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This study adopts individual and societal-level approaches to examine the contribution of childhood risk factors to major depressive episodes (MDE) in 2526 American young adults. Nationally representative data from the 2017 U.S. Panel Study of Income Dynamics – Transition into Adulthood Supplement (PSID-TAS) were analyzed using multivariate methods to assess the impact of parental mental illness, childhood adversities, childhood mental disorders, and childhood physical conditions. Adjusted odds ratios and population attributable risk proportions (PARPs) are calculated to estimate the proportion of MDE cases related to risk factors. The 12-month prevalence of positive screens for MDE was 25.4 %. Approximately 34 % of these were attributable to childhood mental disorders, 24 % to childhood physical conditions, 21 % to childhood adversities, and 16 % to parental mental illness. Childhood and parental depression were critical risk factors, both at the individual (odds ratio exceeding 2) and societal (PARP approximately 24 %) levels. Gender-specific risk factors were identified, with childhood physical abuse and childhood anxiety disorders constituting risk factors for females, and childhood externalizing disorders and childhood headaches as risk factors for males. Approximately 60 % of U.S. young adult MDE cases are attributable to risk factors before age 18. Possible over reporting of MDE may have biased the associations between predictors and depression. Exposure to depression at a young age—one's own or parental depression—is a robust risk factor for both genders. Policies and interventions focused at alleviating the societal burden of depression should value its generational transmission. • Most U.S. young adult MDE cases are attributable to risk factors before age 18. • Pre-pandemic 12-month prevalence of young adult MDE was 25.4 %. • Approximately 34 % of cases were attributable to childhood mental disorder. • Identifying depression-prone youth is a crucial step for curative interventions. • Implementing early, developmentally sensitive strategies is vital for prevention. [ABSTRACT FROM AUTHOR]

Background: Adolescence is a critical period for the onset of mental health issues. In China, high school students face significant academic and social pressures, leading to high rates of mental health challenges. Gender differences in the manifestation of these symptoms have been observed, with boys and girls exhibiting distinct psychological profiles. Objective: This study aims to explore the structure of psychological symptoms among Chinese high school students using network analysis, focusing on identifying core symptoms and gender differences in symptom networks. The key objectives are to: 1) identify the central psychological symptoms for boys and girls, and 2) uncover the interactions between symptoms to inform targeted interventions. Methods: A cluster sampling method was used to recruit 3,769 high school students (2,206 males and 1,563 females) in Shanghai. The Middle School Students Mental Health Scale (MSSMHS) was administered, and network analysis was conducted using the R packages bootnet and qgraph to assess symptom network edges, centrality, and network strength. Comparisons between male and female networks were made. Results: Network analysis showed tightly connected symptom networks for both genders, with 43 non-zero edges for boys (sparsity 0.04) and 39 for girls (sparsity 0.13). Depression was the core symptom for boys (centrality 1.20), while anxiety was central for girls (centrality 1.46). Boys showed a stronger link between interpersonal sensitivity and depression (edge value 0.20), while girls exhibited a stronger connection between anxiety and obsessive-compulsive symptoms (edge value 0.16). Network comparison tests revealed no significant differences in overall network strength between boys (4.625) and girls (4.660), with P-values greater than 0.05 across all comparisons. Conclusion: This study highlights significant gender differences in the psychological symptom networks of Chinese high school students. Depression and anxiety emerged as core symptoms for boys and girls, respectively. These findings provide a foundation for developing gender-sensitive mental health interventions, emphasizing the need for tailored approaches based on gender-specific symptom profiles. Highlights: Significant gender differences in the symptom networks of adolescents, with depression and anxiety as key central nodes. A tight link between anxiety and depression in female students, whereas a strong connection exists between depression and interpersonal sensitivity in male students. Emphasizes the importance of designing targeted educational and mental health interventions. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Method Results Discussion The present longitudinal study examined sex‐specific, symptom‐level relationships among emotion regulation (ER), interpersonal problems (IP), and eating disorder (ED) psychopathology in a large sample of Chinese adolescents.Data were from a project with four waves of data collection (N = 1540; 710 boys and 830 girls) at 6‐month intervals over 18 months. Questionnaires assessed ED psychopathology, ER, and IP at each wave of data collection. Longitudinal network analyses were conducted separately for boys and girls. Sex differences in the network structures were also examined.The results revealed pronounced heterogeneity in the presentation of ED psychopathology, ER, and IP across Chinese adolescent boys and girls longitudinally and intra‐individually. For example, weight/shape preoccupation in ED psychopathology and awareness in ER emerged as important nodes in the temporal network for boys. However, weight/shape preoccupation and dissatisfaction in ED psychopathology were identified as the most important nodes in the temporal network for girls. Regarding bridge strength, awareness in ER emerged as the node with the highest connectivity in the temporal network for boys. At the same time, weight/shape dissatisfaction in ED psychopathology was the node with the highest connectivity for girls.The current study extended network theory to better understand the longitudinal interplay among ER, IP, and ED psychopathology in Chinese adolescents and their sex differences in the importance of symptoms. Such insights may pave the way for developing targeted prevention and treatment strategies for adolescent boys and girls in China. [ABSTRACT FROM AUTHOR]

We investigated differences in risk factors and preventive behaviors by age and sex among persons with reported Lyme disease in Ontario, Canada, during 2015– 2022. Incidence rates peaked among children 5–9 and adults 50–79 years of age. Median age was higher for female than male case-patients (54 vs. 51 years). Male case-patients reported more activity in wooded and tall grass areas than did female case-patients; fewer male case-patients reported sharing living space with outdoor-exposed companion animals. As age increased, more case-patients reported activity in blacklegged tick habitats, exposure to ticks, and wearing adequate clothing, but fewer reported sharing living space with outdoor-exposed companion animals. Adoption of preventive behaviors was relatively low and did not differ by sex. Male case-patients, children 5–9 years of age and their parents or caregivers, and adults >59 years of age represent populations that would benefit from tailored public health messaging on Lyme disease prevention. [ABSTRACT FROM AUTHOR]

Despite the growing interest in gender medicine, the influence of sex and gender on human diseases, including stroke, continues to be underestimated and understudied. The COVID-19 pandemic has overall impacted not only the occurrence and management of stroke but has also exacerbated sex and gender disparities among both patients and healthcare providers. This paper aims to provide an updated overview on the influence of sex and gender in stroke pathophysiology and care during COVID-19 pandemic, through biological, clinical, psychosocial and research perspectives. Gender equity and awareness of the importance of sexual differences are sorely needed, especially in times of health crisis but have not yet been achieved to date. To this purpose, the sudden yet worldwide diffusion of COVID-19 represents a unique learning experience that highlights critical unmet needs also in gender medicine. The failures of this recent past should be kept as food for thought to inspire proper strategies reducing inequalities and to address women's health and wellbeing issues, particularly in case of future pandemics. [ABSTRACT FROM AUTHOR]

Schizophrenia is a complex neuropsychiatric disorder with positive, negative, and cognitive symptoms. In rats, sub-chronic administration of ketamine is used for the induction of schizophrenia model. Increased locomotor activity is one of the most important features of psychotic-like symptoms in rodents. On the other hand, risperidone is a potent antipsychotic medication that is approved for the treatment of schizophrenia and bipolar disorder. In the present research, we aimed to investigate the effect of sub-chronic treatment of ketamine on cognitive and behavioral functions, and brain-derived neurotrophic factor (BDNF) expression level in the prefrontal cortex. Also, we assessed the efficacy of risperidone on cognitive and behavioral impairments induced by ketamine. Possible sex differences were also measured. Ketamine was intraperitoneally injected at the dose of 30 mg/kg for five consecutive days. Risperidone was also intraperitoneally injected at the dose of 2 mg/kg. Novel object recognition memory, pain threshold, locomotor activity, rearing behavior, and BDNF level were evaluated. The results showed that ketamine injection for five consecutive days impaired the acquisition of long-term recognition memory and decreased BDNF level in the prefrontal cortex in both sexes. Also, it decreased pain threshold in females, increased rearing behavior in males, and induced hyperlocomotion with greater effect in females. On the other hand, risperidone restored or attenuated the effect of ketamine on all the behavioral effects and BDNF level. In conclusion, we suggested that there were sex differences in the effects of ketamine on pain perception, locomotion, and rearing behavior in a rat model of schizophrenia. [Display omitted] • Ketamine impaired novel object recognition memory and decreased BDNF in both sexes. • Ketamine decreased pain threshold in females and increased rearing in males. • Ketamine induced hyperlocomotion with greater effect in females. • Risperidone restored ketamine-induced behavioral changes and increased BDNF. • Sex differences were seen in the effects of ketamine on pain, locomotion, rearing. [ABSTRACT FROM AUTHOR]

This article discusses three different studies related to heart failure and valvular heart disease. The first study examines the use of intravenous ferric carboxymaltose (FCM) in patients with heart failure with preserved ejection fraction (HFpEF) and iron deficiency. The study found that FCM improved exercise capacity and had fewer serious adverse events compared to a placebo. However, the study was small and did not assess other symptoms or quality of life. The second study compares transcatheter aortic valve implantation (TAVI) with surgery in low-risk patients with aortic stenosis. The study found that the rate of death, stroke, or rehospitalization at one year was similar between the two treatments. However, TAVI had different risks and outcomes for patients with bicuspid aortic stenosis. The third study explores sex differences in severe native valvular heart disease. It found that women were older, more symptomatic, and had poorer concordance with recommended treatment compared to men. However, survival at six months was similar between men and women. Overall, these studies provide valuable insights into the treatment and management of heart failure and valvular heart disease, but further research is needed to fully understand their impact. [Extracted from the article]

