Objective: To investigate the effects of pre-pregnancy and prenatal exposure to six major air pollutants (CO, NO2, O3, PM10, PM2.5, SO2) on birth weight in newborns and identify critical exposure windows. Methods: This retrospective cohort study analyzed data from 1 561 mother-infant pairs who delivered at Taiyuan Central Hospital between January 2020 and December 2023, combined with contemporaneous air pollution monitoring records. This study used the geographic information system (GIS) technology to evaluate the individual air pollutants exposure level of pregnant women, and calculated the average pollutant concentrations for four stages: preconception (the 12 weeks before conception), first trimester (weeks 1-13), second trimester (weeks 14-27) and third trimester (weeks 28-37). Multiple linear regression models were used to assess the associations between air pollutant exposure and birth weight at different pregnancy stages. The distributed lag nonlinear model (DLNM) was further constructed to characterize the nonlinear exposure-lag-response relationships, identify sensitive windows, and examine sex differences. Results: Preliminary multiple linear regression showed that third-trimester exposures to PM2.5(β^=-43.00, 95%CI:-79.40- -6.68), PM10(β^=-35.00, 95%CI:-66.00- -4.07), NO2(β^=-35.50, 95%CI:-66.90- -4.08) and SO2(β^=-28.80, 95%CI:-52.70- -4.97) were negatively associated with birth weight (all P<0.05), but these associations disappeared after full adjustment for covariates. DLNM analysis revealed exposure-response relationships for CO, O3, PM10, and SO2 on birth weight, with distinct critical exposure windows: CO (weeks 2-13, 14-20), O3 (weeks 4-13, 14-24), PM10 (weeks 22-27, 28-37), and SO2 (weeks 11-13, 14-27 and 28-37). Among these, the largest effect were observed for CO at gestational week 12, O3 at week 13, and for both PM10 and SO2 at week 37. The effect estimates and their 95% confidence intervals were -37.12(-62.78- -11.45), -3.61(-6.45- -0.77), -5.01(-8.98- -1.04) and -8.31(-12.07- -4.56), all P<0.05. Gender differences in pollutant effects were observed: male newborns were more sensitive to SO2 across multiple stages, to CO in mid-pregnancy, and to PM10 in late-pregnancy; female newborns were more susceptible to PM10 in the preconception and early-to-mid-pregnancy periods, to O3 in early-to-mid pregnancy, and to SO2 in late pregnancy. Conclusion: Exposure to air pollutants during pregnancy is associated with reduced birth weight in newborns. Different pollutants have specific exposure windows, and gender differences exist. This finding provides important scientific evidence for preventing adverse pregnancy outcomes and developing intervention strategies to improve neonatal health.

Female underrepresentation in clinical trials of acute coronary syndromes (ACS) may hinder the assessment of sex-based differences in the outcomes of long-term pharmacological therapy. The presence of these differences and their potential association with female representation in clinical trials remain unclear. A systematic search of Embase, Medline Ovid, and Cochrane Central was conducted through July 1, 2025, in accordance with the reporting standards of the PRISMA guidelines. Eligible randomized controlled trials (RCTs) compared long-term pharmacological therapy for ACS with placebo or standard care, included ≥1-year follow-up, and reported a clinical event as the primary outcome. Sex differences in treatment effects were analysed using a random-effects meta-analysis, while meta-regression was used to assess the association between the proportion of females in each trial and these differences. The main outcome was the sex difference in the relative effect measure (REM; mostly a hazard ratio) for the primary efficacy endpoint. Among 102 RCTs, female representation ranged from 10% to 52%. Forty-eight trials provided sex-stratified data. Pooled analysis showed no evidence of sex-related differences in efficacy: the mean difference in the log of the REM of males minus females was 0.00 (95% confidence interval, -0.05 to 0.05; P = 0.98; heterogeneity I² = 0%). Meta-regression indicated no relationship between female trial participation and sex-specific treatment effects. In RCTs of long-term pharmacological therapy after ACS, treatment efficacy was comparable between sexes, irrespective of sex distribution. These findings support current guidelines recommending equivalent long-term pharmacological strategies for secondary prevention in both sexes.

Beyond marbles buried: A multidimensional analysis of the marble burying test in the C57BL/6J mouse strain.

