platforms and their features, such as e-recruitment, e-consent, and matching, aiming to optimize and expedite clinical research.A review with a systematic approach was conducted encompassing literature from January 2000 to October 2024. The MEDLINE, ScienceDirect, Scopus, and Google Scholar databases were examined thoroughly using a customized search string. Inclusion criteria focused on digital platforms involving clinical trial recruitment phases that were in English and had international presence, scientific validation, regulatory approval, and no geographic limitations. Literature reviews and unvalidated digital platforms were excluded. The selected studies underwent meticulous screening by the research team, ensuring a thorough analysis of novel digital platforms and their use and features for clinical trials.A total of 24 digital platforms were identified that supported clinical trial recruitment phases. In general, most of them (n=22, 80%) are headquartered and operating in the United States, providing a range of functionalities including electronic consent (n=14, 60% of the platforms), participant matching, and monitoring of patients' health status. These supplementary features enhance the overall effectiveness of the platforms in facilitating the recruitment process for clinical trials. The analysis and digital platform findings refer to a specific time frame when the investigation took place, and a notable surge was observed in the adoption of these novel digital tools, particularly following the COVID-19 outbreak.This study underscores the vital role of the identified digital platforms in clinical trials, aiding in recruitment, enhancing patient engagement, accelerating procedures, and personalizing vital sign monitoring. Despite their impact, challenges in accessibility, compatibility, and transparency require careful consideration. Addressing these challenges is crucial for optimizing digital tool integration into clinical research, allowing researchers to harness the benefits while managing the associated risks effectively.
©Alexia Georgia Bikou, Elena Deligianni, Foteini Dermiki-Gkana, Nikolaos Liappas, José Gabriel Teriús-Padrón, Maria Eugenia Beltrán Jaunsarás, Maria Fernanda Cabrera-Umpiérrez, Christos Kontogiorgis. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 18.12.2024.
Department of Medicine, Democritus University of Thrace, Alexandroupolis, Greece.
Life Supporting Technologies (LifeSTech), Superior Technical School of Telecommunication Engineers, Universidad Politécnica de Madrid (UPM), Madrid, Spain.
Improving Participant Recruitment in Clinical Trials: Comparative Analysis of Innovative Digital Platforms.
Despite effective secondary prevention, including oral anticoagulant (OAC) therapy, the risk of recurrent stroke (RS) in patients with atrial fibrillation (AF) remains substantial with an annualized risk of 3.2%-6.5% per year. The reasons for this high residual risk are unclear. There is growing need for improved risk prediction tools to identify patients at greatest risk of RS in AF and to find new therapeutic targets for secondary prevention. Our objective was to perform a systematic review to investigate the association of clinical factors and echocardiographic, blood, and neuroimaging biomarkers, with stroke recurrence after AF-related stroke.We searched Embase/Ovid Medline until August 2023. Studies were included irrespective of OAC use. Risk ratios (RRs) were pooled using random effects. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.Of 5,427 records searched, 42 reports from 28 studies including 52,798 patients (5,046 RS events during follow-up) were identified. In addition to the CHA2DS2-Vasc score (RR 1.22, 95% CI 1.15-1.30, per point) and its individual components, the clinical factors associated with recurrence were a qualifying stroke despite OAC (RR 1.55, 1.23-1.94 [vs OAC-naïve]), sustained AF (RR 1.44, 1.19-1.75 [vs paroxysmal]), hyperlipidemia (RR 1.27, 1.05-1.53), chronic kidney disease (RR 1.86, 1.19-2.92), and malignancy (RR 4.36, 1.85-10.78). NIH Stroke Scale scores (RR 0.97, 0.95-0.99) and Asian ethnicity (RR 0.59, 0.36-0.97) were associated with a reduced risk of recurrence. Known AF was not associated with a higher risk of stroke compared with AF detected after stroke (RR 1.20, 0.93-1.55). Neuroimaging markers associated with RS included chronic lacunar (RR 1.91, 1.29-2.84) or embolic-appearing (RR 2.76, 1.32-5.77) infarcts and cerebral microbleeds (RR 1.29, 1.04-1.59). Echocardiographic markers included atrial size (RR 1.40, 1.12-1.75 per cm/m2), intracardiac thrombus (RR 1.99, 1.38-2.87), spontaneous left atrial appendage (LAA) echocardiographic contrast (RR 2.91, 1.21-6.17), or low LAA intensity variation (RR 2.81, 1.48-5.32). Data were limited for blood biomarkers.We identified several clinical factors associated with recurrence after AF-related stroke, with AF burden and stroke despite OAC of particular clinical relevance. Biomarkers of atrial cardiopathy, small vessel disease, or previous infarction were also associated with RS. Collaborative efforts are needed to identify and validate new risk factors and biomarkers of RS in AF.
From the Health Research Board (HRB) Stroke Clinical Trials Network Ireland (SCTNI) (Y.C., M.F., D.B., T.C., R.C., S.C., E.D., S.G., M.O.C., M.J.O.D., P.S., D.W., P.J.K., J.J.M.); Neurovascular Unit for Applied Translational and Therapeutics Research (Y.C., M.F., S.G., P.S., P.J.K., J.J.M.), Catherine McAuley Centre; School of Medicine (Y.C., M.F., T.C., S.G., P.S., P.J.K., J.J.M.), University College Dublin; Stroke Service (Y.C., M.F., S.G., P.S., J.J.M.), Department of Geriatric Medicine, Mater Misericordiae University Hospital; School of Medicine (D.B., R.C.), Trinity College Dublin; Department of Neurology (D.B.), St James Hospital; Department of Geriatric Medicine (T.C.), St Vincent's University Hospital; Stroke Service (R.C.), Department of Geriatric Medicine, Tallaght University Hospital, Dublin; Department of Neurology (S.C.), Cork University Hospital; Clinical Neurosciences (S.C.), School of Medicine, University College Cork; Stroke Service (E.D.), Department of Geriatric Medicine, James Connolly Memorial Hospital, Dublin, Ireland; Department of Clinical Neurosciences (K.K., I.I.), University of Cambridge, Addenbrooke's Hospital, United Kingdom; Department of Neurology & Stroke Centre (M.K., A.Z.), University Hospital Basel, Switzerland; Department of Geriatric Medicine (M.O.C.), Limerick University Hospital; College of Medicine (M.J.O.D.), Nursing and Health Sciences, University of Galway and University Hospital Galway; Department of Geriatric and Stroke Medicine (D.W.), RCSI University of Medicine and Health Sciences; Department of Geriatric Medicine (D.W.), and Department of Geriatric and Stroke Medicine (D.W.), Beaumont Hospital; and Stroke Service (P.J.K.), Department of Neurology, Mater Misericordiae University Hospital, Dublin, Ireland.
Clinical and Biomarker Determinants for Recurrent Stroke in Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis.
Negative pressure wound therapy is used often in the management of surgical incisions, chronic wounds and subacute lesions, and there are numerous publications discussing its clinical application and outcomes. However, whilst clinical use and associated literature have expanded since these systems became commercially available in the 90s, important research and discussion around the mode of action have waned, leading to a deficit in the understanding of how this important therapy influences healing. Further, much research and many publications are predominantly reflective, discussing early theorem, some of which have been proven incorrect, or at least not fully resolved leading to misunderstandings as to how the therapy works, thus potentially denying the clinician the opportunity to optimise use towards improved clinical and economic outcomes. In this narrative review, we discuss established beliefs and challenges to same where appropriate and introduce important new research that addresses the manner in which mechanical strain energy (i.e., deformations) is transferred to tissue and how this influences biological response and healing. In addition, we assess and discuss the effect of different negative pressure dressing formats, how they influence the mode of action and how this understanding can lead to more efficient and effective use and clinical economic outcomes.
© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.
Department of Biomedical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv, Israel.Skin Integrity Research Group (SKINT), University Centre for Nursing and Midwifery, Department of Public Health and Primary Care, Ghent University, Ghent, Belgium.Department of Mathematics and Statistics and the Data Science Institute, Faculty of Sciences, Hasselt University, Hasselt, Belgium.
Mediterranean Institute for Transplantation and Highly Specialized Therapies (ISMETT), Palermo, Italy.
Wound Care Centre (Centro Aziendale di Riparazione Tissutale), Castellammare di Stabia, Italy.
Revisiting negative pressure wound therapy from a mechanobiological perspective supported by clinical and pathological data.
The Epithelial Science Expert Group convened on 18-19 October 2023, in Naples, Italy, to discuss the current understanding of the fundamental role of the airway epithelium in asthma and other respiratory diseases and to explore the future direction of patient care. This review summarises the key concepts and research questions that were raised. As an introduction to the epithelial era of research, the evolution of asthma management throughout the ages was discussed and the role of the epithelium as an immune-functioning organ was elucidated. The role of the bronchial epithelial cells in lower airway diseases beyond severe asthma was considered, as well as the role of the epithelium in upper airway diseases such as chronic rhinosinusitis. The biology and application of biomarkers in patient care was also discussed. The Epithelial Science Expert Group also explored future research needs by identifying the current knowledge and research gaps in asthma management and ranking them by priority. It was identified that there is a need to define and support early assessment of asthma to characterise patients at high risk of severe asthma. Furthermore, a better understanding of asthma progression is required. The development of new treatments and diagnostic tests as well as the identification of new biomarkers will also be required to address the current unmet needs. Finally, an increased understanding of epithelial dysfunction will determine if we can alter disease progression and achieve clinical remission.
Institute for Lung Health, National Institute for Health and Care Research Leicester Biomedical Research Centre, University of Leicester, Leicester, UK ceb17@leicester.ac.uk.Joint first authors.
Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research, School of Medicine, University of Naples Federico II, Naples, Italy.Institute of Experimental Endocrinology and Oncology, National Research Council of Italy, Naples, Italy.Joint first authors.
Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, Belgium.Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.
Department of Respiratory Diseases, Aix-Marseille University, Marseille, France.
Department of Biomedical Sciences, Humanitas University, Pieve Emanuele (MI), Italy.Personalized Medicine, Asthma and Allergy, IRCCS Humanitas Research Hospital, Rozzano (MI), Italy.
Respiratory Medicine, National Institute for Health and Care Research Oxford Biomedical Research Centre, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
LungenClinic Grosshansdorf, Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany.Chirstian-Alrechts University Kiel, Member of the German Center for Lung Research (DZL), Kiel, Germany.
Unit of Respiratory Immunopharmacology, Department of Experimental Medical Science, Lund University, Lund, Sweden.
Center for Heart Lung Innovation, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
European respiratory review : an official journal of the European Respiratory Society
The epithelial era of asthma research: knowledge gaps and future direction for patient care.
Colorectal cancer (CRC) screening programmes have been implemented worldwide, but the evidence of the economic consequences of screening programmes relies on data from short-term trials. The aim of this paper was to describe the costs of CRC screening in a population-based screening programme, using administrative real-world data. Specifically, we aimed to estimate the annual costs of the screening programme and the total costs of the full programme over five consecutive screening rounds.The CRC screening programme of Stockholm-Gotland, Sweden, targeted all resident men and women aged 60-69 years for biennial screening. The screening strategy was faecal occult blood testing (FOBT) sent to individuals' home addresses, with a positive test result leading to an invitation to diagnostic colonoscopy. The cost description was conducted with a retrospective, bottom-up costing design from a healthcare perspective using (1) a prevalence-based approach and (2) an incidence-based approach, with two different study samples.Annual healthcare costs were estimated using a sample of 124 608 individuals who were affected by the screening programme in 2017. Annual healthcare costs of the screening programme summed up to €273 758 per 10 000 people, equivalent to €27.4 per eligible individual. The sum of costs for colonoscopy procedures was more than two times as high as the costs for FOBT. The costs of the full screening programme were estimated using a cohort of 92 689 individuals who were invited to five consecutive rounds of screening between 2009 and 2021. Total healthcare costs over five screening rounds were €960 654 per 10 000 people, equivalent to €96.1 per individual.The costs of diagnostic colonoscopies for a minority of participants were driving the costs of the CRC screening programme. The ongoing population-based screening programme and high-quality individual level data with long-term follow-up provide the opportunity to thoroughly describe the costs of CRC screening.
Department of Clinical Science and Education Södersjukhuset, Karolinska Institutet, Stockholm, Sweden naimi.johansson@ki.se.
Department of Learning, Informatics, Management & Ethics (LIME), Karolinska Institutet, Stockholm, Sweden.Center for Health Economics, Informatics and Healthcare Research, Health Care Services Stockholm County (SLSO), Region Stockholm, Stockholm, Sweden.
Department of Clinical Science and Education Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.Department of Surgery, Södersjukhuset, Stockholm, Sweden.
BMJ Open Gastroenterol. 2024-12-18;11(1):.
Costs of colorectal cancer screening in Sweden: an observational, longitudinal cost description.
In 2021, over one million children developed tuberculosis, resulting in 214 000 deaths, largely due to inadequate diagnosis and treatment. The diagnosis and treatment of tuberculosis is limited in most high-burden countries because services are highly centralised at secondary/tertiary levels and are managed in a vertical, non-integrated way. To improve case detection and treatment among children, the World Health Organisation (WHO) recommends decentralised and integrated tuberculosis care models. The Integrating Paediatric TB Services Into Child Healthcare Services in Africa (INPUT) stepped-wedge cluster-randomised trial evaluated the impact of integrating tuberculosis services into healthcare for children under five in Cameroon and Kenya, compared with usual care, finding a 10-fold increase in tuberculosis case detection in Cameroon but no effect in Kenya.We estimated intervention impact on healthcare outcomes, resource use, health system costs and cost-effectiveness relative to the standard of care (SoC) using a decision tree analytical approach and data from the INPUT trial. INPUT trial data on cascades, resource use and intervention diagnostic rate ratios were used to parametrise the decision tree model. Health outcomes following tuberculosis treatment were modelled in terms of mortality and disability-adjusted life-years (DALYs).For every 100 children starting antituberculosis treatment under SoC, an additional 876 (95% uncertainty interval (UI) -76 to 5518) in Cameroon and -6 (95% UI -61 to 96) in Kenya would start treatment under the intervention. Treatment success would increase by 5% in Cameroon and 9% in Kenya under the intervention compared with SoC. An estimated 350 (95% UI -31 to 2204) and 3 (95% UI -22 to 48) deaths would be prevented in Cameroon and Kenya, respectively. The incremental cost-effectiveness ratio for the intervention compared with SoC was US$506 and US$1299 per DALY averted in Cameroon and Kenya, respectively.Although likely to be effective, the cost-effectiveness of integrating tuberculosis services into child healthcare services depends on baseline service coverage, tuberculosis detection and treatment outcomes.
© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Division of Population Health, The University of Sheffield, Sheffield, UK n.mafirakureva@sheffield.ac.uk.
Elizabeth Glaser Pediatric AIDS Foundation, Geneva, Switzerland.
Research, Elizabeth Glaser Pediatric AIDS Foundation, Yaoundé, Cameroon.
Research, Elizabeth Glaser Pediatric AIDS Foundation, Nairobi, Kenya.
Elizabeth Glaser Pediatric AIDS Foundation, Washington, District of Columbia, USA.
Innovation and New Technology, Elizabeth Glaser Pediatric AIDS Foundation, Geneva, Switzerland.
Elizabeth Glaser Pediatric AIDS Foundation, Washington, District of Columbia, USA.The George Washington University Milken Institute School of Public Health, Washington, District of Columbia, USA.
Division of Population Health, The University of Sheffield, Sheffield, UK.
Cost-effectiveness of integrating paediatric tuberculosis services into child healthcare services in Africa: a modelling analysis of a cluster-randomised trial.
Paediatric tuberculosis (TB) underdiagnosis is a critical concern. The INPUT stepped-wedge cluster-randomised trial assessed the impact of integrating child TB services into child healthcare on TB case detection among children under age 5 years.We compared the standard of care, providing TB care in specific TB clinics (control phase), with the Catalysing Paediatric TB Innovations (CaP-TB) intervention, integrating TB services across all child health services (intervention phase). 12 clusters in Cameroon and Kenya transitioned from the standard of care to the intervention at randomly assigned times. Children with presumptive TB were enrolled after obtaining their parents' consent and were followed throughout TB diagnostic procedures and treatment. Study outcomes included the rate of children with presumptive TB receiving TB investigations and that of children diagnosed with TB (the primary outcome was case detection), per thousand children under 5 years attending facilities. Generalised linear mixed Poisson models estimated the intervention's effect as adjusted rate ratios (aRR) and associated 95% CIs. Ad hoc country-stratified analyses were conducted.During control and intervention phases, respectively, 121 909 and 109 614 children under 5 years attended paediatric entry points, 133 (1.1 per thousand) and 610 (5.6 per thousand) children with presumptive TB received TB investigations, and 79 and 74 were diagnosed with TB, corresponding to a case detection rate of 0.64 and 0.68 per thousand, respectively. CaP-TB significantly increased TB investigations in both countries overall (aRR=3.9, 95% CI 2.4 to 5.4), and in each. Overall, TB case detection was not statistically different between intervention and control (aRR 1.32, 95% CI 0.66 to 2.61, p=0.43). Country-stratified analysis revealed a 10-fold increase (aRR 9.75, 95% CI 1.04 to 91.84, p=0.046) in case detection with CaP-TB in Cameroon and no significant effect in Kenya (aRR 0.94, 95% CI 0.44 to 2.01, p=0.88).CaP-TB increased TB investigations in both study countries and markedly enhanced TB case detection in one, underlining integrated TB services' potential to address paediatric TB underdiagnosis.
Elizabeth Glaser Pediatric AIDS Foundation, Geneva, Switzerland lisedenoeud@yahoo.fr.
Elizabeth Glaser Pediatric AIDS Foundation, Yaoundé, Cameroon.
Elizabeth Glaser Pediatric AIDS Foundation, Nairobi, Kenya.
Division of Health Operations Research, Ministry of Public Health, Yaounde, Cameroon.
Effect of integrating paediatric tuberculosis services into child healthcare services on case detection in Africa: the INPUT stepped-wedge cluster-randomised trial.
Chronic obstructive pulmonary disease (COPD) is a complex disorder with a high degree of interindividual variability. Gastrointestinal dysfunction is common in patients with COPD and has been proposed to influence the clinical progression of the disease. Using the presence of bile acid(s) (BA) in bronchoalveolar lavage (BAL) fluid as a marker of gastric aspiration, we evaluated the relationships between BAs, clinical outcomes and bacterial lung colonisation.We used BAL specimens from a cohort of patients with COPD and healthy controls. BAs were profiled and quantified in BAL supernatants using mass spectrometry. Microbial DNA was extracted from BAL pellets and quantified using quantitative PCR. We profiled the BAL microbiota using an amplicon sequencing approach targeting the V3-V4 region of the 16S rRNA gene.Detection of BAs in BAL was more likely at the earliest clinical stages of COPD and was independent of the degree of airway obstruction. BAL specimens with BAs demonstrated higher bacterial biomass and lower diversity. Likewise, the odds of recovering bacterial cultures from BAL were higher if BAs were also detected. Detection of BAs in BAL was not associated with either inflammatory markers or clinical outcomes. We also observed different bacterial community types in BAL, which were associated with different clinical groups, levels of inflammatory markers and the degree of airway obstruction.Detection of BAs in BAL was associated with alterations in the airway bacterial communities. Further studies are needed to evaluate whether BAs in BAL can be used to stratify patients and predict disease progression trajectories.
© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.