Background and Aims To assess sex differences in disease characteristics and treatment of patients with severe native valvular heart disease (VHD) included in the VHD II EURObservational Research Programme. Methods A total of 5219 patients were enrolled in 208 European and North African centres and followed for 6 months [41.2% aortic stenosis (AS), 5.3% aortic regurgitation (AR), 4.5% mitral stenosis (MS), 21.3% mitral regurgitation (MR), 2.7% isolated right-sided VHD, 24.9% multiple left-sided VHD]. Indications for intervention were considered concordant if corresponding to class I recommendations specified in the 2012 ESC or 2014 AHA/ACC VHD guidelines. Results Overall, women were older, more symptomatic, and presented with a higher EuroSCORE II. Bicuspid aortic valve and AR were more prevalent among men while mitral disease, concomitant tricuspid regurgitation (TR), and AS above age 65 were more prevalent among women. On multivariable regression analysis, concordance with recommended treatment was significantly poorer in women with MS and primary MR (both P <.001). Age, patient refusal, and decline of symptoms after conservative treatment were reported significantly more often as reasons to withhold the intervention in females. Concomitant tricuspid intervention was performed at a similar rate in both sexes although prevalence of significant TR was significantly higher in women. In-hospital and 6-month survival did not differ between sexes. Conclusions (i) Valvular heart disease subtype varied between sexes; (ii) concordance with recommended intervention for MS and primary MR was significantly lower for women; and (iii) survival of men and women was similar at 6 months. [ABSTRACT FROM AUTHOR]

Aging per se is a major risk factor for cardiovascular diseases and is associated with progressive changes in cardiac structure and function. Rodent models are commonly used to study cardiac aging, but do not closely mirror differences as they occur in humans. Therefore, we performed a 2D echocardiographic study in non-human primates (NHP) to establish age- and sex-associated differences in cardiac function and morphometry in this animal model. M mode and 2D echocardiography and Doppler analyses were performed cross-sectionally in 38 healthy rhesus monkeys (20 females and 18 males), both young (age 7–12 years; n = 20) and old (age 19–30 years; n = 18). The diameters of the cardiac chambers did not differ significantly by age group, but males had larger left ventricular diameters (2.43 vs 2.06 cm in diastole and 1.91 vs 1.49 cm in systole, p = 0.0004 and p = 0.0001, respectively) and left atrial diameter (1.981 vs 1.732 cm; p = 0.0101). Left ventricular mass/body surface area did not vary significantly with age and sex. Ejection fraction did not differ by age and females presented a higher ejection fraction than males (54.0 vs 50.8%, p = 0.0237). Diastolic function, defined by early to late mitral peak flow velocity ratio (E/A), was significantly lower in old rhesus monkeys (2.31 vs 1.43, p = 0.0020) and was lower in females compared to males (1.595 vs 2.230, p = 0.0406). Right ventricular function, evaluated by measuring the Tricuspid Annular Plane Systolic Excursion, did not differ by age or sex, and Right Ventricular Free Wall Longitudinal Strain, did not differ with age but was lower in males than in females (-22.21 vs -17.95%, p = 0.0059). This is the first echocardiographic study to evaluate age- and sex-associated changes of cardiac morphometry and function in young and old NHP. The findings of this work will provide a reference to examine the effect of age and sex on cardiac diseases in NHP. [ABSTRACT FROM AUTHOR]

Objective: Insufficient or prolonged sleep each day may contribute to the onset of cardiovascular disease and diabetes, and there may be some variability between genders; however, current research evidence is limited. We aimed to investigate the effects of gender on self-reported sleep duration and the prevalence of cardiovascular disease and diabetes. Research design and methods: This study is a population-based, cross-sectional analysis. Data from a nationally representative sample of US adults obtained from the National Health and Nutrition Examination Survey (NHANES) (2005–2020), and 13,002 participants, including 6,774men and 6,228women, were obtained by excluding the missing values for each variable self-reported sleep duration data obtained by using a habitual baseline questionnaire. Logistic regression models investigated the associations between gender-specific self-reported sleep duration, CVDs, and diabetes events. Result: In all participants, respectively, compared with sleep 7–8 h/day, the multivariable-adjusted odds ratios significantly associated with < 7 h /day and > 8 h /day were (1.43[1.15, 1.78]) and (1.34[1.01, 1.76]) for CHF, (1.62[1.28, 2.06]) for Angina, (1.42[1.17, 1.71]) for heart attack, (1.38[1.13, 1.70]) and (1.54[1.20, 1.97]) for Stroke, (1.21[1.09, 1.35]) and (1.28[1.11, 1.48]) for diabetes. In men, CHF (1.67[1.21, 2.14]), Angina (1.66[1.18, 2.15]), Stroke (1.55[1.13,1.97]), and diabetes (1.15[1.00, 1.32]) were significantly associated with < 7 h /day, and stroke (1.73[1.16, 2.32]) and diabetes (1.32[1.06, 1.52]) were significantly associated with > 8 h /day. In women, angina(1.83[1.16, 2.50]), heart attack(1.63[1.11, 2.15]), and diabetes (1.32[1.11, 1.54]) were significantly associated with < 7 h /day, while diabetes (1.31[1.03, 1.59]) was significantly associated with > 8 h /day. Conclusion: Self-reported long and short sleep duration was independently associated with partial CVDs and diabetes risk. However, sleep duration and gender did not have multiplicative or additive interactions with the onset of diabetes and CVDs. [ABSTRACT FROM AUTHOR]

Background: Lung cancer (LC), a paramount global life-threatening condition causing significant mortality, is most commonly characterized by its subtype, lung adenocarcinoma (LUAD). Concomitant with LC, pulmonary fibrosis (PF) and interstitial lung disease (ILD) contribute to an intricate landscape of respiratory diseases. Idiopathic pulmonary fibrosis (IPF) in association with LC has been explored. However, other fibrotic interrelations remain underrepresented, especially for LUAD-PF and LUAD-ILD. Methods: We analysed data with statistical analysis from 7,137 healthy individuals, 7,762 LUAD patients, 7,955 ILD patients, and 2,124 complex PF patients collected over ten years. Furthermore, to identify blood indicators related to lung disease and its complications and compare the relationships between different indicators and lung diseases, we successfully applied the naive Bayes model for a biomarker-based prediction of diagnosis and development into complex PF. Results: Males predominantly marked their presence in all categories, save for complex PF where females took precedence. Biomarkers, specifically AGR, MLR, NLR, and PLR emerged as pivotal in discerning lung diseases. A machine-learning-driven predictive model underscored the efficacy of these markers in early detection and diagnosis, with NLR exhibiting unparalleled accuracy. Conclusions: Our study elucidates the gender disparities in lung diseases and illuminates the profound potential of serum biomarkers, including AGR, MLR, NLR, and PLR in early lung cancer detection. With NLR as a standout, therefore, this study advances the exploration of indicator changes and predictions in patients with pulmonary disease and fibrosis, thereby improving early diagnosis, treatment, survival rate, and patient prognosis. [ABSTRACT FROM AUTHOR]

Background: Sex differences exist not only in the efficacy but also in adverse event rates of many vaccines. Here we compared the safety of BNT162b2 vaccine administered off-label in female and male children younger than 5 years in Germany. Methods: This is a retrospective cohort study, in which we performed a post-hoc analysis of a dataset collected through an authentication-based survey of individuals having registered children aged 0-<5 years for vaccination against SARS-CoV-2 in six private practices and/or two lay person-initiated vaccination campaigns. We analyzed the safety profiles of the first 3 doses of 3–10 µg BNT162b2. Primary outcome was comparison in frequencies of 4 common post-vaccination symptom categories such as local, general, musculoskeletal symptoms and fever. Data were analyzed according to sex in bivariate analyses and regression models adjusting for age, weight, and dosage. Interaction between sex and BNT162b2 dosage was assessed. An active-comparator analysis was applied to compare post-vaccination symptoms after BNT162b2 versus non-SARS-CoV-2 vaccines. Results: The dataset for the present analysis consisted of 7801 participants including 3842 females (49%) and 3977 males (51%) with an age of 3 years (median, interquartile: 2 years). Among individuals receiving 3 µg BNT162b2, no sex differences were noted, but after a first dose of 5–10 µg BNT162b2, local injection-site symptoms were more prevalent in girls compared to boys. In logistic regression, female sex was associated with higher odds of local symptoms, odds ratio (OR) of 1.33 (95% confidence interval [CI]: 1.15–1.55, p < 0.05) and general symptoms with OR 1.21 (95% CI: 1.01–1.44, p < 0.05). Following non-BNT162b2 childhood vaccinations, female sex was associated with a lower odds of post-vaccination musculoskeletal symptoms (OR: 0.29, 95% CI: 0.11–0.82, p < 0.05). An active comparator analysis between BNT162b2 and non-SARS-CoV-2 vaccinations revealed that female sex positively influenced the association between BNT162b2 vaccine type and musculoskeletal symptoms. Conclusions: Sex differences exist in post-vaccination symptoms after BNT162b2 administration even in young children. These are of importance for the conception of approval studies, for post-vaccination monitoring and for future vaccination strategies (German Clinical Trials Register ID: DRKS00028759). Plain English summary: For many childhood vaccines, the immune responses are different between the sexes. For the COVID-19 vaccine BNT162b2, the symptoms occurring after vaccination in children have not sufficiently been investigated. In this study, we performed an analysis of a dataset of retrospectively collected information on symptoms occurring after vaccinations with BNT162b2 and regular childhood vaccines in 7801 children under the age of 5 years in Germany, with a focus on the sex differences. Among the four categories assessed, local injection-site and general symptoms were more frequent in girls compared to boys. In contrast, following the administration of other childhood vaccines, the caregivers more frequently reported muscle-related symptoms in boys than in girls. In conclusion, sex differences exist in symptoms occurring after vaccinations even in young children, which is important to consider for future studies evaluating vaccine safety. Registration: The present work was registered at the German Clinical Trials Register ID: DRKS00028759. Highlights: Data on mRNA vaccine safety are abundant, but few studies have investigated children aged under 5 years. The CoVacU5 study was a retrospective cohort of off-label vaccinations with BNT162b2 SARS-CoV-2 vaccine in Germany, from which we here present a detailed sex-disaggregated reanalysis of post-vaccination symptoms in 7801 children. Females were more likely than males to experience local injection-site or general symptoms after being administered BNT162b2. Implications of the present data highlight the importance to assess the sex differences in future mRNA vaccine licensure studies and post-vaccination monitoring. [ABSTRACT FROM AUTHOR]