Stroke is a sexually dimorphic disease, with different risk factors, incidence, outcomes, and treatment responses in men and women. While sex differences have been documented in preclinical studies, these findings often come from single-site studies with small sample sizes and require validation across diverse research settings. We used data from the SPAN (Stroke Preclinical Assessment Network), a randomized, placebo-controlled, blinded, multilaboratory trial, to determine if sex differences in neurological outcomes are present in preclinical stroke models. We analyzed data from 665 stroke animals treated with saline, including young mice, diet-induced obese mice, aging mice, young rats, and spontaneously hypertensive rats. We compared the corner test index and brain morphology between the sexes using linear random effect models and assessed the mortality rate using Cox proportional hazard regression models. No significant sex differences were found in neurological outcome measured with the corner test on either day 7 or day 30 after stroke, regardless of the mouse or rat stroke model used. Additionally, female and male mice exhibited similar infarct sizes on day 2 magnetic resonance imaging and on brain atrophy measures on day 30 after stroke, indicating a lack of sex differences in brain injury. Similarly, no sex differences were observed in acute or chronic sensorimotor or tissue outcomes in young rats. In 1 subanalysis, sex differences were seen in the spontaneously hypertensive rats cohort. Female rats exhibited a higher corner test index on day 30 than males, indicating more severe sensorimotor injury. In this multicenter preclinical study, we did not detect sex differences in stroke outcomes in mice, although sex differences in behavioral outcomes were observed in spontaneously hypertensive rats. These findings highlight that sex differences may be model-specific and subtle, emphasizing the need for methodological consistency and thoughtful inclusion of diverse animal models in translational stroke research to better understand if sex-specific responses contribute to stroke outcomes.

Sex differences play a crucial role in determining tumor incidence, treatment sensitivity, and prognosis among men and women. However, current clinical cancer treatment strategies fail to account for these differences. Furthermore, the underlying mechanisms of tumor disparities between sexes remain elusive. Sex differences in sex chromosomes, hormone levels, metabolism, and immunity synergistically contribute to tumor-related disparities. As the demand for precision medicine escalates, there is an urgent need to conduct further exploration and research to address the tumor differences between sexes. In this review, we discuss the impact of biological sex differences on tumor cells and the tumor microenvironment, aiming to identify more effective strategies for tumor prevention and treatment.

Postoperative recovery following adolescent idiopathic scoliosis (AIS) surgery includes multimodal pain management and physical therapy. Though virtual reality (VR) has been explored as a non-pharmacologic strategy for reducing pain and anxiety during bedside procedures, its impact on postoperative pain and opioid use following AIS correction has not been well characterized. Adolescent patients undergoing spinal fusion for AIS between March 2024 and June 2025 were eligible for recruitment. Patients completed a 20-minute immersive underwater VR scenario prior to each postoperative inpatient physical therapy (PT) session. Pain scores (measured on a 10-point Likert scale) before and after PT, opioid usage, number of completed PT sessions, and length of hospitalization were recorded for study subjects and were compared to controls. Ten patients in the VR cohort were compared to 10 controls. There were no differences in sex (p=0.58), race (p=0.07), ethnicity (p>0.99), or average age at surgery (15.1 vs 15.8 years, p=0.30). Patients in the VR cohort had a greater average reduction in pain scores associated with postoperative PT compared to controls (-0.72 vs +0.61, p=0.02). Patients in the VR and control groups did not differ significantly with regard to total opioid usage in morphine equivalents (55.7 vs 49.9 mg, p=0.71), completed PT sessions (3.2 vs 3.2 sessions, p>0.99), or length of hospitalization (2.6 vs 2.4 days, p=0.53). Side effects of the VR intervention included fatigue (n=3), nausea (n=3), headache (n=2), eye strain (n=1), and dizziness (n=1). Our pilot study demonstrated that an immersive VR session prior to each postoperative PT session significantly reduced the change in PT-associated pain scores among patients undergoing spinal fusion for AIS. Future investigations utilizing a randomized-controlled design will continue to elucidate the impact of VR on postoperative recovery for patients undergoing AIS correction.

Chronic pain affects approximately one-third of active-duty service members (ADSMs), yet effective treatment remains challenging. Salivary cortisol and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) are established non-invasive biomarkers of stress and oxidative DNA damage and may provide reliable unbiased indicators of treatment efficacy in chronic pain. However, their associations with pain outcomes and potential sex differences remain unclear. It was hypothesized that interdisciplinary pain treatment would result in decreased levels of stress and oxidative DNA damage biomarkers, as well as decreased pain intensity, and that the magnitude of challenge might vary by sex. Our objective was to compare longitudinal changes in salivary cortisol and urinary 8-OHdG in relation to pain outcomes and sex. A total of 190 ADSMs who referred for chronic pain treatment completed data collection on the Patient-Reported Outcomes Measurement Information System (PROMIS) measures and urine and saliva samples at baseline and post-treatment. Multivariable regression models were used to predict changes in PROMIS scores relative to changes in cortisol and 8-OHdG, while adjusting for baseline levels. Interaction terms between participants' sex and changes in biomarkers were added to each model. Given the study's exploratory nature, a significance threshold of p < .10 was used for all analyses. Five statistically significant sex-by-cortisol interactions were identified for pain measures (pain impact, pain interference, physical functioning, sleep impairment, and social functioning), but none for 8-OHdG. Future work is needed to replicate these findings in larger samples. The research protocol was registered in ClinicalTrials.gov (NCT03297905; https://clinicaltrials.gov/study/NCT03297905).

