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Background Posttraumatic stress disorder (PTSD) is two to three times more common in women than in men. To better understand this phenomenon, we need to know why men, women, and possibly individuals with other sex/gender identities respond differently to trauma. To stimulate sex and gender sensitive research, the European Journal of Psychotraumatology (EJPT) was the first journal to adopt a gender policy. In addition, a call for papers entitled Integrating and Evaluating Sex and Gender in Psychotrauma Research was announced. Objective This special issue synthesizes the past five years of psychotrauma research with regard to sex/gender differences. Method Seventy-seven articles were identified from EJPT archives, including five systematic reviews. These articles examined sex differences and/or gender differences in exposure to trauma, posttraumatic stress responses, or how sex and gender impacts (mental) health outcomes or treatment responses. Results Findings from these studies outlined that: 1. sex and gender still need to be more clearly defined, also in relation to the context that codetermine trauma responses, like other ‘diversity’ variables; 2. in most studies, sex and gender are measured or reported as binary variables; 3. sex and gender are important variables when examining trauma exposure, responses to these events, symptoms trajectories, and mental and physical health outcomes across the life span; and 4. in PTSD treatment studies, including a meta-analysis and a systematic review, sex and gender were not significant predictors of treatment outcome.Conclusion Future research must focus on sex and gender as important and distinct variables; they should include sex and gender in their statistical analyses plan to better clarify associations between these variables and (responses to) psychotrauma. To enhance reporting of comparable data across studies, we provide suggestions for future research, including ho

Background Cardiac troponins are the preferred biomarkers for the diagnosis of acute myocardial infarction. Although sex‐specific 99th percentile thresholds of troponins are recommended in international guidelines, the clinical effect of their use is poorly investigated. The DANSPOT Study (The Danish Study of Sex‐ and Population‐Specific 99th percentile upper reference limits of Troponin) aims to evaluate the clinical effect of a prospective implementation of population‐ and sex‐specific diagnostic thresholds of troponins into clinical practice. Methods This study is a nationwide, multicenter, stepped‐wedge cluster‐randomized trial of the implementation of population‐ and sex‐specific thresholds of troponins in 22 of 23 clinical centers in Denmark. We established sex‐specific thresholds for 5 different troponin assays based on troponin levels in a healthy Danish reference population. Centers will sequentially cross over from current uniform manufacturer‐derived thresholds to the new population‐ and sex‐specific thresholds. The primary cohort is defined as patients with symptoms suggestive of acute coronary syndrome having at least 1 troponin measurement performed within 24 hours of arrival with a peak troponin value between the current uniform threshold and the new sex‐specific female and male thresholds. The study will compare the occurrence of the primary outcome, defined as a composite of nonfatal myocardial infarction, unplanned revascularization, and all‐cause mortality within 1 year, separately for men and women before and after the implementation of the new sex‐specific thresholds. Conclusions The DANSPOT Study is expected to show the clinical effects on diagnostics, treatment, and clinical outcomes in patients with myocardial infarction of implementing sex‐specific diagnostic thresholds for troponin based on a national Danish reference population. Registration URL: https://www.clinicaltrials.gov; Unique identifier, BACKGROUND: Cardiac troponins are the preferred biomarkers for the diagnosis of acute myocardial infarction. Although sex-specific 99th percentile thresholds of troponins are recommended in international guidelines, the clinical effect of their use is poorly investigated. The DANSPOT Study (The Danish Study of Sex- and Population-Specific 99th percentile upper reference limits of Troponin) aims to evaluate the clinical effect of a prospective implementation of population- and sex-specific diagnostic thresholds of troponins into clinical practice. METHODS: This study is a nationwide, multicenter, stepped-wedge cluster-randomized trial of the implementation of population- and sex-specific thresholds of troponins in 22 of 23 clinical centers in Denmark. We established sex-specific thresholds for 5 different troponin assays based on troponin levels in a healthy Danish reference population. Centers will sequentially cross over from current uniform manufacturer-derived thresholds to the new population- and sex-specific thresholds. The primary cohort is defined as patients with symptoms suggestive of acute coronary syndrome having at least 1 troponin measurement performed within 24 hours of arrival with a peak troponin value between the current uniform threshold and the new sex-specific female and male thresholds. The study will compare the occurrence of the primary outcome, defined as a composite of nonfatal myocardial infarction, unplanned revascularization, and all-cause mortality within 1 year, separately for men and women before and after the implementation of the new sex-specific thresholds. CONCLUSIONS: The DANSPOT Study is expected to show the clinical effects on diagnostics, treatment, and clinical outcomes in patients with myocardial infarction of implementing sex-specific diagnostic thresholds for troponin based on a national Danish reference population. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05336435.

Background Cardiac troponins are the preferred biomarkers for the diagnosis of acute myocardial infarction. Although sex‐specific 99th percentile thresholds of troponins are recommended in international guidelines, the clinical effect of their use is poorly investigated. The DANSPOT Study (The Danish Study of Sex‐ and Population‐Specific 99th percentile upper reference limits of Troponin) aims to evaluate the clinical effect of a prospective implementation of population‐ and sex‐specific diagnostic thresholds of troponins into clinical practice. Methods This study is a nationwide, multicenter, stepped‐wedge cluster‐randomized trial of the implementation of population‐ and sex‐specific thresholds of troponins in 22 of 23 clinical centers in Denmark. We established sex‐specific thresholds for 5 different troponin assays based on troponin levels in a healthy Danish reference population. Centers will sequentially cross over from current uniform manufacturer‐derived thresholds to the new population‐ and sex‐specific thresholds. The primary cohort is defined as patients with symptoms suggestive of acute coronary syndrome having at least 1 troponin measurement performed within 24 hours of arrival with a peak troponin value between the current uniform threshold and the new sex‐specific female and male thresholds. The study will compare the occurrence of the primary outcome, defined as a composite of nonfatal myocardial infarction, unplanned revascularization, and all‐cause mortality within 1 year, separately for men and women before and after the implementation of the new sex‐specific thresholds. Conclusions The DANSPOT Study is expected to show the clinical effects on diagnostics, treatment, and clinical outcomes in patients with myocardial infarction of implementing sex‐specific diagnostic thresholds for troponin based on a national Danish reference population. Registration URL: https://www.clinicaltrials.gov; Unique identifier, BACKGROUND: Cardiac troponins are the preferred biomarkers for the diagnosis of acute myocardial infarction. Although sex-specific 99th percentile thresholds of troponins are recommended in international guidelines, the clinical effect of their use is poorly investigated. The DANSPOT Study (The Danish Study of Sex- and Population-Specific 99th percentile upper reference limits of Troponin) aims to evaluate the clinical effect of a prospective implementation of population- and sex-specific diagnostic thresholds of troponins into clinical practice. METHODS: This study is a nationwide, multicenter, stepped-wedge cluster-randomized trial of the implementation of population- and sex-specific thresholds of troponins in 22 of 23 clinical centers in Denmark. We established sex-specific thresholds for 5 different troponin assays based on troponin levels in a healthy Danish reference population. Centers will sequentially cross over from current uniform manufacturer-derived thresholds to the new population- and sex-specific thresholds. The primary cohort is defined as patients with symptoms suggestive of acute coronary syndrome having at least 1 troponin measurement performed within 24 hours of arrival with a peak troponin value between the current uniform threshold and the new sex-specific female and male thresholds. The study will compare the occurrence of the primary outcome, defined as a composite of nonfatal myocardial infarction, unplanned revascularization, and all-cause mortality within 1 year, separately for men and women before and after the implementation of the new sex-specific thresholds. CONCLUSIONS: The DANSPOT Study is expected to show the clinical effects on diagnostics, treatment, and clinical outcomes in patients with myocardial infarction of implementing sex-specific diagnostic thresholds for troponin based on a national Danish reference population. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05336435.