Wal-yan Respiratory Research Centre, The Kids Research Institute Australia, Nedlands, Western Australia, Australia.Curtin Health Innovation Research Institute (CHIRI), Curtin University, Bentley, Western Australia, Australia.The University of Western Australia, Perth, Western Australia, Australia.
Curtin Health Innovation Research Institute (CHIRI), Curtin University, Bentley, Western Australia, Australia.
Wal-yan Respiratory Research Centre, The Kids Research Institute Australia, Nedlands, Western Australia, Australia.The University of Western Australia, Perth, Western Australia, Australia.European Virus Bioinformatics Centre, Jena, TH, Germany.
Immune Health Program, Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, Australia.
School of Microbiology, University College Cork, Cork, Ireland.Synthesis and Solid-State Pharmaceutical Centre, University College Cork, Cork, Ireland.
Centre for Respiratory Health, School of Biomedical Science, The University of Western Australia, Nedlands, Western Australia, Australia.Cell Biology Group, Institute for Respiratory Health, Nedlands, Western Australia, Australia.Department of Respiratory Medicine, Fiona Stanley Hospital, Murdoch, Western Australia, Australia.Institute of Respiratory Health and Medical School, The University of Western Australia, Nedlands, Western Australia, Australia.
Institute of Respiratory Health and Medical School, The University of Western Australia, Nedlands, Western Australia, Australia.
The University of Western Australia, Perth, Western Australia, Australia.Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, Western Australia, Australia.
Faculty of Medicine Nursing and Health Sciences, Monash University, Prahran, Victoria, Australia.
Wal-yan Respiratory Research Centre, The Kids Research Institute Australia, Nedlands, Western Australia, Australia f.ogara@ucc.ie.BIOMERIT Research Centre, School of Microbiology, University College Cork, Cork, Ireland.
Bile acids in the lower airways is associated with airway microbiota changes in chronic obstructive pulmonary disease: an observational study.
Acute and chronic pancreatitis (CP) are inflammatory conditions of the pancreas that cause local and systemic complications. The epidemiology of these conditions are not well-known in India.We describe the protocol and procedures of a multicentre study for delineating the epidemiology of pancreatitis in India. We plan to cover 110 000 people across 10 geographically distributed sites in 10 states of India to estimate the burden and risk factors of CP. Trained investigators will make house visits and screen for abdominal pain requiring hospitalisation or pre-diagnosed CP. The screened positive participants will be reviewed by a gastroenterologist to confirm the diagnosis of CP based on radiological imaging. For each case, four controls will be selected and data on risk factors for CP (tobacco, alcohol, family history, metabolic causes) and blood for genetic markers will be collected. Information on the cost of treatment and quality of life will be collected from patients with CP. For estimating incidence of acute pancreatitis (AP), hospital-based sentinel surveillance will be conducted in 10 districts across these 10 states. All hospitals in the district will be contacted to provide a line list of admissions due to acute abdomen including AP for 2 years. The spread of acute abdomen cases will be used to define the catchment area and estimate the denominator population. The line-listed cases with AP living in the catchment area will form the numerator to calculate the incidence. The study will provide critical information for planning pancreatitis-related services in the country.The institutional ethics committee (IECs) at all the participating sites have given their approval for the study. All the participants whose data will be collected will be included after written informed consent. The results may be presented at national or international conferences and will be reported in peer-reviewed publications.
All India Institute of Medical Sciences New Delhi, New Delhi, India kanandiyer@yahoo.com.
Translational Health Science and Technology Institute, Faridababd, Haryana, India.
All India Institute of Medical Sciences New Delhi, New Delhi, India.
All India Institute of Medical Sciences, Jodhpur, Rajasthan, India.
Institute of Postgraduate Medical Education and Research, Kolkata, West Bengal, India.
Guwahati Medical College, Guwahati, Assam, India.
Christian Medical College and Hospital Vellore, Vellore, Tamil Nadu, India.
All India Institute of Medical Science Bhopal, Bhopal, Madhya Pradesh, India.
Indian Council of Medical Research, New Delhi, Delhi, India.
All India Institute of Medical Sciences - Nagpur, Nagpur, Maharashtra, India.
Government Medical College Thiruvananthapuram, Thiruvananthapuram, Kerala, India.
Indira Gandhi Medical College and Hospital, Shimla, Himachal Pradesh, India.
Consultant Gastroenterologist, Jainamshree multi-speciality hospital, Bhopal, Madhya Pradesh, India.
King George Medical College, Lucknow, Uttar Pradesh, India.
Epidemiology of chronic and acute pancreatitis in India (EPICAP-India): protocol for a multicentre study.
A prospective randomized controlled study was conducted to investigate the early postoperative analgesic effectiveness of using liposomal bupivacaine (LB) for local infiltration anesthesia (LIA) in unicompartmental knee arthroplasty (UKA).Between January 2024 and July 2024, a total of 80 patients with knee osteoarthritis (KOA) who met the selection criteria were enrolled in the study. Patients were randomly assigned to either the LB group or the cocktail group in a 1∶1 ratio using a random number table, with 40 patients in each group. Baseline characteristics, including gender, age, body mass index, operated side, Kellgren-Lawrence grade, and preoperative American Society of Anesthesiologists (ASA) classification, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and knee joint range of motion, showed no significant difference between the two groups ( P>0.05). Both groups received LIA and comprehensive pain management. The surgical duration, incision length, pain-related indicators [resting and activity visual analogue scale (VAS) scores, total dosage of oral morphine, WOMAC scores], knee joint range of motion, first ambulation time after operation, length of hospital stay, and postoperative adverse events.There was no significant difference between the two groups in surgical duration, incision length, first ambulation time after operation, length of hospital stay, total dosage of oral morphine, and pre-discharge satisfaction with surgery and WOMAC scores ( P>0.05). At 4, 12, and 24 hours after operation, the resting and activity VAS scores in the cocktail group were lower than those in the LB group; at 60 and 72 hours postoperatively, the resting VAS scores in the LB group were lower than those in the cocktail group, with the activity VAS scores also being lower at 60 hours; all showing significant differences ( P<0.05). There was no significant difference in the above indicators between the two groups at other time points ( P>0.05). On the second postoperative day, the sleep scores of the LB group were significantly higher than those of the cocktail group ( P<0.05), while there was no significant difference in sleep scores on the day of surgery and the first postoperative day ( P>0.05). Additionally, the incidence of complications showed no significant difference between the two groups ( P>0.05).The use of LB for LIA in UKA can provide prolonged postoperative pain relief; however, it does not demonstrate a significant advantage over the cocktail method in terms of short-term analgesic effects or reducing opioid consumption and early functional recovery after UKA. Nevertheless, LB may help reduce postoperative sleep disturbances, making it a recommended option for UKA patients with cardiovascular diseases and insomnia or other mental health issues.
Department of Orthopedics, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing Jiangsu, 210029, P. R. China.
Department of Anesthesiology, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing Jiangsu, 210029, P. R. China.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi
Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery
采用前瞻性随机对照研究，探究在膝关节单髁置换术（unicompartmental knee arthroplasty，UKA）中使用布比卡因脂质体（liposomal bupivacaine，LB）进行局部浸润麻醉（local infiltration anesthesia，LIA）术后早期镇痛效果。. 2024年1月—7月共80例膝关节骨关节炎（knee osteoarthritis，KOA）患者符合选择标准纳入研究。按随机数字表法以1∶1比例将患者分为LB组和“鸡尾酒”组，每组40例。两组患者性别、年龄、身体质量指数、手术侧别、Kellgren-Lawrence分级及术前美国麻醉医师协会（ASA）分级、西安大略与麦克马斯特大学骨关节炎指数（WOMAC）评分、膝关节活动度等基线资料比较差异均无统计学意义（ P>0.05）。两组患者接受LIA及全病程镇痛管理。记录并比较两组手术时间、切口长度、疼痛相关指标 ［静息以及活动疼痛视觉模拟评分（VAS），口服吗啡总用量、WOMAC评分］、膝关节活动度、术后首次下地时间、住院时间以及术后不良事件。. 两组患者手术时间、切口长度、术后首次下地时间、术后住院时间、口服吗啡总用量及出院前手术满意度和WOMAC评分比较差异均无统计学意义（ P>0.05）。术后4、12、24 h“鸡尾酒”组患者静息VAS评分和活动VAS评分均明显低于LB组，术后60、72 h LB组静息VAS评分明显低于“鸡尾酒”组，术后60 h LB组运动VAS评分明显低于“鸡尾酒”组，差异均有统计学意义（ P<0.05）；其余各时间点两组上述各指标比较差异均无统计学意义（ P>0.05）。术后2 d LB组患者睡眠评分高于“鸡尾酒”组（ P<0.05）；术后当天和术后1 d两组患者睡眠评分比较差异无统计学意义（ P>0.05）。两组并发症发生率比较差异无统计学意义（ P>0.05）。. 在UKA术中使用LB进行LIA能够较长时间缓解患者术后疼痛，而短效止痛效果较“鸡尾酒”疗法差，对于减少阿片类药物的使用和UKA术后早期功能康复未见显著优势。但LB能减少患者术后睡眠障碍发生，对于患有心脑血管疾病以及失眠等精神疾病的UKA患者推荐使用LB。.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2024-12-15;38(12):1458-1465.
[Observation of analgesic efficacy of liposomal bupivacaine for local infiltration anesthesia in unicompartmental knee arthroplasty: a prospective randomized controlled study].
Biologics provide significant benefits in asthma, reducing exacerbations and symptoms. Some biologics have shown promising results in small subgroups of patients with chronic obstructive pulmonary disease (COPD) and frequent exacerbations. Nevertheless, real-life data on the size of the COPD target population remain scarce.We analysed the characteristics of COPD and coexisting asthma and COPD patients included in the prospective multicentre, French COhort of BRonchial obstruction and Asthma, between 2008 and 2023 and evaluated the number of patients who could correspond to the inclusion criteria of randomised controlled trials evaluating various biologics targeting interleukin 33 (IL-33) (-receptor), IL-5 (-receptor), IL-4Rα or TSLP, in routine clinical practice.Among 434 COPD patients, only 21.7% met inclusion criteria for at least one biologic. Among patients with asthma, 54 (3.5%) had coexisting features of COPD in terms of age, smoking status and airflow obstruction and met inclusion criteria for at least one biologic. Notably, these patients were predominantly female, with worse lung function. Globally, the target chronic airway diseases population of the eagerly awaited biologics remains limited to a small part (ie, 1.3%-8%, depending on the biologic).In a real-life COPD and asthma population (including asthmatic patients with features of COPD), the proportion of patients satisfying selection criteria applied in randomised controlled trials assessing the efficacy of biologics remains limited to less than 10% of the whole population.
© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.
Centre de Recherche Cardio-Thoracique de Bordeaux, U1045, CIC 1401, Université de Bordeaux, Bordeaux, France maeva.zysman@chu-bordeaux.fr.Département de Pneumologie, Service des Maladies Respiratoires, Hôpital du Haut Lévêque, CHU Bordeaux, Bordeaux, France.
CHU de Montpellier, Montpellier, France.
Département de Pneumologie, Service des Maladies Respiratoires, Hôpital du Haut Lévêque, CHU de Bordeaux, Pessac, France.
Service de Pneumologie et Centre de Référence des Maladies Pulmonaires Rares, Hôpital Bichat - Claude-Bernard, Paris, France.
UMRS1158 Neurophysiologie respiratoire expérimentale et clinique, (1) Sorbonne Universités, UPMC Univ Paris 06, INSERM, Paris, France.Groupe Hospitalier Pitié-Salpêtrière, Service de Pneumologie et Réanimation Médicale, Assistance Publique - Hopitaux de Paris, Paris, France.
Département de Pneumologie, Service des Maladies Respiratoires, Hôpital du Haut Lévêque, CHU de Bordeaux, Bordeaux, France.
Service de Pneumologie, Hôpital Cochin, AP-HP Centre, Paris, France.
Département de Pneumologie, Service des Maladies Respiratoires, Hôpital du Haut Lévêque, CHU Bordeaux, Bordeaux, France.
Centre de Recherche Cardio-Thoracique de Bordeaux, U1045, CIC 1401, CHU de Bordeaux, Bordeaux, France.
Clinical Research and Epidemiology Unit, CHU Montpellier, Univ Montpellier, Montpellier, France.
Centre de Recherche Cardio-Thoracique de Bordeaux, U1045, CIC 1401, Université de Bordeaux, Bordeaux, France.Department of Physiology, University Hospital, Bordeaux, France.
What is the true target population for biologics in real-life COPD or asthma-COPD overlap patients?
The management of a chronic and frequent pathology, such as obstructive sleep apnoea (OSA), requires personalised programmes that implement new technology-based tools to improve the comprehensive treatment of the patient to reduce the morbidity associated with this disease. This study will evaluate the effectiveness of an eHealth tool in managing the pathophysiological consequences of OSA and how they impact the quality of life after 3 months of intervention among adults.This is a mixed-method sequential exploratory study protocol. Participants will be≥18 years with a new diagnosis of moderate OSA and diagnosed with hypertension. The qualitative phase will consist of personal semistructured interviews. The quantitative phase will be a triple-blind randomised controlled trial. The experimental group (n=135) will receive an eHealth intervention using an electronic wrist device and a mobile application that will offer specific healthcare recommendations, physical activity indications and hygienic and dietary advice. These recommendations will be based on the information obtained in the qualitative phase. Those in the control group (n=135) will receive the usual educational materials from the sleep unit. The primary outcome will be blood pressure changes at 3 months. Secondary outcomes are subjective sleep quality, sleep apnoea-related parameters, daytime sleepiness, physical activity, empowerment and motivation for change, quality of life, anthropometry, cost-benefit and adherence.Ethical approval for the study has been obtained from the Hospital Universitari Arnau de Vilanova (CEIC-2511). Results will be published in a peer-reviewed journal.ClinicalTrials.gov Identifier: NCT05380726.
Department of Nursing and Physiotherapy, University of Lleida, Lleida, Spain.Consolidated Research Group: Society, Health, Education and Culture, University of Lleida, Lleida, Spain.Research Group of Healthcare (GRECS) , Institute for Biomedical Research Dr Pifarre Foundation, Lleida, Spain.
Department of Nursing and Physiotherapy, University of Lleida, Lleida, Spain.Research Group of Healthcare (GRECS) , Institute for Biomedical Research Dr Pifarre Foundation, Lleida, Spain.
Department of Nursing and Physiotherapy, University of Lleida, Lleida, Spain oriol.martinez@udl.cat.Consolidated Research Group: Society, Health, Education and Culture, University of Lleida, Lleida, Spain.Research Group of Healthcare (GRECS) , Institute for Biomedical Research Dr Pifarre Foundation, Lleida, Spain.
Department of Nursing and Physiotherapy, University of Lleida, Lleida, Spain.Consolidated Research Group: Society, Health, Education and Culture, University of Lleida, Lleida, Spain.Research Group of Healthcare (GRECS) , Institute for Biomedical Research Dr Pifarre Foundation, Lleida, Spain.Biomedical Research Network Center in Frailty and Healthy Aging (CIBERFES), Madrid, Spain.
Research Group of Healthcare (GRECS) , Institute for Biomedical Research Dr Pifarre Foundation, Lleida, Spain.Almoosa College of Health Sciences, Al Ahsa, Saudi Arabia.
Department of Nursing and Physiotherapy, University of Lleida, Lleida, Spain.Consolidated Research Group: Society, Health, Education and Culture, University of Lleida, Lleida, Spain.Research Group of Healthcare (GRECS) , Institute for Biomedical Research Dr Pifarre Foundation, Lleida, Spain.Diabetes and Associated Metabolic Diseases Networking Biomedical Research Centre (CIBERES), Madrid, Spain.
Department of Nursing and Physiotherapy, University of Lleida, Lleida, Spain.Onze de Setembre Pimary Care Center, Catalan Health Institute, Lleida, Spain.
Translation Research in Respiratory Medicine, Hospital Universitari Arnau de Vilanova-Santa María, IRB Lleida, Lleida, Spain.Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain.Precision Medicine in Chronic Diseases, Hospital Universitari Arnau de Vilanova-Santa Maria, IRB Lleida, Lleida, Spain.
Sequential exploratory mixed-method research of an eHealth intervention on blood pressure, sleep quality and physical activity in obstructive sleep apnoea: rationale and methodology of the Moore4Medical trial protocol.
To explore physiotherapists' experiences and perceived acceptability of delivering a bracing intervention for knee osteoarthritis (OA) in the 'PROvision of braces for Patients with knee OA' (PROP OA) randomised controlled trial.Semi-structured telephone interviews with consenting physiotherapists who received the PROP OA training programme and delivered the knee bracing intervention (advice, information and exercise instruction plus knee brace matched to patients' clinical and radiographic presentation and with adherence support). Interviews were recorded and transcribed verbatim. Two-stage analytic framework: inductive thematic analysis preceded mapping to constructs of the Theoretical Framework of Acceptability.Eight physiotherapists were interviewed and six key themes were developed. Perceptions of the training programme were generally positive, but additional formal training and experiential learning consolidated confidence and skills in novel intervention components. Advice, information, and exercise instruction reflected usual physiotherapy care for knee OA. Physiotherapists were confident in delivering the knee brace, but determining the pattern of knee OA to inform brace type selection was challenging. Physiotherapists valued brace adherence enhancing strategies and the follow-up appointment to facilitate adherence. Perceived impact of the bracing intervention for people with OA was positive. The bracing intervention was perceived as acceptable, although improving self-efficacy to deliver novel intervention components (e.g., reading x-rays) would enhance acceptability.The complex knee bracing intervention was broadly perceived as acceptable by physiotherapists. If implemented within clinical practice beyond the trial, physiotherapists might benefit from not only initial training in brace selection but also ongoing support and mentoring to increase self-efficacy in delivery.
© 2024 The Author(s). Musculoskeletal Care published by John Wiley & Sons Ltd.
School of Medicine, Primary Care Centre Versus Arthritis, Keele University, Keele, UK.Centre for Musculoskeletal Research, Keele University, Keele, UK.
Institute of Applied Health Research, University of Birmingham, Birmingham, UK.
Department of Psychology, School of Health, Education, Policing and Sciences, Staffordshire University, Stoke-on-Trent, UK.
Henry M Goldman School of Dental Medicine, Boston University, Boston, Massachusetts, USA.Manchester Centre for Health Psychology, Division of Psychology and Mental Health, School of Health Sciences, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK.
Centre for Musculoskeletal Research, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, UK.Faculty of Health and Education, Manchester Metropolitan University Manchester, Manchester, UK.Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
MRC-Versus Arthritis Centre for Integrated Research Into Musculoskeletal Ageing, Newcastle University, Newcastle upon Tyne, UK.Northumbria Healthcare NHS Foundation Trust, North Tyneside, UK.
School of Medicine, Primary Care Centre Versus Arthritis, Keele University, Keele, UK.Keele Clinical Trials Unit, Keele University, Keele, UK.
Connect Health, Newcastle Upon Tyne, UK.
Research User Group, Primary Care Centre Versus Arthritis, School of Medicine, Keele University, Keele, UK.
School of Primary Care, Population Sciences and Medical Education, University of Southampton, Southampton, UK.
School of Medicine, Primary Care Centre Versus Arthritis, Keele University, Keele, UK.Centre for Musculoskeletal Research, Keele University, Keele, UK.Impact Accelerator Unit, Keele University, Keele, UK.
School of Medicine, Primary Care Centre Versus Arthritis, Keele University, Keele, UK.Surgical Treatment and Rehabilitation Service (STARS) Education and Research Alliance, The University of Queensland and Metro North Health, Brisbane, Australia.