The document titled "2024 ESC Guidelines for the management of chronic coronary syndromes" provides comprehensive guidelines for the diagnosis and management of chronic coronary syndromes. It covers various topics such as initial management, diagnostic testing, medical therapy, revascularization options, and treatment for specific patient groups. The guidelines emphasize shared decision-making, patient education, and adherence to healthy lifestyle behaviors. It also highlights the importance of long-term follow-up and care, including strategies to improve medication adherence. These resources can be useful for library patrons conducting research on chronic coronary syndrome and seeking evidence-based guidance on its diagnosis and treatment. [Extracted from the article]

Autoimmune diseases are a leading cause of disability worldwide. Most autoimmune diseases occur more often in women than men, with rheumatic autoimmune diseases being among those most highly expressed in women. Several key factors, identified mainly in animal models and cell culture experiments, are important in increasing autoimmune disease in females. These include sex hormones, immune genes including those found on the X chromosome, sex-specific epigenetic effects on genes by estrogen and the environment, and regulation of genes and messenger RNA by microRNAs found in extracellular vesicles. Evidence is also emerging that viruses as well as drugs or toxins that damage mitochondria may contribute to increased levels of autoantibodies against nuclear and mitochondrial antigens, which are common in many autoimmune diseases. The purpose of this Review is to summarize our current understanding of mechanisms that may determine sex differences in autoimmune disease. [ABSTRACT FROM AUTHOR]

Introduction: Although sex differences in allergic diseases such as atopic dermatitis (AD), allergic rhinitis (AR), and asthma are considered important, a limited number of studies during the COVID-19 pandemic investigated this aspect. Therefore, this study aimed to analyze sex-specific and long-term trends and risk factors for allergic diseases before and during the pandemic. Methods: This study utilized data from the Korea National Health and Nutrition Examination Survey, 2007–2022, including 92,135 participants aged 19 years and older. This study used weighted multivariate regression analysis to examine the estimates of related factors and assessed weighted odds ratios or β-coefficients for these factors across multiple categories. Results: During the study period (2007–2022), the prevalence of AR was more common in females than in males. Particularly in 2022, the prevalence among females was 19.3% (95% confidence interval, 17.3–21.3), while among males, it was 15.6% (13.8–17.4). The prevalence of AD and asthma showed a slight disparity between males and females. Before and during the pandemic, the prevalence of AD and AR showed a continuous increase (AD: from 2.8% [2.5–3.2] in 2007–2009 to 4.7% [3.9–5.4] in 2022; AR: from 11.7% [11.1–12.4] in 2007–2009 to 17.4% [16.0–18.9] in 2022), while asthma maintained a relatively stable trend. Moreover, this study identified several sex-specific factors that seem to be associated with a higher prevalence of allergic diseases in females, such as high household income, smoking, and being overweight or obese. Conclusions: Throughout all the periods examined, females consistently exhibited a higher prevalence of AR compared to males. Moreover, the risk factors for males and females varied depending on the disease, with females generally facing a greater number of risk factors. Consequently, this study highlights the necessity for sex-specific health interventions and further research to comprehend the complex influence of socioeconomic factors and lifestyle choices on the prevalence and risk of AD, AR, and asthma. [ABSTRACT FROM AUTHOR]

Background: Sex differences exist in the prevalence and progression of major glomerular diseases. Podocytes are the essential cell-type in the kidney which maintain the physiological blood-urine barrier, and pathological changes in podocyte homeostasis are critical accelerators of impairment of kidney function. However, sex-specific molecular signatures of podocytes under physiological and stress conditions remain unknown. This work aimed at identifying sexual dimorphic molecular signatures of podocytes under physiological condition and pharmacologically challenged homeostasis with mechanistic target of rapamycin (mTOR) inhibition. mTOR is a crucial regulator involved in a variety of physiological and pathological stress responses in the kidney and inhibition of this pathway may therefore serve as a general stress challenger to get fundamental insights into sex differences in podocytes. Methods: The genomic ROSAmT/mG-NPHS2 Cre mouse model was used which allows obtaining highly pure podocyte fractions for cell-specific molecular analyses, and vehicle or pharmacologic treatment with the mTOR inhibitor rapamycin was performed for 3 weeks. Subsequently, deep RNA sequencing and proteomics were performed of the isolated podocytes to identify intrinsic sex differences. Studies were supplemented with metabolomics from kidney cortex tissues. Results: Although kidney function and morphology remained normal in all experimental groups, RNA sequencing, proteomics and metabolomics revealed strong intrinsic sex differences in the expression levels of mitochondrial, translation and structural transcripts, protein abundances and regulation of metabolic pathways. Interestingly, rapamycin abolished prominent sex-specific clustering of podocyte gene expression and induced major changes only in male transcriptome. Several sex-biased transcription factors could be identified as possible upstream regulators of these sexually dimorphic responses. Concordant to transcriptomics, metabolomic changes were more prominent in males. Remarkably, high number of previously reported kidney disease genes showed intrinsic sexual dimorphism and/or different response patterns towards mTOR inhibition. Conclusions: Our results highlight remarkable intrinsic sex-differences and sex-specific response patterns towards pharmacological challenged podocyte homeostasis which might fundamentally contribute to sex differences in kidney disease susceptibilities and progression. This work provides rationale and an in-depth database for novel targets to be tested in specific kidney disease models to advance with sex-specific treatment strategies. Plain Language Summary: The global burden of chronic kidney diseases is rapidly increasing and is projected to become the fifth most common cause of years of life lost worldwide by 2040. Sexual dimorphism in kidney diseases and transplantation is well known, yet sex-specific therapeutic strategies are still missing. One reason is the lack of knowledge due to the lack of inclusion of sex as a biological variable in study designs. This work aimed at identification of molecular signatures of male and female podocytes, gate-keepers of the glomerular filtration barrier. Like cardiomyocytes, podocytes are terminally differentiated cells which are highly susceptible towards pathological challenges. Podocytes are the decisive cell-type of the kidney to maintain the physiological blood-urine barrier, and disturbances of their homeostasis critically accelerate kidney function impairment. By help of a genomic mouse model, highly purified podocytes were obtained from male and female mice with and without pharmacological challenge of the mechanistic target of rapamycin (mTOR) signaling pathway which is known to be deregulated in major kidney diseases. Deep RNA sequencing, proteomics and metabolomics revealed strong intrinsic sex differences in the expression levels of mitochondrial, translation and structural transcripts, protein abundances and regulation of metabolic pathways which might fundamentally contribute to sex differences in kidney disease susceptibilities and progression. Remarkably, high number of previously reported kidney disease genes showed so far unknown intrinsic sexual dimorphism and/or different response patterns towards mTOR inhibition. Our work provides an in-depth database for novel targets to be tested in kidney disease models to advance with sex-specific treatment strategies. Highlights: First study to describe sexually dimorphic molecular signature of podocytes, "gate-keepers" of the kidney glomerular filtration barrier. Large number of known kidney-disease related genes are newly identified for intrinsic sexual dimorphic expression as well as after pharmacological intervention with rapamycin. Male podocytes appear more susceptible to transcriptomic changes. Metabolomics supports higher functional consequences of mTOR inhibition on protein synthesis and impaired energy balance in male kidneys. Study provides an in-depth database for further research in the field of highly sexually dimorphic kidney diseases. [ABSTRACT FROM AUTHOR]