BackgroundFamily meals are associated with adolescent health outcomes. Studies have reported that girls are less likely than boys to have dinner with their families.PurposeThis study examined gender differences in family meal frequency and the relationship between meal frequency and other health measures, using a large and representative sample of California middle and high school students.MethodsThis study analyzed data from the 2019-2020 California Student Tobacco Survey (159,904 students in grades 8, 10, and 12). Dinner with the family 5-7 times per week was defined as high frequency. Students reported substance use (of tobacco, marijuana, and alcohol) and rated their mental health and happiness in their home life. All analyses were weighted to reflect the California student population.ResultsFewer than half (44.7%) of students reported a high frequency of family meals, with boys more likely than girls and those who identified their gender in another way the least likely to do so (48.3%, 42.2%, 34.0%, respectively). Gender differences persisted across demographics and the quality of family relationships, and were evident as early as eighth grade. Less frequent family meals were associated with poorer mental health (OR = 1.34, 95% CI: 1.29-1.40) and substance use (OR = 1.27, 95% CI: 1.21-1.32), controlling for the effects of demographics and family dynamics.ConclusionGender differences in family meal frequency emerge early in adolescence and persist across demographics and family relationships. Given that family meals play a protective role in an adolescent's life, these gender differences are concerning.

Decision-makers often are faced with uncertain situations in which they have incomplete information. While risky decisions include the probabilities of the possible outcomes, ambiguous decisions involve both unknown probabilities and unknown outcomes. Prior research has suggested that there are differences in how men and women evaluate risk, but evidence related to gender and ambiguity is mixed. The present work approaches this problem from a novel angle, focusing on the use of information that is present rather than the impact of information that is absent. It examines how individuals assign value in uncertain decisions based on the partial information they do have. While a main effect of gender on value is not observed, there is an enhanced optimism bias in how both favorable and unfavorable information influences the subjective value of ambiguous financial prospects for male compared to female participants. Unpacking these effects suggests multiple mechanisms, including a significant contribution of risk processing. Specifically, favorable and unfavorable information are over- and underweighted respectively in male participants estimated likelihood of a winning outcome, and unfavorable information is underweighted in estimating certainty. There also is an interaction of gender and risk preferences, such that value increases more for male participants as the subjectively estimated likelihood of winning increases. A second experiment demonstrates this risk interaction effect is also observed for objective probabilities of winning, suggesting that the relationship between value and risk uses similar mechanisms across layers of uncertainty.

INTRODUCTION: Bilingualism has historically been claimed to be a risk factor for developmental stuttering. The Early Childhood Longitudinal Study, Kindergarten Class of 2010-11 (ECLS-K:2011) ostensibly contains evidence to test that claim. METHODS: We analyze data from monolingual and bilingual children in Kindergarten through fifth grade in the ECLS-K:2011. RESULTS AND DISCUSSION: The prevalence, male/female ratio, and onset and recovery of reported stuttering in the ECLS are inconsistent with widely-accepted clinical reports of stuttering. We argue that the reported figures may be misleading. We discuss some factors that may inflate the reported prevalence, including a lack of awareness of the difference between stuttering vs. normal disfluencies, and the informal usage of the word stuttering on the part of teachers and parents to describe typical disfluencies.

HIV-related stigma can affect health by compromising coping and social support. Gender differences in stigma experiences and social support are underexplored, particularly in the Caribbean. We conducted semi-structured interviews (N = 32) with patients at two HIV clinics in the Dominican Republic. Transcripts were coded using qualitative content analysis (deductive and inductive approaches) to identify themes regarding stigma experiences and social support, which were then compared across men and women participants to identify gender differences. While both men and women described experienced stigma, including verbal abuse, mens experience of stigma were subtler and women described outright rejection and instances of physical violence, including intimate partner violence. Both men and women described job discrimination, but women described severe disempowerment as well as permanent loss of income and/or employment whereas men described temporary changes in employment and /or decrease in income. Men and women described modifying behavior due to anticipated stigma, but only women discussed isolating themselves and discomfort taking HIV medication in front of others. Regarding internalized stigma, both men and women described shame, guilt, and depression over their HIV status, though these experiences were more common among women. Womens experiences prevented health care seeking and included suicidality, while men sometimes blamed women for their HIV status and expressed a desire to move on and look ahead. Both men and women described receiving financial support from family and friends, community support from neighbors, governmental support, and support from other people living with HIV. Women most frequently discussed receiving support from family and friends and using religiosity to cope, whereas men referenced general family support and government benefits and were less forthcoming about personal relationships and social networks, oftentimes not disclosing HIV statu

Women voted for the Democratic candidate more than men did in each US presidential election since 1980. We show that part of the gender gap stems from the fact that a higher proportion of women than men voters are Black, and Black voters overwhelmingly choose Democratic candidates. Past research shows that Black men have especially high rates of death, incarceration, and disenfranchisement due to criminal convictions. These disparities reduce the share of men voters who are Black. We show that the gender difference in racial composition explains 24% of the gender gap in voting Democratic. The gender gap in voting Democratic is especially large among those who are never-married, and, among them, the differing racial composition of men and women voters is more impactful than in the population at large, explaining 43% of the gender gap. We consider an alternative hypothesis that income differences between single men and women explain the gender gap in voting, but our analysis leads us to reject it. Although unmarried women are poorer than unmarried men, and lower-income voters vote slightly more Democratic, the latter difference is too small for income to explain much of the gender gap in voting. In short, the large gender gap among unmarried voters is not a reflection of the lower incomes of women's households but does reflect the fact that women voters are disproportionately Black. We used the General Social Survey as the data source for the analysis, then replicated results with the American National Election Survey data.

Women remain underrepresented in most math-intensive fields. [Breda and Napp, Proc. Natl. Acad. Sci. U.S.A. 116, 15435 (2019)] reported that girls comparative advantage in reading over math (i.e., the intraindividual differences between girls reading vs. math performance, compared to such differences for boys) could explain up to 80% of the gender gap in students intentions to pursue math-intensive studies and careers, in conflict with findings from previous research. We conducted a conceptual replication and expanded upon Breda and Napps study by using new global data (PISA2018, N = 466,165) and a recent US nationally representative longitudinal study (High School Longitudinal Study of 2009, N = 6,560). We coded students intended majors and careers and their actual college majors. The difference between a students math vs. reading performance explained only small proportions of the gender gap in students intentions to pursue math-intensive fields (0.4 to 10.2%) and in their enrollment in math-intensive college majors (12.3%). Consistent with previous studies, our findings suggest girls comparative advantage in reading explains a minority of the gender gap in math-related majors and occupational intentions and choices. Potential reasons for differences in the estimated effect sizes include differences in the operationalization of math-related choices, the operationalization of math and reading performance, and possibly the timing of measuring intentions and choices. Therefore, it seems premature to conclude that girls comparative advantage in reading, rather than the cumulative effects of other structural and/or psychological factors, can largely explain the persistent gender gap in math-intensive educational and career choices.

INTRODUCTION: Sex differences in dementia risk, and risk factor (RF) associations with dementia, remain uncertain across diverse ethno-regional groups. METHODS: A total of 29,850 participants (58% women) from 21 cohorts across six continents were included in an individual participant data meta-analysis. Sex-specific hazard ratios (HRs), and women-to-men ratio of hazard ratios (RHRs) for associations between RFs and all-cause dementia were derived from mixed-effect Cox models. RESULTS: Incident dementia occurred in 2089 (66% women) participants over 4.6 years (median). Women had higher dementia risk (HR, 1.12 [1.02, 1.23]) than men, particularly in low- and lower-middle-income economies. Associations between longer education and former alcohol use with dementia risk (RHR, 1.01 [1.00, 1.03] per year, and 0.55 [0.38, 0.79], respectively) were stronger for men than women; otherwise, there were no discernible sex differences in other RFs. DISCUSSION: Dementia risk was higher in women than men, with possible variations by country-level income settings, but most RFs appear to work similarly in women and men.

Alzheimer's Disease (AD) is a neurodegenerative disorder that is still not fully understood. Sex modifies AD vulnerability, but the reasons for this are largely unknown. We utilize two independent electronic medical record (EMR) systems across 44,288 patients to perform deep clinical phenotyping and network analysis to gain insight into clinical characteristics and sex-specific clinical associations in AD. Embeddings and network representation of patient diagnoses demonstrate greater comorbidity interactions in AD in comparison to matched controls. Enrichment analysis identifies multiple known and new diagnostic, medication, and lab result associations across the whole cohort and in a sex-stratified analysis. With this data-driven method of phenotyping, we can represent AD complexity and generate hypotheses of clinical factors that can be followed-up for further diagnostic and predictive analyses, mechanistic understanding, or drug repurposing and therapeutic approaches.