School of Medicine, Primary Care Centre Versus Arthritis, Keele University, Keele, UK.Health Economics Unit, Department of Applied Health Research, School of Health Sciences, University of Birmingham, Birmingham, UK.
School of Medicine, Primary Care Centre Versus Arthritis, Keele University, Keele, UK.Centre for Applied Health & Social Care Research (CARe), Sheffield Hallam University, Sheffield, UK.
Physiotherapists' Experiences and Perceived Acceptability of Delivering a Knee Bracing Intervention for People With Symptomatic Knee Osteoarthritis in a Randomised Trial (PROP OA): A Qualitative Study.
To compare the efficacy and safety of gecacitinib (also known as jaktinib) with hydroxyurea (HU) in treating myelofibrosis (MF) patients. In this multicenter, randomized phase 3 trial (ZGJAK016), intermediate- or high-risk primarily JAK inhibitor naïve MF patients were assigned in a 2:1 ratio to receive either gecacitinib (100 mg twice a day, BID) or HU (500 mg BID). The primary endpoint was the proportion of patients with ≥35% reduction in spleen volume (SVR35) from baseline at week 24. Secondary endpoints included the best spleen response rate, the proportion of patients with a ≥50% reduction in total symptom score (TSS50), anemia improvement, and safety profile. At 24 weeks, the SVR35 was reached by 64.8% of patients on gecacitinib (46/71), compared to 26.5% on HU (9/34), P = 0.0002. The best spleen response rates were also superior for gecacitinib at 81.7%, vs 32.4% for HU, P < 0.0001. The TSS50 rates were 62.0% for gecacitinib- and 50% for HU-treated patients. Among non-transfusion-dependent patients with baseline hemoglobin (HGB) ≤ 100 g/L, 31.0% (13/42) in the gecacitinib group showed a ≥20 g/L increase in HGB, compared to 15.0% (3/20) in HU group. The common grade ≥ 3 treatment-emergent adverse events (TEAEs), including anemia (26.8% vs 44.1%), thrombocytopenia (15.5% vs 32.4%), leukopenia (2.8% vs 20.6%), and neutropenia (1.4% vs 20.6%), were less frequent with gecacitinib than HU. Treatment discontinuation due to TEAEs was lower in gecacitinib (7.0%) compared to HU (11.8%). Gecacitinib demonstrates superior efficacy and a more favorable safety profile compared to HU, making it a promising treatment option for managing MF, particularly in patients with anemia (This trial was registered with ClinicalTrials.gov, (NCT04617028)).
Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China.Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, PR China.Zhejiang Provincial Clinical Research Center for Hematological Disorders, Hangzhou, PR China.Zhejiang University Cancer Center, Hangzhou, PR China.
Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, PR China.
Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, PR China.
Department of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, PR China.
Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, PR China.
The First Hospital of Hebei Medical University, Shijiazhuang, PR China.
Department of Hematology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, PR China.
Department of Hematology, The First Hospital of Jilin University, Changchun, PR China.
Department of Hematology, The Second Hospital of Jilin University, Changchun, PR China.
Department of Hematopathology, The First Hospital of China Medical University, Shenyang, PR China.
Department of Hematology, Henan Provincial People's Hospital, Zhengzhou, PR China.
Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
Department of Hematology, West China Hospital, Sichuan University, Chengdu, PR China.
Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Key Laboratory of Hematology of Nanjing Medical University, Collaborative Innovation Center for Cancer Personalize, Nanjing, PR China.
Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
Department of Hematology, Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, PR China.
Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China.
Department of Hematology, Peking University Third Hospital, Beijing, PR China.
Department of Hematology, Affiliated Hospital of Guizhou Medical University, Guiyang, PR China.
Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, PR China.
Department of Hematology, Lanzhou University Second Hospital, Lanzhou, PR China.
Department of Hematology, Wenzhou Central Hospital, Wenzhou, PR China.
Department of Hematology, The Second Affiliated Hospital of Kunming Medical University, Kunming, PR China.
Department of Hematology, Jiangxi Provincial People's Hospital, Nanchang, PR China.
Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha, PR China.
Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China.
Department of Hematology, Xiangya Hospital, Central South University, Changsha, PR China.
Department of Hematology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, PR China.
Department of Hematology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, PR Hangzhou, PR China.
Suzhou Zelgen Biopharmaceuticals Co., Ltd., Suzhou, PR China.
Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, PR China.
Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China. jiej0503@zju.edu.cn.Zhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, PR China. jiej0503@zju.edu.cn.Zhejiang Provincial Clinical Research Center for Hematological Disorders, Hangzhou, PR China. jiej0503@zju.edu.cn.Zhejiang University Cancer Center, Hangzhou, PR China. jiej0503@zju.edu.cn.
Evaluation of gecacitinib vs hydroxyurea in patients with intermediate-2 or high-risk myelofibrosis: final analysis results from a randomized phase 3 study.
Studies have proposed that probiotic intake may ameliorate some of the clinical components of metabolic syndrome (MetS). This study aimed to determine the effects of a new developed synbiotic yogurt containing Lactobacillus plantarum, Lactobacillus pentosus, and Chloromyces marcosianos yeast on the components of MetS in adults with MetS.In this randomized, placebo-controlled, clinical trial, 44 participants were divided into two groups to receive 300 grams of synbiotic yogurt or regular yogurt daily for 12 weeks. Anthropometric measurements, blood pressure, and biochemical parameters evaluated before and after the intervention.Daily consumption of synbiotic yogurt containing L. plantarum, L. pentosus, and C. marcosianos yeast in adults with MetS caused a significant decrease in the levels of fasting blood glucose (FBG) (p = 0.005), fasting insulin (p = 0.001), homeostatic model assessment for insulin resistance (HOMA-IR) index (p < 0.001), waist to hip ratio (WHR) (p = 0.02) and systolic blood pressure (p = 0.008) in the intervention group compared to the control group.According to the findings of this study, daily consumption of the synbiotic yogurt was associated with improvements in insulin resistance, systolic blood pressure and WHR, which could be beneficial in patients with MetS.
Department of Clinical Nutrition, Faculty of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
Social Determinants of Health Research Center, Yasuj University of Medical Science, Yasuj, Iran.
Department of Clinical Nutrition, Faculty of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran. asghari.nut@gmail.com.
The effect of a new developed synbiotic yogurt consumption on metabolic syndrome components in adults with metabolic syndrome: a randomized controlled clinical trial.
Road traffic injuries are a global public health challenge. This study was conducted to describe the epidemiological patterns of road traffic injuries in a large tertiary care hospital in the West Bank of Palestine. In addition, associations between the different variables of the victims and the patterns of road traffic injuries were also assessed.This study was conducted in a retrospective cohort observational design between January 2021 and July 2023 at a large tertiary care hospital in Nablus, Palestine. The data were collected from the electronic medical record system of the large tertiary care hospital using a data collection form.A total of 1,544 victims of traffic road injuries were included in this study. Lower limb (43.0%), neck (41.2), and upper limb (39.8%) injuries were the most common types of road traffic injuries sustained by the victims admitted to the large tertiary care hospital. The victims who were 30 years or older were more likely to sustain back injuries (aOR = 1.71, 95% CI: 1.20-2.45) pelvic injuries (aOR = 1.84, 95% CI: 1.08-3.12), chest injuries (aOR = 1.59, 95% CI: 1.06-2.38), and neck injuries (aOR = 2.54, 95% CI: 1.68-3.82) compared to the victims who were younger than 30 years. The victims who did not use seatbelts were more likely to sustain abdominal injuries (aOR = 1.88, 95% CI: 1.34-2.63) and head injuries (aOR = 1.49, 95% CI: 1.06-2.10) compared to the victims who used seatbelts. The victims who did not have the airbag deployed were more likely (aOR = 1.85, 95% CI: 1.31-2.63) to sustain neck injuries compared to the victims who had the airbag deployed.The epidemiological patterns of road traffic injuries in a large tertiary care hospital in Nablus, Palestine were described and the associations between the different variables of the victims and the patterns of road traffic injuries were assessed. The findings indicated a need to design measures to prevent/minimize these injuries. Future studies are still needed to determine the best measures to avoid/minimize the incidence of serious road traffic injuries.
Department of Medicine, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine. a.rostom@najah.ed.An-Najah National University Hospital, Nablus, 44839, Palestine. a.rostom@najah.ed.
Department of Medicine, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine.
Department of Physiology, Pharmacology and Toxicology, Faculty of Medicine and Health Sciences, An-Najah National University, P.O. Box 7, New Campus, Building: 19, Office: 1340, Nablus, Palestine. ramzi_shawahna@hotmail.com.Clinical Research Center, An-Najah National University Hospital, Nablus, 44839, Palestine. ramzi_shawahna@hotmail.com.
Epidemiological pattern of injuries among road traffic crash victims: the first experience of a large tertiary care hospital in the West Bank of Palestine.
Department of Endocrinology, Erciyes University Medical School, Kayseri, Turkey.
Department of Endocrinology, Yeditepe University Medical School, Istanbul, Turkey.
Response to commentary: Primary hypophysitis and the benefits of glucocorticoids, a still unresolved question .
Candidatus Accumulibacter is a unique and pivotal genus of polyphosphate-accumulating organisms prevalent in wastewater treatment plants and plays mainstay roles in the global phosphorus cycle. However, the efforts to fully understand their genetic and metabolic characteristics are largely hindered by major limitations in existing sequence-based annotation methods. Here, we reported an integrated approach combining pangenome analysis, protein structure prediction and clustering, and meta-omic characterization, to uncover genetic and metabolic traits previously unexplored for Ca. Accumulibacter. The identification of a previously overlooked pyrophosphate-fructose 6-phosphate 1-phosphotransferase gene (pfp) suggested that all Ca. Accumulibacter encoded a complete Embden-Meyerhof-Parnas pathway. A homologue of the phosphate-specific transport system accessory protein (PhoU) was suggested to be an inorganic phosphate transport (Pit) accessory protein (Pap) conferring effective and efficient phosphate transport. Additional lineage members were found to encode complete denitrification pathways. A pipeline was built, generating a pan-Ca. Accumulibacter annotation reference database, covering >200,000 proteins and their encoding genes. Benchmarking on 27 Ca. Accumulibacter genomes showed major improvement in the average annotation coverage from 51% to 82%. This pipeline is readily applicable to diverse cultured and uncultured bacteria to establish high-coverage annotation reference databases, facilitating the exploration of genomic dark matter in the bacterial domain.
School of Environment and Energy, South China University of Technology, Guangzhou 510006, China.
School of Environment and Energy, South China University of Technology, Guangzhou 510006, China.Guangdong Provincial Key Laboratory of Solid Wastes Pollution Control and Recycling, Guangzhou 510006, China.
Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore 637551, Singapore.
School of Environment and Energy, South China University of Technology, Guangzhou 510006, China.Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore 637551, Singapore.Guangdong Provincial Key Laboratory of Solid Wastes Pollution Control and Recycling, Guangzhou 510006, China.The Key Lab of Pollution Control and Ecosystem Restoration in Industry Clusters, Ministry of Education, Guangzhou 510006, China.
From Gene to Structure: Unraveling Genomic Dark Matter in Ca. Accumulibacter.
Accurate analysis of surface water pollution mechanisms is critical for effective environmental restoration and protection. However, evaluation methods for small watersheds with dense populations and complex pollution sources remain limited. This study integrates partial least squares structural equation modeling (PLS-SEM) with fluorescence fingerprinting data from excitation-emission matrix-parallel factor analysis (EEM-PARAFAC) to investigate nutrient sources in rivers of southeastern China. The findings reveal that land use intensity (LUI) significantly influences pollutant concentrations, but the presence of outliers underscores complex pollution mechanisms. Using EEM-PARAFAC components as mediators, the C5 component, representing sewage-derived substances, was identified as a key driver, fully mediating nitrogen (β = 0.953, p < 0.001, VAF = 117.5%) and phosphorus (β = 0.921, p < 0.001, VAF = 113.2%) levels. In contrast, agricultural non-point sources (C1 and C2: β = -0.270, p > 0.05) had negligible direct effects on nutrient concentrations, emphasizing the need to prioritize domestic sewage control. Additionally, components C1 and C2 exerted strong direct effects on dissolved organic carbon (β = 0.495, p < 0.001), surpassing the influence of sewage (β = 0.380, p < 0.001). These results demonstrate that the combined use of PLS-SEM and EEM-PARAFAC is a robust approach for identifying pollution sources in data-limited small watersheds, supporting cost-effective aquatic environmental restoration strategies.
School of Civil & Environmental Engineering and Geography Science, Ningbo University, Ningbo, 315211, China.
School of Civil & Environmental Engineering and Geography Science, Ningbo University, Ningbo, 315211, China; College of Environment and Resources, College of Carbon Neutrality, Zhejiang A&F University, Hangzhou, 311300, China. Electronic address: xyu@zafu.edu.cn.
Ecology and Environment Institute, Ningbo Academy of Agricultural Science, Ningbo, 315040, China.
Analysis of the complex correlations between land use and water quality using the PLS-SEM method combined with fluorescence fingerprinting data.
Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Rehabilitation Based on Cognitive Behavioral Model for Post-COVID-19 Condition.
A novel glycoprotein assay was developed by integrating the hairpin aptamer (H-APT)-mediated glycoprotein recognition and the reactive oxygen species-sensitive microcapsule (ROS-MC)-induced signal amplification. The analyzing process begins with the transfer of the target glycoprotein to a chlorin e6 (Ce6)-labeled DNA sequence via H-APT-mediated DNA displacement. Subsequently, the Ce6-labeled DNA was used to induce the disassembly of fluorophore-loaded ROS-MC under 650-nm light irradiation. Leveraging the rapid release of the fluorophore and the high loading capacity of the MC, this glycoprotein assay is capable of quantifying glycoprotein content in native biofluids within 2.5 h, achieving a detection limit of 0.034 ng/mL. We applied this assay to determine the glycoprotein composition in plasma samples of colorectal cancer patients, revealing a significant increase in glycoprotein content for those with a poor prognosis. In summary, we have developed an innovative method for glycoprotein determination that shows potential for clinical translation.
State Key Laboratory of Functions and Applications of Medicinal Plants, School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang City and Guian New District, No.6 Ankang Avenue, Guizhou, 561113, China. wxj_gmu@126.com.The High Efficacy Application of Natural Medicinal Resources Engineering Center of Guizhou Province, School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang City and Guian New District, No.6 Ankang Avenue, Guizhou, 561113, China. wxj_gmu@126.com.
State Key Laboratory of Functions and Applications of Medicinal Plants, School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang City and Guian New District, No.6 Ankang Avenue, Guizhou, 561113, China.The High Efficacy Application of Natural Medicinal Resources Engineering Center of Guizhou Province, School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang City and Guian New District, No.6 Ankang Avenue, Guizhou, 561113, China.
Center for Clinical Laboratories, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, China. huangjian810309@gmc.edu.cn.School of Clinical Laboratory Science, Guian New District, Guizhou Medical University, University Town, Guizhou, 550025, China. huangjian810309@gmc.edu.cn.
State Key Laboratory of Functions and Applications of Medicinal Plants, School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang City and Guian New District, No.6 Ankang Avenue, Guizhou, 561113, China. shenxiangchun@126.com.The High Efficacy Application of Natural Medicinal Resources Engineering Center of Guizhou Province, School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang City and Guian New District, No.6 Ankang Avenue, Guizhou, 561113, China. shenxiangchun@126.com.
Hairpin aptamer and ROS-sensitive microcapsule-mediated glycoprotein determination for the prognosis of colorectal cancer.
An efficient dual-state blue-emitting zinc-based metal-organic frameworks (MOFs), designated as UoZ-8 has been developed. Coordination-induced emission causes the UoZ-8 to give the blue emission in both solid and dispersed form in liquid. Upon the addition of tetracycline (TC), a noticeable shift from blue emission to greenish-yellow emission occurred, with a marked increase in intensity, which was attributed to the inner filter effect accompanied by aggregation-induced emission (IFE-AIE). Consequently, ratiometric-based fluorometry (in solution) and color tonality visual detection platform (on paper) were developed, exploiting the dual-state property of UoZ-8 alone and UoZ-8:TC. The detection limit using the ratiometric-based fluorescence method was 3.8 nM, while on paper it was 3.5 µM. Paper-based visual mode was used for the detection of TC in tap and river water samples showing satisfactory accuracy and precision.
Department of Chemistry, College of Science, University of Zakho, 42002, Zakho, Kurdistan Region, Iraq. sameera.m.ameen@uoz.edu.krd.
Department of Chemistry, College of Science, University of Sulaimani, Qliasan St. 46002, Sulaymaniyah, Kurdistan Region, Iraq. khalid.omer@univsul.edu.iq.
Lanthanide and functionalization-free dual-state emitting zinc-based MOFs followed by dual-state detection: ratiometric and color-tonality visual detection of tetracycline in solution and on paper in food and environmental samples.
A dual supersaturation recrystallization method was employed to synthesize water-stable, highly sensitive cesium-lead halide perovskite nanocrystals (CsPbBr3 PNCs). The PNCs exhibited excellent water stability, a significant photoluminescence quantum efficiency of 83.03%, along with a narrow full width at half maximum (FWHM) of 20 nm. Following iodide ion treatment, the fluorescence emission peak of CsPbBr3 PNCs can be tuned from 520 to 681 nm, causing a color transition from green to red. Within the 0-300 μM range, the red shift showed a linear correlation with I- concentration, achieving a detection limit as low as 0.40 μM. It is worth noting that excessive iodide ions could have allowed PNCs to exhibit dual emission with maximum wavelengths of 520 and 681 nm. A ratiometric perovskite nanoprobe was constructed with the green emission peak as an internal standard and the red emission peak as the response signal. The probe demonstrated a strong linear correlation with tetracycline concentrations ranging from 0 to 8 μM, with a detection limit of 88.60 nM (S/N = 3). This research offers valuable insights into the design and development of ratiometric perovskite sensors capable of detecting in aqueous solutions, while also emphasizing the importance of rapidly establishing hydrogen-bonding networks when analyzing such detection systems.
Key Laboratory of Chemistry and Engineering of Forest Products, State Ethnic Affairs Commission, Guangxi Key Laboratory of Chemistry and Engineering of Forest Products/Guangxi Collaborative Innovation Center for Chemistry and Engineering of Forest Products, Guangxi Colleges Universities Key Laboratory of Optic-Electric Chemo/Biosensing and Molecular Recognition, Guangxi Minzu University, Nanning, 530006, China.
Key Laboratory of Chemistry and Engineering of Forest Products, State Ethnic Affairs Commission, Guangxi Key Laboratory of Chemistry and Engineering of Forest Products/Guangxi Collaborative Innovation Center for Chemistry and Engineering of Forest Products, Guangxi Colleges Universities Key Laboratory of Optic-Electric Chemo/Biosensing and Molecular Recognition, Guangxi Minzu University, Nanning, 530006, China. dufangkai501@163.com.
A ratiometric fluorescent probe based on water-soluble CsPbX3 (Br/I) perovskite nanocrystals for sensitive detection of tetracycline.
