Examine Sex Differences Research Articles

Device-measured vigorous intermittent lifestyle physical activity (VILPA) and major adverse cardiovascular events: evidence of sex differences.

Vigorous intermittent lifestyle physical activity (VILPA) refers to brief bouts of intense physical activity embedded into daily life. To examine sex differences in the dose-response association of VILPA with major adverse cardiovascular events (MACE) and its subtypes. Using multivariable-adjusted cubic splines, we examined the associations of daily VILPA duration with overall MACE and its subtypes (incident myocardial infarction, heart failure and stroke) among non-exercisers (individuals self-reporting no leisure-time exercise and no more than one recreational walk per week) in the UK Biobank. We also undertook analogous analyses for vigorous physical activity among exercisers (individuals self-reporting participation in leisure-time exercise and/or recreational walking more than once a week). Among 13 018 women and 9350 men, there were 331 and 488 all MACE, respectively, over a 7.9-year follow-up. In women, daily VILPA duration exhibited a near-linear dose-response association with all MACE, myocardial infarction and heart failure. In men, dose-reponse curves were less clear with less evidence of statistical signifigance. Compared with women with no VILPA, women's median daily VILPA duration of 3.4 min was associated with hazard ratios (HRs; 95% confidence intervals) of 0.55 (0.41 to 0.75) for all MACE and 0.33 (0.18 to 0.59) for heart failure. Women's minimum doses of 1.2-1.6 min of VILPA per day were associated with HRs of 0.70 (0.58 to 0.86) for all MACE, 0.67 (0.50 to 0.91) for myocardial infarction, and 0.60 (0.45 to 0.81) for heart failure. The equivalent analyses in UK Biobank's accelerometry sub-study exercisers suggested no appreciable sex differences in dose-response. Among non-exercising women, small amounts of VILPA were associated with a substantially lower risk of all MACE, myocardial infarction and heart failure. VILPA may be a promising physical activity target for cardiovascular disease prevention, particularly in women unable or not willing to engage in formal exercise.

Sex differences in tuberculosis infection and disease among people with HIV.

Worldwide, adult men experience an excess burden of tuberculosis (TB) disease compared to women, but few studies have examined sex differences in TB among people with HIV. In this study, we aimed to investigate sex differences in TB infection and disease among people with HIV in Rio de Janeiro, Brazil. Analysis of data from a randomized controlled trial and retrospective cohort study. We analyzed data from two studies conducted between 2005 and 2017. The THRio Study (2005-2012) evaluated increasing tuberculin skin testing (TST) and TB preventive therapy (TPT) and UnivART (2010-2017) was a virtual cohort study of people with HIV and TB with data from four national electronic registries. Among 4,606 people with HIV in THRio, 2,992 (65.0%) had a TST placed and read, of whom 312/1,865 (17%) males and 203/1,127 (18%) females (p = 0.37) had prevalent TB infection. TB disease incidence was higher among males compared to females overall (IRR 1.33, 95% CI 1.04-1.69), among males compared to females who did not receive TPT (IRR 1.30, 95% CI 1.01-1.67), and among males compared to females on ART (IRR 1.64, 95% CI 1.17-2.29). Among 54,957 people with HIV in UnivART, TB disease incidence rates were higher among males than females overall (IRR 1.28, 95% CI 1.18-1.39), among males compared to females on ART (IRR 1.58, 95% CI 1.40-1.77), and among males compared to females not on ART (IRR 1.11, 95% CI 0.99-1.25). In this medium TB and HIV burden setting, TB disease incidence was higher among males than females with HIV, despite similar prevalence of TB infection.

Sexual Dimorphism in Impairment of Acetylcholine-Mediated Vasorelaxation in Zucker Diabetic Fatty (ZDF) Rat Aorta: A Monogenic Model of Obesity-Induced Type 2 Diabetes.