BackgroundWe have analyzed sex, race/ethnicity or socioeconomic disparities in the incidence of metastatic bone disease (MBD).MethodsPatients with the diagnosis of MBD at presentation for five most common primary anatomical sites was extracted from Surveillance, Epidemiology, and End Results Census tract-level dataset. Mean incidence of MBD for different sex, racial/ethnic and socioeconomic groups were compared.ResultsThe five most common anatomical sites with MBD at presentation include "lung: (n = 59 739), "prostate" (n = 19 732), "breast" (n = 16 244), "renal" (n = 7718) and "colon" (n = 3068). There was an increase in incidence of MBD among cancers originating from prostate (annual percentage change [APC] 4.94), renal (APC 2.55), and colon (APC 3.21) (p < 0.05 for all). Non-Hispanic Blacks had higher incidence of MBD for prostate and breast primary sites (p < 0.001). Non-Hispanic American Indian Alaskan Native had higher incidence of MBD for cancers originating from renal (p < 0.001) and colon (p = 0.049). A higher incidence of MBD was seen in lower socioeconomic status (SES) groups for the selected sites (p < 0.001).ConclusionsThese findings suggest that there are multiple sex-related, racial/ethnic and SES disparities in the incidence of MBD from the 5 most common primary sites. Higher incidence seen among lower SES suggests delay in diagnosis and limited access to screening modalities.

BackgroundAs mobile phone uptake in India continues to grow, there is also continued interest in mobile platform-based interventions for health education. There is a significant gender gap in mobile phone access-women's access to mobile phones is constrained by economic and social barriers. Pregnancy and postpartum care is one of many targets for mobile health (mHealth) interventions that particularly rely upon women's access to and facility with mobile phone use.ObjectiveWe aimed to describe the dynamics and patterns of married pregnant and postpartum women's mobile phone access and use (among both phone owners and nonowners) who participated in an mHealth postpartum care intervention and to identify potential barriers to their participation in mobile platform-based interventions.MethodsA secondary analysis was performed on mixed methods data obtained for a pilot mHealth intervention for postpartum care of mothers in rural Punjab from July 2020 to February 2021. Two formative sources included exploratory in-depth interviews among postpartum women (n=20; 1-3 months postpartum) and quantitative maternal health survey among women who were pregnant or who had recently given birth (n=102). We also utilized mixed methods intervention assessment data from early postpartum women who participated in the pilot intervention (n=29), including intervention moderator perspectives. Qualitative and quantitative analyses were performed, and pertinent findings were grouped thematically.ResultsThe majority of women owned a phone (maternal health survey: 75/102, 74%; demographic survey: 17/29, 59%), though approximately half (53/102, 52%) still reported sharing phones with other family members. Sharing a phone with female family members typically allowed for better access than sharing with male family members. Some households had strict preferences against daughters-in-law having phones, or otherwise significantly restricted women's phone access. Others reported concerns about phone u

BackgroundAlthough biological males and females are equally likely to become infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), evidence has mounted that males experience higher severity and fatality compared to females. MAIN: The objective of this review is to examine the existing literature on biological mechanisms underlying sex-based differences that could contribute to SARS-CoV-2 infection clinical outcomes. Sex-based differences in immunologic response and hormonal expression help explain the differences in coronavirus disease 2019 (COVID-19) outcomes observed in biological males and females. X inactivation facilitates a robust immune response to COVID-19 in females, who demonstrate a more profound antibody response and faster recovery when compared to males. Low testosterone levels also help explain the dysregulated inflammatory response and poor outcomes observed in some males with COVID-19. Gender differences in health expression and behaviors further compound these observed differences.ConclusionUnderstanding the biology of sex-based differences in COVID-19 severity and mortality could help inform preventative measures, treatment decisions, and development of personalized, sex-specific therapies.

The utility of ambulatory electrocardiography (AECG) to evaluate cats with subclinical hypertrophic cardiomyopathy (HCM) for arrhythmias and heart rate variability (HRV) is not well defined but may provide information regarding risk stratification. This prospective study used AECG to evaluate ectopy and HRV in subclinical HCM cats compared to healthy controls and is the first to implement a pharmacologic cardiac stress test. Twenty-three purpose-bred, Maine coon cross cats (16 HCM, 7 control) underwent 48-h of continuous AECG. Terbutaline (0.2-0.3 mg/kg) was administered orally at 24 and 36 h. Heart rate, ectopy frequency and complexity and HRV parameters, including standard deviation of normal R-R intervals (SDNN), were compared pre-terbutaline and post-terbutaline and across phenotype, genotype and sex. Genotype for an HCM-causative mutation was significantly associated with the frequency of supraventricular (P = 0.033) and ventricular (P = 0.026) ectopy across all cats. Seven HCM cats and zero healthy cats had a sinus arrhythmia. Mean heart rate was significantly higher post-terbutaline (p < 0.0001). HCM cats had significantly greater HRV compared to controls (SDNN: p = 0.0006). Male cats had significantly higher HRV (SDNN: p = 0.0001) and lower mean heart rates (p = 0.0001). HRV decreased post-terbutaline (SDNN: p = 0.0008) and changes in HRV observed between sexes were attenuated by terbutaline.

BackgroundAlthough biological males and females are equally likely to become infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), evidence has mounted that males experience higher severity and fatality compared to females. MAIN: The objective of this review is to examine the existing literature on biological mechanisms underlying sex-based differences that could contribute to SARS-CoV-2 infection clinical outcomes. Sex-based differences in immunologic response and hormonal expression help explain the differences in coronavirus disease 2019 (COVID-19) outcomes observed in biological males and females. X inactivation facilitates a robust immune response to COVID-19 in females, who demonstrate a more profound antibody response and faster recovery when compared to males. Low testosterone levels also help explain the dysregulated inflammatory response and poor outcomes observed in some males with COVID-19. Gender differences in health expression and behaviors further compound these observed differences.ConclusionUnderstanding the biology of sex-based differences in COVID-19 severity and mortality could help inform preventative measures, treatment decisions, and development of personalized, sex-specific therapies.

BackgroundWe have analyzed sex, race/ethnicity or socioeconomic disparities in the incidence of metastatic bone disease (MBD).MethodsPatients with the diagnosis of MBD at presentation for five most common primary anatomical sites was extracted from Surveillance, Epidemiology, and End Results Census tract-level dataset. Mean incidence of MBD for different sex, racial/ethnic and socioeconomic groups were compared.ResultsThe five most common anatomical sites with MBD at presentation include "lung: (n = 59 739), "prostate" (n = 19 732), "breast" (n = 16 244), "renal" (n = 7718) and "colon" (n = 3068). There was an increase in incidence of MBD among cancers originating from prostate (annual percentage change [APC] 4.94), renal (APC 2.55), and colon (APC 3.21) (p < 0.05 for all). Non-Hispanic Blacks had higher incidence of MBD for prostate and breast primary sites (p < 0.001). Non-Hispanic American Indian Alaskan Native had higher incidence of MBD for cancers originating from renal (p < 0.001) and colon (p = 0.049). A higher incidence of MBD was seen in lower socioeconomic status (SES) groups for the selected sites (p < 0.001).ConclusionsThese findings suggest that there are multiple sex-related, racial/ethnic and SES disparities in the incidence of MBD from the 5 most common primary sites. Higher incidence seen among lower SES suggests delay in diagnosis and limited access to screening modalities.