A pasting-3D microfluidic paper-based analytical device (P-3D μPAD) was developed. It enabled an efficient cascade reaction between urate oxidase (UOX) and Fe/Pt-doped carbon nanoparticles (Fe/Pt-CNPs) for visual colorimetric detection of uric acid (UA). The novel Fe/Pt-CNP nanozyme performed high peroxidase-like activity toward 3,3',5,5'-tetramethylbenzidine (TMB) and H2O2 with Michaelis - Menten constants (Km) of 0.97 and 2.30 mM, respectively. The UOX-Fe/Pt-CNP system was incorporated into P-3D μPAD: the 1st layer was UOX hydrolysis reaction under alkaline pH, and the 2nd layer was Fe/Pt-CNPs catalyzing H2O2 to oxidize TMB at acidic pH. The separated two layers allowed cascade reaction under different working pH without sacrificing the activity of UOX or Fe/Pt-CNPs. The images were captured and analyzed by the camera and Color Recognition application using a smartphone. The linear range of P-3D μPAD for UA was 25-1000 μM with a limit of detection of 10 μM which met the requirements for clinical applications. The high accuracy of P-3D μPAD for UA detection in invasive (blood) and noninvasive (saliva) samples has been confirmed by the biochemical analyzer. This work offers a sensitive, flexible, affordable, and disposable tool for on-site UA level monitoring and provides new insight into natural enzyme and nanozyme tandem systems for biosensing.
Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, 030032, China.
School of Pharmacy, Shanxi Medical University, Taiyuan, 030001, China.
School of Physics and Information Engineering, Shanxi Normal University, Taiyuan, 031000, China. guojing@sxnu.edu.cn.
Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, 030032, China. zhangly@sxbqeh.com.cn.
Fe/Pt-doped carbon nanoparticles with peroxidase-like activity for point-of-care determination of uric acid.
School of Food Science and Engineering, Yangzhou University, Yangzhou, 225127, Jiangsu, China.
School of Food Science and Engineering, Yangzhou University, Yangzhou, 225127, Jiangsu, China. liyi062@yzu.edu.cn.
School of Food Science and Engineering, Yangzhou University, Yangzhou, 225127, Jiangsu, China. xuechaoxu@yzu.edu.cn.
Publisher Correction: Establishment of a visual assessment platform for total antioxidant capacity of Ganoderma sichuanense based on Arg-CeO2 hydrogel nanozyme utilizing a self-programmed smartphone app and a self-designed 3D-printed device.
Antibiotic resistance genes (ARGs) pose serious threats to environmental and public health, and monitoring ARGs in wastewater is a growing need because wastewater is an important source. Microfluidic devices can integrate basic functional units involved in sample assays on a small chip, through the precise control and manipulation of micro/nanofluids in micro/nanoscale spaces, demonstrating the great potential of ARGs detection in wastewater. Here, we (1) summarize the state of the art in microfluidics for recognizing ARGs, (2) determine the strengths and weaknesses of portable microfluidic chips, and (3) assess the potential of portable microfluidic chips to detect ARGs in wastewater. Isothermal nucleic acid amplification and CRISPR/Cas are two commonly used identification elements for the microfluidic detection of ARGs. The former has better sensitivity due to amplification, but false positives due to inappropriate primer design and contamination; the latter has better specificity. The combination of the two can achieve complementarity to a certain extent. Compared with traditional microfluidic chips, low-cost and biocompatible paper-based microfluidics is a very attractive test for ARGs, whose fluid flow in paper does not require external force, but it is weaker in terms of repeatability and high-throughput detection. Due to that only a handful of portable microfluidics detect ARGs in wastewater, fabricating high-throughput microfluidic chips, developing and optimizing recognition techniques for the highly selective and sensitive identification and quantification of a wide range of ARGs in complex wastewater matrices are needed.
School of Resources, Environment and Materials, Guangxi University, Nanning, 530004, Guangxi, China.State Key Laboratory of Environmental Geochemistry, Institute of Geochemistry, Chinese Academy of Sciences, Guiyang, 550081, China.
State Key Laboratory of Environmental Geochemistry, Institute of Geochemistry, Chinese Academy of Sciences, Guiyang, 550081, China. maokang@mail.gyig.ac.cn.
State Key Laboratory of Environmental Geochemistry, Institute of Geochemistry, Chinese Academy of Sciences, Guiyang, 550081, China.
School of Resources, Environment and Materials, Guangxi University, Nanning, 530004, Guangxi, China. zhx@gxu.edu.cn.
Yunnan Provincial Key Laboratory of Soil Carbon Sequestration and Pollution Control, Faculty of Environmental Science & Engineering, Kunming University of Science & Technology, Kunming, 650500, China.
School of Water, Energy and Environment, Cranfield University, Cranfield, MK43 0AL, UK.
School of Resources, Environment and Materials, Guangxi University, Nanning, 530004, Guangxi, China.
Portable microfluidic devices for monitoring antibiotic resistance genes in wastewater.
Single particle inductively coupled plasma mass spectrometry (SP-ICP-MS) is a powerful tool for metallic nanoparticle (NP) characterisation in terms of concentration and, taking into account several assumptions, also size. However, this technique faces challenges, such as the intrinsic matrix effect, which significantly impact the results when analysing real complex samples. This issue is critical for the calculations of key SP-ICP-MS parameters ultimately altering the final outcomes. Novel analytical approaches with high metrological quality such as isotope dilution analysis (IDA) can overcome these limitations by improving signal discrimination in challenging SP-ICP-MS scenarios. This alternative has mainly been applied for NP size characterisation but remains underexplored in modern ICP-MS and SP set-ups. Thus, the implementation of a revised version of IDA-SP-ICP-MS, including recent advances in quadrupole ICP-MS and SP data processing, which enables reliable NP sizing and counting, would be of utmost interest. In this work, this combination using the species-unspecific IDA mode has been investigated as an alternative to tackle matrix effect caused by complex matrices with platinum NPs as a case study. The optimum ionic tracer concentration has been evaluated for different PtNP sizes, resulting in a range of 500 to 1000 ng L-1 due to differences in the mean NP signal. A valuable in-house spreadsheet for the data treatment has also been developed. The successful applicability of the methodology for determining the size and particle number concentration of 30 and 50 nm PtNPs has been demonstrated not only in environmental samples (synthetic and natural seawater), but also, for the first time, in biological matrices such as cell culture media and human urine.
Department of Analytical Chemistry and Food Technology, Environmental Sciences Institute (ICAM), University of Castilla-La Mancha, Avda. Carlos III S/N, 45071, Toledo, Spain.
Department of Analytical Chemistry and Food Technology, Environmental Sciences Institute (ICAM), University of Castilla-La Mancha, Avda. Carlos III S/N, 45071, Toledo, Spain. rosacarmen.rodriguez@uclm.es.
Determination of size and particle number concentration of metallic nanoparticles using isotope dilution analysis combined with single particle ICP-MS to minimise matrix effects.
Ultra-processed foods (UPF), defined using the Nova classification system, are associated with increased chronic disease risk. More recently, evidence suggests the UPF subgroup of whole-grain breads and cereals is in fact linked with reduced chronic disease risk. This study aimed to explore associations of cardiometabolic risk measures with Nova UPF intake v. when foods with ≥ 25 or ≥ 50 % whole grains are excluded from the definition. We considered dietary data from the Australian National Nutrition and Physical Activity Survey 2011-2012. Impacts on associations of UPF intake (quintiles) and cardiometabolic risk measures were analysed using regression models. The median proportion of UPF intake from high whole-grain foods was zero for all quintiles. Participants in the highest Nova UPF intake quintile had significantly higher weight (78·1 kg (0·6)), BMI (27·2 kg/m2 (0·2)), waist circumference (92·7 cm (0·5)) and weight-to-height ratio (0·55 (0·003)) compared with the lowest quintile (P< 0·05). Associations were the same when foods with ≥ 25 and ≥ 50 % whole grains were excluded. Adjusted R-squared values remained similar across all approaches for all outcomes. In Australia, high whole-grain foods considered UPF may not significantly contribute to deleterious cardiometabolic risk associations. Until conclusive evidence on Nova UPF is available, prioritisation should be given to the nutrient density of high whole-grain foods and their potential contribution to improving whole-grain intakes and healthful dietary patterns in Australia.
School of Health Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia.
School of Health Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia.The George Institute for Global Health, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia.
National Institute for Applied Statistics Research Australia and Statistical Consulting Centre, School of Mathematics and Applied Statistics, Faculty of Engineering and Information Sciences, University of Wollongong, Wollongong, NSW, Australia.
School of Health Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia.School of Medical, Indigenous, and Health Sciences, Faculty of Science, Medicine, and Health, University of Wollongong, Wollongong, NSW, Australia.
Whole-grain modified Nova ultra-processed food definitions: a cross-sectional analysis of the impact on cardiometabolic risk measures when excluding high whole-grain foods from the ultra-processed food category in Australia.
An electrochemical aptasensor has been developed specifically for the sensitive and selective determination of ochratoxin A (OTA), one of the most important mycotoxins. The aptasensor utilizes a glassy carbon electrode that has been modified with toluidine blue (TB) encapsulated in a Zn-based metal-organic framework (TB@Zn-MOF). The results demonstrate that in the presence of OTA, the peak current of the differential pulse voltammogram (DPV) related to TB oxidation is notably decreased. The changes in the oxidation peak current of TB encapsulated in Zn-MOF, both in the absence and presence of OTA, serve as an analytical signal for accurately measuring its concentration. With the proposed aptasensor, OTA can be determined within a linear concentration range 1.0 × 10-4 - 200.0 ng mL-1, with a detection limit of 2.1 × 10-5 ng mL-1. The aptasensor design is suitable for measuring OTA concentration in coffee powder samples. This represents the first report to utilize TB@Zn-MOF in designing an applicable aptasensor to OTA measurement. The high porosity of the Zn-MOF allows for a large number of TB molecules to be encapsulated in its cavities, while its large surface area enables more OTA aptamers to be immobilized on the electrode surface. These two key features significantly enhance the sensitivity of the aptasensor in measuring OTA concentration.
Department of Chemistry, Yazd University, Yazd, 89195-741, Iran.
Department of Chemistry, Yazd University, Yazd, 89195-741, Iran. hrzare@yazd.ac.ir.
Quantification of ochratoxin A in a coffee sample utilizing an electrochemical aptasensor fabricated through encapsulation of toluidine blue within a Zn-based metal-organic framework.
Department of Psychiatry, College of Medicine, University of Saskatchewan, Saskatoon, Canada evyn.peters@usask.ca .
Examining Alternative Inclusion Criteria Based on Core Symptoms of Depression in Antidepressant Clinical Trials.
Recurrent Clozapine-Associated Pneumonia: A Case Report.
Service de Médecine Interne et d'Immunologie Clinique, Hôpital de La Conception, Assistance Publique Hôpitaux de Marseille (AP-HM), Marseille, France.
Department of Neuroradiology, La Conception Hospital, Marseille, France.
Aix Marseille Université, INSERM U1251, Marseille Medical Geneticas, Marmara Institute, Department of Endocrinology, Assistance Publique Hôpitaux de Marseille (AP-HM), Hôpital de La Conception, CRMR HYPO, Marseille, France.
Letter to the editor: Primary hypophysitis and the benefits of glucocorticoids, a still unresolved question.
Citalopram Associated with the Development of Tinnitus in an Adolescent Girl: A Case Report.
State Key Laboratory of Medical Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, China. hefc@bmi.ac.cn.International Academy of Phronesis Medicine (Guangdong), Guangdong, China. hefc@bmi.ac.cn.
Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland. aebersold@imsb.biol.ethz.ch.
Macquarie Medical School, Macquarie University, Sydney, New South Wales, Australia.
Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University) and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, China.
Institute of Health Service and Transfusion Medicine, Beijing, China.
Department of Pathology and The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
State Key Laboratory of Medical Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, China.
Key Laboratory of Systems Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China.
Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, China.
Institute of Chemistry, Academia Sinica, Taipei, China.
National Biomedical Imaging Center, State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Peking-Tsinghua Center for Life Sciences, College of Future Technology, Peking University, Beijing, China.
School of Biological Sciences, Queen's University of Belfast, Belfast, UK.
Functional Proteomics Laboratory, Centro Nacional de Biotecnología-CSIC, Madrid, Spain.
Computational Systems Biochemistry Research Group, Max-Planck Institute of Biochemistry, Martinsried, Germany.
AI for Science Institute, Beijing, China.Center for Machine Learning Research, Peking University, Beijing, China.
Advanced Clinical Biosystems Research Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA.
Department of Liver Surgery and Transplantation, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
Centre for Cancer Research, Hudson Institute of Medical Research, Clayton, Victoria, Australia.Monash Proteomics and Metabolomics Platform, Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
School of Pharmaceutical Sciences and Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
The D. H. Chen School of Universal Health, Zhejiang University, Hangzhou, China.
Pengcheng Laboratory, Shenzhen, China.School of Electronic Engineering and Computer Science, Peking University, Beijing, China.
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Department of Chemistry, University of Tokyo, Tokyo, Japan.Department of Bioengineering, University of California, Los Angeles, California, USA.Institute of Technological Sciences, Wuhan University, Wuhan, Hubei, China.
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
School of Medicine, Southern University of Science and Technology, Shenzhen, China.
Department of Nutrition, Tianjin Institute of Environmental and Operational Medicine, Tianjin, China.
School of Medicine, Westlake University, Hangzhou, China.Westlake Center for Intelligent Proteomics, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China.Research Center for Industries of the Future, School of Life Sciences, Westlake University, Hangzhou, China.
International Academy of Phronesis Medicine (Guangdong), Guangdong, China.
Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Utrecht, the Netherlands.Netherlands Proteomics Center, Utrecht, the Netherlands.
European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Cambridge, UK.
Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA.
Department of Head & Neck Surgery, Division of Surgery & Surgical Oncology, Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore.
OncoProteomics Laboratory, Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.
Advanced Glycoscience Research Cluster, School of Biological and Chemical Sciences, University of Galway, Galway, Ireland.
Departments of Molecular Biosciences, Departments of Chemistry, Northwestern University, Evanston, IL, USA.
David R. Cheriton School of Computer Science, University of Waterloo, Waterloo, Ontario, Canada.Central China Institute of Artificial Intelligence, Henan, China.
Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore, Singapore.
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Department of Structural Biology, Leibniz-Forschungsinstitut für MolekularePharmakologie (FMP), Berlin, Germany.
State Key Laboratory of Membrane Biology, Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Cancer Biology Institute, Yale University School of Medicine, West Haven, CT, USA.
State Key Laboratory of Molecular Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
Department of Critical Care Medicine and Hematology, The Third Xiangya Hospital, Central South University; Department of Hematology and Critical Care Medicine, The Third Xiangya Hospital, Central South University, Changsha, China.
Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.
School of Life Sciences, Tsinghua University, Tsinghua-Peking Center for Life Sciences, Beijing, China.
Institute for Systems Biology, Seattle, WA, USA.
Clinical Biomarker Discovery and Validation, Monash University, Clayton, Victoria, Australia.
Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai, China.Shanghai Key Laboratory for Endocrine Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
Department of Oral Biological and Medical Sciences, University of British Columbia, Vancouver, British Columbia, Canada.Yonsei Frontier Lab, Yonsei University, Seoul, Republic of Korea.
Glycoproteomics Laboratory, Department of Parasitology, University of São Paulo, Sao Paulo, Brazil.
Institute of Zoology, Chinese Academy of Sciences, Beijing, China.Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China.University of the Chinese Academy of Sciences, Beijing, China.
Institut de Recherche en Santé Environnement et Travail, Univ. Rennes, Inserm, EHESP, Irset, Rennes, France.
Pilot Laboratory, MOE Frontier Science Centre for Precision Oncology, Centre for Precision Medicine Research and Training, Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau, China.
Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.
ProCan®, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney, Westmead, New South Wales, Australia.
Department of Health Sciences, University Magna Græcia of Catanzaro, Catanzaro, Italy.
Department of Systems Biology, Harvard Medical School, Boston, MA, USA.Broad Institute of MIT and Harvard, Cambridge, MA, USA.
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
Indian Institute of Technology Bombay, Mumbai, India.
Department of Health Sciences, Faculty of Applied Health Sciences, Brock University, St. Catharines, Ontario, Canada.
Center for Quantitative Biology, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
Department of Chemistry, Southern University of Science and Technology, Shenzhen, China.
State Key Laboratory of Respiratory Health and Multimorbidity, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China.
Department of Neurology, Clinical Neuroscience Center, University Hospital Zurich and University of Zurich, Zurich, Switzerland.
Technical University of Munich, Freising, Germany.
Advanced Genomics Unit, Center for Research and Advanced Studies, Irapuato, Mexico.
Institute of Translational Medicine, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland.
Department of Computer Science, National University of Singapore, Singapore, Singapore.Department of Pathology, National University of Singapore, Singapore, Singapore.
Guangzhou National Laboratory, Guangzhou, China.School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, China.
Guangzhou National Laboratory, Guangzhou, China.
The Scripps Research Institute, La Jolla, CA, USA.
China Science and Technology Exchange Center, Beijing, China.
CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
State Key Laboratory of Medical Proteomics, National Chromatography R. & A. Center, CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
School of Mathematical Sciences, Peking University, Beijing, China.Wuhan University, Wuhan, China.
International Academy of Phronesis Medicine (Guangdong), Guangdong, China.Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Author Correction: π-HuB: the proteomic navigator of the human body.
Department of Psychiatry, Weill Cornell Medical College New York, NY kap9161@med.cornell.edu.
Question: What Are the Latest Guidelines for Treating Individuals With Body Dysmorphic Disorder?
In this study we monitored exposure to airborne dust in workers performing various tasks at two biomass-fuelled thermal power plants (27 and 46 MW) over six years. The plants are mainly fuelled by forest wood chips and, to a lesser extent, by agro-food products, with annual consumption of about 300 and 450 kt. We focused on inhalable wood dust because of its potential carcinogenicity to humans. Worker exposure was assessed with personal samplers, drawing ambient air in their breathing zone to determine the real external dose of dust inhaled by the workers and the associated occupational risk. With but a few exceptions, exposure to inhalable wood dust complies to the limit of 2 mg/m3 given by the European Directives 2019/130 and 2017/2398. Further investigations will be necessary to obtain a larger number of measurements that allow for a more robust statistical investigation of the results.
© 2024 Giovanna Bregante et al., published by Sciendo.
Pio XI Hospital, Clinical Unit of Occupational Health, Desio, Italy.
U ovom smo istraživanju šest godina pratili izloženost lebdećim česticama drvne prašine u radnika na različitim poslovima u dvjema termoelektranama na biomasu snage 27 odnosno 46 MW. U objema se termoelektranama mahom za gorivo rabi mljeveno drvo te u manjoj mjeri otpadni poljoprivredno-prehrambeni proizvodi, a godišnja potrošnja doseže oko 300 odnosno 450 kt. Istraživanje se ograničilo na lebdeće drvne čestice koje mogu biti kancerogene za ljude. Izloženost radnika mjerena je osobnim skupljačima zraka u razini disanja ne bi li se utvrdila stvarna doza udahnute prašine i s njom povezani profesionalni rizik. Uz tek nekoliko iznimaka, izloženost drvnoj prašini bila je u skladu s graničnom vrijednosti od 2 mg/m3 propisanom europskim direktivama 2019/130 i 2017/2398. Potrebna su daljnja istraživanja s većim brojem mjerenja, koja bi omogućila robusniju statističku analizu.
Occupational exposure to carcinogenic wood dust in two Italian biomass power plants.
