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Because some stakeholders within medicine seek to diversify and attain greater workforce equity, it is critical to understand gender-based divisions within specialization. Radiation oncology (RO) has one of the smallest proportions of women representation of all specialties, and to our knowledge, no prior studies have investigated gender differences in all the disease site specializations within RO. Thus, we analyzed the relationship between gender and disease site(s) treated in academic RO (ARO). Faculty gender and disease site(s) treated by faculty from ARO departments were collected via publicly available department websites in January 2020. X2 analyses were conducted to assess differences between the proportions of women faculty treating each disease site. Of 1337 ARO faculty, 408 (30.5%) were identified as women. Breast, gynecology, and pediatrics had the largest proportions of women faculty (all >40%; P <.001). A majority (53%; P <.001) of women ARO faculty treated breast. Genitourinary, thoracic, and head and neck had the smallest proportions of women faculty (all <25%; P <.001). Women ARO faculty were twice as likely to treat breast and gynecologic malignancies compared with men faculty (risk ratio [RR] with 95% CI, 2.01 [1.75-2.50]; P <.001 and RR [95% CI], 2.06 [1.72-2.79]; P <.001, respectively). Men ARO faculty were 3 times more likely to treat genitourinary cancer compared with women faculty (RR [95% CI], 0.40 [0.34-0.48]; P <.001). There was no difference in the mean number of disease sites treated between women and men ARO faculty (2.63 vs 2.53; P =.29). Gender differences in disease site specialization were observed in ARO. Future research into the drivers of disease site selection should be explored. [ABSTRACT FROM AUTHOR]

Early detection of Alzheimer's disease (AD) is crucial to maximize clinical outcomes. Most disease progression analyses include people with diagnoses of cognitive impairment, limiting understanding of AD risk among those with normal cognition. The objective was to establish AD progression models through a deep learning approach to analyze heterogeneous, multi-modal datasets, including clustering analyses of population subsets. A multi-head deep-learning architecture was built to process and learn from biomedical and imaging data from the National Alzheimer's Coordinating Center. Shapley additive explanation algorithms for feature importance ranking and pairwise correlation analysis were used to identify predictors of disease progression. Four primary disease progression clusters (slow, moderate and rapid converters or non-converters) were subdivided into groups by race and sex, yielding 16 sub-clusters of participants with distinct progression patterns. A multi-head and early-fusion convolutional neural network achieved the most competitive performance and demonstrated superiority over a single-head deep learning architecture and conventional tree-based machine-learning methods, with 97% test accuracy, 96% F1 score and 0.19 root mean square error. From 447 features, 2 sets of 100 predictors of disease progression were extracted. Feature importance ranking, correlation analysis and descriptive statistics further enriched cluster analysis and validation of the heterogeneity of risk factors. [ABSTRACT FROM AUTHOR]

Aim Method Results Conclusion Pilonidal sinus disease (PSD) is a common condition, but no data on disease occurrence exist outside highly selected settings. The aim of this study was to assess time trends in the incidence of PSD in a nationwide setting.Using data from nationwide Danish registries, we identified 48 247 patients recorded with diagnostic or surgical procedure codes representing PSD between 1996 and 2021. We stratified by sex and computed the age‐adjusted and age‐specific incidence rate, comparing 5‐year intervals with the incidence rate ratio (IRR).The overall incidence of PSD increased from 26.1 to 39.6/100 000 person‐years (PY) from the period 1996–2000 to the period 2016–2021 (IRR 1.52, 95% CI 0.78–2.94). The incidence increased from 35.8 to 56.9/100 000 PY (IRR 1.59, 95% CI 0.52–4.89) in male patients and from 16.4 to 22.5/100 000 PY (IRR 1.37, 95% CI 0.68–2.76) in female patients. The peak of age‐specific incidence was 215.7/100 000 PY (95% CI 206.1–245.4) among 20‐year‐old men and 107.9/100.000 PY (95% CI 100.0–114.0) among 18‐year‐old women. Over the study period, the median age at first hospital contact decreased from 27 years [interquartile range (IQR) 22–34 years) to 25 years (IQR 20–34 years) in men but remained stable around 23 years (IQR 18–32 years) in women. However, for both sexes, the highest increase in incidence was seen in early adolescence.The incidence of PSD has increased significantly over the last decades. The increase is driven primarily by men and boys, with the highest increase in incidence seen in early adolescence. The increased burden of disease is not reflected in the literature, and more studies are warranted to understand the drivers of this development. [ABSTRACT FROM AUTHOR]

Background: Alpha‐synucleinopathies, such as Parkinson's disease (PD), Parkinson's disease dementia (PDD), and dementia with Lewy bodies (DLB), demonstrate sex differences with regard to prevalence, age of onset, and motor manifestations. Neuropsychiatric symptoms (NPS) are common early and late manifestations of these disorders. Objectives: We aimed to describe sex differences in NPS across alpha‐synucleinopathies. Methods: We searched Web of Science Core collection databases to identify observational studies published between January 1, 2000, and June 1, 2022, reporting the prevalence or severity of NPS among individuals with a diagnosis of PD, PDD, or DLB. Prevalence and severity were pooled for each NPS according to sex using random‐effects models. Results: Two‐hundred‐and‐forty studies, representing 796,026 participants (45% females), were included in the meta‐analysis. Female sex was associated with a higher prevalence of anxiety (OR = 1.60 [95% CI: 1.40, 1.82]), depression (OR = 1.56 [1.45, 1.67]), fatigue (OR = 1.21 [1.02, 1.43]), and psychotic symptoms (OR = 1.26 [1.14, 1.40]) and more severe anxiety (g = 1.35 [95% CI: 0.58, 2.13]), depression (g = 1.57 [1.05, 2.08]), and fatigue (g = 0.86 [0.41, 1.32]), while male sex was associated with a higher prevalence of apathy (OR = 0.77 [0.63, 0.93]), impulse control disorders (OR = 0.67 [0.55, 0.82]), REM sleep behavior disorder (OR = 0.54 [0.42, 0.70]), hypersomnolence (OR = 0.67 [0.56, 0.80]), and suicide (OR = 0.30 [0.20, 0.44]). Conclusions: NPS have different prevalences and severities in alpha‐synucleinopathies according to sex. These findings support consideration of sex in the elaboration of clinical tools. [ABSTRACT FROM AUTHOR]