Background: While sex-based differences in various health scenarios have been thoroughly acknowledged in the literature, we lack sufficient tools and methods that allow for an in-depth analysis of sex as a variable in biomedical research. To fill this knowledge gap, we created MetaFun as an easy-to-use web-based tool to meta-analyze multiple transcriptomic datasets with a sex-based perspective to gain major statistical power and biological soundness. Description: MetaFun is a complete suite that allows the analysis of transcriptomics data and the exploration of the results at all levels, performing single-dataset exploratory analysis, differential gene expression, gene set functional enrichment, and finally, combining results in a functional meta-analysis. Which biological processes, molecular functions or cellular components are altered in a common pattern in different transcriptomic studies when comparing male and female patients? This and other biological questions of interest can be answered with the use of MetaFun. This tool is available at https://bioinfo.cipf.es/metafun while additional help can be found at https://gitlab.com/ubb-cipf/metafunweb/-/wikis/Summary. Conclusions: Overall, Metafun is the first open-access web-based tool to identify consensus biological functions across multiple transcriptomic datasets, helping to elucidate sex differences in numerous diseases. Its use will facilitate the generation of novel biological knowledge that can be used in the research and application of Personalized Medicine considering the sex of patients. [ABSTRACT FROM AUTHOR]

A unique interplay between body and environment embeds and reflects host–microbiome interactions that contribute to sex‐differential disease susceptibility, symptomatology, and treatment outcomes. These differences derive from individual biological factors, such as sex hormone action, sex‐divergent immune processes, X‐linked gene dosage effects, and epigenetics, as well as from their interaction across the lifespan. The gut microbiome is increasingly recognized as a moderator of several body systems that are thus impacted by its function and composition. In humans, biological sex components further interact with gender‐specific exposures such as dietary preferences, stressors, and life experiences to form a complex whole, requiring innovative methodologies to disentangle. Here, we summarize current knowledge of the interactions among sex hormones, gut microbiota, immune system, and vascular health and their relevance for sex‐differential epidemiology of cardiovascular diseases. We outline clinical implications, identify knowledge gaps, and place emphasis on required future studies to address these gaps. In addition, we provide an overview of the caveats associated with conducting cardiovascular research that require consideration of sex/gender differences. While previous work has inspected several of these components separately, here we call attention to further translational utility of a combined perspective from cardiovascular translational research, gender medicine, and microbiome systems biology. [ABSTRACT FROM AUTHOR]

This article examines the issue of women being underrepresented in clinical trials for new antidiabetic drugs, particularly those focusing on cardiac and renal outcomes. The study reveals that this underrepresentation hampers the development of safe and effective medical interventions for women. It highlights the importance of including more women in these trials to improve the accuracy and progress of medical knowledge. The authors recommend that future researchers prioritize recruiting women in proportions that reflect their representation in the population to enhance the precision and relevance of medical interventions. [Extracted from the article]

Fragmentation/loss of the structural protein elastin represents the precipitating event translating to aortic expansion and subsequent aneurysm formation. The present study tested the hypothesis that greater protein expression of tissue inhibitor of matrix metalloproteinase‐1 (TIMP‐1) and neointimal growth secondary to a reduction of medial elastin content represent sex‐dependent events limiting aortic vessel expansion in females. TIMP‐1 protein levels were higher in the ascending aorta of female versus male patients diagnosed with a bicuspid aortic valve (BAV). The latter paradigm was recapitulated in the aorta of adult male and female rats complemented by greater TIMP‐2 expression in females. CaCl2 (0.5 M) treatment of the infrarenal aorta of adult male and female rats increased the in situ vessel diameter and expansion was significantly smaller in females despite a comparable reduction of medial elastin content. The preferential appearance of a neointimal region of the CaCl2‐treated infrarenal aorta of female rats may explain in part the smaller in situ expansion and neointimal growth correlated positively with the % change of the in situ diameter. Neointimal formation was secondary to a significant increase in the density of medial/neointimal vascular smooth muscle cells (VSMCs) that re‐entered the G2‐M phase whereas VSMC cell cycle re‐entry was attenuated in the CaCl2‐treated infrarenal aorta of male rats. Thus, greater TIMP‐1 expression in the aorta of female BAV patients may prevent excessive elastin fragmentation and preferential neointimal growth following CaCl2‐treatment of the infrarenal aorta of female rats represents a sex‐dependent biological event limiting vessel expansion secondary to a significant loss of the structural protein. [ABSTRACT FROM AUTHOR]

Numerous studies have been conducted in other countries on the health effects of exposure to particulate matter with a diameter of 10 microns or less P M 10 , but little research has been conducted in Malaysia, particularly during the haze season. This study intends to investigate how exposure of P M 10 influenced hospital admissions for respiratory diseases during the haze period in peninsula Malaysia and it was further stratified by age group, gender and respiratory diseases categories. The study includes data from all patients with respiratory diseases in 92 government hospitals, as well as P M 10 concentration and meteorological data from 92 monitoring stations in Peninsula Malaysia starting from 1st January 2000 to 31st December 2019. A quasi-poison time series regression with distributed lag nonlinear model (DLNM) was employed in this study to examine the relationship between exposure of P M 10 and hospital admissions for respiratory diseases during the haze period. Haze period for this study has been defined from June to September each year. According to the findings of this study, P M 10 was positively associated with hospitalisation of respiratory disease within 30 lag days under various lag patterns, with lag 25 showing the strongest association (RR = 1.001742, CI 1.001029,1.002456). Using median as a reference, it was discovered that females were more likely than males to be hospitalized for P M 10 exposure. Working age group will be the most affected by the increase in P M 10 exposure with a significant cumulative RR from lag 010 to lag 030. The study found that P M 10 had a significant influence on respiratory hospitalisation in peninsula Malaysia, particularly for lung diseases caused by external agents(CD5). Therefore, it is important to implement effective intervention measures to control P M 10 and reduce the burden of respiratory disease admissions. [ABSTRACT FROM AUTHOR]

There are controversies regarding the impact of sex on mortality and postoperative complications in patients undergoing on-pump coronary artery bypass grafting (CABG), although some studies demonstrate comparable outcomes. This study sought to evaluate sex differences regarding risk factors associated with hospital mortality and postoperative clinical outcomes among patients undergoing isolated on-pump CABG. We conducted a retrospective observational cohort study of patients who underwent isolated on-pump CABG from January 1996 to January 2020. Patients were divided into two groups (male and female) and compared regarding preoperative characteristics, surgical technical variables, and in-hospital outcomes. All-cause mortality between groups was compared using logistic regression. Risk factors for mortality, along with their respective odds ratios (OR), were separately assessed using a logistic regression model with p-values for interaction. We analyzed 4,882 patients, of whom 31.6% were female. Women exhibited a higher prevalence of age >75 years (12.2% vs 8.3%, p<0.001), obesity (22.6% vs 11.5%, p<0.001), diabetes (41.6% vs 32.2%, p<0.001), hypertension (85.2% vs 73.5%, p<0.001), and NYHA functional classes 3 and 4 (16.2% vs 11.2%, p<0.001) compared to men. Use of the mammary artery for revascularization was less frequent among women (73.8% vs 79.9%, p<0.001), who also received fewer saphenous vein grafts (2.17 vs 2.27, p = 0.002). A history of previous or recent myocardial infarction (MI) had an impact on women's mortality, unlike in men (OR 1.61 vs 0.94, p = 0.014; OR 1.86 vs 0.99, p = 0.015, respectively). After adjusting for several risk factors, mortality was found to be comparable between men and women, with an OR of 1.20 (95% CI 0.94–1.53, p = 0.129). In conclusion, female patients undergoing isolated on-pump CABG presented with a higher number of comorbidities. Previous and recent MI were associated with higher mortality only in women. In this cohort analysis, female gender was not identified as an independent risk factor for outcome after CABG. [ABSTRACT FROM AUTHOR]

This document contains abstracts from the 2024 Pediatric Endocrine Society Annual Meeting, covering a range of topics related to pediatric endocrinology. The abstracts discuss hormone-related conditions such as congenital adrenal hyperplasia, adrenal insufficiency, X-linked adrenoleukodystrophy, and Cushing syndrome, emphasizing the importance of understanding and managing these conditions in pediatric patients. Other abstracts focus on growth disorders, hormonal deficiencies, and the use of growth hormone therapy. Additionally, there are abstracts related to transgender healthcare, genetic syndromes, and diabetes in pediatric patients. These abstracts provide valuable insights for researchers and healthcare professionals working in these areas. The document also includes abstracts on medical education in pediatric endocrinology, addressing topics such as transition processes for patients with diabetes, type 1 diabetes education, standardized curriculum implementation, and training sessions for infant genital examinations and testicular volume estimation. These abstracts shed light on the current state of medical education in pediatric endocrinology and suggest areas for improvement. [Extracted from the article]