Several reports, including our previous studies, indicate that hyperglycemia and diabetes mellitus exert differential effects on vascular function in males and females. This study examines sex differences in the vascular effects of type 2 diabetes (T2D) in an established monogenic model of obesity-induced T2D, Zucker Diabetic Fatty (ZDF) rats. Acetylcholine (ACh) responses were assessed in phenylephrine pre-contracted rings before and after apocynin, a NADPH oxidase (NOX) inhibitor. The mRNA expressions of aortic endothelial NOS (eNOS), and key NOX isoforms were also measured. We demonstrated the following: (1) diabetes had contrasting effects on aortic vasorelaxation in ZDF rats, impairing relaxation to ACh in females while enhancing it in male ZDF rats; (2) inhibition of NOX, a major source of superoxide in vasculature, restored aortic vasorelaxation in female ZDF rats; and (3) eNOS and NOX4 mRNA expressions were elevated in female (but not male) ZDF rat aortas compared to their respective leans. This study highlights sexual dimorphism in ACh-mediated vasorelaxation in the aorta of ZDF rats, suggesting that superoxide may play a role in the impaired vasorelaxation observed in female ZDF rats.

Psychopathy checklist-youth version scores and recurring victimisation by an intimate partner in a justice-involved sample: A comparison of young men and women using longitudinal data.

People involved in the criminal justice system are at increased risk of recurring intimate partner violent (IPV) victimisation. Experience of trauma is linked to a variety of negative outcomes, including repeated experiences, so it is important to identify factors that may distinguish non-victims, single-event victims and recurring victims at an early stage as this could hold potential for intervention efforts. Research studies have identified individual-level risk factors for IPV victimisation but have not investigated psychopathy traits or sex differences. To examine sex differences in psychopathy scores and later IPV victimisation. Using the Pathways to Desistance study, a longitudinal study of 1354 adjudicated adolescent offenders, relationships between psychopathy checklist-youth version (PCL-YV) scores measured during the baseline wave, independent/control variables in wave 6 and self-reported IPV victimisation in wave 7 were explored using multinomial regression models. Among justice-involved young adults (average age 19), PCL-YV scores differentiated between non-victims, single-event victims and recurring victims. Higher total scores and higher ratings on the antisocial behaviours facet of psychopathy significantly increased the relative risk of recurring victimisation by an intimate partner overall, and specifically of emotional or physical intimate partner violence. For the young women but not the young men, a higher scoring on the interpersonal manipulation facet of psychopathy specifically increased the relative risk of being a recurring victim of any intimate partner violence. Sex-specific differences in relationships between high PVL-YV scores and recurring IPV victimisation can be used to screen for risk of repeated trauma for justice-involved young adults, which may change a trajectory of continued involvement in the criminal justice system to a trajectory of resilience and recovery.

Men (but not women) prefer to live in economically equal societies when it comes to mating: A five-study investigation

It is generally believed that people prefer societies with economic equality. No studies thus far have systematically examined sex differences in this preference specifically concerning mating—an important life stage. Building upon theoretical frameworks of mating strategies (i.e., hypergyny), we hypothesized that men, in comparison to women, are less inclined to prefer and reside in a highly unequal society when it comes to mating. This could be because economically unequal environments lead men to expect poorer life quality after marriage than women. These hypotheses were confirmed across five studies using a mixed-method approach. In particular, we first provided evidence by focusing on fertile age populations and employing the panel data across 50 states of the USA from 2006 to 2019 (Study 1A), the most recent cross-sectional data at the county level of the USA (Study 1B), and a large-scale survey data on the individual migration records of American residents (N = 4,746,718, Study 2). In addition, we conducted two controlled experiments by manipulating mating motivation (Study 3) and economic inequality level (high versus low, Studies 3 and 4, N = 812, N = 418). Our studies, employing both archival data high in ecological validity and experimental evidence allowing causal inferences, show that men exhibit a stronger aversion than women toward economic inequality. Our findings contribute to a deeper understanding of how evolutionary mating strategies and sex differences jointly influence the economic inequality preference.

Sex differences in the molecular profile of adult diffuse glioma are shaped by IDH status and tumor microenvironment.