Introduction: There are sex differences in the extent, severity, and outcomes of coronary artery disease. We aimed to assess the influence of sex on coronary atherosclerotic plaque activity measured using coronary 18F-sodium fluoride (18F-NaF) positron emission tomography (PET), and to determine whether 18F-NaF PET has prognostic value in both women and men. Methods: In a post-hoc analysis of observational cohort studies of patients with coronary atherosclerosis who had undergone 18F-NaF PET CT angiography, we compared the coronary microcalcification activity (CMA) in women and men. Results: Baseline 18F-NaF PET CT angiography was available in 999 participants (151 (15%) women) with 4282 patient-years of follow-up. Compared to men, women had lower coronary calcium scores (116 [interquartile range, 27–434] versus 205 [51–571] Agatston units; p = 0.002) and CMA values (0.0 [0.0-1.12] versus 0.53 [0.0-2.54], p = 0.01). Following matching for plaque burden by coronary calcium scores and clinical comorbidities, there was no sex-related difference in CMA values (0.0 [0.0-1.12] versus 0.0 [0.0-1.23], p = 0.21) and similar proportions of women and men had no 18F-NaF uptake (53.0% (n = 80) and 48.3% (n = 73); p = 0.42), or CMA values > 1.56 (21.8% (n = 33) and 21.8% (n = 33); p = 1.00). Over a median follow-up of 4.5 [4.0–6.0] years, myocardial infarction occurred in 6.6% of women (n = 10) and 7.8% of men (n = 66). Coronary microcalcification activity greater than 0 was associated with a similarly increased risk of myocardial infarction in both women (HR: 3.83; 95% CI:1.10-18.49; p = 0.04) and men (HR: 5.29; 95% CI:2.28–12.28; p < 0.001). Conclusion: Although men present with more coronary atherosclerotic plaque than women, increased plaque activity is a strong predictor of future myocardial infarction regardless of sex. [ABSTRACT FROM AUTHOR]

Immune responses to parasitic infections differ between males and females as the result of distinct sex chromosomal complement and sex hormones – particularly testosterone has been shown to influence the immune response and modulate the outcome of parasitic diseases. Many tropical parasitic diseases, including Chagas' disease, leishmaniasis, amebiasis, malaria and certain helminth infections, exhibit a bias towards the male sex, whereas a female bias exists in tapeworm infection. Selected murine models accurately mirror the male predominance in human parasitosis, including the modulation by sex hormones, and can thus be used as tools for the study of sex differences in infection. Since comprehensive knowledge of these differences is still lacking for many diseases, the availability of these models is particularly valuable. The effect of sex on the prevalence and severity of parasitic diseases is an emerging area of research. Several factors underlie sex-based differences, including sociocultural influences that affect exposure to parasites, and physiological disparities linked to biological sex. Hence, human studies must be interpreted cautiously; however, studies conducted under controlled laboratory conditions are important to validate findings in humans. Such research can more effectively elucidate the role of sex-determining physiological factors (particularly their impact on immune responses), as well as the role of sex-specific differences in resistance to, or severity of, parasitic diseases. This review focuses on the overarching impact of biological sex variables on immunity. Both human and rodent experimental data are discussed, with a focus on selected protozoan and helminth infections. [ABSTRACT FROM AUTHOR]

Gender differences have been identified in the co-occurrence of anxiety and depressive symptoms. However, the underlying mechanisms that give rise to this gender difference remain unclear, and few studies have examined the issue at the symptom level. The current study employed the 7-item Generalized Anxiety Disorder scale (GAD-7) and the 9-item Patient Health Questionnaire (PHQ-9) to assess anxiety and depressive symptoms in a national sample of early adolescents (N = 15 391). A network approach was applied to investigate the gender differences in symptom interconnectivity. Gender differences were found in the co-occurrence of anxiety and depressive symptoms. The results indicated that girls with higher global strength (p < 0.01) exhibited stronger interconnectivity between symptoms. Central symptom PHQ2 (Sad mood) was significantly stronger in girls (p < 0.01), whereas PHQ6 (Guilt) was stronger in boys (p < 0.05). GAD7 (Feeling afraid) was identified as a prominent bridge symptom in girls, while PHQ6 (Guilt) was observed to play a similar role in boys. The directed acyclic graphs (DAGs) demonstrated that one symptom of anxiety triggered a series of emotional symptoms of anxiety and depression, ultimately resulting in a depressive somatic symptom in girls, whereas leading to both depressive somatic and anxiety symptoms in boys. These findings enhance our understanding and provide insights into potential intervention targets to prevent the co-occurrence of anxiety and depressive symptoms at an early stage. [ABSTRACT FROM AUTHOR]

Objectives: Chronic diseases impact people's quality of life (QoL). Behçet's disease (BD) is a multisystemic chronic disease characterized by vasculitis of various vessels. We aimed to assess QoL in paediatric BD (PEDBD) patients and their parents. Methods: We conducted a cross-sectional study from June to December 2022, including PEDBD patients meeting classification criteria. We recorded clinical characteristics and assessed QoL using PedsQL for patients and WHOQOL-Bref for parents. Results: A study of 38 patients (60.5% girls, 39.5% boys), median age 15.5 years (range 10–17), with oral aphthae and various mucocutaneous symptoms: genital ulcers (78.9%), pseudofolliculitis (76.3%), erythema nodosum (23.6%), and some with uveitis (13.1%), vascular (13.1%), neurological (10.5%), and gastrointestinal (5.2%) involvement. All were in remission under treatment. Median PedsQL scores: total 74.5 (range 40–94.8), physical health 76.5 (43–100), psychosocial health 75 (25–92); 14 patients scored below cutoff. Girls had lower physical health scores (P = .004), and disease duration correlated negatively with PedsQL score (r = -0.648, P = .001). Median WHOQOL score for parents: 50 (25–100), with 20 scoring below cutoff. Conclusion: One-third of PEDBD children and over half of their parents had low QoL. Disease duration and gender, as with many chronic illnesses, correlated with QoL in PEDBD. [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 study investigated sex differences in acute myocarditis patients during index hospitalization. We included 365 patients with acute myocarditis, hospitalized with continuous monitoring at the intensive care unit from 2000-2023 into the Basel Myocarditis Cohort study. We compared sex differences in clinical presentation, the presenting electrocardiogram, prior medical history, inflammatory and cardiac biomarkers, cardiac imaging, arrhythmia occurrence, and short- to midterm outcomes. Mean age was 41.3 years, and 26.3% were female. Compared with men, women were older (median 49.7 vs 38.3 years, P <.001) at the time of diagnosis and presented more frequently with dyspnea (41 vs 26%, P =.013) and a higher Killip class (P =.011). In the presenting electrocardiogram, men had a higher occurrence of diffuse ST-elevation (38 vs 9%, P <.001) and PQ-depression (31 vs 20%, P =.042), compared with women. Women had higher N-terminal pro B-type natriuretic peptide levels (1180 vs 387 ng/L, P =.015), lower cardiac troponin T levels (389 vs 726 ng/L, P =.006), and fewer segments with nonischemic late gadolinium enhancement on cardiac magnetic resonance imaging (1 vs 3, P =.005), but similar left ventricular ejection fraction (55 vs 55%, P =.629), compared with men. Overall, hospital stay was longer in women compared with men (7 vs 5 days, P =.018), with a similar length of intensive care unit stay (2.6 vs 2.7 days, P =.922). Women more often developed severe arrhythmia (8.3 vs 2.2%, P =.015) and heart failure during the hospitalization (31.3 vs 16.4%, P =.003). Compared with men, women with acute myocarditis were older at the time of diagnosis, presented more often with heart failure, and had an increased frequency of severe arrhythmia. [ABSTRACT FROM AUTHOR]