The widespread use of plastics in the food industry raises concerns about plastic migration and health risks. The degradation of primary polymers like polystyrene (PS) and polyethylene (PE) can generate nanoplastics (NPs), increasing food biohazard. This study assessed the impact of PS, PE, and PS + PE NPs on Chlorella vulgaris (CV) and Haematococcus pluvialis (HP) before and after in vitro and ex vivo digestion, focusing on particle size, polydispersity index, and surface charge. The modulation of total phenolic content (TPC) induced by NP contamination was also evaluated. Results demonstrated that NP behavior varied with the microalgae medium and persisted postdigestion, posing health risks. Significant size increases were noted for PS + PE in the CV and HP. TPC increased significantly with NP exposure, especially PS + PE. These findings underline the need for regulatory measures to ensure food safety in cases of plastic contamination and to address the behavior and toxicity of NPs.
Department of Veterinary Medicine and Animal Science (DIVAS), Università degli Studi di Milano, Via dell'Università 6, 29600 Lodi, Italy.
European Commission, Joint Research Centre (JRC), 20127 Ispra, Italy.
CEB - Centre of Biological Engineering, University of Minho, 4710-057 Braga, Portugal.
Department of Veterinary Medicine and Animal Science (DIVAS), Università degli Studi di Milano, Via dell'Università 6, 29600 Lodi, Italy.Institute for Food, Nutrition and Health, University of Reading, Reading RG6 5 EU, U.K.
Impact of Nanoplastics on the Functional Profile of Microalgae Species Used as Food Supplements: Insights from Comparative In Vitro and Ex Vivo Digestion Studies.
The γ-butyrolactone scaffold, commonly present in natural products and bioactive compounds, has played a crucial role in the development of novel pesticides. In this study, a series of α-methylene-γ-butyrolactone derivatives containing a diphenyl ether moiety were designed and synthesized using the scaffold splicing strategy. Bioassays revealed that several target compounds demonstrated potent fungicidal activities, particularly against Phytophthora capsici and Valsa mali. Notably, compound B7 (EC50 = 0.809 mg/L) exhibited the highest antioomycete activity against P. capsici, outperforming famoxadone (EC50 = 41.0 mg/L) but being less effective than dimethomorph (EC50 = 0.180 mg/L). Meanwhile, compound C22 (EC50 = 1.47 mg/L) showed the strongest antifungal activity against V. mali, which was higher than those of famoxadone (EC50 = 1.80 mg/L) and dimethomorph (EC50 = 13.6 mg/L). In vivo experiments confirmed that compound B7 has satisfactory protective and curative effects against P. capsici, which were better than those of famoxadone. Additionally, compound B7 was found to inhibit sporangia formation, zoospore release, and cystospore germination of P. capsici at 10 mg/L. Physiological and biochemical studies indicated that compound B7 can induce changes in the mycelial morphology of P. capsici, increase cell membrane permeability, and modulate respiratory metabolism. Furthermore, both in vitro enzymatic inhibition assays and molecular docking analysis suggested that the primary mechanism of action of compound B7 may involve binding to complex III on the respiratory chain. This work provides valuable insights for the development of α-methylene-γ-butyrolactone derivatives incorporating a diphenyl ether moiety as novel agricultural fungicidal agents.
Key Laboratory of Plant Protection Resources and Pest Management of Ministry of Education, Key Laboratory of Integrated Pest Management on the Loess Plateau of Ministry of Agriculture and Rural Affairs, College of Plant Protection, Northwest A&F University, Yangling 712100, Shaanxi, China.
Key Laboratory of Plant Protection Resources and Pest Management of Ministry of Education, Key Laboratory of Integrated Pest Management on the Loess Plateau of Ministry of Agriculture and Rural Affairs, College of Plant Protection, Northwest A&F University, Yangling 712100, Shaanxi, China.Institute of Cotton Research, Shanxi Agricultural University, Yuncheng 044000, Shanxi, China.
Key Laboratory of Plant Protection Resources and Pest Management of Ministry of Education, Key Laboratory of Integrated Pest Management on the Loess Plateau of Ministry of Agriculture and Rural Affairs, College of Plant Protection, Northwest A&F University, Yangling 712100, Shaanxi, China.Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling 712100, Shaanxi, China.
Key Laboratory of Plant Protection Resources and Pest Management of Ministry of Education, Key Laboratory of Integrated Pest Management on the Loess Plateau of Ministry of Agriculture and Rural Affairs, College of Plant Protection, Northwest A&F University, Yangling 712100, Shaanxi, China.State Key Laboratory for Crop Stress Resistance and High-Efficiency Production, Key Laboratory of Botanical Pesticide R&D in Shaanxi Province, Yangling 712100, Shaanxi, China.
Design, Synthesis, and Fungicidal Activity of α-Methylene-γ-Butyrolactone Derivatives Bearing a Diphenyl Ether Moiety.
A novel detection technique is introduced that offers sensitive and reliable ochratoxin A (OTA) detection. The method leverages the etching of gold nanorods (AuNRs) stabilized by hexadecyl trimethyl ammonium bromide (CTAB) using the oxidized form of 3,3',5,5'-tetramethyl benzidine sulfate (TMB2+), creating a susceptible multicolor visual detection system for OTA. The visual detection is enabled by Mg2+-assisted DNAzyme catalysis combined with the catalytic hairpin assembly (CHA) signal amplification strategy. The presence of OTA triggers CHA and signaling responses along with the formation of G-quadruplex-hemin DNAzyme, which promotes the oxidation of TMB with H2O2, leading to the etching of AuNRs and a reduction in their aspect ratio. AuNRs experienced a blue shift in the longitudinal localized surface plasmon resonance peak, resulting in a color change. The technique has been shown to detect OTA with a low detection limit of 0.309 pg/mL, demonstrating high sensitivity and specificity. The detection technique offers versatility by enabling the detection of other pollutants through a simple replacement of the aptamer, expanding the range of detection platforms available for pollutant determinations.
Key Laboratory of Chemical Sensing & Analysis in Universities of Shandong, School of Chemistry and Chemical Engineering, University of Jinan, Jinan, 250022, People's Republic of China.
School of Water Conservancy and Environment, University of Jinan, Jinan, 250022, People's Republic of China.
School of Biological Sciences and Technology, University of Jinan, Jinan, 250022, People's Republic of China.Jinan Engineering Research Center of Plant-Microbial Interaction, Jinan, 250022, People's Republic of China.
School of Water Conservancy and Environment, University of Jinan, Jinan, 250022, People's Republic of China.Jinan Engineering Research Center of Plant-Microbial Interaction, Jinan, 250022, People's Republic of China.
Key Laboratory of Chemical Sensing & Analysis in Universities of Shandong, School of Chemistry and Chemical Engineering, University of Jinan, Jinan, 250022, People's Republic of China. chm_huangjd@ujn.edu.cn.Jinan Engineering Research Center of Plant-Microbial Interaction, Jinan, 250022, People's Republic of China. chm_huangjd@ujn.edu.cn.
Effective multicolor visual biosensor for ochratoxin A detection enabled by DNAzyme catalysis and gold nanorod etching.
The ultrahigh-sensitive detection of H2S is reported using a novel dual-ligand metal-organic framework (MOF) electrochemiluminescence (ECL) sensor. By combining tetrakis(4-carboxyphenyl) porphyrin (TCPP) and 1,3,6,8-tetrakis(4-carboxyphenyl) pyrene (TBAPy) as ligands and employing zirconium as the metal source, a spindle-shaped Zr-PyTCPPMOF was successfully designed and synthesized. Notably, the multiple nitrogen structures of porphyrin provided abundant binding sites for sulfur (S), further enhancing the ECL signal of Zr-PyTCPPMOF. The sensor shows a good linear relationship in the 0.01-100 μM range, with a detection limit reaching 1.18 nM (S/N = 3). When analyzing actual serum samples, the recovery was between 96.6 and 106.2%. Ultimately, the dual-ligand ECL platform based on Zr-PyTCPPMOF achieved trace detection of H2S, which is expected to provide reliable technical support for early environmental monitoring and disease diagnosis.
Jiangxi University of Chinese Medicine, Nan Chang, 330004, Jiangxi, China.
Jiangxi University of Chinese Medicine, Nan Chang, 330004, Jiangxi, China. fanhao11@aliyun.com.
Clinical Medical Research Center, Yichun People's Hospital, Yichun, 336000, Jiangxi, China. yinzhaoj@126.com.
Efficient electrochemiluminescence sensor utilizing Zr-PyTCPPMOF for swift hydrogen sulfide detection.
A novel copper and iron doped containing chitosan and heparin sodium carbon dots (CS-Cu,Fe/HS) nanozyme was formulated through a single-step microwave digestion method. CS-Cu,Fe/HS exhibits excellent peroxidase (POD)-like activity and positive charge characteristics, and it can oxidize the negatively charged 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) in the presence of H2O2 to produce a green compound (ox-ABTS). Furthermore, CS-Cu,Fe/HS enhances electron transfer and provides additional active sites through the valence state transformations of Fe2+/Fe3+ and Cu2+/Cu+. Interestingly, the POD-like activity of CS-Cu,Fe/HS is inhibited with the introduction of ampicillin (AMP), which may be because the Cu and Fe ions in CS-Cu,Fe/HS form complexes with AMP, leading to changes in the structure or surface properties of the nanozyme, thereby reducing the number of active sites on the nanozyme. Drawing from this, a straightforward and reliable colorimetric sensor was constructed for AMP detection, featuring a linear range of 0.033 to 110 μg/mL and a detection limit as low as 11.6 ng/mL. The proposed detection method for AMP performed well in real samples, with recoveries ranging from 94.8% to 110.2%.
Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, 650500, People's Republic of China.
Yunnan High-Tech Enterprise Development Promotion Association, Kunming, 650021, People's Republic of China.
Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, 650500, People's Republic of China. dzyang9@kust.edu.cn.
Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, 650500, People's Republic of China. yangyl2016@qq.com.
A colorimetric sensor for the sensitive and rapid detection of ampicillin based on CS-Cu,Fe/HS nanozyme.
A novel proposal is introduced with an unlabeled electrochemical immunosensor for the detection of tumor broad-spectrum biomarker vascular endothelial growth factor (VEGF165) Copper-based metal organic frameworks (Cu MOFs)-carbon nanotubes (MWCNTs) were employed as its substrates, functionalized with methylene blue (MB) for signal enhancement. Cu-MOFs-MWCNTs nanocomposites were synthesized successfully via a solvothermal method and were then deposited on the surface of a glassy carbon electrode (GCE), with the addition of methylene blue to amplify the signal. Due to the expansive specific surface area provided by the carbon nanotubes and the amino groups facilitated by the metal-organic framework nanomaterials, the anti-VEGF165 monoclonal antibody was immobilized on the electrochemical immunosensor through covalent bonding, which could bind specifically to VEGF165, thereby causing a detectable change in the current. The developed immunosensor exhibited a linear detection range for VEGF165 spanning from 1 to 100,000 pg/ml, with the R2 value of 0.997 by differential pulse voltammetry (DPV) method, and the limit of detection was as low as 0.9686. Additionally, the electrochemical immunosensor presented commendable selectivity, availability, and reproducibility, along with an effective capacity for detecting VEGF165 in clinical samples. Consequently, the immunosensor is expected to revolutionize early screening for VEGF165-related diseases, which offer a promising, cost-effective, and precise diagnostic tool for clinical utility.
School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing, 400054, China.
School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing, 400054, China. sxwu2004@cqut.edu.cn.
Chongqing Jiulongpo District People's Hospital, Chongqing, 400050, China.
Department of Physics and Energy, Chongqing University of Technology, Chongqing, 400054, China.
School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing, 400054, China. gukui0404@cqut.edu.cn.
A novel electrochemical immunosensor for the ultrasensitive detection of vascular endothelial growth factor based on MB@Cu-MOFs/MWCNTs composite.
GO/Co-MOF/PPy-350 (GPC-350) was synthesized by in situ growth of ultrafine Co-MOF on graphene oxide (GO), followed by encapsulation with polypyrrole (PPy) and calcination at 350.0℃. Meanwhile, MoS2-MWCNTs (MoS2-CNTs) were produced via the in situ synthesis of MoS2 within multi-walled carbon nanotubes (MWCNTs). The electrochemically superior GPC-350/MoS2-CNTs nanocomposite was then achieved by combining GPC-350 with MoS2-CNTs. The polypyrrole encapsulation serves to protect the ultrafine Co-MOF, preventing its degradation during the calcination process. The linear detection range of the GPC-350/MoS2-CNTs/GCE sensor for the determination of catechin (CA) in phosphate buffered saline (PBS) was from 5.0 to 1800.0 nM with a limit of detection of 1.78 nM. In addition, the materials were characterized using SEM, EDX, TEM, XRD, EIS, XPS, FTIR, and Raman. These results indicate that the synthesis of GPC-350/MoS2-CNTs nanocomposites is successful and CA in beverages samples can be effectively detected using electrochemical sensors. Additionally, the reaction mechanism of CA was explored through cyclic voltammetry. The application of GPC-350/MoS2-CNTs nanocomposites in sensor technology offers innovative approaches for the ultrasensitive detection of flavonoids.
Key Laboratory of Environmentally Friendly Chemistry and Applications of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan, 411105, People's Republic of China.
Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Xiangtan University, Xiangtan, 411105, People's Republic of China.
Key Laboratory of Environmentally Friendly Chemistry and Applications of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan, 411105, People's Republic of China. pczhao@xtu.edu.cn.
Key Laboratory of Environmentally Friendly Chemistry and Applications of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan, 411105, People's Republic of China. fei_junjie@xtu.edu.cn.Hunan Institute of Advanced Sensing and Information Technology, Xiangtan University, Xiangtan, 411105, People's Republic of China. fei_junjie@xtu.edu.cn.
Ultrafine metal-organic framework @ graphitic carbon with MoS2-CNTs nanocomposites as carbon-based electrochemical sensor for ultrasensitive detection of catechin in beverages.
Cancer is a major cause of death globally, and early detection is a key to improving outcomes. Traditional diagnostic methods have limitations such as being invasive and lacking sensitivity. Immunosensors, which detect cancer biomarkers using antibodies, offer a solution with high sensitivity and selectivity. When combined with 3D printing, these immunosensors can be customized to detect specific cancer markers, creating rapid, cost-effective, and scalable diagnostic tools. The article reviews the principles behind immunosensors, different 3D fabrication methods such as Fused Deposition Modeling (FDM) and Stereolithography (SLA), and discusses how functionalization strategies, such as surface modifications, can enhance the sensitivity of these devices. The integration of 3D printing allows for the creation of complex sensor structures, offering advantages such as customization, rapid prototyping, and multi-material printing. These advancements make immunosensors arrays highly promising for early cancer detection, tumor profiling, and personalized medicine. The article also explores challenges like scalability, material biocompatibility, and the need for clinical validation. Future perspectives suggest the potential of integrating nanomaterials, multiplexed detection, and wearable technology to further improve the performance and accessibility of these diagnostic tools.
Department of Pharmaceutics, SCSSS's Sitabai, Thite College of Pharmacy, Shirur-412210, Dist-Pune, Maharashtra, India. sachin.kothawade23@gmail.com.
Department of Pharmaceutics, SCSSS's Sitabai, Thite College of Pharmacy, Shirur-412210, Dist-Pune, Maharashtra, India.
Cutting-edge 3D printing in immunosensor design for early cancer detection.
Clinical and immunological assays of white blood cells (WBCs) in human peripheral blood are of significance for disease diagnosis and immunological studies. However, separating WBCs from blood with high recovery and high purity remains challenging. In this study, by incorporating a pair of linearly tapered filter arrays, a crossflow filtration-based microfluidic chip was designed and fabricated for separation of WBCs from blood. The implementation of the linearly tapered filter arrays not only ensures a minimal and consistent flow through each sieve, but also achieves a high filtration ratio (~ 19). The validity and robustness of this straightforward design were substantiated through theoretical analysis, simulations, and model microparticle tests. The microfluidic chip achieved an almost perfect (> 99.2%) recovery and a ~ 20-fold enrichment of the targeted 8 μm particles (as surrogates for WBCs) from undesired 2 μm particles (as substitutes for red blood cells, RBCs) at flow rates ranging from 50 to 200 μL/min, irrespective of the filter array length and particle concentration. When applied to a twenty times diluted blood sample, the chip achieved a 96.6% recovery and 19.7-fold enrichment of WBCs, as well as a 95.0% removal of RBCs, at the optimal flow rate of 100 μL/min. With its simple design, cost-effectiveness, high recovery, substantial enrichment ratio, and considerable throughput, this chip offers an alternative solution that is potentially applicable to scenarios involving the separation of WBCs as well as other particles/cells.
Frontier Research Centre, Songshan Lake Materials Laboratory, Dongguan, 523830, Guangdong, China. huangyuanding@sslab.org.cn.
Department of Health Examination, Dongguan Songshan Lake Tungwah Hospital, Dongguan, 523820, Guangdong, China.
Department of Interventional Radiology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, Liaoning, China.
Frontier Research Centre, Songshan Lake Materials Laboratory, Dongguan, 523830, Guangdong, China.
Robust and efficient separation of white blood cells from blood using a microfluidic chip with a pair of linearly tapered crossflow filter arrays.
Polymeric high internal phase emulsions decorated with covalent organic frameworks (polyHIPEs-COFs) were synthesized and used as the sorbent for cyantraniliprole and chlorantraniliprole. Pickering high internal phase emulsions stabilized by covalent organic frameworks solid particles and liquid surfactants (Span80 and polyvinylpyrrolidone) endow the composites with open-cell structures and superwettability. The amphiphilicity and open-cell structures enable rapid adsorption and desorption for cyantraniliprole and chlorantraniliprole, and the solid-phase extraction process can be completed in 5 min. The adsorption efficiencies of polyHIPEs-COFs for cyantraniliprole and chlorantraniliprole are above 85.19%, but lower than 10% for fenvalerate, anti-aphid, and chlorpyrifos, demonstrating the good adsorption selectivity for cyantraniliprole and chlorantraniliprole. The adsorption efficiencies of cyantraniliprole and chlorantraniliprole using a same polyHIPEs-COFs and five different batches of polyHIPEs-COFs range from 94.25 to 100.00%, revealing the good reproducibility of the sorbent. In addition, the polyHIPEs-COF-based solid-phase extraction combined with high-performance liquid chromatography-ultraviolet detector (HPLC-UV) was developed for determination of bisamide insecticides in vegetable (eggplants, tomatoes, and peppers) samples. Results showed that the method was feasible to determine the cyantraniliprole and chlorantraniliprole in real vegetable samples with a linear range of 0.012-1.2 μg/kg and limits of detection of 0.0075-0.0090 μg/kg. The recoveries of cyantraniliprole and chlorantraniliprole spiked in vegetable samples ranged from 85.00 to 100.00% with relative standard deviations less than 3.52%. The study indicates the feasibility of amphiphilic polyHIPEs-COFs in extraction and enrichment of bisamide insecticides from vegetable samples for HPLC-UV analysis.
Guangxi Colleges and Universities Key Laboratory of Food Safety and Detection, College of Chemistry and Bioengineering, Guilin University of Technology, Guilin, 541004, Guangxi, China.
Guangxi Colleges and Universities Key Laboratory of Food Safety and Detection, College of Chemistry and Bioengineering, Guilin University of Technology, Guilin, 541004, Guangxi, China. guihuaruan@hotmail.com.
Guangxi Colleges and Universities Key Laboratory of Food Safety and Detection, College of Chemistry and Bioengineering, Guilin University of Technology, Guilin, 541004, Guangxi, China. huangyp@glut.edu.cn.
Covalent organic frameworks hybridized polymeric high internal phase emulsions with amphiphilicity for extraction of trace bisamide insecticides in food samples.