Introduction We evaluated the risk factors associated with gastrointestinal disorders (GD) among the soldiers of the Army and Marine Aviation community (AMAC) using an exposomic approach. Specifically, we aimed to determine the medical and operational factors associated with reported GD in the Military Health System. Methods Longitudinal data were obtained from the Medical Assessment and Readiness System (MARS) housed at Womack Army Medical Center, Fort Liberty, NC, for a retrospective cohort study that included 79,249 active duty United States AMAC active duty service members (ADSMs) from October 2015 to December 2019. Multivariable mixed-effects logistic regression was used to assess the relationship between the incidence occurrence of GD and variables including rank, service time, deployment, Armed Forces Qualification Test score, education, tobacco use, alcohol use, age, gender, race, ethnicity, body mass index (BMI), and marital status. Results The incidence of GD included 22,813 person-years of observations with a rate of 2.2 per 100 person-years and a period prevalence of 3.2%. GD was independently associated with rank, service time, and deployment (all P  < 0.05). Conclusion The high-risk categories associated with GD in the AMAC included age, BMI, race (not ethnicity), marital status, and service time. Our data also show that deployment time, not geographical location, was associated with a higher risk of GD. Together, these analyses suggest that White ADSMs older than 33 years of age who have experienced marriage, longer service time, and deployments appear to have a higher risk of GDs. Our assessment shows the utility of using an exposomic approach to create a member-specific, big data-informed personalized clinical algorithm of health outcomes. [ABSTRACT FROM AUTHOR]

The lack of sex-specific cardiovascular disease criteria contributes to the underdiagnosis of women compared to that of men. For more than half a century, the Framingham Risk Score has been the gold standard to estimate an individual's risk of developing cardiovascular disease based on the age, sex, cholesterol levels, blood pressure, diabetes status, and the smoking status. Now, machine learning can offer a much more nuanced insight into predicting the risk of cardiovascular diseases. The UK Biobank is a large database that includes traditional risk factors and tests related to the cardiovascular system: magnetic resonance imaging, pulse wave analysis, electrocardiograms, and carotid ultrasounds. Here, we leverage 20,542 datasets from the UK Biobank to build more accurate cardiovascular risk models than the Framingham Risk Score and quantify the underdiagnosis of women compared to that of men. Strikingly, for a first-degree atrioventricular block and dilated cardiomyopathy, two conditions with non-sex-specific diagnostic criteria, our study shows that women are under-diagnosed 2× and 1.4× more than men. Similarly, our results demonstrate the need for sex-specific criteria in essential primary hypertension and hypertrophic cardiomyopathy. Our feature importance analysis reveals that out of the top 10 features across three sexes and four disease categories, traditional Framingham factors made up between 40% and 50%; electrocardiogram, 30%–33%; pulse wave analysis, 13%–23%; and magnetic resonance imaging and carotid ultrasound, 0%–10%. Improving the Framingham Risk Score by leveraging big data and machine learning allows us to incorporate a wider range of biomedical data and prediction features, enhance personalization and accuracy, and continuously integrate new data and knowledge, with the ultimate goal to improve accurate prediction, early detection, and early intervention in cardiovascular disease management. Our analysis pipeline and trained classifiers are freely available at https://github. com/LivingMatterLab/CardiovascularDiseaseClassification. [ABSTRACT FROM AUTHOR]

Background: Few studies have been undertaken to detect the presence of cardiovascular risk factors (CRFs) in healthy populations (individuals auto-reported as healthy). These risk factors include high body mass index (BMI), high waist-to-hip ratio (WHR), high systolic and diastolic blood pressure (SBP, DBP), high uric acid and high Castelli's risk index (CRI); this last is the ratio of total cholesterol to HDL cholesterol (TC/HDL-c). In addition, the correlations between CRFs and the biomarker C-reactive protein (CRP) has not been explored in each sex. Aim: Therefore, this study aimed to determine sex differences in the abnormalities in blood and urine analyses, including CRFs and their correlation with CPR in a non-representative sample of healthy Mexican individuals. Results: A total of 238 subjects were included, 123 (51.7%) of whom were women. The main blood alterations detected were high serum lipids, including high total cholesterol, LDL-cholesterol, triglycerides, and the CRI, which were higher in men than in women. The men's samples had a higher frequency of hypertensives and pre-hypertensives than the women's sample. The CRP showed positive significant correlations with the CRFs: BMI, WHR, SBP, DBP, uric acid, and the CRI, with a higher correlation for BMI and WHR, and most of these correlations were higher in women than in men. Additionally, all these factors showed a positive correlation among them. Conclusion: In conclusion, the main alterations observed in blood are related to cardiovascular risk and were reported with a higher frequency in men when compared with women. This finding can be related to the higher values of WHR in this sex; additionally, the inflammatory marker CRP was more correlated with the cardiometabolic risk factors in women than in men, which suggests a different relationship between inflammation and cardiometabolic risk factors in each sex. [ABSTRACT FROM AUTHOR]

By demethylating or clipping histones, Jumonji C domain-containing (JMJD) proteins induce chromatin changes that lie beneath the epigenetic control of gene expression. Through a wide repertoire of catalytic activities (hydroxylation, demethylation, proteolytic cleavage) and non-catalytic activities affecting non-histone proteins, JMJD proteins shape various cellular processes beyond epigenetics. Several oncometabolites, oxygen tension, reactive oxygen species (ROS), and heavy metals all affect JMJD catalytic activity, allowing JMJD proteins to sense metabolic changes. Pathogenic JMJD mutations or dysregulated JMJD activity underlie various diseases, including cancer and neurodevelopmental defects, and may also account for sex-dependent differences in disease prevalence and manifestation. Inhibiting or activating specific JMJD proteins may be efficacious in clinical therapy. Jumonji C domain-containing (JMJD) proteins are found in bacteria, fungi, animals, and plants. They belong to the 2-oxoglutarate-dependent oxygenase superfamily and are endowed with various enzymatic activities, including demethylation of histones and hydroxylation of non-histone proteins. Many JMJD proteins are involved in the epigenetic control of gene expression, yet they also modulate a myriad other cellular processes. In this review we focus on the 33 human JMJD proteins and their established and controversial catalytic properties, survey their epigenetic and non-epigenetic functions, emphasize their contribution to sex-specific disease differences, and highlight how they sense metabolic changes. All this underlines not only their key roles in development and homeostasis, but also that JMJD proteins are destined to become drug targets in multiple diseases. [ABSTRACT FROM AUTHOR]

Sex differences in renal physiology and pathophysiology are now well established in rodent models and in humans. Epigenetic programming is known to be a critical component of renal injury, as studied mainly in male rodent models; however, not much is known about the impact of biological sex and age on the kidney epigenome. We sought to determine the influence of biological sex and age on renal epigenetic and injury markers, using male and female mice at 4 mo (4M; young), 12 mo (12M), and 24 mo (24M; aged) of age. Females had a significant increase in kidney and body weights and serum creatinine levels and a decrease in serum albumin levels from 4M to 24M of age, whereas minor changes were observed in male mice. Kidney injury molecule-1 levels in serum and renal tissue greatly enhanced from 12M to 24M in both males and females. Circulating histone 3 (H3; damage-associated molecular pattern molecules) levels extensively increased with age; however, males had higher levels than females. Overall, females had markedly high histone acetyltransferase (HAT) activity than age-matched males. Aged mice had decreased HAT activity and increased histone deacetylase activity than sex-matched 12M mice. Aged females had substantially decreased renal H3 methylation at lysine 9 and 27 and histone methyltransferase (HMT) activity than aged male mice. Antiaging protein Klotho levels were significantly higher in young males than age-matched females and decreased substantially with age in males, whereas epigenetic repressor of Klotho, trimethylated H3K27, and its HMT enzyme, enhancer of zeste homolog 2, increased consistently with age in both sexes. Moreover, nuclear translocation and activity of proinflammatory transcription factor nuclear factor-κB (p65) were significantly higher in aged mice. Taken together, our data suggest that renal aging lies in a range between normal and diseased kidneys but may differ between female and male mice, highlighting sex-related differences in the aging process. NEW & NOTEWORTHY: Although there is evidence of sex-specific differences in kidney diseases, most preclinical studies have used male rodent models. The clinical data on renal injury have typically not been stratified by sex. Our findings provide convincing evidence of sex-specific differences in age-regulated epigenetic alterations and renal injury markers. This study highlights the importance of including both sexes for better realization of underlying sex differences in signaling mechanisms of aging-related renal pathophysiology. [ABSTRACT FROM AUTHOR]

Major histocompatibility complex class I (MHC I) molecules present peptides to CD8+ T‐cells for immunosurveillance of infection and cancer. Recent studies indicate lineage‐specific heterogeneity in MHC I expression. While respiratory diseases rank among the leading causes of mortality, studies in mice have shown that lung epithelial cells (LECs) express the lowest levels of MHC I in the lung. This study aims to answer three questions: (i) Do human LECs express low levels of MHC I? (ii) Is LEC MHC I expression modulated in chronic respiratory diseases? (iii) Which factors regulate MHC I levels in human LECs? We analyzed human LECs from parenchymal explants using single‐cell RNA sequencing and immunostaining. We confirmed low constitutive MHC I expression in human LECs, with significant upregulation in chronic respiratory diseases. We observed a sexual dimorphism, with males having higher MHC I levels under steady‐state conditions, likely due to differential redox balance. Our study unveils the complex interplay between MHC I expression, sex, and respiratory disease. Since MHC I upregulation contributes to the development of immunopathologies in other models, we propose that it may have a similar impact on chronic lung disease. [ABSTRACT FROM AUTHOR]