Sustained release microspheres loaded with goserelin are regarded as a promising candidate for treating prostate cancer and other sex hormone diseases. However, their widespread adoption has been hindered by issues such as wide particle size distribution and unstable release characteristics. To address these challenges, we employed a combination of the solid-in-oil-in-water microspheres preparation approach (S/O/W) and innovative premix membrane emulsification technology and deeply investigated the effects of four key parameters on the loaded performance of microspheres and the microscopic mechanisms behind them. With this approach, we successfully produced goserelin-loaded sustained release microspheres of narrow particle size distribution (Span 0.642), remarkable encapsulation efficiency (DL = 4.23 %, EE = 93.98 %), low initial burst release (about 0.50 % within 2 h), and compatibility with small injection needles (23-G, inner diameter 0.33 mm, outer diameter 0.64 mm, maximal force 59 N). In the animal model(administered dose, 2.4 mg·Kg−1), goserelin long-acting sustained release microspheres sustained release for over 32 days, maintaining effective concentrations above 2 ng·mL−1, and effectively reduced serum testosterone concentrations to castration levels (<1.0 ng·mL−1) by day 4, maintaining this inhibition for up to 21 days, exhibiting comparable efficacy to the positive control group. In vivo release kinetics analysis revealed that goserelin-loaded sustained release microspheres exhibited a release pattern dominated by diffusion with corrosion assistance in vivo. In summary, the systematic and comprehensive evaluation of uniform-sized goserelin-loaded sustained release microspheres has highlighted their excellent translational potential, and the study herein may provide new strategies and ideas for the development of microsphere dosage forms. [Display omitted] • Developed uniform-sized goserelin microspheres (GOS-M) with high encapsulation efficiency. • Achieved low initial burst release and sustained release for over 32 days in vivo. • Uniform-sized GOS-M adapted to 23-G needles, ideal for low-pain administration. • Offers New strategies for microsphere release regulation and prescription screening. [ABSTRACT FROM AUTHOR]

Purpose: This study explores the relationship between depression and cardiovascular disease (CVD) in the US adult population, focusing on sex differences. Design: Cross-sectional study. Setting: National Health and Nutrition Examination Survey data (2013-2018). Participants: A total of 14 699 community-dwelling adults (≥20 years). Measure: The Patient Health Questionnaire (PHQ-9) depression screening tool assessed depressive symptoms. CVD events included heart failure, coronary heart disease, angina, heart attack, or stroke. Analysis: Adjusted prevalence ratios were estimated using a Poisson regression model. Results: The study finds a positive association between CVD incidents and both mild to moderate depressive symptoms (aPR:1.42, P =.002) and moderately severe to severe depression (aPR:1.72, P =.024). Overall, females exhibit a 47% lower likelihood of CVD incidents compared to males. However, in a subgroup analysis, increased depressive symptoms correlate with higher CVD incidents in females (aPRs range: 2.09 to 3.43, P <.001) compared to males (aPRs range: 1.45 to 1.77, P <.001). Conclusion: Depression is associated with increased cardiovascular disease (CVD) risk. Females generally have a lower CVD risk than males, but more severe depressive symptoms elevate CVD risk in females. These findings emphasize the significance of considering sex differences. Further research is needed to understand the underlying mechanisms. [ABSTRACT FROM AUTHOR]

• A reduced functional connectivity of the olfactory system is observed in PD. • Hyposmia and decreased functional connectivity is also present in MCI. • Males showed increased functional connectivity than females in OFC. • Decreased functional connectivity particularly involves the limbic system. • Functional connectivity of olfactory network can help to identify PD. Olfactory dysfunction is an early sign of such neurodegenerative diseases as Parkinson's (PD) and Alzheimer's (AD), and is often present in Mild Cognitive Impairment (MCI), a precursor of AD. Understanding neuro-temporal relationships, i.e., functional connectivity, between olfactory eloquent structures in such disorders, could shed light on their basic pathophysiology. To this end, we employed region-based analyses using resting-state functional magnetic resonance imaging (rs-fMRI) obtained from cognitively normal (CN), MCI, and PD patients with cognitive impairment (PD-CogImp). Using machine learning (linear and ensemble learning), we determined whether the identified functional patterns could classify abnormal function from normal function. Olfaction, as measured by objective testing, was found to be most strongly associated with diagnostic status, emphasizing the fundamental association of this primary sensory system with these conditions. Consistently lower functional connectivity was observed in the PD-CogImp cohort compared to the CN cohort among all identified brain regions. Differences were also found between PD-CogImp and MCI at the level of the orbitofrontal and cingulate cortices. MCI and CN subjects had different functional connectivity between the posterior orbitofrontal cortex and thalamus. Regardless of study group, males showed significantly higher connectivity than females in connections involving the orbitofrontal cortex. The logistic regression model trained using the top discriminatory features revealed that caudate was the most involved olfaction-related brain structure (accuracy = 0.88, Area under the Receiver operator characteristic curve of 0.90). In aggregate, our study demonstrates that resting functional connectivity among olfactory eloquent structures has potential value in better understanding the pathophysiology of several neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

The shift to electronic health records has led to both patient portal messaging and large amounts of digital, real-world data for research. The objective of this study was to examine the association between portal messaging and survival among radiation oncology patients, using real-world data. This retrospective cohort study included patients at least 21 years old and seen by radiation oncology providers between January 14, 2014, and April 23, 2023, at the University of California, San Francisco. We developed Cox proportional hazards models for the outcome of death and examined factors associated with portal messaging using logistic regression models. Among 25,367 patients, the median age was 64 (interquartile range [IR], 54-72), 13,175 (52%) were White, and 14,389 (57%) were male. Overall, as the first message in a thread, 8986 (35%) patients sent messages to radiation oncology providers, and 4218 (17%) patients were sent messages from radiation oncology providers. Patients with head and neck or genitourinary malignancies were more likely than those with other diagnoses to send portal messages to and be sent portal messages from radiation oncology providers. Both sending portal messages to radiation oncology providers (hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.84-0.96; P =.001) and being sent messages from radiation oncology providers (HR, 0.77; CI, 0.70-0.84; P <.001) as the first message in a thread were associated with patient survival after adjusting for socioeconomic, disease, and treatment characteristics. There were disparities among patients sending portal messages to radiation oncology providers, including for Black versus White patients (odds ratio [OR], 0.60; CI, 0.51-0.69; P <.001) and for Medicaid versus Medicare patients (OR, 0.70; CI, 0.62-0.79; P <.001). There were also disparities among patients being sent portal messages by radiation oncology providers, including for Black versus White patients (OR, 0.77; CI, 0.64-0.91; P =.003), for Medicaid versus Medicare patients (OR, 0.76; CI, 0.65-0.89; P <.001), and for patients with female versus male providers (OR, 1.47; CI 1.34-1.62; P <.001). Sending portal messages to and being sent portal messages from radiation oncology providers were associated with better survival. Future studies should elucidate how best to support patient and provider engagement. [ABSTRACT FROM AUTHOR]