Sex differences in adult diffuse glioma (ADG) are well-established clinically, yet the underlying molecular mechanisms remain inadequately understood. Here, we aim to reveal molecular features and cellular compositions unique to each sex in ADG to comprehend the role of sex in disease etiology. We quantified sex differences in transcriptome of ADG using multiple independent glioma patient datasets. Next, we delved into the single-cell landscape to examine sex differences in gene expression and cellular composition. To explore how sex influences disease progression, we analyzed paired samples from primary and recurrent ADG cases, aiming to identify sex-specific differences in molecular and cellular features. Our analysis revealed that mutations in isocitrate dehydrogenase (IDH) genes and the tumor microenvironment emerged as primary influencers of sex-differential molecular enrichments. In IDHwt tumors, genes in neuronal signaling pathway are found to be enriched in male tumors, while genes in hypoxia and inflammatory response pathways are enriched in female tumors. This pattern was reversed in IDHmut gliomas. We hypothesized that these distinctions could be attributed to heterogeneous cellular composition between sexes. Using single-cell data, we observed distinctive patterns of sex differences in cell states, cell composition and cell-cell interaction in IDHwt and IDHmut tumors separately. Further, by comparing molecular changes in paired primary and recurrent ADG samples, we identified sex-specific differences in molecular characteristics and cellular compositions of recurrent tumors. Our results provide a comprehensive multi-level characterization of sex differences in ADG, such findings provide novel insights into glioma disease progression in each sex.

Examination of sex differences in fatigability and neuromuscular responses during continuous, maximal, isometric leg extension

Objective.This study examined sex-related differences in fatigability and neuromuscular responses using surface electromyographic (sEMG) and mechanomyographic (sMMG) amplitude (AMP) and frequency (MPF) during fatiguing, maximal, bilateral isometric leg extensions.Approach.Twenty recreationally active males and females with resistance training experience performed continuous, maximal effort, bilateral isometric leg extensions until their force reduced by 50%. Linear mixed effect models analyzed patterns of force, sEMG, and sMMG AMP and MPF responses in the dominant limb. An independent samples t-test compared time-to-task failure (TTF) between sexes.Main Results.There were no significant differences in TTF between males and females. However, males experienced a greater rate of force loss compared to females. Furthermore, sEMG AMP and MPF and sMMG AMP responses followed similar linear trends for both sexes, while sMMG MPF showed non-linear responses with sex-dependent differences.Significance.These data suggest that although TTF was similar, males had a higher rate of force reduction, likely due to greater absolute strength. Furthermore, despite parallel changes in sEMG AMP and MPF, as well as sMMG AMP, the divergent responses observed in sMMG MPF highlight sex-dependent differences in how males and females experience changes in the firing rates of active motor units during sustained maximal contractions.

Examining Sex Differences In Concussed Individuals Perceived Total Number Of Concussions They Can Incur Before Retirement

Examining Sex Differences In Concussed Individuals Perceived Total Number Of Concussions They Can Incur Before Retirement

The role of socioeconomic factors in sex differences in intrinsic capacity among older adults: A cross-sectional study in Taiwan

ObjectivesThe World Health Organization’s Integrated Care for Older People (ICOPE) framework launched in 2019 is used to assess the intrinsic capacity of older individuals. Older women may face greater socioeconomic disadvantages, which can impact their physical and mental well-being. Therefore, we examined sex differences in intrinsic capacity and the influence of socioeconomic status. MethodsWe conducted a cross-sectional study in Tainan, Taiwan, recruiting 1,268 adults aged 60 or older in 2022. The ICOPE screening assessed cognitive decline, limited mobility, malnutrition, visual impairment, hearing loss, and depressive symptoms. Intrinsic capacity scores ranged from 0 to 6 and were categorized as impairment (1 or higher) or no impairment (0). Binary logistic regression models were used to analyze sex differences in intrinsic capacity, adjusting sequentially for demographics, lifestyle, and socioeconomic factors. ResultsThe prevalence of intrinsic capacity impairment was 34 %. Women had significantly higher odds of intrinsic capacity impairment (women vs. men, odds ratio [OR] = 1.39, 95 % CI = 1.10–1.75). After sequentially adjusting for demographic characteristics, lifestyle, and socioeconomic factors, the ORs were 1.46 (95 % CI = 1.12–1.90), 1.69 (95 % CI = 1.23–2.31), and 1.24 (95 % CI = 0.88–1.73), respectively. Stratified analyses showed that higher odds of impairment in women than in men was evident only in the financially dependent group (P for interaction = 0.059). ConclusionsOlder women in Taiwan have poorer intrinsic capacity than men, a disparity largely attributable to women’s lower socioeconomic status. Strategies to promote healthy aging among women from disadvantaged socioeconomic backgrounds may help mitigate this sex difference in intrinsic capacity.