Lentiviral infection of rhesus macaques represents a robust model for HIV persistence and a key system to evaluate HIV cure-directed interventions. How sex impacts viral reservoirs in macaques is unknown. We sought to uncover potential sex differences in viral measurements during antiretroviral therapy (ART) using data from 19 studies conducted at Emory Primate Center. Sex differences in total and intact SIV/SHIV-DNA levels in blood and lymph node CD4+ T-cells were not observed, although subgroup analysis of SIV-infected adult macaques revealed higher reservoir levels in females. Age (adult versus infant) was a significant effect for all viral outcomes studied.

Background Data on Canalis Sinuosus (CS) morphology in South Asian populations remain limited, despite frequent anterior maxillary implant placements. This study aimed to evaluate the occurrence, positional characteristics, and morphometric features of the CS in Indian adults using cone-beam computed tomography (CBCT) and to assess sex-related differences. Methods A cross-sectional analysis was conducted on 245 CBCT scans with intact maxillary incisors and canines. Multiplanar reconstructions were used to identify the CS and document its laterality, tooth relationship, and orientation. Measurements included canal diameter at the alveolar crest and distances to the alveolar crest, buccal cortical plate, and nasal floor. Inter-observer agreement was assessed using Cohen’s κ. Sex differences were analyzed using χ 2 and independent-samples t-tests (α = 0.05). Results CS was detected in 67.3% of individuals, with bilateral presentation in 55.9% and unilateral in 11.4%. Detection rates were similar between sides (left: 62.4%, right: 60.8%). The canal was most frequently adjacent to the lateral incisor (44.7% left, 50.3% right), and approximately half of the canals showed palatal orientation. The mean canal diameter was 0.8 mm. Mean distances to the alveolar crest, buccal cortical plate, and nasal floor were 9.2 mm, 7.0 mm, and 11.5 mm, respectively. Males showed significantly larger canal diameters on the left side (p = 0.008), greater buccal cortical distances bilaterally (p &lt; 0.001), and larger right nasal floor distances (p = 0.011). Conclusions The CS is a frequently observed, typically bilateral anatomical structure in the anterior maxilla of Indian adults, mostly located palatal adjacent the lateral incisor. The morphometric and sex-specific data obtained provide valuable reference parameters for implant planning and minimizing surgical complications.

Humans exposed to cold environments for leisure or occupational activities may experience cold stress. Cold-related physical and mental stress can negatively affect cognitive performance. A recent literature review has pointed out that a single acute exposure to cold under controlled laboratory conditions (e.g., cold air or cold water) induces cognitive impairment with attention, processing speed, memory, and executive function being the most affected cognitive domains. Males and females seem to respond differently to short-term cold exposure, although results are not consistent. The aim of the study was to investigate the effect of acute and brief (15min) exposure to low ambient temperatures of -10°C compared with 5°C and 20°C on selected cognitive performance (reaction time, processing speed, and risky decision-making). We hypothesized that cognitive performance decreases at low temperatures with a sex difference, before core temperature changes. This randomized, controlled, crossover study was conducted in an environmental chamber (terraXcube) under controlled, replicable, and safe conditions in twenty-four healthy volunteers, females and males, aged between 18 and 60 years. Measurements included Psychomotor Vigilance Test (PVT), Balloon Analogue Risk Task (BART), and Digit Symbol Substitution Test (DSST). Cognitive performance, stress, and cold were subjectively rated with a visual analogue scale (VAS). Physiological data (including core and skin temperatures) were continuously recorded with a physiological monitoring system. Data were analysed using repeated measures analysis of variance (ANOVA), Friedman test, Generalised Estimating Equations (GEE), and correlation analysis. We identified transient impairments in cognitive performance in individuals wearing appropriate clothing. Cold exposure (-10°C) affected attention by slowing response times and increasing the lapses, and decision-making by reducing risky behaviour. Heart rate, cold sensation, and stress, as well as thermal sensation and comfort, but not core temperature were different in the three experimental temperature exposures. No differences were found between male and female subjects in their cognitive performance. Our data support the distraction theory in the decline of cognitive performance even during a short exposure to cold temperatures. Such impairment should be carefully considered in people performing different activities in cold environments, even for a short time.