BackgroundAs mobile phone uptake in India continues to grow, there is also continued interest in mobile platform-based interventions for health education. There is a significant gender gap in mobile phone access-women's access to mobile phones is constrained by economic and social barriers. Pregnancy and postpartum care is one of many targets for mobile health (mHealth) interventions that particularly rely upon women's access to and facility with mobile phone use.ObjectiveWe aimed to describe the dynamics and patterns of married pregnant and postpartum women's mobile phone access and use (among both phone owners and nonowners) who participated in an mHealth postpartum care intervention and to identify potential barriers to their participation in mobile platform-based interventions.MethodsA secondary analysis was performed on mixed methods data obtained for a pilot mHealth intervention for postpartum care of mothers in rural Punjab from July 2020 to February 2021. Two formative sources included exploratory in-depth interviews among postpartum women (n=20; 1-3 months postpartum) and quantitative maternal health survey among women who were pregnant or who had recently given birth (n=102). We also utilized mixed methods intervention assessment data from early postpartum women who participated in the pilot intervention (n=29), including intervention moderator perspectives. Qualitative and quantitative analyses were performed, and pertinent findings were grouped thematically.ResultsThe majority of women owned a phone (maternal health survey: 75/102, 74%; demographic survey: 17/29, 59%), though approximately half (53/102, 52%) still reported sharing phones with other family members. Sharing a phone with female family members typically allowed for better access than sharing with male family members. Some households had strict preferences against daughters-in-law having phones, or otherwise significantly restricted women's phone access. Others reported concerns about phone u

There is a continuing debate concerning "adjustments" to heart period variability [i.e., heart rate variability (HRV)] for the heart period [i.e., increases inter-beat-intervals (IBI)]. To date, such arguments have not seriously considered the impact a demographic variable, such as gender, can have on the association between HRV and the heart period. A prior meta-analysis showed women to have greater HRV compared to men despite having shorter IBI and higher heart rate (HR). Thus, it is plausible that men and women differ in the association between HRV and HR/IBI. Thus, the present study investigates the potential moderating effect of gender on the association between HRV and indices of cardiac chronotropy, including both HR and IBI. Data from 633 participants (339 women) were available for analysis. Cardiac measures were assessed during a 5-min baseline-resting period. HRV measures included the standard deviation of inter-beat-intervals, root mean square of successive differences, and autoregressive high frequency power. Moderation analyses showed gender significantly moderated the association between all HRV variables and both HR and IBI (each p < 0.05). However, results were not consistent when using recently recommended HRV variables "adjusted" for IBI. Overall, the current investigation provides data illustrating a differential association between HRV and the heart period based on gender. Substantial neurophysiological evidence support the current findings; women show greater sensitivity to acetylcholine compared to men. If women show greater sensitivity to acetylcholine, and acetylcholine increases HRV and the heart period, then the association between HRV and the heart period indeed should be stronger in women compared to men. Taken together, these data suggest that routine "adjustments" to HRV for the heart period are unjustified and problematic at best. As it relates to the application of future HRV research, it is imperative that researchers continu

ObjectiveThe present study aimed to examine the prevalence of dyscalculia, dyslexia, and their comorbidity rates in a large population-based sample of children with idiopathic epilepsy (N = 2282) and a comparison sample of typically developing schoolchildren (N = 2371).MethodsBoth groups of children were screened using an arithmetic fluency test for dyscalculia and a reading fluency test for dyslexia. Their comorbidity rates were assessed. The prevalence rates of dyscalculia, dyslexia, comorbidity, and isolated dyscalculia/dyslexia (ie, participants with comorbid dyslexia and dyscalculia were excluded) were analyzed.ResultsIn both -1.5 SD and -1 SD cutoff criterion, the prevalence rates were about two times higher in children with idiopathic epilepsy than in other schoolchildren; the prevalence rates of isolated dyslexia were higher in children with idiopathic epilepsy than in other schoolchildren (-1 SD: 10.9% vs 8.6%; -1.5 SD: 6.5% vs 4.7%). Meanwhile, comorbidity rates of dyscalculia and dyslexia were higher in children with idiopathic epilepsy than in other schoolchildren (32.7% vs 26.6%; 38.3% vs 23.5%, respectively). Overall, patterns of prevalence rates were different for children with idiopathic epilepsy and schoolchildren, in which children with idiopathic epilepsy had a higher prevalence rate of dyscalculia than dyslexia, while schoolchildren had a higher prevalence of dyslexia than dyscalculia, regardless of cutoff criteria. Interestingly, gender differences in the prevalence rates of all types of learning disabilities were found in schoolchildren, but there were only gender differences in the prevalence rates of dyslexia in children with idiopathic epilepsy.SignificanceThe results highlight the vulnerability of children with idiopathic epilepsy for learning disabilities and a differential pattern of gender differences in dyslexia. Moreover, different patterns of prevalence rates suggest that children with idiopathic epilepsy and schoo

Alzheimer's disease (AD) is a pervasive neurodegenerative disorder that disproportionately affects women. Since neural anatomy and disease pathophysiology differ by sex, investigating sex-specific mechanisms in AD pathophysiology can inform new therapeutic approaches for both sexes. Previous bulk human brain RNA sequencing studies have revealed sex differences in dysregulated molecular pathways related to energy production, neuronal function, and immune response; however, the sex differences in disease mechanisms are yet to be examined comprehensively on a single-cell level. We leveraged nearly 74,000 cells from human prefrontal and entorhinal cortex samples from the first two publicly available single-cell RNA sequencing AD datasets to perform a case versus control sex-stratified differential gene expression analysis and pathway network enrichment in a cell type-specific manner for each brain region. Our examination at the single-cell level revealed sex differences in AD prominently in glial cells of the prefrontal cortex. In the entorhinal cortex, we observed the same genes and networks to be perturbed in opposing directions between sexes in AD relative to healthy state. Our findings contribute to growing evidence of sex differences in AD-related transcriptomic changes, which can fuel the development of therapies that may prove more effective at reversing AD pathophysiology.

During adolescence, frequent and heavy cannabis use can lead to serious adverse health effects and cannabis use disorder (CUD). Rodent models of adolescent exposure to the main psychoactive component of cannabis, delta-9-tetrahydrocannabinol (THC), mimic the behavioral alterations observed in adolescent users. However, the underlying molecular mechanisms remain largely unknown. Here, we treated female and male C57BL6/N mice with high doses of THC during early adolescence and assessed their memory and social behaviors in late adolescence. We then profiled the transcriptome of five brain regions involved in cognitive and addiction-related processes. We applied gene coexpression network analysis and identified gene coexpression modules, termed cognitive modules, that simultaneously correlated with THC treatment and memory traits reduced by THC. The cognitive modules were related to endocannabinoid signaling in the female dorsal medial striatum, inflammation in the female ventral tegmental area, and synaptic transmission in the male nucleus accumbens. Moreover, cross-brain region module-module interaction networks uncovered intra- and inter-region molecular circuitries influenced by THC. Lastly, we identified key driver genes of gene networks associated with THC in mice and genetic susceptibility to CUD in humans. This analysis revealed a common regulatory mechanism linked to CUD vulnerability in the nucleus accumbens of females and males, which shared four key drivers (Hapln4, Kcnc1, Elavl2, Zcchc12). These genes regulate transcriptional subnetworks implicated in addiction processes, synaptic transmission, brain development, and lipid metabolism. Our study provides novel insights into disease mechanisms regulated by adolescent exposure to THC in a sex- and brain region-specific manner.

Alzheimer's Disease (AD) is a neurodegenerative disorder that is still not fully understood. Sex modifies AD vulnerability, but the reasons for this are largely unknown. We utilize two independent electronic medical record (EMR) systems across 44,288 patients to perform deep clinical phenotyping and network analysis to gain insight into clinical characteristics and sex-specific clinical associations in AD. Embeddings and network representation of patient diagnoses demonstrate greater comorbidity interactions in AD in comparison to matched controls. Enrichment analysis identifies multiple known and new diagnostic, medication, and lab result associations across the whole cohort and in a sex-stratified analysis. With this data-driven method of phenotyping, we can represent AD complexity and generate hypotheses of clinical factors that can be followed-up for further diagnostic and predictive analyses, mechanistic understanding, or drug repurposing and therapeutic approaches.