Examination Of Sex-differences In Fatigability And Semg Spectral Shifts During Sustained, Isometric Leg Extensions

Examination Of Sex-differences In Fatigability And Semg Spectral Shifts During Sustained, Isometric Leg Extensions

Sex Differences in Risk Factors for Generalized Anxiety Disorder in Korean Adolescents.

This study aimed to examine sex differences in the risk factors associated with generalized anxiety disorder (GAD) among Korean adolescents to provide insights for drafting more effective prevention strategies. Data from 51845 middle and high school students in the 18th Korea Youth Risk Behavior Web-based Survey were analyzed. GAD was assessed using the 7-item Generalized Anxiety Disorder tool, and factors such as grade, academic performance, economic status, living arrangements, smoking, drinking, sexual experience, and physical activity were included. The prevalence of GAD and its association with these factors were compared between male and female students using chi-square tests and logistic regression. Odds ratios were compared statistically to identify sex-specific differences. GAD prevalence was higher among girls (42.1%) than boys (30.1%). Both sexes showed increased GAD risk with lower academic performance, lower economic status, smoking, drinking, and sexual experience. Boys living apart from their families had a higher GAD risk, but this was not significant for girls. Additionally, smoking and drinking were associated with a higher increase in GAD risk in girls than in boys. This study underscores the importance of considering sex differences in the prevention of GAD among adolescents. Tailored sex-specific interventions are crucial for effective prevention and management of GAD in Korean adolescents.

Sex Differences in Prescription Patterns and Medication Adherence to Guideline-directed Medical Therapy Among Patients with Ischemic Stroke.

Background: Ischemic stroke is a leading cause of death and disability. Society guidelines recommend pharmacotherapies for secondary stroke prevention. However, the role of sex differences in prescription and adherence to guideline-directed medical therapies (GDMT) after ischemic stroke remains understudied. The aim of this study was to examine sex differences in prescription and adherence to GDMT at 1-year after ischemic stroke in a cohort of commercially insured patients. Methods: Using the Truven Health MarketScan database from 2016-2020, we identified patients admitted with ischemic stroke. GDMT was defined as any statin, antihypertensive, and anticoagulant prescription within 30-days after discharge. Medication adherence was estimated using the proportion of days covered (PDC) at 1-year. PDC <0.80 was used to define non-adherence. A multivariable model adjusting for covariates was performed to identify the factors associated with non-adherence at 1-year. This analysis was restricted to new users of GDMT. Results: Among 155220 patients admitted with acute ischemic stroke during the study period, 15,919 met the inclusion criteria. The mean age was 55.7 years, and 7,701 (48.3%) were women. Women were less likely prescribed statins (58.0% vs 71.8%), and antihypertensives (27.7% vs 41.8%). In this subset of patients with atrial flutter/fibrillation, women were also less likely prescribed anticoagulants (41.2% vs 45.0%). Women were more likely to be non-adherent (i.e., PDC <0.80) to statins (47.3% vs 41.6%, P<0.0001), antihypertensives (33.3% vs 32.2%, P=0.005), and the combination of both (49.6% vs 45.0%, P=0.003). On multivariable analysis, women were likely to be non-adherent to GDMT at 1-year (odds ratio 1.23, 95% confidence interval 1.08-1.41). Conclusions: In this real-world analysis of commercially insured patients with ischemic stroke, women were less likely initiated on GDMT within 30 days after discharge. Women were more likely to be non-adherent to statins and antihypertensive agents at 1-year. Future efforts and novel interventions are needed to understand the reasons and minimize these disparities.

Sex differences in behavior and glutamic acid decarboxylase in Long Evans rats after prolonged social isolation beginning in adolescence.