Sex differences have been observed in individuals with schizophrenia and for those at clinical high risk (CHR) for psychosis. However, specific differences in CHR individuals who transition to psychosis remain inconsistent and understudied. This study aimed to investigate sex differences in 156 CHR individuals who made the transition to psychosis. A wide range of demographics, positive and negative symptoms, depression, anxiety, social and role functioning, trauma, and substance use were assessed at baseline and symptoms and diagnoses at the time of transition. Fluctuations in positive and negative symptoms and different medications were also assessed. No sex differences were observed at baseline for those who later transitioned to psychosis. At transition, males were significantly more likely to be diagnosed as having schizophrenia or schizophreniform disorder and through the course of the study, males were more likely to be taking stimulants. Limitations in this study was the lack of longitudinal follow-up post transition. The study highlights the need for further research on sex differences in individuals who transition to psychosis. Understanding these differences can have implications for treatment and monitoring of CHR individuals. [ABSTRACT FROM AUTHOR]

Background: Digital monitoring of people with multiple sclerosis (PwMS) using smartphone-based monitoring tools is a promising method to assess disease activity and progression. Objective: To study cross-sectional and longitudinal associations between active and passive digital monitoring parameters and MRI volume measures in PwMS. Methods: In this prospective study, 92 PwMS were included. Clinical tests [Expanded Disability Status Scale (EDSS), Timed 25 Foot Walk test (T25FW), 9-Hole Peg Test (NHPT), and Symbol Digit Modalities Test (SDMT)] and structural MRI scans were performed at baseline (M0) and 12-month follow-up (M12). Active monitoring included the smartphone-based Symbol Digit Modalities Test (sSDMT) and 2 Minute Walk Test (s2MWT), while passive monitoring was based on smartphone keystroke dynamics (KD). Linear regression analyses were used to determine cross-sectional and longitudinal relations between digital and clinical outcomes and brain volumes, with age, disease duration and sex as covariates. Results: In PwMS, both sSDMT and SDMT were associated with thalamic volumes and lesion volumes. KD were related to brain, ventricular, thalamic and lesion volumes. No relations were found between s2MWT and MRI volumes. NHPT scores were associated with lesion volumes only, while EDSS and T25FW were not related to MRI. No longitudinal associations were found for any of the outcome measures between M0 and M12. Conclusion: Our results show clear cross-sectional correlations between digital biomarkers and brain volumes in PwMS, which were not all present for conventional clinical outcomes, supporting the potential added value of digital monitoring tools. [ABSTRACT FROM AUTHOR]

Disturbed CNS zinc homeostasis is suggested as part of the pathophysiology of schizophrenia. Our data, from multiple studies, suggests levels of cortical RNA for the solute carrier family 39 member 12 (SLC39A12), a putative zinc transporter, is higher in people with schizophrenia and is more perturbed in a sub-group of people with the disorder that can be separated because they have very low levels of muscarinic M1 receptors (MRDS). In this study qPCR was used to measure levels of two RNA splice variants of SLC39A12 (a and b) in Brodmann's area (BA) 44 from new cohorts of controls and people with schizophrenia. For the first time, in our study cohort as a whole, we report levels of both splice variants of SLC39A12 are lower in females compared to males and there are correlations between levels of SLC39A12 a and b and CNS pH. Levels of both splice variants were also lower in people with schizophrenia who were suicide completers compared to those who were not. Accounting for these factors, we showed levels of SLC39A12 a and b were higher in BA 44 in schizophrenia compared to controls. In further analyses, with and without our previous data on SLC39A12 a and b , we confirmed changes in levels of SLC39A1 2 RNAs were more profound in MRDS. In conclusion, our study argues there are higher levels of SLC39A12 a and b in BA 44 in schizophrenia which could be contributing to the breakdown in CNS zinc homeostasis suggested as part of the pathophysiology of schizophrenia, particularly in those with MRDS. [ABSTRACT FROM AUTHOR]

This study examined sex differences for health risk factors as potential mediators in the association between posttraumatic stress disorder (PTSD) and cardiovascular disease (CVD). Secondary data from the 2012–2013 National Epidemiological Survey on Alcohol and Related Conditions Wave 3 was used. This cross-sectional survey contains a nationally representative sample of 36,309 U.S. adults (n females = 20,447, M age = 47.16, 95% CI = [46.74, 47,57]; n males = 15,682, M age = 45.88, 95% CI = [45.42, 46.34]). Natural effect models and logistic regression analyses were conducted to evaluate health risk factors (smoking, substance use, low physical activity, high body mass index [BMI], binge eating, and multiple health risk factors) as potential mediators for the PTSD-CVD relationship in females and males. High BMI (indirect AOR = 1.05, 95% CI = [1.02, 1.07]) and substance use (indirect AOR = 0.93, 95% CI = [0.88, 0.98], p = 0.005) were potential mediators in females and males respectively. Binge eating, smoking, and low physical activity were not mediators in either sex. The number of health risk factors was also a potential mediator in females (indirect AOR = 1.12, 95% CI = [1.07, 1.19], p = <0.001) though not males (indirect AOR = 1.09, 95% CI = [1.00, 1.19], p =.059). The results inform prevention strategies, such as screening for health risk factors to mitigate the adverse effect of PTSD on CVD risk. Findings also inform important directions for future longitudinal research to establish causal pathways. • BMI and substance use were potential mediators in females and males, respectively. • Binge eating, smoking and low physical activity did not mediate the PTSD-CVD relationship. • The number of health risk factors was a potential mediator in females, though not males. • Screening for health risk factors may help to mitigate the adverse effect of PTSD on CVD risk. [ABSTRACT FROM AUTHOR]

This study reports on gender differences in psychosocial symptoms and suicidal thoughts and behaviors from the first longitudinal, national survey of veterans with a recent nonfatal suicide attempt to inform women-tailored suicide prevention. We recruited all female veterans with a documented nonfatal suicide attempt between October 2018 and September 2019 and a stratified matched sample of males. Surveys were administered at baseline, month 6, and month 12; 968 veterans completed the baseline survey with valid gender data. Surveys assessed psychosocial constructs, suicidal ideation severity, and suicidal behavior. Administrative datasets provided healthcare and suicide attempt data during the one year follow up. Women retained higher social rejection and institutional betrayal, and lower self-compassion and autonomy than men over follow up. Higher overall self-compassion was associated with lower baseline suicide ideation for both women and men; however, this association was stronger for women (Δ = −0.19; 95 % CI = -0.31, −0.07; d = −0.15). Individuals with higher overall psychological distress had greater odds of a subsequent suicide attempt (AOR = 2.20, 95 % CI = 1.56, 3.11). Social rejection had the strongest association with worsening psychological distress, both within individuals (b = 0.18; 95 % CI = 0.14, 0.23; d = 0.23) and between individuals (b = 0.07; 95 % CI = 0.04, 0.10; d = 0.09). Results may not generalize beyond a VHA-utilizing veteran population. Findings from this study inform potential therapeutic targets and topics for future research on tailoring suicide prevention for women veterans. While all veterans may need support reducing distress, women may need additional support in multiple other areas. • Tailored suicide prevention strategies for women veterans are needed. • Psychological distress is a core contributor to suicide risk among veterans. • Women veterans carry higher psychosocial risk and lower resilience than men. • Chronic illness approaches are warranted for veterans with recent suicide attempts. [ABSTRACT FROM AUTHOR]

It is widely known that sex differences have a significant impact on patients with major depressive disorder (MDD). This study aims to evaluate the sex-related connection between serum trace elements and changes in neurometabolism in the anterior cingulate cortex (ACC) of MDD patients. 109 untreated MDD patients and 59 healthy controls underwent proton magnetic resonance spectroscopy (1H-MRS) under resting conditions. We measured metabolic ratios in the ACC from both sides. Additionally, venous blood samples were taken from all participants to detect calcium (Ca), phosphorus, magnesium (Mg), copper (Cu), ceruloplasmin (CER), zinc (Zn), and iron (Fe) levels. We performed association and interaction analyses to explore the connections between the disease and gender. In individuals with MDD, the Cu/Zn ratio increased, while the levels of Mg, CER, Zn and Fe decreased. Male MDD patients had lower Cu levels, while female patients had an increased Cu/Zn ratio. We observed significant gender differences in Cu, CER and the Cu/Zn ratio in MDD. Male patients showed a reduced N -acetyl aspartate (NAA)/phosphocreatine + creatine (PCr + Cr) ratio in the left ACC. The NAA/PCr + Cr ratio decreased in the right ACC in patients with MDD. In the left ACC of male MDD patients, the Cu/Zn ratio was inversely related to the NAA/PCr + Cr ratio, and Fe levels were negatively associated with the GPC + PC/PCr + Cr ratio. Our findings highlight gender-specific changes in Cu homeostasis among male MDD patients. The Cu/Zn ratio and Fe levels in male MDD patients were significantly linked to neurometabolic alterations in the ACC. • Serum levels of Cu and CER decreased in men with MDD, while the Cu/Zn ratio increased in women with MDD. • In males with MDD, a gender-specific decrease in the NAA/PCr + Cr ratio was noted in the left ACC. • The Cu/Zn ratio and Fe levels in male MDD patients are associated with changes in neurometabolism in the ACC. [ABSTRACT FROM AUTHOR]