PurposeBoys represent a small proportion of samples in randomized clinical trials (RCT) investigating evidence-based treatment for adolescents with anorexia nervosa (AN). Consequently, knowledge of potential gender differences in clinical characteristics and treatment response in adolescents is considerably limited.MethodsSecondary analyses of aggregated data from two RCTs were used to characterize baseline and end-of-treatment clinical features in male and female adolescents with AN (n = 228, 10.53% male). Mixed analyses of variance were used to investigate potential gender differences in treatment response relative to weight outcomes (% median BMI) and eating disorder cognitions (Eating Disorder Examination Global scores; EDE).ResultsThere were no significant gender differences in prior inpatient care, illness duration, psychiatric comorbidity, or psychotropic medication use at baseline. Nor were there significant gender differences in binge eating, purging, or driven exercise at baseline or end-of-treatment. Girls reported elevated weight and shape concern compared to boys at baseline but overall reduction in EDE Global scores over the course of treatment did not differ according to gender. Boys gained more relative weight during treatment than girls, but this difference was statistically non-significant.ConclusionOverall findings do not suggest significant differences in treatment outcome relative to weight or ED cognitions, by gender. Current evidence suggests that, with the exception of shape and weight concerns, boys present with cognitive and behavioral symptoms as severe as their female counterparts which underscores the need for increased accuracy in assessment of these disorders in boys and young men.Level of evidenceLevel 1, secondary data analysis of randomized controlled trials.

BackgroundFatty infiltration (FI) is one of the most important prognostic factors for outcomes after rotator cuff surgery. Established risk factors include advancing age, larger tear size, and increased tear chronicity. A growing body of evidence suggests that sex and obesity are associated with FI; however, data are limited.MethodsWe recruited 2 well-characterized multicenter cohorts of patients with rotator cuff tears (Multicenter Orthopaedic Outcomes Network [MOON] cohort [n = 80] and Rotator Cuff Outcomes Workgroup [ROW] cohort [n = 158]). We used multivariable logistic regression to evaluate the relationship between body mass index (BMI) and the presence of FI while adjusting for the participant's age at magnetic resonance imaging, sex, and duration of shoulder symptoms, as well as the cross-sectional area of the tear. We analyzed the 2 cohorts separately and performed a meta-analysis to combine estimates.ResultsA total of 27 patients (33.8%) in the Multicenter Orthopaedic Outcomes Network (MOON) cohort and 57 patients (36.1%) in the Rotator Cuff Outcomes Workgroup (ROW) cohort had FI. When BMI < 25 kg/m2 was used as the reference category, being overweight was associated with a 2.37-fold (95% confidence interval [CI], 0.77-7.29) increased odds of FI and being obese was associated with a 3.28-fold (95% CI, 1.16-9.25) increased odds of FI. Women were 4.9 times (95% CI, 2.06-11.69) as likely to have FI as men.ConclusionsAmong patients with rotator cuff tears, obese patients had a substantially higher likelihood of FI. Further research is needed to assess whether modifying BMI can alter FI in patients with rotator cuff tears. This may have significant clinical implications for presurgical surgical management of rotator cuff tears. Sex was also significantly associated with FI, with women having higher odds of FI than men. Higher odds of FI in female patients may also explain previously reported early suboptimal outcomes of rotator cuff surge

BackgroundHigh-density lipoprotein (HDL) plays a critical role in protection against atherosclerosic and cardiovascular disease (ASCVD). In addition to contributing to clearing excess vascular cholesterol, HDL particles exhibit antioxidative functions, helping to attenuate adverse effects of oxidized low-density lipoproteins. However, these beneficial properties can be undermined by oxidative stress, inflammation, and unhealthy lifestyles and diet, as well as influenced by race and sex. Thus, when assessing cardiovascular risk, it is important to consider multifactorial aspects of HDL, including antioxidant activity rather than just total amount and type of HDL-cholesterol (HDL-C) particles. Because prior research showed HDL peroxide content (HDLperox) can be inversely associated with normal anti-oxidant HDL activity, elevated HDLperox may serve as a bioindicator of HDL dysfunction.MethodsIn this study, data from a large national cohort of Americans was utilized to determine the impact of sex, race, and diabetes status on HDLperox in middle-aged and older adults. A previously developed cell-free fluorometric method was utilized to quantify HDLperox in serum depleted of apo-B containing lipoproteins.ResultsIn keeping with predictions, white men and diabetics exhibited HDLperox in the atypical upper range, suggestive of less functional HDL. White men had higher HDLperox levels than African American males (13.46 ± 6.10 vs. 10.88 ± 5.81, p < .001). There was also a significant main effect of type 2 diabetes (F(1,1901) = 14.9, p < .0001). Overall, African Americans evinced lower HDLperox levels, despite more obesity (10.3 ± 4.7 vs.11.81 ± 5.66 for Whites) suggesting that other aspects of lipid metabolism and psychosocial factors account for the higher prevalence of ASCVD in African Americans.ConclusionThis research helps to provide a more comprehensive understanding of HDL function in a racially and metabolically diverse adult population. HDLperox content

Strong epidemiological evidence now exists that sex is an important biologic variable in immunity. Recent studies, for example, have revealed that sex differences are associated with the severity of symptoms and mortality due to coronavirus disease 2019 (COVID-19). Despite this evidence, much remains to be learned about the mechanisms underlying associations between sex differences and immune-mediated conditions. A growing body of experimental data has made significant inroads into understanding sex-influenced immune responses. As physicians seek to provide more targeted patient care, it is critical to understand how sex-defining factors (e.g., chromosomes, gonadal hormones) alter immune responses in health and disease. In this review, we highlight recent insights into sex differences in autoimmunity; virus infection, specifically severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; and cancer immunotherapy. A deeper understanding of underlying mechanisms will allow the development of a sex-based approach to disease screening and treatment.

The coronavirus disease 2019 (COVID-19) pandemic has created unprecedented challenges worldwide. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 and has a complex interaction with the immune system, including growing evidence of sex-specific differences in the immune response. Sex-disaggregated analyses of epidemiological data indicate that males experience more severe symptoms and suffer higher mortality from COVID-19 than females. Many behavioural risk factors and biological factors may contribute to the different immune response. This review examines the immune response to SARS-CoV-2 infection in the context of sex, with emphasis on potential biological mechanisms explaining differences in clinical outcomes. Understanding sex differences in the pathophysiology of SARS-CoV-2 infection will help promote the development of specific strategies to manage the disease.

Question-and-answer (Q&A) sessions following research talks provide key opportunities for the audience to engage in scientific discourse. Gender inequities persist in academia, where women are underrepresented as faculty and their contributions are less valued than men's. In the present research, we tested how this gender difference translates to face-to-face Q&A-session participation and its psychological correlates. Across two studies examining participation in three conferences, men disproportionately participated in Q&A sessions in a live, recorded conference (N = 189 Q&A interactions), and women were less comfortable participating in Q&A sessions and more likely to fear backlash for their participation (N = 234 conference attendees). Additionally, women were more likely to hold back questions because of anxiety, whereas men were more likely to hold back questions to make space for others to participate. To the extent that men engage more than women in Q&A sessions, men may continue to have more influence over the direction of science.

OBJECTIVES: Disparities in substance use disorder (SUD) treatment use persist across groups, including gender. Using a gender-informed approach to expand treatment capacity and reduce barriers to treatment engagement is vital. We examined SUD treatment need and receipt among people with SUD in the United States, by gender, and assessed gender-specific sociodemographic factors associated with unmet need for SUD treatment and reported treatment barriers. METHODS: We conducted an analysis of data among adults aged ≥18 with a past-year SUD from the National Survey on Drug Use and Health (2015-2018). We computed population-adjusted frequencies and proportions for SUD treatment need and receipt and assessed gender differences. Multivariate logistic regression assessed gender-specific sociodemographic variables associated with SUD treatment receipt. RESULTS: Among adults with a past-year SUD, 63.4% were men and 36.6% were women (P < .001), only 10.6% received SUD treatment, and a greater percentage of women than men needed treatment for opioid use disorder (11.9% vs 9.9%; P = .002). Receipt of SUD treatment was lowest among women with alcohol use disorder followed by men with alcohol use disorder (7.5% vs 8.9%; P = .052). Non-Latinx Black men had fewer than half the adjusted odds of receiving SUD treatment than non-Latinx White men (adjusted odds ratio [aOR] = 0.44; 95% CI, 0.27-0.71). Latinx women (aOR = 0.37; 95% CI, 0.18-0.73) and non-Latinx Black women (aOR = 0.51; 95% CI, 0.27-0.94) had significantly lower odds of receiving SUD treatment than non-Latinx White women. CONCLUSIONS: As public health efforts target expanding SUD treatment capacity and addressing disparities in use of SUD treatment, interventions informed by gender and culture should be prioritized.