Social isolation can have long-term effects on brain development and behavior and increases the risk of developing clinical conditions, including anxiety disorders. One modulator of the stress response is gamma-aminobutyric acid, an inhibitory neurotransmitter synthesized by glutamic acid decarboxylase (GAD). This study examined sex differences in behavior and GAD expression following prolonged social isolation beginning in adolescence in Long Evans rats. Males and females were equally divided into group-housed (GH) and socially isolated conditions on Postnatal Day 28 (n = 8 per group). Beginning 5 weeks later, tests were conducted for anxietylike behaviors (open-field test and elevated plus maze), social interactions (sociability test), and spatial memory (novel object location). Sex differences in behavior were observed, with GH females showing fewer anxietylike behaviors in the open-field test and elevated plus maze and spending more time with objects (sociability task) compared to GH males. Isolation had no effect on males but increased anxiety and reduced neophilic measures in females, removing sex differences. On the sociability task, all groups spent more time with novel rats compared to objects, suggesting social interest was retained after isolation. In the hippocampus, isolation reduced GAD in both sexes, and sex differences were seen (F > M). However, no group differences in behavior were observed in the hippocampal-dependent novel object location task. Our findings suggest that prolonged social isolation beginning in adolescence is anxiogenic for female Long Evans rats. Furthermore, sex and housing impact hippocampal GABA-ergic activity, which may have important implications in the treatment of anxiety disorders. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Thyroid Function, Diabetes, and Common Age-Related Eye Diseases: A Mendelian Randomization Study.

Background: Previous Mendelian randomization (MR) studies showed an association between hypothyroidism and cataract and between high-normal free thyroxine (FT4) and late age-related macular degeneration (AMD), but not between FT4, thyroid stimulating hormone (TSH), or hyperthyroidism and diabetic retinopathy or cataract. These studies included a limited number of genetic variants for thyroid function and did not investigate autoimmune thyroid disease (AITD) or glaucoma, include bidirectional and multivariable MR (MVMR), and examine sex differences or potential mediation effects of diabetes. We aimed to address this knowledge gap. Methods: We examined the causality and directionality of the associations of AITD, and FT4 and TSH within the reference range with common age-related eye diseases (diabetic retinopathy, cataract, early and late AMD, and primary open-angle glaucoma). We conducted a bidirectional two-sample MR study utilizing publicly available genome-wide association study (GWAS) summary statistics from international consortia (ThyroidOmics, International AMD Genetics Consortium, deCODE, UK Biobank, FinnGen, and DIAGRAM). Bidirectional MR tested directionality, whereas MVMR estimated independent causal effects. Furthermore, we investigated type 1 diabetes (T1D) and type 2 diabetes (T2D) as potential mediators. Results: Genetic predisposition to AITD was associated with increased risk of diabetic retinopathy (p = 3 × 10-4), cataract (p = 3 × 10-3), and T1D (p = 1 × 10-3), but less likely T2D (p = 0.01). MVMR showed attenuated estimates for diabetic retinopathy and cataract when adjusting for T1D, but not T2D. We found pairwise bidirectional associations between AITD, T1D, and diabetic retinopathy. Genetic predisposition to both T1D and T2D increased the risk of diabetic retinopathy and cataract (p < 4 × 10-4). Moreover, genetically predicted higher FT4 within the reference range was associated with an increased risk of late AMD (p = 0.01), particularly in women (p = 7 × 10-3). However, we neither found any association between FT4 and early AMD nor between TSH and early and late AMD. No other associations were observed. Conclusions: Genetic predisposition to AITD is associated with risk of diabetic retinopathy and cataract, mostly mediated through increased T1D risk. Reciprocal associations between AITD, diabetic retinopathy, and T1D imply a shared autoimmune origin. The role of FT4 in AMD and potential sex discrepancies needs further investigation.

Effect of Acute Alcohol Consumption in a Novel Rodent Model of Decision Making.