Suicidal ideation (SI) assumes a pivotal role in predicting suicidal behaviors. The incidence of SI among high (junior and senior) school students is significantly higher than that of other age groups. The aim of this study is to explore the gender differences in SI among high school students in Yunnan Province. A total of 6180 students in grades 7–12 in Yunnan province, China from May 2021 to May 2022 participated in this survey. Univariate analysis was employed to describe the influencing factors of male and female students' SI. Subsequently, data were stratified by gender. Adopting machine learning technique, including Least Absolute Shrinkage and Selection Operator (Lasso) and Boruta algorithm, and logistic regression model to estimate the direction and effect magnitude of the influencing factors. The prevalence of SI was significantly higher for females (31.34 %) than males (16.73 %). The logistic regression model was established using the variables screened by Boruta algorithm, indicated that anxiety, depression, suffering emotion abuse or emotion neglect in childhood, non-suicidal self-injury, evening chronotype are common risk factors for SI in male and female students. Notably, female students who exhibited aggressive behavior, have experienced bullying, and were in the junior high school learning stage were more likely to report SI than their male counterparts. Females showed more vulnerability to SI than males especially among females in junior high school, reporting aggressive behavior and bullying experiences. Tailored prevention strategies, informed by these gender-related distinctions, should be developed and implemented. • Females who exhibit aggressive behaviors and experience campus bullying face a heightened risk of suicidal ideation compared to males. Prevention strategies for suicidal ideation based on gender-specific risk factors are proposed. [ABSTRACT FROM AUTHOR]

Adverse Childhood Experiences (ACEs) refer to early life stress events, including abuse, neglect, and other psychosocial childhood traumas that can have long-lasting effects on a wide range of physiological functions. ACEs provoke sex-specific effects, whereas women have been shown to display a strong positive correlation with obesity and cardiometabolic disease. Notably, rodent models of chronic behavioral stress during postnatal life recapitulate several effects of ACEs in a sex-specific fashion. In this review, we will discuss the potential mechanisms uncovered by models of early life stress that may explain the greater susceptibility of females to obesity and metabolic risk compared with their male counterparts. We highlight the early life stress-induced neuroendocrine shaping of the adrenal-adipose tissue axis as a primary event conferring sex-dependent heightened sensitivity to obesity. [ABSTRACT FROM AUTHOR]

Background: Chronic cigarette smokers report withdrawal symptomology, including affective dysfunction and cognitive deficits. While there are studies demonstrating sex specific withdrawal symptomology in nicotine-dependent individuals, literature examining the underlying biological mediators of this is scant and not in complete agreement. Therefore, in this study, we evaluated the sex specific effects of nicotine and withdrawal on contextual fear memory, a hippocampally dependent aspect of cognition that is disrupted in nicotine withdrawal. Methods: Male and female B6/129F1 mice (8–13 weeks old) were used in all experiments. For the acute nicotine experiment, mice received intraperitoneal saline or nicotine (0.5 mg/kg) prior to contextual fear conditioning and test. For the chronic nicotine experiment, mice received nicotine (18 mg/kg/day) or saline for 11 days, then underwent contextual fear conditioning and test. Following the test, mice underwent minipump removal to elicit withdrawal or sham surgery, followed by the fear extinction assay. Bulk cortical tissue was used to determine nicotinic acetylcholine receptor levels via single point [3H]Epibatidine binding assay. Gene expression levels in the dorsal and ventral hippocampus were quantified via RT-PCR. Results: We found that female mice had a stronger expression of contextual fear memory than their male counterparts. Further, following acute nicotine treatment, male, but not female, subjects demonstrated augmented contextual fear memory expression. In contrast, no significant effects of chronic nicotine treatment on fear conditioning were observed in either sex. When examining extinction of fear learning, we observed that female mice withdrawn from nicotine displayed impaired extinction learning, but no effect was observed in males. Nicotine withdrawal caused similar suppression of fosb, cfos, and bdnf, our proxy for neuronal activation and plasticity changes, in the dorsal and ventral hippocampus of both sexes. Additionally, we found that ventral hippocampus erbb4 expression, a gene implicated in smoking cessation outcomes, was elevated in both sexes following nicotine withdrawal. Conclusions: Despite the similar impacts of nicotine withdrawal on gene expression levels, fosb, cfos, bdnf and erbb4 levels in the ventral hippocampus were predictive of delays in female extinction learning alone. This suggests sex specific dysfunction in hippocampal circuitry may contribute to female specific nicotine withdrawal induced deficits in extinction learning. Plain text summary: Smokers undergoing nicotine withdrawal report increased feelings of anxiety, depression, and cognitive deficits. However, there are sex differences in these symptoms, with women reporting higher feelings of anxiety compared to men and men having worse cognitive deficits than women. The mechanisms underlying these sex differences in nicotine withdrawal symptoms are not well understood. The hippocampus is a brain region highly implicated in both the cognitive and anxiety-like symptoms of nicotine withdrawal. Therefore, we evaluated the effects of nicotine and withdrawal on contextual fear memory, a hippocampally dependent learning and memory task, in male and female mice. We found that female mice had a stronger contextual fear memory expression than their male counterparts. However, following acute nicotine treatment male mice had enhanced contextual fear memory compared to non-nicotine treated males, while acute nicotine had no impact on female mice. When examining extinction of contextual fear, we found female mice withdrawn from nicotine displayed impaired extinction learning, but no effect was observed in males. The female specific deficits in extinction learning due to nicotine withdrawal were correlated to hippocampal gene expression related to neuronal activity. This suggests hippocampal dysfunction may be driving the female specific nicotine withdrawal induced deficits in extinction learning. Highlights: Female mice, but not males, showed deficits in contextual fear extinction during forced nicotine withdrawal. Despite the sex specific impact of nicotine withdrawal on contextual extinction learning, with females alone showing deficits in extinction, we observed suppression of immediate early genes in the dorsal and ventral hippocampus and increased erbb4 mRNA in the ventral hippocampus in both sexes. The deficits in female extinction were predicted by specific alterations in gene expression in the ventral hippocampus, highlighting a potential sex specific mechanism of nicotine withdrawal induced endophenotypes. [ABSTRACT FROM AUTHOR]

Recognising sex differences in disease prevalence can lead to clues as to its pathogenesis, for example the role of hormonal factors and related influences such as body composition, as well as forming the basis for new treatments. However, if different methods are used to define the disorder it can be difficult to explore differences in prevalence, making it necessary to draw on multiple sources of evidence. This narrative review addresses sex differences in the prevalence of knee and hip osteoarthritis, which are the most common forms of large joint osteoarthritis. Females appear to have a higher prevalence of knee osteoarthritis across a wide range of disease definitions, while findings for the hip vary depending on how the disease is defined. Clinically or symptomatically defined hip osteoarthritis is more common in females, whereas radiographically defined hip osteoarthritis is more common in males. Therefore, understanding sex differences in large joint arthritis requires consideration that osteoarthritis, as defined structurally, more commonly affects females at the knee, whereas the opposite is true at the hip. Furthermore, despite structural changes in hip osteoarthritis being more common in males, symptomatic hip osteoarthritis is more common in females. The basis for these disparities is currently unclear, but may reflect a combination of hormonal, biomechanical and behavioural factors. [ABSTRACT FROM AUTHOR]