Introduction: Emerging data suggest that the COVID-19 pandemic has disproportionately impacted women in academic medicine, potentially eliminating recent gains that have been made toward gender equity. This study examined possible pandemic-related gender disparities in research grant submissions, one of the most important criteria for academic promotion and tenure evaluations. Methods: Data were collected from two major academic institutions (one private and one public) on the gender and academic rank of faculty principal investigators who submitted new grants to the National Institutes of Health (NIH) during COVID-19 (March 1st, 2020, through August 31, 2020) compared with a matched period in 2019 (March 1st, 2019, through August 31, 2019). t-Tests and chi-square analyses compared the gender distribution of individuals who submitted grants during the two periods of examination. Results: In 2019 (prepandemic), there was no significant difference in the average number of grants submitted by women compared with men faculty. In contrast, women faculty submitted significantly fewer grants in 2020 (during the pandemic) than men. Men were also significantly more likely than women to submit grants in both 2019 and 2020 compared with submitting in 2019 only, suggesting men faculty may have been more likely than their women colleagues to sustain their productivity in grant submissions during the pandemic. Discussion: Womens loss of extramural funding may compound over time, as it impedes new data collection, research progress, and academic advancement. Efforts to support womens research productivity and career trajectories are urgently needed in the following years of pandemic recovery.

There is a longstanding belief in relationship science and popular opinion that women are the barometers in mixed-gender relationships such that their perceptions about the partnership carry more weight than men's in predicting future relationship satisfaction, but this idea has yet to be rigorously tested. We analyze data from two studies to test within-person links between men's and women's relationship satisfaction on their own and their partner's next-day and next-year satisfaction. Study 1 combined nine daily diary datasets from Canada and the United States with 901 mixed-gender couples who provided 29,541 daily reports of relationship satisfaction. Study 2 analyzed five annual waves of data from the German Family Panel (pairfam) that surveyed 3,405 mixed-gender couples who provided 21,115 relationship satisfaction reports. Latent curve models with structured residuals (LCM-SR) revealed that in both studies, men's and women's relationship satisfaction significantly predicted their own and their partner's relationship satisfaction, with no gender differences in the magnitude of these effects. Results underscore the interdependence of romantic partners' satisfaction and indicate that both men and women jointly shape romantic relationship satisfaction.

Adaptations to infectious and dietary pressures shape mammalian physiology and disease risk. How such adaptations affect sex-biased diseases remains insufficiently studied. In this study, we show that sex-dependent hepatic gene programs confer a robust (~300%) survival advantage for male mice during lethal bacterial infection. The transcription factor B cell lymphoma 6 (BCL6), which masculinizes hepatic gene expression at puberty, is essential for this advantage. However, protection by BCL6 protein comes at a cost during conditions of dietary excess, which result in overt fatty liver and glucose intolerance in males. Deleting hepatic BCL6 reverses these phenotypes but markedly lowers male survival during infection, thus establishing a sex-dependent trade-off between host defense and metabolic systems. Our findings offer strong evidence that some current sex-biased diseases are rooted in ancient evolutionary trade-offs between immunity and metabolism.

BackgroundThere is an increasing burden of cardiovascular disease, including coronary artery disease (CAD) and heart failure (HF), among women Veterans. Clinical practice guidelines recommend multiple pharmacotherapies that can reduce risk of mortality and adverse cardiovascular outcomes.ObjectiveTo determine if there are disparities in the use of guideline-directed medical therapy by gender among Veterans with incident CAD and HF.DesignRetrospective.ParticipantsVeterans (934,504; 87.8% men and 129,469; 12.2% women) returning from Operations Enduring Freedom, Iraqi Freedom, and New Dawn.Main measuresDifferences by gender in the prescription of Class 1, Level of Evidence A guideline-directed medical therapy among patients who developed incident CAD and HF at 30 days, 90 days, and 12 months after diagnosis. For CAD, medications included statins and antiplatelet therapy. For HF, medications included beta-blockers and renin-angiotensin-aldosterone system inhibitors.Key resultsOverall, women developed CAD and HF at a younger average age than men (mean 45.8 vs. 47.7 years, p<0.001; and 43.7 vs. 45.4 years, p<0.02, respectively). In the 12 months following a diagnosis of incident CAD, the odds of a woman receiving a prescription for at least one CAD drug was 0.85 (95% confidence interval [CI], 0.68-1.08) compared to men. In the 12 months following a diagnosis of incident HF, the odds of a woman receiving at least one HF medication was 0.54 (95% CI, 0.37-0.79) compared to men.ConclusionsDespite guideline recommendations, young women Veterans have approximately half the odds of being prescribed guideline-directed medical therapy within 1-year after a diagnosis of HF. These results highlight the need to develop targeted strategies to minimize gender disparities in CVD care to prevent adverse outcomes in this young and growing population.

Being strong is a prominent male stereotype that children learn early in life; however, it is unknown as to when children start to value being strong and when gender differences in valuing strength might emerge. In the current study, we interviewed an ethnically diverse sample of 168 3-5 year-olds (88 girls, 80 boys) to address this gap in the literature. Results showed that boys as young as age 3 generally valued strength more than girls: (1) boys, on average, said it was more important to be strong than girls did, and (2) boys were more likely to prefer strength-related occupations than girls. Boys were also more likely to select boys than girls as the gender who cares more about physical strength. Additionally, with age, both girls and boys demonstrated knowledge of the stereotype that boys care about physical strength, with girls also being less likely to associate being a girl with being strong. Overall, the results suggest that valuing physical strength starts in early childhood, and gender differences in valuing strength are evident at the eve of gender identity development. Possible implications for boys' later well-being and health are discussed.

Polybrominated diphenyl ethers (PBDEs) are a class of flame-retardant organohalogen pollutants that act as endocrine/neuroendocrine disrupting chemicals (EDCs). In humans, exposure to brominated flame retardants (BFR) or other environmentally persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs) and novel organophosphate flame retardants has been associated with increasing trends of diabetes and metabolic disease. However, the effects of PBDEs on metabolic processes and their associated sex-dependent features are poorly understood. The metabolic-disrupting effects of perinatal exposure to industrial penta-PBDE mixture, DE-71, on male and female progeny of C57BL/6N mouse dams were examined in adulthood. Dams were exposed to environmentally relevant doses of PBDEs daily for 10 weeks (p.o.): 0.1 (L-DE-71) and 0.4 mg/kg/d (H-DE-71) and offspring parameters were compared to corn oil vehicle controls (VEH/CON). The following lipid metabolism indices were measured: plasma cholesterol, triglycerides, adiponectin, leptin, and liver lipids. L-DE-71 female offspring were particularly affected, showing hypercholesterolemia, elevated liver lipids and fasting plasma leptin as compared to same-sex VEH/CON, while L- and H-DE-71 male F1 only showed reduced plasma adiponectin. Using the quantitative Folch method, we found that mean liver lipid content was significantly elevated in L-DE-71 female offspring compared to controls. Oil Red O staining revealed fatty liver in female offspring and dams. General measures of adiposity, body weight, white and brown adipose tissue (BAT), and lean and fat mass were weighed or measured using EchoMRI. DE-71 did not produce abnormal adiposity, but decreased BAT depots in L-DE-71 females and males relative to same-sex VEH/CON. To begin to address potential central mechanisms of deregulated lipid metabolism, we used RT-qPCR to quantitate expression of hypothalamic genes in energy-regulating circuits that control lipid homeostas