Alcohol use, especially at high consumption levels, can lead to irrational decision-making. In humans, this can lead to harmful outcomes often seen in the context of driving under the influence and or aggressive behavior. To date, the field is lacking comprehensive animal models to examine the impact of alcohol use on decision making in rodents, particularly to examine sex differences in choice behavior. To address this issue, the present study examined the effects of acute alcohol consumption during a behavioral approach-avoidance task that captures momentary changes in decision-making behavior and choice selection in female and male rats. Our team has developed a novel behavioral protocol involving a concurrent choice to consume four different concentrations of alcohol and sucrose combinations. During the task, female or male rats can approach or avoid drinking solutions in four distinct corners of our test apparatus. The solutions were prepared in inverse concentrations (higher sucrose was paired with lower alcohol and vice versa) so that the rodents pursue minimal alcohol use by consuming the higher sucrose concentrations or higher concentrations of alcohol by drinking the lower sucrose concentrations. The animals also have the option to avoid drinking alcohol by not approaching any of the drinking cups. Behavior and choice were tracked during task performance involving different solution concentrations of alcohol and sucrose. The choice of consuming different concentrations of alcohol or sucrose resulted in sex-dependent differences in an approach-avoid trade-off pattern of behavior that was sensitive to different concentrations of alcohol/sucrose combinations. Notably, males were greatly affected by the introduction of alcohol into the task environment, approaching higher alcohol concentrations significantly more often than the non-alcohol containing options. In contrast, females choice patterns and task performance were largely unchanged during alcohol and non-alcohol containing tasks. Regardless of sex, we identify a novel method for identifying individual subject decision-making abnormalities during and after alcohol consumption. This research reveals a novel approach for examining the effects of acute alcohol exposure during a trade-off task, with decision patterns being more impacted by alcohol use in males as compared to females. We also offer the field a novel approach for identifying individual abnormalities in decision making behavior with the presentation of alcohol. Future research can explore these abnormal patterns in both acute and chronic alcohol conditions to develop methods for identifying subjects at-risk for developing an alcohol use disorder and the deleterious impact of alcohol on rational decision making.

Exploring sex differences in cardiac interoceptive accuracy using the phase adjustment task.

Previous evidence suggests males and females differ with respect to interoception-the processing of internal bodily signals-with males typically outperforming females on tasks of interoceptive accuracy. However, interpretation of existing evidence in the cardiac domain is hindered by the limitations of existing tools. In this investigation, we pooled data from several samples to examine sex differences in cardiac interoceptive accuracy on the phase adjustment task, a new measure that overcomes several limitations of the existing tools. In a sample of 266 individuals, we observed that females outperformed males, indicative of better cardiac interoceptive accuracy, but had lower confidence than males. These results held after controlling for sex differences in demographic, physiological and engagement factors. Importantly, these results were specific to the measure of cardiac interoceptive accuracy. No sex differences were observed for individuals who completed the structurally identical screener task, although a similar pattern of results was observed in relation to confidence. These surprising data suggest the presence of a female advantage for cardiac interoceptive accuracy and potential differences in interoceptive awareness (metacognition). Possible reasons for mixed results in the literature, as well as implications for theory and future research, are discussed.

Implementation of the Methyl-Seq platform to identify tissue- and sex-specific DNA methylation differences in the rat epigenome

ABSTRACT Epigenomic annotations for the rat lag far behind those of human and mouse, despite the rat’s immense utility in pharmacological and behavioral studies and the need to understand their epigenetic mechanisms. We have designed a targeted-enrichment method followed by next-generation sequencing (Methyl-Seq) to identify DNA methylation (DNAm) signatures across the rat genome. The design reflected an attempt to create a more comprehensive investigation of the rat epigenome, as it included promoters, CpG islands, and island shores of all RefSeq genes. In this study, we implemented the rat Methyl-Seq platform and tested its ability to distinguish differentially methylated regions (DMRs) among three different tissue types, three distinct brain regions, and, in the hippocampus, between males and females. These comparisons yielded DNAm differences of differing magnitudes, many of which were independently validated by bisulfite pyrosequencing, including autosomal regions that were predicted to show the least degree of difference in DNAm between males and females. Quantitative reverse transcription PCR revealed that most genes associated with the DMRs showed tissue-, brain region-, and sex-specific differences in expression. In particular, we found evidence for sex-specific DNAm and expression differences at Tubb6, Lrrn2, Tex26, and Sox5l1, all of which play important roles in neurodevelopment and have been implicated in studies examining sex differences. Our results demonstrate the utility of the rat Methyl-Seq platform and suggest the presence of DNAm differences between the male and female hippocampus. The rat Methyl-Seq has the potential to provide epigenomic insights into pharmacological and behavioral studies performed in the rat.

Inflammatory protein associations with brain MRI measures: Framingham Offspring Cohort.