Hepatitis B virus is a global health concern with a high death rate in Afghanistan. Limited data exist on the disease's impact on quality of life in low‐resource settings. This case–control study aims to identify potential risk factors and assess the quality of life among hepatitis B patients in Herat, Afghanistan, with a focus on sex differences. Understanding these factors can inform prevention, care, and sex‐specific interventions. A cross‐sectional study conducted at Herat Regional Hospital examined hepatitis B patients above 18 years old, between October 2020 and February 2021. The control group consisted of age and sex‐matched individuals without a history of hepatitis B. Data were collected through a structured questionnaire covering socio‐demographic characteristics, signs and symptoms of hepatitis B, and the SF‐36 questionnaire for measuring the quality of life of study participants. Statistical analysis was performed using multivariate General Linear Models, and logistic regression. We identified several potential risk factors for hepatitis B infection, including male sex, younger age groups, tobacco use, lower education levels, rural residence, family history, weak social networks, specific family structures and underlying chronic diseases (p <.05). The study found that hepatitis B cases had significantly lower mean scores across all SF‐36 components, indicating an overall reduced quality of life (p <.05). These differences were more pronounced in males, although females had lower scores in most components. Role limitations due to physical and emotional health were particularly affected. These findings highlight the urgent need for targeted interventions, sex‐specific strategies, improved healthcare access and comprehensive policies. These findings can inform prevention efforts to improve the overall quality of life of people with hepatitis B in Afghanistan. [ABSTRACT FROM AUTHOR]

Brain-derived neurotrophic factor (BDNF) and glycolipid metabolism have been implicated in cognitive impairments and depression among Parkinson's disease (PD). However, the role of sex differences in this relationship remains elusive. This study aimed to investigate the potential sex differences in the link between serum BDNF levels, glycolipid metabolism and cognitive performance among depressive PD patients. PD patients comprising 108 individuals with depression and 108 without depression were recruited for this study. Cognitive function was assessed using the Montreal Cognitive Assessment Beijing version (MOCA-BJ). The severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale (HAMD-17), while motor symptoms were evaluated using the Revised Hoehn and Yahr rating scale (H-Y) and the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III). Laboratory testing and enzyme-linked immunosorbent assay (ELISA) are used to measure serum levels of glycolipid metabolism and BDNF. Females showed superior performance in delayed recall (all p < 0.05), male PD patients exhibited higher scores in naming tasks compared to females in non-depression group. There was no sex differences in serum BDNF levels between depression and non-depression groups. Liner regression analysis indicated BDNF as an independent risk factor for language deficits in male PD patients with depression (p < 0.05), while cholesterol (CHOL) emerged as a cognitive influencing factor, particularly in delayed recall among male PD patients with depression (p < 0.05). Our study reveals extensive cognitive impairments in PD patients with depression. Moreover, BDNF and CHOL may contribute to the pathological mechanisms underlying cognitive deficits, particularly in male patients with depression. [ABSTRACT FROM AUTHOR]

Background/Objectives: Depression and anxiety are prevalent disorders, particularly during emerging adulthood. Uncertainty about the future, exacerbated by unstable times, can lead to heightened future anxiety in this group. This study aimed to examine the complex associations of depression symptoms, future anxiety, and self-efficacy in adults from Poland. Additionally, we investigated age and gender differences in depression symptoms, future anxiety, and self-efficacy. Methods: A cross-sectional online survey study was performed in 2023 in Poland using snowball sampling. A convenience sample of 284 adults participated in this study, ranging in age between 18 and 65 years old (M = 32.18, SD = 11.87), including 95 men (33.45%) and 189 (66.55%) women, and also 157 (55.63%) emerging adults (18–28 years old) and 126 (44.37%) middle-aged adults (29–65 years old). The Patient Health Questionnaire (PHQ-9), Dark Future Scale (DFS-5), and Generalized Self-Efficacy Scale (GSES) were used to measure depression, future anxiety, and self-efficacy, respectively. Results: A 2-way ANOVA showed that both emerging adults and women scored significantly higher in depression symptoms and future anxiety than middle-aged adults and men, respectively. Furthermore, women scored lower in self-efficacy than men. Analyses revealed that there was a positive correlation between depression and future anxiety. Self-efficacy was negatively correlated with depression and future anxiety. Self-efficacy and future anxiety accounted for 48% of depression variance, controlling for age and gender. Future anxiety was found to be a partial mediator of the relationship between self-efficacy and depression. Conclusions: This study significantly advances the understanding of mental health in adults, grounded in social cognitive theories, revealing that low self-efficacy heightens future anxiety, thereby exacerbating depression symptoms in the Polish adult population, independent of age and gender. Emerging adults and women need psychological support to reduce depression and future anxiety. Women, in particular, should be the main focus of interventions to boost self-efficacy. Implementing targeted preventive measures and support systems can mitigate the challenges faced by emerging adults and women. [ABSTRACT FROM AUTHOR]

Sucrose intake is a potential risk factor for non-alcoholic fatty liver disease (NAFLD). Individual characteristics such as sex, play arole in the biological variation of the disease, potentially related to genetic regulation. This research evaluated sex differences in biochemical, histopathological, and gene expression responses associated with NAFLD in C57bl/6N mice on a high sucrose diet. Female and male mice were assigned to control or high sucrose diets (50% sucrose solution) for 20 weeks. After sacrifice, blood and hepatic tissue were collected for analysis. Female mice revealed moderate-to-high NAFLD, whereas male mice showed mild-to-moderate NAFLD. Sex-specific variations were observed in Cd36 gene expression, an upregulation in females compared with the male group, and Adipor1 gene expression showed significant downregulation in the female group in response to high sucrose diet compared with the control group. These findings highlight the importance of considering gender disparities in the treatment and management of NAFLD. [ABSTRACT FROM AUTHOR]

This article provides a comprehensive overview of Narcissistic Personality Disorder (NPD) from both a psycholinguistic and neuroscientific perspective. It explores the distinct communication patterns associated with different subtypes of NPD and identifies specific brain regions and functional abnormalities associated with the disorder. The integration of psycholinguistic and neuroscientific findings can improve diagnosis and treatment for individuals with NPD by addressing cognitive distortions and emotional dysregulation. The article acknowledges the need for further research to refine diagnostic criteria and deepen our understanding of the disorder. Additionally, a list of references is provided, offering a valuable resource for further research on NPD. [Extracted from the article]

Neurodegeneration occurs naturally as humans age, but the presence of additional pathogenic mechanisms yields harmful and consequential effects on the brain. Alzheimer's disease (AD), the most common form of dementia, is a composite of such factors. Despite extensive research to identify the exact causes of AD, therapeutic approaches for treating the disease continue to be ineffective, indicating important gaps in our understanding of disease mechanisms. Long non-coding RNAs (lncRNAs) are an endogenous class of regulatory RNA transcripts longer than 200 nucleotides, involved in various regulatory networks, whose dysregulation is evident in several neural and extraneural diseases. LncRNAs are ubiquitously expressed across all tissues with a wide range of functions, including controlling cell differentiation and development, responding to environmental stimuli, and other physiological processes. Several lncRNAs have been identified as potential contributors in worsening neurodegeneration due to altered regulation during abnormal pathological conditions. Within neurological disease, lncRNAs are prime candidates for use as biomarkers and pharmacological targets. Gender-associated lncRNA expression is altered in a gender-dependent manner for AD, suggesting more research needs to be focused on this relationship. Overall, research on lncRNAs and their connection to neurodegenerative disease is growing exponentially, as commercial enterprises are already designing and employing RNA therapeutics. In this review we offer a comprehensive overview of the current state of knowledge on the role of lncRNAs in AD and discuss the potential implications of lncRNA as potential therapeutic targets and diagnostic biomarkers in patients with Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Background: Myasthenia gravis (MG) is an autoimmune disease characterized by fluctuating muscle weakness due to autoantibodies targeting neuromuscular junction proteins. Mycophenolate mofetil (MMF), an immunosuppressive therapy, has shown potential for managing MG with fewer side effects compared to other treatments. This study aims to evaluate the effectiveness and safety of MMF in MG patients in a real-life multicenter setting. Methods: A retrospective cohort study was conducted on generalized MG patients, refractory to azathioprine (AZA) and treated with MMF alone or with steroids, at three Italian centers from January 2011 to February 2024. Patients were assessed using the Myasthenia Gravis Foundation of America (MGFA) classification, MG composite score (MGCS), and MG activity of daily living (MGADL) scores at baseline, 6, 12, 18, and 24 months. Statistical analyses included the Spearman correlation, the Friedman test, and ANOVA. Results: Thirty-two patients were enrolled (13 males, mean age 66.5 ± 11.5 years). Significant improvements in MGADL and MGCS scores were observed at 6 and 12 months (p < 0.001), with continued improvement over 24 months. Side effects were reported in 12% of patients. MMF showed a faster onset of symptom control compared to azathioprine, with a significant improvement noted within 6 months. Conclusions: A recent study found that MMF and AZA were equally effective in improving patients' quality of life, but because AZA had more serious adverse events than MMF, lower doses of AZA were therefore recommended to reduce the adverse events while maintaining efficacy. Conversely, results showed that MMF is effective and well-tolerated in the long-term management of MG, providing faster symptom control and a favorable safety profile. Future prospective studies with larger cohorts are needed to confirm these findings and explore sex differences in response to MMF treatment. [ABSTRACT FROM AUTHOR]