Traditional surface-enhanced Raman scattering (SERS) substrates seeking uniformity and reproducibility of the Raman signal often assume and require that hot spots remain consistently stable during Raman testing. Recently, the non-uniform accumulation in SERS sample pre-concentration strategies have inspired the direct use of self-healing noble metal aerogels (NMAs), as the sample pretreatment presented in this work, and uncovered more diverse Raman information of substances during the dynamic process of laser irradiation. Rare characteristic peaks such as 820 cm⁻1 for R6G within a specific concentration range were observed, and potential processes including R6G dimerization and desorption were analyzed. These results provide insights into how to obtain more Raman information of diverse molecule forms under conventional conditions to distinguish the aggregation state, which turn the blinking of signals at low concentration or single molecule level into useful information.
Electronic Materials Research Laboratory, Key Laboratory of the Ministry of Education International Center for Dielectric Research & Shannxi Engineering Research Center of Advanced Energy Materials and Devices, Xi'an Jiaotong University, Xi'an, 710049, China.
Electronic Materials Research Laboratory, Key Laboratory of the Ministry of Education International Center for Dielectric Research & Shannxi Engineering Research Center of Advanced Energy Materials and Devices, Xi'an Jiaotong University, Xi'an, 710049, China. mqwang@xjtu.edu.cn.
State Key Laboratory for Artificial Microstructure and Mesoscopic Physics, School of Physics, Peking University, Beijing, 100871, China.
Belarusian State University of Informatics and Radioelectronics, P. Browki 6, 220013, Minsk, Belarus.
Centre for Micro and Nano Devices, Department of Physics, COMSATS Institute of Information Technology, Islamabad, 44500, Pakistan.
Surface-enhanced Raman scattering of R6G dimerization during self-healing of gel.
Oxidative stress is present in chronic obstructive pulmonary disease (COPD); however, the effect of increased dietary antioxidants on reducing COPD risk remains unclear. The aim of this study was to investigate the association of the composite dietary antioxidant index (CDAI) with COPD in adults. This study conducted a cross-sectional investigation using data from the National Health and Nutrition Examination Survey (NHANES) spanning from 2015 to March 2020 to explore the association between CDAI and COPD in adults. This study included 9295 participants. Three logistic regression models (crude model, partially adjusted model and fully adjusted model) and restricted cubic spline (RCS) curves were utilised to assess the association between CDAI levels and COPD risk. Subsequently, a two-sample Mendelian randomisation (MR) was employed to analyse the causal impact of antioxidant levels within CDAI on the occurrence of COPD. CDAI levels were inversely associated with COPD after adjusting for confounders (OR = 0·97, 95 % CI 0·95, 1·00), and the association was linear (P < 0·001), and the results of the RCS showed that CDAI was linearly correlated with COPD occurrence (P < 0·001). MR analysis revealed a causal relationship between vitamin C and COPD occurrence (OR = 0·99, 95 % CI 0·98, 1·00, P < 0·05). Our study indicates that dietary sources of antioxidants may reduce the risk of COPD occurrence, and the results of the MR analysis further show that vitamin C is causally associated with a reduced risk of COPD occurrence. However, further exploration is needed to understand how antioxidants prevent COPD.
Chongqing Medical University, Chongqing, PR China.
Association between composite dietary antioxidant index and chronic obstructive pulmonary disease in adults: results of NHANES 2015-2020 and Mendelian randomisation study.
A SiO2@Au@Polyaniline (SiO2@Au@PAN) system has been successfully fabricated leveraging the synergistic effects of gold nanoparticles (AuNPs) to realize enhanced photothermal performance. The SiO2@Au@PAN exhibited strong near-infrared (NIR) absorbance, excellent photothermal conversion efficiency, good dispersibility, and outstanding photostability. The SiO2 nanospheres as the template provided numerous binding sites for coating of AuNPs. Subsequently, aniline was grafted onto SiO2 to form PAN, which further facilitated the growth of AuNPs. The high efficiency of electron transfer from PAN to AuNPs was utilized to enhance the photothermal performance, resulting in a photothermal conversion efficiency of 41.47%. Additionally, the effects of SiO2 with different sizes on the anchoring of AuNPs and the impact of aniline with varying concentrations on the morphology and photothermal properties of the materials were investigated. Finally, we verified the photothermal therapeutic (PTT) effect of SiO2@Au@PAN at cellular level, with results demonstrating effective destruction of cancer cells. This work may provide an approach for establishing a multi-component PTT platform based on the synergistic effects of AuNPs, holding significant potential for biomedical and biochemistry applications.
School of Chemistry and Chemical Engineering, Linyi University, Linyi, 276005, China.
School of Chemistry and Chemical Engineering, Linyi University, Linyi, 276005, China. liuguodong2@lyu.edu.cn.
Synergistic effects of Au nanoparticles in SiO2@Au@Polyaniline system for improved photothermal performance.
As a blood flow control technique for embolization using glue (n-butyl cyanoacrylate; NBCA) for peripheral artery aneurysm/pseudoaneurysm, we placed a vascular plug or coils at the proximal inflow vessel before glue injection. We describe this maneuver, which we call the glue in lockdown technique. Four peripheral aneurysms-two pulmonary artery pseudoaneurysms, one pancreaticoduodenal arcade pseudoaneurysm, and one internal iliac artery aneurysm-deemed unsuitable for conventional embolization because of abnormal blood flow, coagulopathy, or anatomical complexity were embolized with our technique. Technical and clinical outcomes were reviewed to evaluate the effectiveness of the procedure. Reliable and rapid embolization was achieved in coagulopathy cases and hemodynamically or anatomically complicated lesions. Glue in lockdown technique was successfully used to treat peripheral aneurysms and can be further developed for application to other lesions.
Department of Radiology, Nippon Medical School Chiba Hokusoh Hospital.
Department of Cardiovascular Surgery, Nippon Medical School Chiba Hokusoh Hospital.
Department of Radiology, Nippon Medical School.
Journal of Nippon Medical School = Nippon Ika Daigaku zasshi
Glue in Lockdown Technique to Embolize Peripheral Arterial Aneurysms.
A variety of autoimmune disorders are associated with an increased risk of thrombosis. Previous studies have suggested combined therapy of heparin and therapeutic plasma exchange (TPE) with fresh frozen plasma (FFP) as the replacement fluid is beneficial in some cases of acute flare-up of autoimmune diseases complicated by thrombotic events. Nevertheless, it remains unknown whether clinicians do more harm than good by exposing patients to a thrombotic storm through simultaneous administration of heparin and the clotting factors in the FFP during TPE. A variety of data are currently available on therapeutic interventions for autoimmune diseases complicated with acute thrombosis; however, there is limited evidence on the exact efficacy of each individual approach and combinations of these measures. Herein, we report a case of catastrophic antiphospholipid syndrome (CAPS) to highlight the difficulty of therapeutic decision-making when complicated interactions occur between heparin and TPE. To our knowledge, this is the first case report of a patient diagnosed with CAPS successfully treated with a novel therapeutic strategy of escalating the heparin dosage when performing TPE by monitoring the partial prothrombin time to reduce the risk of the progression of thrombosis.
School of Medicine, China Medical University.
School of Medicine, China Medical University.Division of Nephrology and Kidney Institute, Department of Internal Medicine, China Medical University Hospital.
Intravenous Unfractionated Heparin vs. Therapeutic Plasma Exchange in Patients with Autoimmune Disease with Acute Thrombotic Events: Sampling in a Case of Catastrophic Antiphospholipid Syndrome.
Lung cancer is a leading cause of cancer-related mortality. Non-small cell lung cancer (NSCLC) comprises 85% of cases with rising incidence among never-smokers (NS). This study seeks to compare clinical, imaging, pathology, and outcomes between NS and ever-smokers (S) NSCLC patients to identify significant differences if any.Retrospective cohort study of 155 NSCLC patients (88 S and 67 NS). The main predictor was smoking. Clinical, imaging, and pathology findings were evaluated at initial biopsy for staging. The primary outcome was all-cause mortality, and the secondary outcome was 12-month progression-free survival.Imaging: NS and S had similar nodule size (0.81), calcification (> 0.99), and invasion of adjacent structures (> 0.99) (p values). NS slightly trended to more commonly involve the RLL vs S the RUL (p = 0.11). NS had higher numbers of extrathoracic metastases at initial biopsy for staging (p = 0.055).NS more commonly had adenocarcinoma compared to S, who had equal numbers of adenocarcinoma and squamous cell carcinoma (p = 0.001). Rates of lymphovascular and pleural invasion were similar (p = 0.84 and 0.28). Initial staging: NS were more often initially diagnosed with stage IV disease (p = 0.046), positive nodal disease (p = 0.002), and metastatic disease (p = 0.004).S had a non-significant trend toward worse 12-month progression-free survival (rate ratio = 1.31, p = 0.31; HR = 1.33, p = 0.28). NS and S had similar 1-year all-cause mortality (HR = 1.06, p = 0.90). S had nearly double the risk of all-cause mortality in 5 years (HR = 1.73, p = 0.056) and 10 years (HR = 1.77, p = 0.02). Median survival was 6.6 years for NS and 3.9 years for S, with NS surviving 2.7 years longer on average (p = 0.045).CT nodule features were similar in NS and S. NS more often had metastatic adenopathy, distant metastases, and stage IV disease at initial biopsy. Despite similar 12-month progression-free survival and 1-year all-cause mortality, S had nearly double the risk of mortality in the first 5 and 10 years post-diagnosis.Retrospectively registered.
Department of Radiology, Cardiothoracic Imaging, University of Utah, Spencer Fox Eccles School of Medicine, 50 N Medical Dr, Salt Lake City, UT, 84132, USA. radhopkins@hsc.utah.edu.Department of Radiology, Medical University of South Carolina, 171 Ashley Ave, Charleston, SC, 29425, USA. radhopkins@hsc.utah.edu.
Department of Radiology, Cardiothoracic Imaging, University of Utah, Spencer Fox Eccles School of Medicine, 50 N Medical Dr, Salt Lake City, UT, 84132, USA.
Department of Biomedical Informatics, University of Utah, Salt Lake City, UT, 84132, USA.
Spencer Fox Eccles School of Medicine, University of Utah, Salt Lake City, UT, 84132, USA.
University of Utah Health, Salt Lake City, UT, 84132, USA.
Department of Radiology, Medical University of South Carolina, 171 Ashley Ave, Charleston, SC, 29425, USA.
Non-small cell lung cancer in ever-smokers vs never-smokers.
Pulmonary hamartomas are common. However, extrapulmonary hamartomas on the Visceral Pleura are very rare. We treated a patient with a pulmonary nodule at the left lower lobe by uniportal video-assisted thoracoscopic wedge resection, which showed a yellow nodule located on the visceral pleura. Pathology showed that the nodule contained a small amount of cartilage tissue and was diagnosed as hamartoma. Fat-coated extrapulmonary hamartomas located on the visceral pleura have not been previously documented in the literature. This article presents a case of such an extrapulmonary hamartoma.
Department of Thoracic Surgery, Ningbo No.2 Hospital, 41 Xibei Road, Ningbo, 315010, P. R. China. huangshaoqing7@163.com.
Department of Biotherapy, Shanghai University Affiliated Mengchao Cancer Hospital, Shanghai, 201805, China. 657720056@qq.com.
Department of Thoracic Surgery, Ningbo No.2 Hospital, 41 Xibei Road, Ningbo, 315010, P. R. China. xueshan20042007@aliyun.com.
A rare case of extrapulmonary hamartoma on the visceral pleura treated by uniportal VATS: case report and literature review.
Pulmonary sequestration is a rare congenital anomaly, characterized by aberrant lung tissue supplied by an aberrant systemic artery or arteries coursing within the inferior pulmonary ligament. The intralobar variety is the most frequent form. Clinical presentation may include recurrent haemoptysis and infection. Standard treatment involves surgical resection of the affected tissue with maximal preservation of healthy lung. This video tutorial presents the surgical technique for resecting intralobar pulmonary sequestration involving the right lower lobe. Rather than attempting to skeletonize the frequently friable aberrant artery(ies), the lung is mobilized, and the inferior pulmonary ligament containing the aberrant artery is isolated before being divided en masse; in this way, one may decrease the risk of intraoperative arterial injury and haemorrhage. Subsequent lung resection is performed in the standard fashion, in this case, an S10 segmentectomy. Transarterial embolization has been described both as a definitive treatment and as a preoperative intervention to decrease the risk of intraoperative bleeding. In the case of preoperative embolization, one must be wary to avoid embolic material when positioning the vascular stapler to divide the aberrant artery.
© The Author 2025. Published by MMCTS on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
Medical Student, University of Montreal School Medicine, Montreal, Quebec, Canada.
Section for Thoracic Surgery; Hôpital Maisonneuve-Rosemont, University of Montreal School of Medicine, Montreal, Quebec, Canada.
Interventional Radiology; Department of Radiology, Hôpital Maisonneuve-Rosemont, University of Montreal School of Medicine, Montreal, Quebec, Canada.
Hôpital Maisonneuve-Rosemont (University of Montreal) 5415, l'Assomption, Montréal, QC, Canada.
Multimedia manual of cardiothoracic surgery : MMCTS
Multimed Man Cardiothorac Surg. 2025-01-06;2025():.
Pulmonary sequestration 1: right lower lobe.
School of Nursing, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Sacred Space, Caring for Patients in the Hospital Dying from COVID-19: Part 4.
We investigated the amount and distribution of waste generated by commercial tobacco, electronic cigarette, and cannabis (TEC) use to inform policy options aimed at mitigating the environmental harm caused by these products. Using disproportionate stratified random sampling, we selected 60 census blocks from the eight largest cities in San Diego County, California. We twice surveyed publicly accessible areas in these blocks to quantify TEC waste accumulation and its re-accumulation. All collected items were photographed, classified, geocoded, counted, and properly discarded. We identified demographic, land use, and behavioral data from public sources and direct observations. We modeled total cigarette butt quantities for all census blocks across the eight cities and found similar results for Round 1 (8.63 million) and Round 2 (8.66 million) collections. Single-use plastic cigarette filters were the primary contributor to TEC waste (94%). Total TEC waste counts and cigarette butt counts showed strong linear associations (r = +0.86 and r = +0.91). The area surveyed, land use category, resident demographics, smoking prevalence, and walkability explained 78% of the variance in cigarette butt count. The interval between Round 1 and 2 counts did not affect re-accumulation counts, suggesting that baseline TEC waste levels were re-established within 1-2 months after cleanup. Annually, we estimate up to 200 million cellulose acetate plastic filters may be discarded in public areas of the eight cities. Given the continuous deposition, vast quantity, heterogeneous distribution, and rapid re-accumulation of TEC waste after cleanup, increasing removal efforts alone are financially untenable and impractical downstream solutions for TEC waste. Community-wide policies (e.g., filter bans, outdoor smoking restrictions) and individual behavior changes (e.g., reduced smoking rates, proper disposal of cigarette butts) are necessary to effectively mitigate the environmental impact of TEC waste in urban settings.
Copyright: © 2025 Matt et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Department of Psychology, San Diego State University, San Diego, California, United States of America.Center for Tobacco and the Environment, San Diego State University, San Diego, California, United States of America.
Center for Tobacco and the Environment, San Diego State University, San Diego, California, United States of America.
Center for Tobacco and the Environment, San Diego State University, San Diego, California, United States of America.Department of Sociology, San Diego State University, San Diego, California, United States of America.
Center for Tobacco and the Environment, San Diego State University, San Diego, California, United States of America.School of Public Health, San Diego State University, San Diego, California, United States of America.
Center for Tobacco and the Environment, San Diego State University, San Diego, California, United States of America.Department of Economics, San Diego State University, San Diego, California, United States of America.
Estimating the accumulation and re-accumulation of commercial tobacco, electronic cigarette, and cannabis waste based on a stratified random sample of census blocks.
Tao and Corry used metadynamics, an enhanced sampling method to identify and classify Nav channel blockers.
Division of Physics and Applied Physics, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore, Singapore.
How could simulations elucidate Nav1.5 channel blockers mechanism?
Zika virus (ZIKV) and dengue virus (DENV) are two major mosquito-borne flaviviruses that pose a significant threat to the global public health system, particularly in tropical regions. The clinical outcomes related to these viral pathogens can vary from self-limiting asymptomatic infections to various forms of life-threatening pathological conditions such as haemorrhagic disorders. In addition to the direct effects of the viral pathogens, immune processes play also a significant function in the development of diseases mediated by ZIKV and DENV. Studing these processes is important for developing safer vaccines and targeted therapeutic strategies. These viruses have been reported to trigger various autoimmune disorders affecting different parts of human organ systems. It also has been shown that preexisting immunity to ZIKV or DENV can impact the outcome of subsequent infections caused by another virus. ZIKV and DENV infection can promote the development of autoimmune disorders by different mechanisms, such as molecular mimicry and autoantibody formation. The present review provides an overview of various autoimmune disorders associated with ZIKV and DENV infection and their potential underlying mechanisms.
Department of Critical Care Medicine, Affiliated Hospital of Jiangnan University, Wuxi, China.
The Second Clinical College, Zhejiang Chinese Medical University, Hangzhou, China.
Department of Stomach Enterochirurgia, Affiliated Hospital of Jiangnan University, Wuxi, China.
Zika and Dengue Virus Autoimmunity: An Overview of Related Disorders and Their Potential Mechanisms.
Considering, the changes in lifestyle during the last decade the main aim of this study was to investigate the pooled prevalence of metabolic syndrome (MetS) and its components in Iran.For implementing a comprehensive search strategy related to the objectives of the present meta-analysis, all international databases like PubMed (Medline), Scopus, Embase, Web of Sciences (Elsevier), and CINHAL were searched up to January 2024. The quality of the final selected studies was evaluated according to the Joanna Briggs Institute Critical Appraisal (JBI) tool for analytical cross-sectional studies. The subgroup analysis was performed based on gender, province, area, criteria of diagnosis, and components of metabolic syndrome. All of the analyses were carried out in STATA version 17.Among 2,034 relevant primary studies, 194 articles were entered into the meta-analysis. the prevalence of MetS in Iran was assessed using various criteria. The overall pooled prevalence was (31%, 95% CI: 28-34%), with a higher occurrence in females and individuals aged over 65 years. The central region, particularly Qom, reported the highest prevalence, while Tehran had the lowest. Low HDL cholesterol and waist circumference were the most common MetS components. The study provides critical data for health policy and intervention strategies in Iran.Higher rates in females and the elderly and the predominance of low HDL cholesterol and waist circumference as MetS components call for targeted public health interventions. These insights are pivotal for formulating strategic health policies to mitigate MetS and its impact on the Iranian population.
Student of the Research Committee, Kurdistan University of Medical Sciences, Sanandaj, Iran.
Department of Epidemiology and Biostatistics, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.
Department of Endocrinology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.
Department of Epidemiology, School of Public Health, Iran University of Medical Sciences, Tehran, Iran.
Social Determinants of the Health Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran. Yousefmoradi211@yahoo.com.
Prevalence of metabolic syndrome and its components in Iran: an updated meta-analysis.