Brain magnetic resonance imaging (MRI) and inflammatory biomarkers are crucial for investigating preclinical neurocognitive disorders. Current investigations focus on a few inflammatory markers. The study aims to investigate the associations between inflammatory biomarkers and MRI measures and to examine sex differences among the associations in the Framingham Heart Study. Dementia and stroke-free participants underwent OLINK Proteomics profiling and MRI measurements within 5 years. Pairwise cross-sectional analysis assessed 68 biomarkers with 13 brain MRI volumes, adjusting for covariates and familial correlations. Elevated CDCP1, IL6, OPG, and 4E.BP1 were related to smaller total cerebral brain volume (TCBV), whereas higher HGF, IL8, and MMP10 were associated with smaller TCBV, total and frontal white matter volumes. Higher SCF and TWEAK were associated with larger TCBV. In sex-stratified analyses, associations were observed exclusively among males. We report several associations between inflammatory biomarkers and brain volumes, highlighting different associations within sex subgroups. Higher CDCP1, IL6, OPG, and 4E.BP1 levels were associated with smaller TCBV. Higher levels of HGF, IL8 and MMP10 were associated with smaller TCBV, CWV and FWV. Higher levels of SCF and TWEAK, were associated with larger TCBV. Significance diminished in models adjusting for CVD risk factors. Associations were observed exclusively in males.

Male Predominance in West Virginia Unintentional Overdose Deaths is Influenced by Alcohol and Co-Intoxicants.

To examine sex differences in overdose (OD) mortality based upon substances involved. A retrospective database analysis of West Virginia OD decedents (12,666 unintentional OD deaths, 2005-early 2023). Exposures were substances judged to contribute to death. The main outcome measure was determination of male to female death ratios with varying co-intoxicant involvement, particularly related to alcohol and fentanyl. Secondary outcomes included associations of fentanyl concentrations with alcohol concentrations and male sex, including fentanyl (F) and inactive metabolite norfentanyl (N) concentration variability between sexes. Alcohol co-intoxication in OD deaths was associated with higher male:female death ratios, from 2.0 (alcohol absent) to 3.3 (alcohol present). There was a greater increase over time in alcohol involvement in recent deaths involving females compared to males (relative increases of 52% vs. 6%, respectively). Male:female ratios with alcohol and fentanyl co-involvement ranged from 5.9:1 (only two drugs involved) to 2.4:1 (= 5 substances), with females significantly more likely to have multiple substances contributing to death. Overall, males had statistically significantly larger fentanyl (F) to norfentanyl (N) median concentration ratios compared to females (8.8 vs. 6.9, respectively). Multivariable analyses found alcohol presence was associated with a statistically significant 22% reduction in predicted fentanyl concentrations. Male:female ratios in unintentional OD deaths were higher with greater alcohol involvement and lower with fewer co-intoxicants. Fentanyl and norfentanyl concentration differences by sex were observed. It is important to determine possible contributors to sex differences in OD death rates to better target prevention and treatment initiatives.

Consideration of absolute intensity when examining sex differences in blood pressure responses during static exercise.

Low- to moderate-intensity submaximal static contractions are commonly used to study the effects of biological sex on the cardiovascular response to exercise. Under this paradigm, premenopausal females frequently demonstrate smaller blood pressure responses than age-matched males. These differences are preserved during postexercise circulatory occlusion, implicating the muscle metaboreflex as an important driver of sex differences in the blood pressure response to static exercise. The mechanisms responsible for these differences are incompletely understood but often attributed to innate sex differences in skeletal muscle fiber type distribution, muscle metabolism, and/or sympathetic control of the circulation. However, one potential confounding factor is that the majority of studies use relative intensity exercise (e.g., 30% of maximal voluntary contraction), such that on average, females are completing static contractions at a lower absolute intensity. In this review, we summarize human evidence showing that sex differences in blood pressure responses to static exercise are attenuated or abolished when controlling for absolute intensity and muscle strength, either by statistical methods or strength-matched cohorts. We highlight evidence that the effect of higher absolute contraction intensity on exercise blood pressure likely occurs through increased mechanical occlusion of skeletal muscle microvasculature, leading to greater activation of the muscle metaboreflex. These findings highlight an important need to account for absolute intensity when studying and interpreting sex differences in cardiovascular responses to exercise.