Objective: Sarcopenia is linked to escalating health costs, heightened risk of physical disability, diminished quality of life and an increased demand for care services. This study aimed to assess the economic impact of sarcopenia-related disability in Iran. A prevalence-based economic burden study was conducted utilizing the Population Attributable Risk (PAR) method, based on 2022 price index. Prevalence data for sarcopenia, categorized by gender and disease severity, were extracted from recent comprehensive studies. The relative risk of sarcopenia disability was determined from the most robust available evidence. Subsequently, direct medical costs, direct non-medical costs, and indirect costs for each individual with sarcopenia were computed and adjusted to 2022 values to estimate disability costs. Results: Taking into account the prevalence of sarcopenia and the Iranian population across various age groups, 2,192,168 adults aged ≥ 60 years with sarcopenia in Iran were included. The total PAR of sarcopenia for men and women was estimated at 49% and 28%, respectively. The cumulative direct medical costs, direct non-medical costs, and indirect costs amounted to $215.1 million, $7.76 million, and $34.1 million, respectively. Additionally, the average total economic burden of sarcopenia-related disability in Iranian population aged ≥ 60 years was estimated at $257.1 million. [ABSTRACT FROM AUTHOR]

Background: Acute ischemic stroke (AIS) is a major public health issue, and women have a disproportionate share of stroke-related disability and mortality, which is poorly understood. This study aimed to determine the effect of sex differences on AIS treated by thrombolysis using recombinant tissue plasminogen activator (rTPA). The study included 134 AIS patients eligible for rTPA. Risk factors, clinical presentation, thrombolysis response, complications, and outcomes were recorded. The outcomes were measured using the National Institute of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS) 3 months after stroke. The incidence of intracranial haemorrhage was also determined. Results: Among 134 AIS patients treated with rTPA (59% male, 41% female), females had higher rates of hypertension (67.3% versus 49.4%, p = 0.040) and atrial fibrillation (AF) (12.7% versus 2.5%, p = 0.020), while smoking was more prevalent in males (31.6% versus 0%, p < 0.0001). Cardioembolism was more frequent in females than in males (23.6% versus 6.3%, p = 0.004). Females also had shorter onset-to-door (110.7 ± 63 versus 131.1 ± 50.2 min, p = 0.035) and onset-to-needle times (151.6 ± 66.5 versus 173.7 ± 50.6 min, p = 0.046). Both sexes showed significant improvements in NIHSS (males: 11.58 ± 3.7 to 6.05 ± 5.6; females: 11.64 ± 4.7 to 6.9 ± 5.9; p < 0.0001) and mRS scores (males: 3.34 ± 1.05 to 2.03 ± 2; females: 3.53 ± 1 to 2.02 ± 2; p < 0.0001) over 3 months, with no significant differences between sexes. Predictors of poor outcome (mRS 3–6) differed: diabetes mellitus (DM) (OR 7.79, p = 0.002) and longer door-to-needle time (OR 1.04, p = 0.008) for males, and hemorrhage (OR 9.41, p = 0.048) for females. Hemorrhage predicted mortality in males (OR 27.08, p < 0.0001), while AF was associated with increased mortality in females (OR 8.06, p = 0.024). Conclusions: This study revealed sex-specific differences in AIS risk factors, aetiology, and rTPA treatment timelines, although post-treatment improvements were comparable between sexes. Notably, outcome predictors and mortality factors differed by sex. These findings emphasize the need for sex-specific considerations in AIS management and risk assessment. [ABSTRACT FROM AUTHOR]

Although abdominal aortic aneurysms (AAA) are more common in men, women are at greater risk for AAA growth/rupture. Vascular deformation mapping (VDM) utilizes deformable image registration to qualify and quantify 3D-AAA growth using computed tomography angiograms (CTA). In this study we leveraged VDM to investigate sex differences in AAA growth patterns. Patients with infra-renal AAA and ≥ 2 CTA were identified. Males and females were matched for age, hypertension, and smoking history. Patient characteristics, maximum diameter (Dmax), and AAA volume were obtained. CTA images were segmented, and VDM was conducted to quantify 3D AAA growth rate per year (GR, cm/year). Statistical shape modeling was utilized to compute mean aneurysm shapes and 3D GR. Average GR was evaluated at specific regions of the aortic surface for males and females. Seventeen males and 17 females were matched. At the individual level, there were no sex differences in changes in Dmax or AAA volume. However, females had larger GR across the anterior and right lateral AAA (1.33 vs 0.89 and 1.56 vs 0.74 cm/year, respectively), despite no difference in posterior or left lateral AAA GR. Despite comparable changes in Dmax, AAA volume, and GR magnitude, women demonstrated a more eccentric, anterior-predominant, AAA growth pattern. [ABSTRACT FROM AUTHOR]

Astrocytes are essential for maintaining brain homeostasis. Alterations in their activity have been associated with various brain pathologies. Sex differences were reported to affect astrocyte development and activity, and even susceptibility to different neurodegenerative diseases. This review aims to summarize the current knowledge on the effects of sex on astrocyte activity in health and disease. [ABSTRACT FROM AUTHOR]

Coloproctological diseases, including both benign and malignant conditions, are among the most common diagnoses in clinical practice. Several disorders affect both men and women, while others are unique to women, or women are at a greater risk of developing them. This is due to anatomical, biological, and social conditions and also due to females' exclusive capabilities of reproduction and pregnancy. In this context, the same proctological disease could differ between men and women, who can experience different perceptions of health and sickness. There is a raised awareness about the impact of different diseases in women and a growing need for a personalized approach to women's health. In this review, we aim to summarize the specific features of the main coloproctological diseases, specifically in the female population. This includes common complaints during pregnancy, conditions linked to vaginal delivery, functional consequences after colorectal resections, and conditions presenting a gender disposition. [ABSTRACT FROM AUTHOR]

Maternal nutrition during the critical period of pregnancy increases the susceptibility of offspring to the development of diseases later in life. This study aimed to analyze metabolite profiles to investigate the effect of maternal diet during pregnancy on changes in offspring plasma metabolites and to identify correlations with metabolic parameters. Pregnant Sprague-Dawley rats were exposed to under- and overnutrition compared to controls, and their offspring were fed a standard diet after birth. Plasma metabolism was profiled in offspring at 16 weeks of age using liquid chromatography–mass spectrometry (LC-MS/MS) and gas chromatography–tandem mass spectrometry (GC-MS/MS). We analyzed 80 metabolites to identify distinct metabolites and metabolic and neurodegenerative disease-associated metabolites that were sex-differentially altered in each group compared to controls (p < 0.05, VIP score > 1.0). Specifically, changes in 3-indolepropionic acid, anthranilic acid, linoleic acid, and arachidonic acid, which are involved in tryptophan and linoleic acid metabolism, were observed in male offspring and correlated with plasma leptin levels in male offspring. Our results suggest that fatty acids involved in tryptophan and linoleic acid metabolism, which are altered by the maternal diet during pregnancy, may lead to an increased risk of metabolic and neurodegenerative diseases in the early life of male offspring. [ABSTRACT FROM AUTHOR]