Trigeminal neuralgia (TN) is a prevalent and debilitating craniofacial pain disorder characterized by severe, unilateral, shock-like pain. Standard treatments include anti-epileptic drugs and surgical interventions, but many patients experience limited relief or adverse effects. Non-invasive therapies, such as transcutaneous electrical nerve stimulation (TENS), have emerged as alternative options. This systematic review and meta-analysis aimed to evaluate the efficacy of TENS in managing primary trigeminal neuralgia.A comprehensive search of PubMed, Cochrane Library, and Google Scholar was conducted, yielding 89 papers. Following selection criteria, five clinical trials involving 101 patients with primary TN and TENS treatment were included. Data on pain severity, TENS parameters, and outcomes were extracted. Statistical analysis was performed using RevMan software, with outcomes assessed using Visual Analogue Scale (VAS) scores before and after TENS treatment.Pre-treatment VAS scores averaged 8.75 ± 0.18, indicating severe pain. Post-treatment, the mean VAS score significantly decreased to 1.17 ± 0.55, demonstrating substantial pain relief. The meta-analysis revealed a mean difference of 7.49 (95% CI: 7.05 to 7.93) in VAS scores, with a p-value < 0.05, indicating statistically significant pain reduction. Heterogeneity among studies was moderate (I2 = 57%). Complications were infrequently reported, with one study noting paresthesia in a small number of patients.TENS appears to be an effective and safe intervention for reducing pain in patients with primary trigeminal neuralgia. Despite variability in treatment protocols and follow-up periods, the overall evidence supports TENS as a viable option for managing TN pain. Future research should focus on standardizing TENS protocols and evaluating long-term efficacy and safety.
Department of Medicine, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, 00970, Palestine. yazanalhabil@gmail.com.
Director of Quality, Patient Safety, Infection Control, and Governance Department, Primary Health Care, Palestinian Ministry of Health, Ramallah, 00970, Palestine.
General Physician, Arab Care Hospital, Ramallah, 00970, Palestine.
Trigeminal neuralgia improvement following Transcutaneous Electrical Nerve Stimulation (TENS): a systematic review and meta-analysis.
Dental caries is one of the most common non-communicable diseases in humans. Various interventions are available for the management, of which microinvasive techniques such as infiltration, sealants, glass ionomers, are novel and convenient. The purpose of this systematic review and meta-analysis was to compare microinvasive techniques with noninvasive or invasive treatment modalities in terms of effectiveness in halting interproximal caries lesion progression radiographically assessed.The review was registered on PROSPERO (CRD42024557636). Three electronic databases, PubMed, Google Scholar and Cochrane Oral Health Group Trial Register, were searched for the randomized controlled trials comparing any of the microinvasive techniques with either non- invasive or invasive treatments for non-cavitated proximal lesions both in primary and permanent teeth. The radiographic lesion progression was set as primary outcome. Rayyan and EndNote X9 were used for screening and full text review respectively. The risk of bias was assessed using Cochrane Risk of Bias tool. We performed analysis with the help of RevMan5.4 and calculated odds ratio and 95% confidence interval for evaluation of efficacy. The quality of evidence was assessed with the help of GRADEpro.A total of 185 studies were recruited after initial search, of which 18 were recruited after screening. Finally, 13 studies were included, and all were split mouth randomized controlled trials comparing various microinvasive techniques with non-invasive techniques. Five of the included trials studied primary teeth in children ranging from 3 to 9 years and seven trials assessed permanent teeth in children and adults ranging from 11 to 45 years while one trial included children having lesions on both primary and permanent teeth. The risk of bias assessment showed that 2 of the included studies had unclear risk of bias whereas 11 were at low risk of bias. Tau2, I2, and Chi-Square tests (0.04, 10% and 7.50 respectively) showed minimum level of heterogeneity. The overall odds ratio (95% confidence interval) of 0.29 (95% CI 0.19-0.38) showed that microinvasive techniques were superior as compared to noninvasive techniques for the management of proximal lesions. The subgroup analysis was also performed for types of dentitions, various microinvasive interventions and levels of caries depth. All showed improved outcomes in case of microinvasive interventions as compared to noninvasive techniques. The publication bias was assessed using forest plot and there was no significant publication bias. The quality of evidence assessed by GRADEpro came out to be moderate.This review concludes that microinvasive techniques are superior to noninvasive interventions for the treatment of non-cavitated proximal lesions in both primary and permanent dentition. However, cost effectiveness, feasibility, durability, and long-term effects of microinvasive techniques need to be explored further.
Department of Prosthodontics, King Khalid University, College of Dentistry, Abha, Kingdom of Saudi Arabia. robinatdr@gmail.com.
Department of Restorative Dental Sciences, King Khalid University, College of Dentistry, Abha, Kingdom of Saudi Arabia.
Department of Diagnostic Sciences & Oral Biology, King Khalid University, College of Dentistry, Abha, Kingdom of Saudi Arabia.
Sharif Medial and Dental College, Lahore, Pakistan.
Agha Khan University, Karachi, Pakistan.
Microinvasive interventions in the management of proximal caries lesions in primary and permanent teeth- systematic review and meta-analysis.
Trials were inconsistent while reporting findings on the benefits of the intermittent regimen. Recent conclusive evidence to show overall effect was limited. This review compared intermittent and daily iron folic acid supplementation (IFAS) on pregnancy outcomes. Protocol is registered at Prospero with registration number CRD42023409161. The major data sources searched were PubMed/Medline, Hinari, and Google Scholar. The process was reported using a PRISMA flow diagram. The included studies were trials with English language reports. The population was pregnant women. The intervention was an intermittent oral iron folic acid regimen, and the control was a daily regimen. The outcome measures were blood hemoglobin level, side effects, and medication adherence. The GRADE approach and Cochrane collaboration tool were used in the quality evaluation. The selected trials were narrated for basic characteristics and major findings. The standardized mean difference was used for continuous outcomes and the relative risk for binary outcomes. A sensitivity analysis was performed to report the robustness of the estimate. Twenty-two trials were selected for analysis. The quality of the evidence ranges from high to very low. Maternal blood hemoglobin levels were different between the intermittent and daily groups (mean difference (MD), - 0.24 g/dl; 95%CI, - 0.35, - 0.12). However, either early initiation or frequently intermittent regimen in the subgroup analysis showed no difference in hemoglobin levels. Intermittent regimens had lower gastric side effects (relative risk (RR), 0.27; 95%CI, 0.11, 0.69) and better medication adherences (relative risk (RR), 1.6; 95%CI, 1.34, 1.91). There was no clear evidence of a difference in anaemia incidence between the groups (relative risk (RR), 1.09; 95%CI, 0.77, 1.54). The overall level of hemoglobin in pregnancy was different between the groups. However, anaemia incidence was similar. The combined results suggest the intermittent regimen had better benefits in pregnancy than daily.
College of Medicine and Health Sciences, School of Public Health, Hawassa University, Hawassa, Ethiopia. lserawit@yahoo.com.
College of Medicine and Health Sciences, School of Public Health, Hawassa University, Hawassa, Ethiopia.
Ethiopian Public Health Institute, Addis Ababa, Ethiopia.
Intermittent versus daily oral iron folic acid supplementation and pregnancy outcome in low- and middle-income countries: a systematic review and meta-analysis of experimental studies.
Research into cancer treatment has been mainly focused on developing therapies to directly target cancer cells. Over the past decade, extensive studies have revealed critical roles of the tumour microenvironment (TME) in cancer initiation, progression, and drug resistance. Notably, cancer-associated fibroblasts (CAFs) have emerged as one of the primary contributors in shaping TME, creating a favourable environment for cancer development. Many preclinical studies have identified promising targets on CAFs, demonstrating remarkable efficacy of some CAF-targeted treatments in preclinical models. Encouraged by these compelling findings, therapeutic strategies have now advanced into clinical evaluation. We aim to provide a comprehensive review of relevant subjects on CAFs, including CAF-related markers and targets, their multifaceted roles, and current landscape of ongoing clinical trials. This knowledge can guide future research on CAFs and advocate for clinical investigations targeting CAFs.
Tumour Targeting Laboratory, Olivia Newton-John Cancer Research Institute, Melbourne, VIC, 3084, Australia. Zhipeng.Cao@onjcri.org.au.School of Cancer Medicine, La Trobe University, Melbourne, VIC, 3086, Australia. Zhipeng.Cao@onjcri.org.au.Department of Molecular Imaging and Therapy, Austin Health, Melbourne, VIC, 3084, Australia. Zhipeng.Cao@onjcri.org.au.
Tumour Targeting Laboratory, Olivia Newton-John Cancer Research Institute, Melbourne, VIC, 3084, Australia.School of Cancer Medicine, La Trobe University, Melbourne, VIC, 3086, Australia.
Tumour Targeting Laboratory, Olivia Newton-John Cancer Research Institute, Melbourne, VIC, 3084, Australia.School of Cancer Medicine, La Trobe University, Melbourne, VIC, 3086, Australia.Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC, 3800, Australia.
Tumour Targeting Laboratory, Olivia Newton-John Cancer Research Institute, Melbourne, VIC, 3084, Australia. Andrew.Scott@onjcri.org.au.School of Cancer Medicine, La Trobe University, Melbourne, VIC, 3086, Australia. Andrew.Scott@onjcri.org.au.Department of Molecular Imaging and Therapy, Austin Health, Melbourne, VIC, 3084, Australia. Andrew.Scott@onjcri.org.au.Department of Medicine, University of Melbourne, Melbourne, VIC, 3010, Australia. Andrew.Scott@onjcri.org.au.
Cancer-associated fibroblasts as therapeutic targets for cancer: advances, challenges, and future prospects.
To assess the therapeutic effects of mesenchymal stem cell (MSC)-derived exosome therapy on periodontal regeneration and identify treatment factors associated with enhanced periodontal regeneration in recent preclinical studies.Searches were conducted in PubMed, Cochrane Library, EMBASE, and Web of Science databases until October 10, 2024. A risk of bias (ROB) assessment was performed using the SYRCLE tool. Osteogenic-related parameters were used as the primary outcome measures.In total, 1360 articles were identified, of which 17 preclinical studies were based on MSC-derived exosome therapy, and they demonstrated a beneficial effect on BV/TV (SMD = 13.99; 95% Cl = 10.50, 17.48; p < 0.00001), CEJ-ABC (SMD = -0.22; 95% Cl = -0.31, -0.13; p < 0.00001), BMD (SMD = 0.29; 95% Cl = 0.14, 0.45; p = 0.0002), and Tp.Sp (SMD = -0.08; 95% Cl= -0.15, -0.02; p = 0.02) compared with the control group. However, no significant differences were observed in Tp.Th (SMD = 0.03; 95% CI = 0.00, 0.07; p = 0.09) between the exosome-treated group and control group. Additionally, subgroup analysis indicated that preconditioned exosomes (p = 0.03) significantly improved BV/TV. In contrast, there were no significant differences in the enhancement of BV/TV with respect to the application method (p = 0.29), application frequency (p = 0.10), treatment duration (p = 0.15), or source of MSCs (p = 0.31).MSC-derived exosomes show great promise for enhancing the quality of periodontal regeneration. However, more standardized and robust trials are needed to reduce heterogeneity and bias across studies and to confirm the therapeutic parameters associated with the enhancement of periodontal regeneration by MSC-derived exosomes.CRD42024546236.
College of Stomatology, Chongqing Medical University, Chongqing, 401147 , China.Chongqing Key Laboratory of Oral Diseases , Chongqing, 401147, China.Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 401147 , China.
Department of Stomatology, Dazhou Central Hospital, Dazhou, 635000, China. 582260761@qq.com.
Department of Stomatology, Dazhou Central Hospital, Dazhou, 635000, China. 1152819817@qq.com.
College of Stomatology, Chongqing Medical University, Chongqing, 401147 , China. xiangg@hospital.cqmu.edu.cn.Chongqing Key Laboratory of Oral Diseases , Chongqing, 401147, China. xiangg@hospital.cqmu.edu.cn.Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 401147 , China. xiangg@hospital.cqmu.edu.cn.
Journal of orthopaedic surgery and research
Therapeutic effect of mesenchymal stem cell-derived exosome therapy for periodontal regeneration: a systematic review and meta-analysis of preclinical trials.
Tissue repair is an extremely crucial part of clinical treatment. During the course of disease treatment, surgery, chemotherapy, and radiotherapy cause tissue damage. On the other hand, Normal tissue from accidental or therapeutic exposure to high-dose radiation can cause severe tissue damage. There is an urgent need for developing medical countermeasures against radiation injury for tissue repair. Tissue repair involves the regeneration, proliferation, differentiation, and migration of tissue cells; imbalance of local tissue homeostasis, progressive chronic inflammation; decreased cell activity and stem cell function; and wound healing. Although many clinical treatments are currently available for tissue repair, they are expensive. The long recovery time and some unavoidable complications such as cell damage and the inflammatory reaction caused by radiotherapy have led to unsatisfactory results. Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have similar tissue repair functions as MSCs. In tissue damage, EVs can be used as an alternative to stem cell therapy, thereby avoiding related complications such as immunological rejection. EVs play a major role in regulating tissue damage, anti-inflammation, pro-proliferation, and immune response, thus providing a diversified and efficient solution for the repair of disease- and radiotherapy-induced tissue damage. This article reviews the research progress of mesenchymal stem cell-derived EVs in promoting the repair of tissue including heart, lung, liver, intestine, skin, blood system, central nervous system, and tissue damage caused by radiotherapy, thereby aiming to offer new directions and ideas for the radiotherapy and regenerative applications.
School of Basic Medicine Sciences, Shandong Second Medical University, Weifang, China.
Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, State Key Laboratory of Advanced Medical Materials and Devices, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China.
School of Basic Medicine Sciences, Shandong Second Medical University, Weifang, China.Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, State Key Laboratory of Advanced Medical Materials and Devices, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China.
Mesenchymal Stem Cell-Derived Extracellular Vesicles for Regenerative Applications and Radiotherapy.
Adolescents with intellectual disabilities (ID) often encounter challenges in walking and mobility due to cognitive and motor impairments. This study aimed to investigate the impact of real-life motor complexity on walking and mobility in this population, particularly focusing on dual-task scenarios. Twenty-four adolescents with ID, divided into trained and sedentary groups, participated in the study. Participants completed the Timed Up and Go Test and the 10-m walk test under various conditions, including holding a water glass, carrying a tray with 2 glasses of water, introducing background noise, and encountering unexpected obstacles. Both groups significantly exhibited increased completion times (P < .001) in the Timed Up and Go Test and 10-m walk test with each added level of difficulty. The trained group demonstrated significantly superior performance (P < .05), only in the single task and holding a water glass. However, the difference between groups diminished as the challenges increased. In conclusion, real-life motor dual-tasking scenarios significantly impact walking and mobility in adolescents with ID. Physical activity may improve mobility and walking, particularly under less challenging conditions. Incorporating real-life challenges into motor dual-task training programs can enhance adaptability and reduce the risk of falls and injuries, ultimately improving the quality of life for individuals with ID.
Research Laboratory Education, Motricité, Sport et Santé (EM2S) LR19JS01, High Institute of Sport and Physical Education of Sfax, University of Sfax, Sfax,Tunisia.
Department of Physical and Occupational Therapy, Vasile Alecsandri University of Bacău, Bacău,Romania.
Tunisian Research Laboratory 'Sports Performance Optimization (LR09SEP01), National Center of Medicine and Science in Sports (CNMSS), Tunis,Tunisia.
Effects of Real-Life Motor Complexity on Walking and Mobility in Trained and Sedentary Adolescents With Intellectual Disabilities: A Motor Dual-Task Investigation.
Trauma is consistently among the top ten causes of death worldwide. The aging population, constituting 15.21% of adults aged over 65 in Taiwan as of November 2019, has significantly impacted healthcare expenditures. This study aimed to explore the prognosis and resource utilization in patients with geriatric trauma.This retrospective analysis included ER admissions between January 2015 and December 2017 at a Level I trauma center in southern Taiwan. Of the 5,185 eligible patients, 1,743 were elderly. Comparisons between the age groups assessed medical resource use, patient characteristics, trauma profiles, and management. Outcomes examined included mortality, complications, length of hospital stay, duration of ICU stay, and costs.Elderly patients, predominantly women, exhibit more blunt injuries often resulting from accidental falls. They experienced longer hospital stays and higher medical expenses, as well as increased complication and mortality rates. Mortality predictors included age, GCS score, trauma severity score (≥16), complications, surgery, and initial hypotension. Complications correlated with prolonged length of hospital stay (LOS), early blood transfusion, and mortality, impacting overall expenditure along with trauma severity, ICU days, surgery, and AIS score (≥3).Elderly patients had a longer LOS, higher mortality and complication rates, and higher total medical costs. The required medical expenses for elderly trauma cases were relatively higher than those for younger individuals. Relevant authorities should consider patient age when formulating policies for trauma reimbursement. Based on our findings, healthcare resource utilization can be reduced by decreasing the length of hospital stay and mitigating trauma severity. We recommend collecting more detailed data, extending the study period, and engaging in multicenter collaborations to validate our findings and provide a roadmap for further research. We suggested that interventional studies are needed to test strategies aimed at reducing resource utilization and improving outcomes in elderly trauma patients, which would be valuable.
Copyright © 2024, the Chinese Medical Association.
Division of Trauma Surgery, Department of Emergency, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC.
Journal of the Chinese Medical Association : JCMA
Analysis of prognosis and medical resource utilization in elderly patients with trauma: A retrospective cohort study in one trauma center.
Since the first transcatheter aortic valve replacement (TAVR) was performed in China in 2010, TAVR has developed rapidly. However, the temporal trends in the 1-year prognosis after TAVR in China have not been described. This study enrolled patients treated at a high-volume Chinese TAVR center, West China Hospital, between 2015 and 2022, to analyze and characterize the temporal trends in 1-year outcomes. After multivariate adjustment, the 30-day mortality, 1-year all-cause mortality, 1-year cardiac mortality, and 1-year permanent pacemaker implantation rates showed a significantly decreasing trend (adjusted p for trend < 0.05). The 1-year major adverse cardiovascular event and 1-year stroke incident rate also decreased but did not reach significance. In conclusion, this study, for the first time, reveals a declining trend in adverse prognosis among patients who underwent TAVR in China.
Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China.
Temporal trends of transcatheter aortic valve replacement outcomes in a high-volume center from China.
Few studies have explored the genetic changes and clinicopathological features of stage II/III gastric cancer (GC) patients with no tumor recurrence, early recurrence, or late recurrence after curative surgery.In this study, 376 patients who underwent curative surgery for stage II/III GC were analyzed. The clinical and genetic features of patients with no recurrence, early recurrence (<2 years), and late recurrence (≥2 years) were compared.Among the 376 patients, 155 experienced tumor recurrence, including 116 with early recurrence and 39 with late recurrence. Patients with early recurrence had larger tumors, fewer superficial tumors, increased lymphovascular invasion, advanced T and N categories, higher TNM stages, and poorer 5-year survival (3.4% vs. 38.5% vs. 63.5%, p <0.001) than those with late recurrence or no recurrence. For intestinal-type GC, patients with early recurrence had more MSI-H tumors than those with late recurrence or no recurrence. For diffuse-type or node-positive GC, patients with early recurrence had more PIK3CA amplifications than did those with late recurrence or with no recurrence. Peritoneal dissemination and lung metastasis were associated with PIK3CA amplifications, whereas liver metastasis was associated with larger numbers of MSI-H tumors and PI3K / Akt pathway mutations. Multivariate analysis revealed that age, tumor recurrence, and pathological T and N categories were independent prognostic factors for both overall survival and disease-free survival.Distinct clinical features and genetic alterations were observed in specific groups of stage II/III GC patients with differences in time to recurrence and recurrence patterns, and targeted therapy and immunotherapy may benefit these groups of patients.
Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC.Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan, ROC.Division of General Surgery, Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC.
Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC.
School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC.Department of Pathology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC.Center of Immuno-Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC.National Yang Ming Chiao Tung University Hospital, Yilan, Taiwan, ROC.
School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC.Department of Anatomical Pathology, Cheng Hsin General Hospital, Taipei, Taiwan, ROC.