The prediction utility of Framingham Risk Score in populations with low conventional cardiovascular risk burden is limited, particularly among women. Gender-specific markers to predict cardiovascular risk in overtly healthy people are lacking. In this study we hypothesize that postprandial responses triggered by a high-calorie meal test differ by gender in their ability to triage asymptomatic subjects into those with and without subclinical atherosclerosis. A total of 101 healthy Chinese subjects (46 females, 55 males) at low risk of coronary heart disease completed the study. Subjects underwent cardiovascular imaging and postprandial blood phenotyping after consuming a standardized macronutrient meal. Prediction models were developed using logistic regression and subsequently subjected to cross-validation to obtain a de-optimized receiver operating characteristic (ROC) curve. Distinctive gender differences in postprandial trajectories of glucose, lipids and inflammatory markers were observed. We used gender-specific association with different combinations of postprandial predictors to develop 2 models for predicting risk of subclinical atherosclerosis in males (ROC AUC = 0.7867, 95% CI 0.6567, 0.9166) and females (ROC AUC = 0.9161, 95% CI 0.8340, 0.9982) respectively. We report novel postprandial models for predicting subclinical atherosclerosis in apparently healthy Asian subjects using a gender-specific approach, complementing the conventional Framingham Risk Score.Clinical Trial Registration: The trial was registered at clinicaltrials.gov as NCT03531879.

The prediction utility of Framingham Risk Score in populations with low conventional cardiovascular risk burden is limited, particularly among women. Gender-specific markers to predict cardiovascular risk in overtly healthy people are lacking. In this study we hypothesize that postprandial responses triggered by a high-calorie meal test differ by gender in their ability to triage asymptomatic subjects into those with and without subclinical atherosclerosis. A total of 101 healthy Chinese subjects (46 females, 55 males) at low risk of coronary heart disease completed the study. Subjects underwent cardiovascular imaging and postprandial blood phenotyping after consuming a standardized macronutrient meal. Prediction models were developed using logistic regression and subsequently subjected to cross-validation to obtain a de-optimized receiver operating characteristic (ROC) curve. Distinctive gender differences in postprandial trajectories of glucose, lipids and inflammatory markers were observed. We used gender-specific association with different combinations of postprandial predictors to develop 2 models for predicting risk of subclinical atherosclerosis in males (ROC AUC = 0.7867, 95% CI 0.6567, 0.9166) and females (ROC AUC = 0.9161, 95% CI 0.8340, 0.9982) respectively. We report novel postprandial models for predicting subclinical atherosclerosis in apparently healthy Asian subjects using a gender-specific approach, complementing the conventional Framingham Risk Score.Clinical Trial Registration: The trial was registered at clinicaltrials.gov as NCT03531879.

Heavy alcohol consumption and other drug use are prominent across Africa and increase the risk of exposure to violence, HIV acquisition, and other life-threatening injuries. This review synthesizes evidence on alcohol and other drug (AOD) interventions in Africa; evaluates the differences between interventions that do and do not specifically target populations that use AODs; and highlights the impact of comprehensive vs. brief interventions and those that address syndemic issues from a gender and contextualized lens. Literature searches were conducted to identify research outcomes of randomized interventions published between January 2010 and May 2022 that address AOD use in Africa. Thirty-five full-text articles were included in this review. Most of the identified research studies were concentrated in a few countries. Most studies were conducted in South Africa. Many of the studies comprised brief interventions. However, the most comprehensive interventions were the most effective for AOD outcomes. Several studies indicated the importance of addressing AOD use alongside gender-based violence, mental health needs, gender roles, and other social determinants that affect health outcomes. Intervening on AOD use and addressing social determinants from a gender and contextually relevant perspective is essential to ensuring the long-term health and well-being of people in Africa.

Increased cerebrospinal fluid neurofilament light (NfL) is a recognized biomarker for neurodegeneration that can also be assessed in blood. Here, we investigate plasma NfL as a marker of neurodegeneration in 13 neurodegenerative disorders, Down syndrome, depression and cognitively unimpaired controls from two multicenter cohorts: King's College London (n = 805) and the Swedish BioFINDER study (n = 1,464). Plasma NfL was significantly increased in all cortical neurodegenerative disorders, amyotrophic lateral sclerosis and atypical parkinsonian disorders. We demonstrate that plasma NfL is clinically useful in identifying atypical parkinsonian disorders in patients with parkinsonism, dementia in individuals with Down syndrome, dementia among psychiatric disorders, and frontotemporal dementia in patients with cognitive impairment. Data-driven cut-offs highlighted the fundamental importance of age-related clinical cut-offs for disorders with a younger age of onset. Finally, plasma NfL performs best when applied to indicate no underlying neurodegeneration, with low false positives, in all age-related cut-offs.

To provide a multi-omics resource and investigate transcriptional regulatory mechanisms, we profile the transcriptome, chromatin accessibility, and methylation status of over 70,000 single nuclei (sn) from adult mouse pituitaries. Paired snRNAseq and snATACseq datasets from individual animals highlight a continuum between developmental epigenetically-encoded cell types and transcriptionally-determined transient cell states. Co-accessibility analysis-based identification of a putative Fshb cis-regulatory domain that overlaps the fertility-linked rs11031006 human polymorphism, followed by experimental validation illustrate the use of this resource for hypothesis generation. We also identify transcriptional and chromatin accessibility programs distinguishing each major cell type. Regulons, which are co-regulated gene sets sharing binding sites for a common transcription factor driver, recapitulate cell type clustering. We identify both cell type-specific and sex-specific regulons that are highly correlated with promoter accessibility, but not with methylation state, supporting the centrality of chromatin accessibility in shaping cell-defining transcriptional programs. The sn multi-omics atlas is accessible at snpituitaryatlas.princeton.edu.

IntroductionThe coronavirus disease 2019 (COVID-19) pandemic continues to be a global threat, with tremendous resources invested into identifying risk factors for severe COVID-19 illness. The objective of this study was to analyze the characteristics and outcomes of male compared to female adults with COVID-19 who required hospitalization within US academic centers.MethodsUsing the Vizient clinical database, discharge records of adults with a diagnosis of COVID-19 between March 1, 2020 and November 30, 2020 were reviewed. Outcome measures included demographics, characteristics, length of hospital stay, rate of respiratory intubation and mechanical ventilation, and rate of in-hospital mortality of male vs female according to age, race/ethnicity, and presence of preexisting comorbidities.ResultsAmong adults with COVID-19, 161,206 were male while 146,804 were female. Adult males with COVID-19 were more likely to have hypertension (62.1% vs 59.6%, p <0.001%), diabetes (39.2% vs 36.0%, p <0.001%), renal failure (22.3% vs 18.1%, p <0.001%), congestive heart failure (15.3% vs 14.6%, p <0.001%), and liver disease (5.9% vs 4.5%, p <0.001%). Adult females with COVID-19 were more likely to be obese (32.3% vs 25.7%, p<0.001) and have chronic pulmonary disease (23.7% vs 18.1%, p <0.001). Gender was significantly different among races (p<0.001), and there was a lower proportion of males versus females in African American patients with COVID-19. Comparison in outcomes of male vs. female adults with COVID-19 is depicted in Table 2. Compared to females, males with COVID-19 had a higher rate of in-hospital mortality (13.8% vs 10.2%, respectively, p <0.001); a higher rate of respiratory intubation (21.4% vs 14.6%, p <0.001); and a longer length of hospital stay (9.5 ± 12.5 days vs. 7.8 ± 9.8 days, p<0.001). In-hospital mortality analyzed according to age groups, race/ethnicity, payers, and presence of preexisting comorbidities consistently showed highe