Sex differences in the association between relative Fat Mass and cognitive impairment in hospitalized middle-aged and older patients with type 2 diabetes mellitus in China: a single-center cross-sectional study.

Cardiac rehabilitation (CR) is a secondary prevention program that is associated with a decrease all-cause mortality. Physical inactivity is a major risk factor for disease, and long-term physical activity (PA) adherence is an essential component of CR. The purpose of this study is to assess self-reported PA adherence 1year after CR completion. We hypothesize that individuals would not meet nationally recommended Physical Activity Guidelines (PAG) 1-year post-CR, but males would meet PAG at higher rates than females. Using a prospective, cross-sectional design, 172 CR graduates completed the International Physical Activity Questionnaire-Short Form telephone survey on self-reported PA and sitting time. Meeting PAG was defined as ≥150 minutes of moderate PA, ≥75 minutes of vigorous PA, or any combination of ≥150 minutes of moderate to vigorous PA. The cohort (n=172; 38 [19%] female; mean age 67±11 y, range 35-90) attended 31±8 (of 36) CR sessions and were surveyed 13.6 (2.7) months post-CR (76.1% response rate). Participants reported an average of 97±125 min/week of moderate to vigorous PA, with 32% (n=55, 80% male) meeting PAG and 5.3±3.3 hr/day of sitting. There were no sex differences in how PAG was met or in minutes per day, days per week, or sitting time. Only 32% of CR graduates met PAG 1-year post-CR, with both sexes failing to achieve national guidelines. Significance/Implications:Providers should recognize that patients often fail to meet PAG after CR, undermining CR's long-term goals. Continued interventions targeting both sexes are needed to promote sustained long-term PA to support disease prevention.

Gastric cancer is the fifth most common cancer globally and the fourth leading cause of cancer-related mortality. While gender and sex differences in gastric cancer care are underexplored in Germany, international studies have revealed disparities in aspects such as histology, comorbidities, treatment approaches and survival outcomes. This study aims to explore gender/sex-specific variations in clinical management and their impact on mortality, complications and survival rates in gastric carcinoma patients in Germany. The findings may inform revisions to clinical guidelines and support the development of more personalised treatment strategies. This study aims to improve the quality of care for gastric cancer patients and promote more individualised, sex-sensitive medical practices. This nationwide, retrospective cohort study will analyse data from the German Diagnosis-Related Groups statistic and regional clinical cancer registries from 2017 to 2021. The study will evaluate both datasets separately, providing a comprehensive view of sex differences in gastric cancer care. Primary outcomes include hospital mortality and survival rates, while secondary endpoints include surgical complications, treatment modalities and postoperative outcomes. The analysis will investigate whether sex influences tumour characteristics, access to treatment and therapy effectiveness. Statistical methods such as descriptive analysis, regression models and survival analysis will be applied to identify sex-related variations in diagnosis, treatment and outcomes. This study uses anonymised secondary data; thus, ethics approval is not necessary. Findings will be submitted to a peer-reviewed journal, reported to the Innovation Fund of the Federal Joint Committee of Germany, and a patient leaflet for the involved self-help groups will be made. NCT06902337.

Lamotrigine is one of the most widely prescribed antiseizure medication (ASM) and mood stabilizer in the United States due to its favorable side-effect profile, lower risk of teratogenicity, and minimal drug-drug interactions. This study aimed to examine age- and sex-associated variability in prescribing and pharmacokinetics, focusing on postmenopausal women. Data were from electronic health records. Individuals were included if ≥18 years and received an ASM between January 1, 2015 and December 31, 2021. Lamotrigine prescriptions were compared based on age, sex, epilepsy diagnosis, and monotherapy/polytherapy. Statistical comparisons of proportions were conducted using two-proportion tests. To characterize age- and sex-related differences in LTG apparent oral clearance and assess the impact of covariates, linear mixed-effects modeling was employed. Records were available for 314 890 individuals, with 23 906 patients being prescribed lamotrigine at least once (as monotherapy or polytherapy) for both epilepsy and non-epilepsy diagnoses. The lamotrigine prescription rate was lower in postmenopausal women compared to younger women but higher than in older men, irrespective of diagnosis. Notably, lamotrigine was prescribed as monotherapy more frequently to patients without epilepsy than those with epilepsy, regardless of sex and age. The clearance of lamotrigine was 22% lower in postmenopausal women compared to younger women and 9% in older men. Lamotrigine clearance increased by 49% and 11% with co-administration of inducers or the presence of smoking, respectively. Lamotrigine clearance decreased by 51% in the presence of an inhibiting medication. Prescription rates for lamotrigine varied between patients with epilepsy and those with non-epilepsy conditions. Age and sex differences in pharmacokinetics suggest the need for lamotrigine dose adjustments, highlighting the importance of therapeutic drug monitoring in personalized epilepsy care. Lamotrigine use was less frequent in postmenopausal women compared to younger women but higher compared to older men. Postmenopausal women were prescribed lamotrigine as monotherapy to a lesser extent than younger women and older men.