Patients with chronic pancreatitis are at risk of developing malabsorption and malnutrition. Exocrine pancreatic insufficiency is accompanied by decreased serum micronutrient levels and low vitamin D levels are a frequent finding in up to 60-80% of patients. The aim of our prospective study was to investigate vitamin D in the blood serum of subjects with chronic pancreatitis with the possibility of influencing the reduced vitamin D levels with supplementation therapy. MATERIAL AND METHODOLOGY: Fifty patients with chronic pancreatitis and 20 subjects in the control group without gastrointestinal tract diseases, including pancreatic disease, were examined. The vitamin D level in blood serum was determined. The results were evaluated according to the age distribution of subjects with pancreatic disease and according to gender. Patients with low vitamin D levels were treated for 24 weeks with a dose of 1.500.000 IU of vitamin D3 per day, and then blood serum vitamin D levels were determined. RESULTS: In people with chronic pancreatitis, vitamin D levels were statistically significantly reduced compared to the control group. There was no statistically significant relationship of vitamin D with gender and age. Supplementation with vitamin D3 achieved an adjustment of vitamin D level to the level of the control group. CONCLUSION: Blood serum vitamin D levels are significantly reduced in people with chronic pancreatitis. Its correction by oral vitamin D supplementation was effective. Whether this adjustment of levels will be effective also in terms of e.g. beneficial effect on fibrogenesis will require further representative studies, because the limitation of the interpretation of the results of our study is the smaller number of subjects with chronic pancreatitis [ABSTRACT FROM AUTHOR]

Women are at higher risk than men for developing posttraumatic stress disorder (PTSD), but underlying mechanisms are still unclear. Comprehensive knowledge about these mechanisms is necessary to develop tailored, sex- and gender-sensitive preventive interventions. This systematic review and meta-analysis examined sex-/gender-dependent risk factors, that is, risk factors with sex/gender differences in (a) vulnerability or (b) prevalence/severity, as well as sex-/gender-specific risk factors, that is, and (c) risk factors present in one sex/gender only. We searched PubMed, Web of Science, PsycINFO, PsycArticles, and PSYNDEX for articles published until October 16, 2022. We included prospective studies that assessed risk factors to predict subsequent PTSD symptom severity, as measured with the Clinician-Administered PTSD scale. The primary outcomes were sex/gender stratified pooled for sex-/gender-dependent vulnerability and sex-/gender-specific risk factors and pooled odds ratio (OR) or standardized mean difference (SMD) for sex-/gender-dependent risk factor prevalence/severity. We screened 17,270 records and included 117 reports from 45 studies (N = 13,752) in the systematic review. Seventeen studies (N = 4,257; 1,827 women, 2,430 men) were included in the meta-analysis. Regarding risk factor vulnerability, analyses revealed no significant sex/gender differences except for acute stress symptoms, with stronger associations for men (b = 0.11, SE = 0.06, p <.05). Regarding risk factor prevalence/severity, women reported more severe immediate psychological stress responses (range SMD = 0.23–0.56) and more commonly had a history of mental illness (OR = 1.81, 1.27–2.58). Men showed higher trauma load (SMD = −0.15, −0.29 to 0.01). Few women-specific and no men-specific factors were identified. Results suggest that women's heightened immediate psychological stress response drives sex/gender disparities in PTSD symptom severity. Preventive interventions should thus target women early after trauma. General Scientific Summary: Women are at higher risk for posttraumatic stress disorder relative to men, but the underlying mechanisms are not fully understood yet. This meta-analysis suggests that women are not more vulnerable to risk factors than men (i.e., risk factors have a similar effect in women and men). Rather higher prevalence or severity of risk factors in women appears to be a driver of known sex/gender disparities in posttraumatic stress disorder risk. Sex- and gender-sensitive etiological knowledge can help to guide targeted interventions for women and men. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is characterized by progressive fibrosis of the skin and internal organs, microvascular damage and cellular and humoral immunity abnormalities. Microvascular damage can be easily detected through nailfold videocapillaroscopy (NVC). A retrospective study of patients with SSc and a NVC performed within the first 6 months after diagnosis was conducted. Visceral involvement in the first 3 years of the disease and NVC findings were collected. The severity of microvascular damage was classified into four categories, according to the worsening of the NVC patterns. The severity of organ involvement was assessed by the disease severity scale of Medsger for each organ and as a global measure of disease severity, the simple summation was used. A total of 86 patients with SSc were included. A moderate correlation was found between the severity of microvascular damage and the global measure of disease severity (r = 0.55, p < 0.001), the severity of peripheral vascular involvement (r = 0.43, p < 0.001) and the severity of skin involvement (r = 0.34, p = 0.001). The presence of a late scleroderma pattern in NVC were predictive in univariate analysis of digital ulcers (OR 6.03, 95% CI 1.52–23.86, p = 0.01), muscular involvement (OR 13.09, 95% CI 1.09–156.78, p = 0.04), calcinosis (OR 27.22, 95% CI 5.56–133.33, p < 0.001) and worse global disease severity score (OR 1.67, 95% CI 1.17–2.38, p = 0.005). Multivariate analysis adjusted for disease duration and gender confirmed late pattern as an independent predictor of calcinosis (OR 42.89, 95% CI 5.53–332.85, p < 0.001). In this study, the worsening of NVC pattern in SSc was associated with the overall disease severity, the severity of peripheral vascular involvement and extension of skin involvement. This study highlights the importance of NVC as a prognostic tool and a possible predictor of systemic visceral involvement. [ABSTRACT FROM AUTHOR]

Objective: This study investigated influence of biological sex on postconcussive symptoms (PCS) following concussion using the Federal Interagency Traumatic Brain Injury Research (FITBIR) database. Method: All studies with publicly released data as of 4/7/21 that included both males and females, enough information to determine severity of injury consistent with concussion, a measure of PCS, and objective measures of neurocognitive functioning were used. This resulted in 6 studies with a total of 9890 participants (3206 females, 6684 males); 815 participants completed the Neurobehavioral Symptom Inventory (NSI), 471 completed the Rivermead Post-Concussion Symptoms Questionnaire (RPSQ), and 8604 completed the Sport Concussion Assessment Tool–3rd Edition (SCAT 3). Questionnaires were harmonized and the following symptom composite scores were computed: total score, somatic, cognitive, and affective. Data were analyzed using linear mixed-effects models. Results: Females endorsed higher total symptoms relative to males and that military personnel endorsed higher symptoms relative to civilians. Additionally, there was a small but significant interaction effect, such that female military personnel endorsed even higher symptoms than would be predicted by the main effects. Similar patterns were observed for somatic, cognitive, and affective symptom domains. Conclusions: Further understanding sex differences in PCS reporting is key to informing the most appropriate treatment options. Future work will need to examine whether sex differences in symptom reporting is due to sex differences in endorsement styles or genuine differences in symptom presentation, as well as the relationship between study population (e.g., military, civilian, sport) and sex on objective cognitive functioning and other functional outcomes. [ABSTRACT FROM AUTHOR]

This article presents a case study of a 55-year-old woman with rheumatoid arthritis who developed complications known as rheumatoid vasculitis (RV). The patient experienced symptoms such as fatigue, muscle pain, and weight loss, and was initially diagnosed with vasculitis. However, she later developed numbness and weakness in her hands and feet, which was diagnosed as severe mononeuritis multiplex. The article provides detailed information on the patient's laboratory findings and electrophysiological values. It emphasizes the importance of early recognition and treatment of RV, as it can lead to significant morbidity and mortality. The authors also call for further research and understanding of this condition. [Extracted from the article]

Two-thirds of Americans with Alzheimer's disease are women, indicating a profound variance between the sexes. Variances exist between the sexes in the age and intensity of the presentation, cognitive deficits, neuroinflammatory factors, structural and functional brain changes, as well as psychosocial and cultural circumstances. Herein, we summarize the existing evidence for sexual dimorphism and present the available evidence for these distinctions. Understanding these complexities is critical to developing personalized interventions for the prevention, care, and treatment of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Studies have raised concerns about possible inequities in the U.S. Department of Veterans Affairs (VA)'s awards of disability for posttraumatic stress disorder (PTSD) to women. However, the diagnoses and opinions made by disability examiners have not been studied. A sample of 270 initial PTSD examination reports and corresponding VA decisions were studied. Compared to men, women veterans were as likely to be diagnosed with a service‐related mental disorder, χ2(1, N = 270) = 2.31, p =.129, odds ratio (OR) = 1.79, 95% CI [0.84, 3.80], and be granted service‐connection, χ2(1, N = 270) = 0.49, p =.483, OR = 1.28, 95% CI [0.65, 2.51]. Women veterans were considered to have more psychiatric symptoms, Z = −2.05, p =.041, r =.16, and more psychiatric impairment, Z = −2.48, p =.013, r =.20, but the percentage of disability awarded by the VA did not differ, χ2(1, N = 270) = 0.49, p =.483; OR = 1.28, 95% CI [0.65, 2.51]. Secondary analyses implicate the role of military sexual trauma and premilitary trauma in explaining sex differences in symptoms and impairment. The findings indicate that neither opinions by examiners nor corresponding decisions by the VA regarding service connection reflect a negative bias toward women veterans. Results indicate that unbiased examinations lead to equitable VA claims decisions for women veterans. Future studies of the VA PTSD disability program nationally, including examination procedures and VA policies and implementation, will promote equity for women veterans in the PTSD claims process. [ABSTRACT FROM AUTHOR]