School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC.Division of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
A comparison of the clinicopathological features and genetic alterations in stage II/III gastric cancer with no recurrence, early recurrence and late recurrence after curative surgery.
Bioabsorbable internal fixation is a well-accepted modality that is especially suitable for application in craniosynostosis. When first introduced, high rates of adverse tissue reactions were observed that have since been ameliorated with more biocompatible polymer formulations. However, the phenomenon has not entirely disappeared, and such reactions remain vexing. It has been suggested that intraoperative use of ultrasonic activation to heat and remodel 50:50 poly(D-lactide-co-L-lactide) fixation devices could potentiate an adverse tissue response following craniosynostosis procedures. The evidence for this was examined based on a clinical literature search, as well as a review of bioabsorbable polymer science principles, to see whether there is a theoretical basis to explain how such a relationship might be possible. Although a trend was evident suggestive of such an association, unequivocal evidence was not found. Also, no obvious potential mechanism that could explain such an association, should it exist, was apparent. The methodological approach used in this analysis and the information presented can help provide a foundation for future analyses of this nature.
Department of Biomedical Engineering, University of Illinois, Chicago, IL.Musculoskeletal Publication and Analysis, Inc., Warsaw, IN.
Intraoperative Application of Ultrasonic Energy to Bioabsorbable Craniosynostosis Fixation Devices and Adverse Tissue Reaction. Is There a Correlation?
Advanced technology and increasing knowledge about aging faces have combined to create the illusion of thread lifting to replace surgical interventions. However, results that came far beyond expectations led to a heavy suspicion of these tools. However, combined treatments with fillers would have better outcomes with a synergetic effect. In this study, 52 patients were treated with a specific thread, whereas soft tissue support was added to supervene the lifting effect of the threads. With a mean age of 48 years, these patients were treated with 3 pairs of mid and lower facial areas, and one for eyebrows. With a median amount of 5 mL fillers were added simultaneously at the same treatment plan. The follow-up period was 32 months. Assessment with a Likert Scale questionnaire revealed most of the patients (n = 42) were delighted, whereas only one patient was unsatisfied. The only unsatisfied patient experienced the most frustrating complication, which was thread removal due to infection. The literature shows unauthorized, unspecialized applications of such medical devices cause failure and loss of reliability. Therefore, the most important point of this technique is the sterile setting. Other issues that are discussed in this paper also aim to direct the reader to achieve the most benefit of these 2 techniques.
Department of Otorhinolaryngology, Bilkay Clinic, Izmir.
Department of Plastic, Reconstructive and Aesthetic Surgery, Faculty of Medicine, İstinye University, Istanbul.
Department of Plastic, Reconstructive, and Aesthetic Surgery, Bilkay Clinic, Izmir, Turkey.
Thread-Filler: A Standardized Combination Therapy.
The State Key Laboratory of Reproductive Medicine; Key Laboratory for Aging & Disease, Research Centre for Bone and Stem Cells, Department of Human Anatomy, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.
Laboratory Centre for Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.
Department of Science and Technology, Jiangsu Jiankang Vocational College, Nanjing, Jiangsu, 210029, China.
The State Key Laboratory of Reproductive Medicine; Key Laboratory for Aging & Disease, Research Centre for Bone and Stem Cells, Department of Human Anatomy, Nanjing Medical University, Nanjing, Jiangsu, 211166, China. lyuxianhui@163.com.
The State Key Laboratory of Reproductive Medicine; Key Laboratory for Aging & Disease, Research Centre for Bone and Stem Cells, Department of Human Anatomy, Nanjing Medical University, Nanjing, Jiangsu, 211166, China. dsmiao@njmu.edu.cn.
Retraction Note: P16INK4a deletion ameliorated renal tubulointerstitial injury in a stress-induced premature senescence model of Bmi-1 deficiency.
Do you need extra training before graduate school? Consider a post-baccalaureate position.
To assess the clinical efficacy of combining autologous fat grafting with hair follicle unit transplantation.The authors conducted a retrospective analysis involving 30 patients at the Department of Plastic Surgery, Second Affiliated Hospital of Nanchang University, between January 2021 and January 2023. Granular fat was harvested from the thigh's posterior aspect using liposuction. The fat was then filtered through cotton pads, fascia was excised, and the fat was implanted into the scar tissue. Postoperatively, beyond the 3-month mark, hair follicle units were harvested from the posterior occipital region of the scalp using an electric device, and these units were transplanted into the scarred alopecic zones. At 1 year postoperatively, the authors evaluated the survival rate of the transplanted hair follicles and the cosmetic outcomes. In addition, patient satisfaction data were compiled.Among the 30 patients, 22 males and 8 females with an age range of 18 to 43 years and a mean age of 29 years were included. Complete coverage was achieved in 23 cases, and substantial coverage in 7 cases. High satisfaction was reported by 28 patients, whereas 2 expressed moderate satisfaction.The integration of autologous fat grafting with hair follicle unit transplantation for the treatment of scar-related alopecia demonstrates significant efficacy and high patient satisfaction, recommending its broader clinical application.
Department of Plastic and Reconstructive Surgery, The Second Affiliated Hospital of Nanchang University.
Hongdu Hospital of Traditional Chinese Medicine, Nanchang, China.
Improving Hair Scar Defects Through the Integration of Autologous Fat Transplantation and Hair Follicle Unit Transplantation.
Will Europe ramp up defence research? War prompts major rethink.
Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania.
Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan.
Sentinel Vessels as Initial Finding with Iris Pigment Epithelial Adenoma.
J Thorac Cardiovasc Surg. 2025-01-17;():.
Commentator Discussion: How soon will surgeons become mere technicians? Chatbot performance in managing clinical scenarios.
Journal of the American Dental Association (1939)
Asymptomatic unilateral gingival swelling.
J Thorac Cardiovasc Surg. 2025-01-15;():.
Commentator Discussion: Revascularization after minimally invasive coronary artery bypass grafting in 566 patients: Is it a problem?
Ann Arbor, Michigan. Electronic address: panewman@med.umich.edu.
Ann Arbor, Michigan and Baltimore, Maryland.
Patient Challenges with Glaucoma Eye Drops: A Need to Identify Nonadherence and Facilitate Appropriate Support and Disease Management.
Acute hand infections (AHIs) remain a challenge for hand surgeons and represent a condition for which clinical outcomes are considerably affected by social barriers. We previously described the looped Penrose drainage technique, where a drain is sutured to itself in a loop and the outflow tract of egress is maintained, thus obviating the need for large incisions, wound closure, or repeat packing, thereby reducing the follow-up burden. In the face of escalating numbers of socioeconomically vulnerable patients, especially in urban settings, we aimed to characterize the clinical features and outcomes of this technique in an urban population of patients with AHI.A review of all surgical irrigations of AHI by a single, fellowship-trained hand surgeon at an urban hospital from 2013 through 2021 was performed. Patient demographics, procedure details, and postprocedure outcomes were analyzed.Fifty-three patients (average age, 48.6 years) with AHI underwent surgical irrigations with the looped Penrose drainage technique. The majority of patients were Black (50.9%). Approximately 81.1% of the patients received public insurance, 22.6% were unemployed, 35.9% had annual incomes <$40,000, and 17% experienced homelessness. Overall, 34% were lost to follow-up with the Penrose still intact, including 78% of those who were homeless. Most of the cases occurred on the hand, with involvement of the deep spaces (24.5%), tenosynovitis (39.3%), and bone (1.9%). Recurrent infection (1.9%) and abscess formation (5.7%) led to one reoperation (1.9%). There were no amputations or readmissions, and all postoperative emergency department visits (7.1%) were discharged.The looped Penrose technique is a simple and less invasive alternative to traditional incision and drainage with packing and serves as an effective single-episode intervention strategy for AHIs, particularly in patients with complex social challenges because of the ease of wound management and low rates of readmission and reoperation.Therapeutic IV.
Copyright © 2024 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.
Division of Plastic Surgery, Department of Surgery, University of Pennsylvania, Philadelphia; University of Colorado School of Medicine, Aurora, CO.
Division of Plastic Surgery, Department of Surgery, University of Pennsylvania, Philadelphia.
Division of Plastic Surgery, Department of Surgery, University of Pennsylvania, Philadelphia; Rutgers-New Jersey Medical School, Newark, NJ.
Division of Plastic, Reconstructive and Oral Surgery, Children's Hospital of Philadelphia, Philadelphia, PA; Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA.
Division of Plastic Surgery, Department of Surgery, University of Pennsylvania, Philadelphia; Division of Plastic, Reconstructive and Oral Surgery, Children's Hospital of Philadelphia, Philadelphia, PA. Electronic address: benjamin.chang@pennmedicine.upenn.edu.
Looped Penrose Drainages of Acute Hand Infections in Vulnerable Populations.
Vitreo-retinal Department, Shijiazhuang AIER Eye Hospital, Shijiazhuang, Hebei, China.
Vitreo-retinal Department, The Eye Hospital of Wenzhou Medical University, Hangzhou, China.
Haller's and Sattler's Layer Dysplasia-Possible Subtype of Choroidal Dysplasia?
Isolated coronal shear fractures of the distal humerus in adolescents are rare injuries with unique surgical challenges. Respect for the posterior blood supply, open physes, and need for direct visualization to achieve anatomic reduction are critical considerations in surgical fixation. This study presents a case series and a surgical approach used in treating these patients.A retrospective review of patients aged 10-19 presenting to a single quaternary-care academic center from 2016 to 2023 with isolated capitellar and trochlear shear fractures was performed. Demographic data, injury mechanism, fracture classification, and surgical approach were recorded. Outcomes included elbow range of motion at the final follow-up, visual analogue scale pain scores, pediatric Patient-Reported Outcome Measurement Information System (PROMIS) scales, radiographic and clinical union, return to sport, and postoperative complications.Eight patients were included, four of whom were treated through a single-incision anterolateral approach. Average age was 13 years. Average time of the final clinical follow-up was 21 months, with a radiographic follow-up of 11 months. Five fractures were classified as Dubberly type 2A, two as type 3A, and one as type 3B. At the final follow-up, average elbow range of motion and visual analogue scale pain scores were 3-137 degrees and 0.28 (range: 0-2), respectively. PROMIS scores demonstrated an average mobility score of 55 (SD: 8), pain interference of 35 (SD: 5), and pediatric upper-extremity score of 55 (SD: 4). One patient with sickle cell disease developed avascular necrosis of the capitellum. There were no other postoperative complications.Short-term clinical outcomes reveal low pain scores, near normal elbow motion, radiographic and clinical union, and normal patient-reported outcome measures in operatively treated coronal shear fractures of the distal humerus in adolescent patients. A single-incision anterolateral approach offers visualization of the anterior articular surface while respecting posterior soft tissues and the olecranon apophysis.Therapeutic V, case series.
Department of Orthopaedic Surgery, Washington University School of Medicine, Saint Louis, MO.
Department of Orthopaedic Surgery, Washington University School of Medicine, Saint Louis, MO. Electronic address: wallli@wustl.edu.
Adolescent Coronal Shear Fractures of the Distal Humerus: Surgical Approach and Outcomes.
The aim of this study was to assess the correlation between the Visual Analog Scale (VAS), Numeric Rating Scale (NRS), and Verbal Rating Scale (VRS). Additionally, the study aimed to determine NRS threshold values for both mild analgesic administration (= without risk of nausea and vomiting [NV] side effects) and strong analgesic administration (= with risk of NV side effects) in the postanaesthetic care unit (PACU).Prospective, observational study design.The study was conducted between August 2019 and April 2022. Patients scheduled for elective surgery under general anesthesia were included. The primary outcome was the correlation between the VAS, NRS, and VRS, assessed at PACU admission and discharge. Secondary outcomes included pain evolution, desire for analgesic administration with or without risk of NV side effects, and preferred tool for pain assessment.VAS, NRS, and VRS were significantly correlated (r = 0.82 to 0.94, P < .001) at both PACU admission and discharge. The median VAS scores significantly improved from 32 (interquartile range [IQR]: 9 to 22) at PACU admission to 27 (IQR: 8 to 39) at PACU discharge (P < .001), while the median NRS scores significantly improved from 3 (IQR: 1 to 6) at PACU admission to 3 (IQR: 1 to 4) at PACU discharge (P < .001). At PACU admission, receiver-operating characteristics curve analysis indicated that an optimal NRS threshold value for the administration of a mild analgesic (= without risk of NV side effects) was greater than 2, and greater than 5 for the administration of a strong analgesic (= with risk of NV side effects). At PACU discharge, patients reported a preferred median NRS score of 5 to be treated with a mild analgesic (= without risk of NV side effects), and a preferred median NRS score of 8 to be treated with a strong analgesic (= with risk of NV side effects).All three pain assessment tools can be used to evaluate postoperative pain in the PACU setting during the recovery from general anesthesia.
Copyright © 2025 The American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.
Department of Anaesthesia, Intensive Care and Pain Medicine, General Hospital Maria Middelares, Ghent, East Flanders, Belgium. Electronic address: Ella.Hermie@mijnziekenhuis.be.
Department of Anaesthesia, Intensive Care and Pain Medicine, General Hospital Maria Middelares, Ghent, East Flanders, Belgium.
Journal of perianesthesia nursing : official journal of the American Society of PeriAnesthesia Nurses
Comparison of Pain Assessment Tools and Numeric Rating Scale Thresholds for Analgesic Administration in the Postanaesthetic Care Unit.
Understanding barriers to compliance can aid in mitigation strategies to address them. This study aims to quantitatively and qualitatively assess the relationship between barriers to ERAS recommendations and perceived ability to assure compliance among multidisciplinary team (MDT) members who deliver Enhanced Recovery After Surgery (ERAS) care.Embedded mixed-methods survey analysis.A survey was distributed to ERAS professionals to assess for each recommendation: how much the recommendation was part of their role; how much they felt they could assure compliance with the recommendation; and the primary barrier to compliance. Imputed datasets were created within each MDT role, significant barriers retained, and prediction models developed. Qualitative data were thematically coded and a mind map visualized themes.Most respondents were surgeons with greater than 10 years' experience. Surgeons and advanced practice providers reported highest averages of compliance assurance, nurses the lowest. Barriers most reported were patient factors and lack of agreement. Lack of familiarity and motivation predicted statistically significant decreases in compliance with oral carbohydrate loading. Qualitatively, nurses and surgeons reported lack of agreement from colleagues as the biggest barrier, followed by lack of resources and motivation to change. Other themes were the importance of teamwork, data audit, staff education, and informatics.Standardized data collection and reporting of barriers to ERAS recommendations may help identify barriers and improve compliance in a multidisciplinary context. A rich, mixed-methods analysis revealed key insights into perceptions of barriers and compliance with ERAS.
Center for Surgical Outcomes Science, Wake Forest University School of Medicine, Atrium Health, Charlotte, NC. Electronic address: Allyson.cochran@atriumhealth.org.
School of Nursing, University of North Carolina at Charlotte, Charlotte, NC.
Department of Public Health Sciences, School of Data Science, University of North Carolina at Charlotte, Charlotte, NC.
Division of Abdominal Transplantation, Carolinas Medical Center, Wake Forest University School of Medicine, Atrium Health, Charlotte, NC.
The Evidence Alone Was Not Enough to Change Practice: A Mixed-methods Analysis Using a Standardized Framework to Understand Perceptions of Barriers and Compliance to ERAS Recommendations.
The purpose of this meta-analysis is to measure the effectiveness of penehyclidine hydrochloride hydrate (PHC)-an antimuscarinic drug-in preventing postoperative nausea and vomiting (PONV) for different surgeries.Meta-analysis.According to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, we conducted an online literature search using PubMed, Web of Science, Scopus, and Embase databases. Randomized control trials comparing PHC with placebo or any other standard treatments were included.Our systematic review screened 54 articles, and four randomized control trials with 766 patients were included. There was no significant difference between PHC and the control group for the prevention of postoperative vomiting (risk ratio [RR] = 0.43). However, the subgroup analysis showed some promise. At 24 hours, PHC significantly decreased the incidence of postoperative nausea (RR = 0.31), postoperative vomiting (RR = 0.17), and PONV (RR = 0.33). While at 48 hours, PHC showed nonsignificant results for the same outcomes. PHC did not result in significantly higher rates of analgesia use, headache, dizziness, longer durations of stay in the postanesthesia care unit, or longer duration for extubation, but it showed significantly lower results for the use of antiemetics. Furthermore, PHC showed higher rates of dry mouth.The findings suggest that PHC offers a promising option for PONV prophylaxis, particularly in surgical settings where early PONV are prevalent, with an acceptable safety profile. Further research is recommended to optimize dosing strategies and compare PHC with established antiemetics.
Copyright © 2024 The American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.
Faculty of Medicine Tanta University, Tanta, Egypt; Medical Research Group of Egypt (MRGE), Negida Academy, Arlington, MA.
Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Riyadh, Saudi Arabia.
Faculty of Medicine, Cairo University, Cairo, Egypt.
Faculty of Medicine Tanta University, Tanta, Egypt.
Mohamed Lamine Debaghine University Hospital Algiers, GP-Bab El Oued, Algeria.
Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Al Quds University Palestine Faculty of Medicine, Al Azhar Branch, Gaza, Palestine.
Department of Internal Medicine, College of Medicine, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia.
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif, Saudi Arabia.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt.
Department of Otorhinolaryngology, Al Mouwasat University Hospital, Faculty of Medicine, Damascus University, Damascus, Syrian Arab Republic; Faculty of Medicine, Syrian Private University, Damascus, Syrian Arab Republic.
Penehyclidine Hydrochloride: A Promising Antimuscarinic Agent for PONV Prophylaxis in Diverse Surgical Procedures.
Exclusive breastfeeding during the first six months of life, and prolonged with complementary feeding until 2 years of age or more, is the best nutritional approach in the first stage of life. Mastitis is a pathology that can jeopardize the continuity of breastfeeding. Different methods have been proposed for the prevention and treatment of mastitis, including probiotics. This narrative review aims to describe the problem of mastitis during lactation and the role of probiotics in its prevention. Mastitis should not be confused with the physiological phenomenon known as milk coming in. In persistent pain, timely medical consultation is key to avoiding complications. The administration of specific probiotics in the perinatal period has shown efficacy in reducing the incidence of mastitis.
Hospital General de Agudos Dr. C. Argerich, City of Buenos Aires, Argentina.
Clínica y Maternidad Suizo Argentina, City of Buenos Aires, Argentina.
Neonatology Service, Sanatorio Otamendi, City of Buenos Aires, Argentina.
Instituto de Lactología Industrial (INLAIN, CONICET-UNL), Faculty of Chemical Engineering, Universidad Nacional del Litoral, Santa Fe, Argentina.
La lactancia exclusiva durante los primeros seis meses de vida, y prolongada junto a la alimentación complementaria hasta los 2 años o más, es el mejor abordaje nutricional en la primera etapa de la vida. La mastitis es una patología que puede poner en riesgo la continuidad de la lactancia. Diferentes abordajes se han planteado para la prevención y tratamiento de la mastitis, entre ellos, el uso de probióticos. El objetivo de esta revisión narrativa es describir la problemática de la mastitis durante la lactancia y el rol de los probióticos en su prevención. La mastitis no se debe confundir con los fenómenos fisiológicos asociados a la comúnmente denominada subida o bajada de la leche. Ante la persistencia del dolor, la consulta médica oportuna es clave para evitar complicaciones. La administración de probióticos específicos en el período perinatal ha demostrado eficacia en la reducción de la incidencia de mastitis.