Background: Amyotrophic lateral sclerosis (ALS) is a devastating and incurable neurodegenerative disease. Accumulating evidence strongly suggests that intrinsic muscle defects exist and contribute to disease progression, including imbalances in whole-body metabolic homeostasis. We have previously reported that tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and fibroblast growth factor inducible 14 (Fn14) are significantly upregulated in skeletal muscle of the SOD1G93A ALS mouse model. While antagonising TWEAK did not impact survival, we did observe positive effects in skeletal muscle. Given that Fn14 has been proposed as the main effector of the TWEAK/Fn14 activity and that Fn14 can act independently from TWEAK in muscle, we suggest that manipulating Fn14 instead of TWEAK in the SOD1G93A ALS mice could lead to differential and potentially improved benefits. Methods: We thus investigated the contribution of Fn14 to disease phenotypes in the SOD1G93A ALS mice. To do so, Fn14 knockout mice (Fn14−/−) were crossed onto the SOD1G93A background to generate SOD1G93A;Fn14−/− mice. Investigations were performed on both unexercised and exercised (rotarod and/or grid test) animals (wild type (WT), Fn14−/−, SOD1G93A and SOD1G93A;Fn14−/−). Results: Here, we firstly confirm that the TWEAK/Fn14 pathway is dysregulated in skeletal muscle of SOD1G93A mice. We then show that Fn14-depleted SOD1G93A mice display increased lifespan, myofiber size, neuromuscular junction endplate area as well as altered expression of known molecular effectors of the TWEAK/Fn14 pathway, without an impact on motor function. Importantly, we also observe a complex interaction between exercise (rotarod and grid test), genotype, disease state and sex that influences the overall effects of Fn14 deletion on survival, expression of known molecular effectors of the TWEAK/Fn14 pathway, expression of myosin heavy chain isoforms and myofiber size. Conclusions: Our study provides further insights on the different roles of the TWEAK/Fn14 pathway in pathological skeletal muscle and how they can be influenced by age, disease, sex and exercise. This is particularly relevant in the ALS field, where combinatorial therapies that include exercise regimens are currently being explored. As such, a better understanding and consideration of the interactions between treatments, muscle metabolism, sex and exercise will be of importance in future studies. [ABSTRACT FROM AUTHOR]

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: Inter-generational interaction is a carrier of Chinese traditional culture, and it can exert important influence on the depressive symptoms on Chinese older adults. The study aims to analyze gender differences in the association between inter-generational interaction and depressive symptoms among Chinese older adults and explore factors contributing to the differences. Method: Data from China Family Panel Studies in 2020 were used. Depressive symptoms were assessed using the 8-item Center for Epidemiologic Studies Depression Scale. The latent class analysis was applied to identify patterns of inter-generational interaction of older adults (aged 60 and above). Before the comparison between older man and older woman, we used Coarsened Exact Matching to control confounding factors and improve causal inferences. Multiple linear regression was conducted to explore the association between inter-generational interaction and depression symptoms. Oaxaca-blinder decomposition method was used to analyze the gender difference and the sources. Result: Our study identified three types of inter-generational interaction: detached, nearby but discordant and two-way tight-knit. Analysis indicated that most of older man (54.39%) and older woman (49.78%) were in the type of nearby but discordant. Older man and older woman who in detached type had higher depression scores than other types, and the depression score of two-way tight-knit type accounted for 12.42 and 13.77 respectively. Our findings demonstrated that two-way tight-knit type (-11.89%) significantly decreased the gender differences in the depression symptoms. Other major contributors also included living without spouse (20.56%), primary school and junior middle school (15.95%), higher middle school and above (9.50%) and no illness for two weeks (47.70%). Conclusion: Our study highlighted three patterns of inter-generational interaction, and most of older man and older woman were in the pattern of nearby but discordant. In addition, the two-way tight-knit pattern significantly can decrease gender differences in depression symptoms. The contributors should be taken into account in more targeted intervention strategies for narrowing gender differences in the depression symptoms, which could achieve a gender dividend in the era of China's aging population. [ABSTRACT FROM AUTHOR]

Dominant X-linked diseases are uncommon due to female X chromosome inactivation (XCI). While random XCI usually protects females against X-linked mutations, Rett syndrome (RTT) is a female neurodevelopmental disorder caused by heterozygous MECP2 mutation. After 6-18 months of typical neurodevelopment, RTT girls undergo a poorly understood regression. We performed longitudinal snRNA-seq on cerebral cortex in a construct-relevant Mecp2e1 mutant mouse model of RTT, revealing transcriptional effects of cell type, mosaicism, and sex on progressive disease phenotypes. Across cell types, we observed sex differences in the number of differentially expressed genes (DEGs) with 6x more DEGs in mutant females than males. Unlike males, female DEGs emerged prior to symptoms, were enriched for homeostatic gene pathways in distinct cell types over time and correlated with disease phenotypes and human RTT cortical cell transcriptomes. Non-cell-autonomous effects were prominent and dynamic across disease progression of Mecp2e1 mutant females, indicating that wild-type-expressing cells normalize transcriptional homeostasis. These results advance our understanding of RTT progression and treatment. Longitudinal snRNA-seq 5' in a Mecp2e1 mutant mouse model reveals sex-specific gene expression differences in specific cell types, with mutant females showing early and dynamic transcriptional changes linked to disease progression, enhancing our understanding of RTT. [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]

OBJECTIVES To evaluate gender-related outcomes during endovascular treatment of thoracic and thoraco-abdominal aortic diseases (TEVAR). METHODS Multicentre, retrospective, observational cohort study. All TEVARs between January 2005 and April 2023 were identified. Primary outcomes were 30-day mortality and cumulative survival. Secondary outcomes were vascular access complications, and freedom from TEVAR-related reintervention. Interventions performed in male patients were matched to females on the basis of a one-to-one coarsened exact matching. RESULTS We identified 151 males who were matched with 151 females. Mortality at 30 days was not statistically different between females and males (11.2% vs 11.2%; P  =   1.0). At binary logistic regression analysis, duration of intervention (P  =   0.001) and emergency TEVAR (P  =   0.001) were associated with mortality at 30 days. Gender did not impact the access vessel complication rate [ n  = 6 (4.0%) vs n  = 5 (3.3%); P  =   1.0]. The median follow-up was 46 (interquartile range, 7–84) months with no difference between males and females [median 50 (11–95) vs 37.5 (3.5–71.2); P  =   0.153]. Estimated survival was not statistically different between females and males [log-rank χ2 = 0.6, P  =   0.442; 95% confidence interval (CI) 110.7–207.3]. At Cox's regression analysis, gender did not impact overall survival (hazard ratio 0.8; 95% CI 0.6–1.3; P  =   0.450). Estimated freedom from TEVAR-related reinterventions was not statistically different between females and males (log-rank χ2 = 0.4, P  =   0.837; 95% CI 187.8–219.3). CONCLUSIONS Female gender itself was not associated with worse 30-day mortality and late survival than males with similar access vessel complication as well as TEVAR-related reintervention rate. [ABSTRACT FROM AUTHOR]