BackgroundCardiovascular disease remains a major source of morbidity and mortality, and population imaging studies have yielded insights into disease etiology and risk.MethodsIn this study, we segment the heart, aorta, and vena cava from abdominal magnetic resonance imaging (MRI) scans using deep learning. We generate six image-derived phenotypes (IDP): heart volume, four aortic and one vena cava cross-sectional areas (CSA), from 44,541 UK Biobank participants, and explore their associations with disease outcomes, as well as genetic and environmental factors.ResultsHere we show concordance between our IDPs and related IDPs from cardiac magnetic resonance imaging, the current gold standard, and replicate previous findings related to sex differences and age-related changes in heart and vessel dimensions. We identify a significant association between infrarenal descending aorta CSA and incident abdominal aortic aneurysm, and between heart volume and several cardiovascular disorders. In a genome-wide association study, we identify 72 associations at 59 loci (15 novel). We derive a polygenic risk score for each trait and demonstrated an association with thoracic aneurysm diagnosis, pointing to a potential screening opportunity. We demonstrate substantial genetic correlation with cardiovascular traits including aneurysms, varicose veins, dysrhythmia, and cardiac failure. Finally, heritability enrichment analysis implicates vascular tissue in the heritability of these traits.ConclusionsThis study illustrates the value of non-specific abdominal MRI for exploring cardiovascular disease risk in cohort studies, and identifies novel genetic associations with vascular dimensions.

Background Traumatic brain injury (TBI) accelerates Alzheimer’s disease (AD) pathology and neuroinflammation, potentially via gut-brain axis disruptions. Whether restoring gut microbial homeostasis mitigates TBI-exacerbated AD features remains unclear, particularly with respect to sex differences. Objective The goal of our study was to test whether fecal microbiota transplantation (FMT) modifies amyloid pathology, neuroinflammation, gut microbial composition, metabolites, and motor outcomes in male and female 5xFAD mice subjected to TBI. Methods Male and female 5xFAD mice received sham treatments or controlled cortical impact, followed 24 h later by vehicle (VH) or sex-matched FMT from C57BL/6 donors. Assessments at baseline, 1-, and 3-days post-injury (dpi) included Thioflavin-S and 6E10 immunostaining for Aβ, Iba-1 and GFAP for glial activation, lesion volume, rotarod performance, 16S rRNA sequencing for microbiome profiling, serum short-chain fatty acids (SCFAs), and gut histology. Results TBI increased cortical and dentate gyrus Aβ burden, with females showing greater vulnerability. FMT reduced Aβ deposition in sham animals and shifted plaque morphology but did not attenuate TBI-induced amyloid escalation. FMT differentially modulated glial responses by sex and region (reduced microgliosis in males) without altering lesion volume at 3 dpi. Rotarod performance was better in sham females compared to males and declined in FMT-treated TBI females. Fecal microbiome alpha diversity and richness were unchanged, while beta diversity revealed marked, time-dependent community shifts after TBI that were slightly altered by FMT. Gut morphology remained broadly intact, but crypt width increased after TBI, particularly in males. Conclusion In 5xFAD mice, TBI drives sex-dependent worsening of amyloid pathology, neuroinflammation, and dysbiosis. Acute FMT partially restores microbial composition and plaque features in sham animals but fails to reverse TBI-induced neuroinflammation or motor deficits. These findings underscore the context- and sex-dependence of microbiome interventions and support longer-term, sex-specific strategies for AD with comorbid TBI.

Sex differences in the cardiovascular and ventilatory responses to arm or leg mechanoreflex activation.

Sex differences in the clinical characteristics of suicide among individuals with bipolar disorder: An observational study of coroner data in Toronto.

Sex differences in microglia morphology and function across the lifespan are mediated by the early hormone environment.

Sex-differences in influenza vaccine efficacy and immunogenicity among Canadian Hutterite children.