Purpose: Most studies about medial open‐wedge high tibial osteotomy (HTO) reported outcomes without focusing on gender differences. Therefore, the study compared the long‐term survival rate and postoperative subjective knee function after HTO in female versus male patients with symptomatic medial compartment knee osteoarthritis. Methods: The data of three cohorts with long‐term outcomes were analysed (n = 245; 32% females; age: 49 ± 7 years; Kellgren Lawrence Grade I 6.1%, II 32.7%, III 42.4%; IV 18.8%). The minimum follow‐up was at least 6 years or an earlier conversion to total knee arthroplasty (TKA). The gender‐specific survival rate after HTO was calculated after 5 and 10 years and compared using Kaplan–Meier analysis and the logrank test. Baseline characteristics and subjective knee function (International Knee Documentation Committee [IKDC]/Lysholm) were analysed between both genders. Results: Forty of 78 (51.3%) women and 41 of 167 men (24.5%) underwent TKA. HTO survival in females was significantly lower (p = 0.0010). The 5‐ and 10‐year survival rates were 85.9% and 62.6% for females and 93.4% and 77.7% for males. In females and males, from preoperative to the last follow‐up, the IKDC (43 ± 15 to 58 ± 17; 47 ± 14 to 67 ± 18) and the Lysholm (42 ± 18 to 72 ± 18; 55 ± 22 to 77 ± 23) improved significantly (all p < 0.0001). Females had significantly lower preoperative and postoperative IKDC (p = 0.0438; p = 0.0035) and Lysholm scores (p = 0.0002; p = 0.0323). But the absolute improvements of the IKDC and Lysholm were not significantly different between genders. Conclusions: Females had higher conversion rates to TKA and lower knee function at the last follow‐up. However, preoperative knee function was lower in females and the absolute improvement following HTO was similar for both genders. In general, females benefit from HTO to treat medial knee arthritis, and TKA could be postponed for half of female patients for more than 10 years. However, surgeons must be aware of the described inferior outcomes in females for realistic patient expectation management. Level of Evidence: Level II. [ABSTRACT FROM AUTHOR]

Epidemiological studies show that exposure to the organochlorine pesticide dieldrin is associated with an increased risk of Parkinson's disease (PD). Animal studies support a link between developmental dieldrin exposure and increased neuronal susceptibility in the α-synuclein preformed fibril and MPTP models in adult male C57BL/6 mice. In a previous study, we showed that developmental dieldrin exposure was associated with sex-specific changes in DNA modifications within genes related to dopaminergic neuron development and maintenance at 12 wk of age. Here, we used capture hybridization-sequencing with custom baits to interrogate DNA modifications across the entire genetic loci of the previously identified genes at multiple time points—birth, 6, 12, and 36 wk old. We identified largely sex-specific dieldrin-induced changes in DNA modifications at each time point that annotated to pathways important for neurodevelopment, potentially related to critical steps in early neurodevelopment, dopaminergic neuron differentiation, synaptogenesis, synaptic plasticity, and glial–neuron interactions. Despite large numbers of age-specific DNA modifications, longitudinal analysis identified a small number of differential modification of cytosines with dieldrin-induced deflection of epigenetic aging. The sex-specificity of these results adds to evidence that sex-specific responses to PD-related exposures may underly sex-specific differences in disease. Overall, these data support the idea that developmental dieldrin exposure leads to changes in epigenetic patterns that persist after the exposure period and disrupt critical neurodevelopmental pathways, thereby impacting risk of late-life diseases, including PD. [ABSTRACT FROM AUTHOR]

Background Access to kidney transplantation (KT) remains challenging for patients with end-stage kidney disease. This study assessed women's access to KT in France by considering comorbidities and neighbourhood social deprivation. Methods All incident patients 18–85 years old starting dialysis in France between 1 January 2017 and 31 December 2019 were included. Three outcomes were assessed: access to the KT waiting list after dialysis start, KT access after waitlisting and KT access after dialysis start. Cox and Fine–Gray models were used. Gender–European Deprivation Index and gender–age interactions were tested and analyses were performed among strata if required. Results A total of 29 395 patients were included (35% of women). After adjusting for social deprivation and comorbidities, women were less likely to be waitlisted at 1 year {adjusted hazard ratio [adjHR] 0.91 [95% confidence interval (CI) 0.87–0.96]} and 3 years [adjHR 0.87 (95% CI 0.84–0.91)] after dialysis initiation. This disparity concerned mainly women ≥60 years of age [adjHR 0.76 (95% CI 0.71–0.82) at 1 year and 0.75 (0.71–0.81) at 3 years]. Access to KT after 2 years of waitlisting was similar between genders. Access to KT was similar between genders at 3 years after dialysis start but decreased for women after 4 years [adjHR 0.93 (95% CI 0.88–0.99)] and longer [adjHR 0.90 (95% CI 0.85–0.96)] follow-up. Conclusions In France, women are less likely to be waitlisted and undergo KT. This is driven by the ≥60-year-old group and is not explained by comorbidities or social deprivation level. [ABSTRACT FROM AUTHOR]

Schizophrenia is a neuropsychiatric illness characterized by altered neurotransmission, in which adenosine, a modulator of glutamate and dopamine, plays a critical role that is relatively unexplored in the human brain. In the present study, postmortem human brain tissue from the anterior cingulate cortex (ACC) of individuals with schizophrenia (n = 20) and sex- and age-matched control subjects without psychiatric illness (n = 20) was obtained from the Bronx–Mount Sinai NIH Brain and Tissue Repository. Enriched populations of ACC pyramidal neurons were isolated using laser microdissection (LMD). The mRNA expression levels of six key adenosine pathway components—adenosine kinase (ADK), equilibrative nucleoside transporters 1 and 2 (ENT1 and ENT2), ectonucleoside triphosphate diphosphohydrolases 1 and 3 (ENTPD1 and ENTPD3), and ecto-5′-nucleotidase (NT5E)—were quantified using real-time PCR (qPCR) in neurons from these individuals. No significant mRNA expression differences were observed between the schizophrenia and control groups (p > 0.05). However, a significant sex difference was found in ADK mRNA expression, with higher levels in male compared with female subjects (Mann–Whitney U = 86; p < 0.05), a finding significantly driven by disease (t(17) = 3.289; p < 0.05). Correlation analyses also demonstrated significant associations (n = 12) between the expression of several adenosine pathway components (p < 0.05). In our dementia severity analysis, ENTPD1 mRNA expression was significantly higher in males in the "mild" clinical dementia rating (CDR) bin compared with males in the "none" CDR bin (F(2, 13) = 5.212; p < 0.05). Lastly, antipsychotic analysis revealed no significant impact on the expression of adenosine pathway components between medicated and non-medicated schizophrenia subjects (p > 0.05). The observed sex-specific variations and inter-component correlations highlight the value of investigating sex differences in disease and contribute to the molecular basis of schizophrenia's pathology. [ABSTRACT FROM AUTHOR]

Numerous genes including sarcospan (SSPN) have been designated as obesity-susceptibility genes by human genome-wide association studies. Variants in the SSPN locus have been linked with sex-dependent obesity-associated traits; however, this association has not been investigated in vivo. To delineate the role SSPN plays in regulating metabolism with potential to impact cardiac function, we subjected young and aged global SSPN-deficient (SSPN−/−) male and female mice to obesogenic conditions (60% fat diet). We hypothesized that loss of SSPN combined with metabolic stress would increase susceptibility of mice to cardiometabolic disease. Baseline and end-point assessments of several anthropometric parameters were performed including weight, glucose tolerance, and fat distribution of mice fed control (CD) and high-fat (HFD) diet. Doppler echocardiography was used to monitor cardiac function. White adipose and cardiac tissues were assessed for inflammation by histological, gene expression, and cytokine analysis. Overall, SSPN deficiency protected both sexes and ages from diet-induced obesity, with a greater effect in females. SSPN−/− HFD mice gained less weight than wild-type (WT) cohorts, while SSPN−/− CD groups increased weight. Furthermore, aged SSPN−/− mice developed glucose intolerance regardless of diet. Echocardiography showed preserved systolic function for all groups; however, aged SSPN−/− males exhibited significant increases in left ventricular mass (CD) and signs of diastolic dysfunction (HFD). Cytokine analysis revealed significantly increased IL-1α and IL-17Α in white adipose tissue from young SSPN−/− male mice, which may be protective from diet-induced obesity. Overall, these studies suggest that several sex-dependent mechanisms influence the role SSPN plays in metabolic responses that become evident with age. NEW & NOTEWORTHY: Young and aged sarcospan (SSPN)-deficient mice were examined to assess the role of SSPN in obesity and cardiometabolic disease. Both sexes displayed a "leaner" phenotype in response to high-fat diet (HFD). Notably, several sex differences were identified in aged SSPN-deficient mice: 1) females developed glucose intolerance (control and HFD) and 2) males exhibited increased left ventricular mass (control) and diastolic dysfunction (HFD). Therefore, we conclude that SSPN exerts a sex-dependent influence on obesity-associated diseases. [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]

Cerebrovascular diseases are the leading cause of death and disability. The epidemiological background and predisposing factors have been the basis of many studies. We aimed to assess the effect of seasonal variability and meteorological factors on stroke incidence in Hungary. National and county-level secondary data were assessed for 2018–2019. We identified stroke with ICD codes I60, I61, I62 (hemorrhagic), I63, I65, and I66 (ischemic). The data were obtained from the University of Pécs Clinical Centre (number of patients per day according to sex and disease subtype, n = 1765). Daily average and maximum wind speed [m/s], precipitation [mm], temperature [°C], and frontal effect [warm/cold/mixed/no effect]) were provided by the Hungarian Meteorological Service. We found that 89.92% of the patients were hospitalized for ischemic and 10.08% for hemorrhagic stroke. We observed a significantly higher number of cases in the other months compared to winter (spring: +35.9%; p = 0.007, summer: +59.0%; p = 0.016, autumn: +36.5%; p = 0.01). In autumn, an increase in temperature increased the incidence of stroke (r = 0.210; p = 0.004). Temperature change affected ischemic stroke incidence (r = 0.112; p = 0.003). In contrast, the number of hemorrhagic stroke cases showed a mild but significant negative association with daily temperature change (r = −0.073; p = 0.049). Overall, a 1 °C temperature change compared to the previous day increased the daily number of admissions by 2.9% (p = 0.017). Air pressure change also affected hemorrhagic stroke incidence (r = 0.083; p = 0.025). Changes in temperature and frontal effects can increase the incidence of stroke. Modern forecasting technology can help the healthcare system prepare for possible increased workloads during critical periods. [ABSTRACT FROM AUTHOR]

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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]

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]

Mitochondrial dysfunction is closely linked to obesity and diabetes, with declining lung function in aging increasing diabetes risk, potentially due to elevated serum levels of dioxin-like mitochondria inhibitor substances (MIS) from prolonged exposure to environmental pollutants. However, the mechanisms connecting MIS, mitochondria, lung function, and metabolic disorder remain unclear. In this study, we analyzed data from 1371 adults aged 40–69 years in the 2008 Korean Genome Epidemiologic Study (KoGES) Ansung cohort. We indirectly estimated dioxin-like MIS levels by measuring intracellular ATP (MISATP) and reactive oxygen species (MISROS) in cultured cells treated with the serum of participants. Using correlation analysis and structural equation modeling (SEM), we explored the relationships among MIS, mitochondrial function, body mass index (BMI), and lung function (FEV1 and FVC). Our findings revealed that MISATP was associated with BMI in females and with FVC in males, while MISROS correlated with both BMI and FVC in males, not in females. Significant associations between BMI and FVC were found in the highest MIS subgroup in both sexes. SEM analyses demonstrated that MIS negatively influenced mitochondrial function, which in turn affected BMI and lung function. Age-related declines in lung function were also linked to mitochondrial dysfunction. This study underscores the potential of MIS assays as alternatives for assessing mitochondrial function and highlights the importance of mitochondrial health in metabolic disorders and lung function. [ABSTRACT FROM AUTHOR]

The article in MedComm discusses the impact of the androgen-type 2 innate lymphoid cells-dendritic cell axis on sex-associated differences in skin immune responses. The study by Chi et al. reveals that sex hormones and the microbiota influence tissue immune set points and dendritic cell network strength, leading to disparities in susceptibility to diseases between males and females. The research highlights the role of androgen signaling in regulating immune responses and emphasizes the potential for gender-tailored therapeutic approaches in various diseases. The findings underscore the complex interplay between sex hormones, microbiota, and immune cells in shaping tissue immune responses and DC network resilience, offering insights into sex differences in disease susceptibility. [Extracted from the article]

Background and Objective: The aim of this study was to analyze sex differences in risk factors associated with hospital mortality in patients with Fournier gangrene (FG). Materials and Methods: A retrospective population-based study (2016–2021) included FG hospitalizations in Spain. To identify the risk factors, we used multivariable logistic regression and reported adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Results: There were 3644 admissions for FG during the study period (82.5% men and 17.5% women). The mean hospitalization rate per 1000 admissions/year was 0.23 for men and 0.05 for women, and the mean hospitalization rate per 100,000 inhabitants/year was 2.7 for men and 0.4 in women. The most common comorbidities were hypertension (44.9%) and diabetes mellitus (35.6%). The main complications were sepsis (22.1%), 29.8% were admitted to the intensive care unit and 16.1% died. Mortality was higher in women (aOR 1.32, 95% CI 1.07–1.63). The main independent risk factors for mortality in the entire sample were older age, neoplasms, chronic kidney disease, heart failure, sepsis, acute kidney injury, and admission to the intensive care unit. In women, they were older age, leukemia, sepsis, acute kidney injury, and admission to the intensive care unit. Conclusions: The overall FG mortality rate was slightly higher in women than in men, people aged >64 years, people with chronic kidney disease, sepsis, and acute kidney injury, and admission to the intensive care unit. The independent factors associated with mortality in women were similar in both sexes. [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]