BackgroundOral pre-exposure prophylaxis (PrEP) is highly effective for HIV prevention, but data are limited on HIV incidence among PrEP users in generalized epidemic settings, particularly outside of selected risk groups. We performed a population-based PrEP study in rural Kenya and Uganda and sought to evaluate both changes in HIV incidence and clinical and virologic outcomes following seroconversion on PrEP.Methods and findingsDuring population-level HIV testing of individuals ≥15 years in 16 communities in the Sustainable East Africa Research in Community Health (SEARCH) study (NCT01864603), we offered universal access to PrEP with enhanced counseling for persons at elevated HIV risk (based on serodifferent partnership, machine learning-based risk score, or self-identified HIV risk). We offered rapid or same-day PrEP initiation and flexible service delivery with follow-up visits at facilities or community-based sites at 4, 12, and every 12 weeks up to week 144. Among participants with incident HIV infection after PrEP initiation, we offered same-day antiretroviral therapy (ART) initiation and analyzed HIV RNA, tenofovir hair concentrations, drug resistance, and viral suppression (<1,000 c/ml based on available assays) after ART start. Using Poisson regression with cluster-robust standard errors, we compared HIV incidence among PrEP initiators to incidence among propensity score-matched recent historical controls (from the year before PrEP availability) in 8 of the 16 communities, adjusted for risk group. Among 74,541 individuals who tested negative for HIV, 15,632/74,541 (21%) were assessed to be at elevated HIV risk; 5,447/15,632 (35%) initiated PrEP (49% female; 29% 15-24 years; 19% in serodifferent partnerships), of whom 79% engaged in ≥1 follow-up visit and 61% self-reported PrEP adherence at ≥1 visit. Over 7,150 person-years of follow-up, HIV incidence was 0.35 per 100 person-years (95% confidence interval [CI] 0.22-0.49) among PrEP initiators. Among matc

BackgroundIn this paper, we argue for Gender as a Sociocultural Variable (GASV) as a complement to Sex as a Biological Variable (SABV). Sex (biology) and gender (sociocultural behaviors and attitudes) interact to influence health and disease processes across the lifespan-which is currently playing out in the COVID-19 pandemic. This study develops a gender assessment tool-the Stanford Gender-Related Variables for Health Research-for use in clinical and population research, including large-scale health surveys involving diverse Western populations. While analyzing sex as a biological variable is widely mandated, gender as a sociocultural variable is not, largely because the field lacks quantitative tools for analyzing the influence of gender on health outcomes.MethodsWe conducted a comprehensive review of English-language measures of gender from 1975 to 2015 to identify variables across three domains: gender norms, gender-related traits, and gender relations. This yielded 11 variables tested with 44 items in three US cross-sectional survey populations: two internet-based (N = 2051; N = 2135) and a patient-research registry (N = 489), conducted between May 2017 and January 2018.ResultsExploratory and confirmatory factor analyses reduced 11 constructs to 7 gender-related variables: caregiver strain, work strain, independence, risk-taking, emotional intelligence, social support, and discrimination. Regression analyses, adjusted for age, ethnicity, income, education, sex assigned at birth, and self-reported gender identity, identified associations between these gender-related variables and self-rated general health, physical and mental health, and health-risk behaviors.ConclusionOur new instrument represents an important step toward developing more comprehensive and precise survey-based measures of gender in relation to health. Our questionnaire is designed to shed light on how specific gender-related behaviors and attitudes contribute to health and disease processes, irr

Trauma can cause dysfunctional fear regulation leading some people to develop disorders, such as post-traumatic stress disorder (PTSD). The amygdala regulates fear, whereas PACAP (pituitary adenylate activating peptide) and PAC1 receptors are linked to PTSD symptom severity at genetic/epigenetic levels, with a strong link in females with PTSD. We discovered a PACAPergic projection from the basomedial amygdala (BMA) to the medial intercalated cells (mICCs) in adult mice. In vivo optogenetic stimulation of this pathway increased CFOS expression in mICCs, decreased fear recall, and increased fear extinction. Selective deletion of PAC1 receptors from the mICCs in females reduced fear acquisition, but enhanced fear generalization and reduced fear extinction in males. Optogenetic stimulation of the BMA-mICC PACAPergic pathway produced EPSCs in mICC neurons, which were enhanced by the PAC1 receptor antagonist, PACAP 6-38. Our findings show that mICCs modulate contextual fear in a dynamic and sex-dependent manner via a microcircuit containing the BMA and mICCs, and in a manner that was dependent on behavioral state.SIGNIFICANCE STATEMENT Traumatic stress can affect different aspects of fear behaviors, including fear learning, generalization of learned fear to novel contexts, how the fear of the original context is recalled, and how fear is reduced over time. While the amygdala has been studied for its role in regulation of different aspects of fear, the molecular circuitry of this structure is quite complex. In addition, aspects of fear can be modulated differently in males and females. Our findings show that a specific circuitry containing the neuropeptide PACAP and its receptor, PAC1, regulates various aspects of fear, including acquisition, generalization, recall, and extinction in a sexually dimorphic manner, characterizing a novel pathway that modulates traumatic fear.

BackgroundIn this paper, we argue for Gender as a Sociocultural Variable (GASV) as a complement to Sex as a Biological Variable (SABV). Sex (biology) and gender (sociocultural behaviors and attitudes) interact to influence health and disease processes across the lifespan-which is currently playing out in the COVID-19 pandemic. This study develops a gender assessment tool-the Stanford Gender-Related Variables for Health Research-for use in clinical and population research, including large-scale health surveys involving diverse Western populations. While analyzing sex as a biological variable is widely mandated, gender as a sociocultural variable is not, largely because the field lacks quantitative tools for analyzing the influence of gender on health outcomes.MethodsWe conducted a comprehensive review of English-language measures of gender from 1975 to 2015 to identify variables across three domains: gender norms, gender-related traits, and gender relations. This yielded 11 variables tested with 44 items in three US cross-sectional survey populations: two internet-based (N = 2051; N = 2135) and a patient-research registry (N = 489), conducted between May 2017 and January 2018.ResultsExploratory and confirmatory factor analyses reduced 11 constructs to 7 gender-related variables: caregiver strain, work strain, independence, risk-taking, emotional intelligence, social support, and discrimination. Regression analyses, adjusted for age, ethnicity, income, education, sex assigned at birth, and self-reported gender identity, identified associations between these gender-related variables and self-rated general health, physical and mental health, and health-risk behaviors.ConclusionOur new instrument represents an important step toward developing more comprehensive and precise survey-based measures of gender in relation to health. Our questionnaire is designed to shed light on how specific gender-related behaviors and attitudes contribute to health and disease processes, irr

Trauma can cause dysfunctional fear regulation leading some people to develop disorders, such as post-traumatic stress disorder (PTSD). The amygdala regulates fear, whereas PACAP (pituitary adenylate activating peptide) and PAC1 receptors are linked to PTSD symptom severity at genetic/epigenetic levels, with a strong link in females with PTSD. We discovered a PACAPergic projection from the basomedial amygdala (BMA) to the medial intercalated cells (mICCs) in adult mice. In vivo optogenetic stimulation of this pathway increased CFOS expression in mICCs, decreased fear recall, and increased fear extinction. Selective deletion of PAC1 receptors from the mICCs in females reduced fear acquisition, but enhanced fear generalization and reduced fear extinction in males. Optogenetic stimulation of the BMA-mICC PACAPergic pathway produced EPSCs in mICC neurons, which were enhanced by the PAC1 receptor antagonist, PACAP 6-38. Our findings show that mICCs modulate contextual fear in a dynamic and sex-dependent manner via a microcircuit containing the BMA and mICCs, and in a manner that was dependent on behavioral state.SIGNIFICANCE STATEMENT Traumatic stress can affect different aspects of fear behaviors, including fear learning, generalization of learned fear to novel contexts, how the fear of the original context is recalled, and how fear is reduced over time. While the amygdala has been studied for its role in regulation of different aspects of fear, the molecular circuitry of this structure is quite complex. In addition, aspects of fear can be modulated differently in males and females. Our findings show that a specific circuitry containing the neuropeptide PACAP and its receptor, PAC1, regulates various aspects of fear, including acquisition, generalization, recall, and extinction in a sexually dimorphic manner, characterizing a novel pathway that modulates traumatic fear.

Multimodal T cell profiling can enable more precise characterization of elusive cell states underlying disease. Here, we integrated single-cell RNA and surface protein data from 500,089 memory T cells to define 31 cell states from 259 individuals in a Peruvian tuberculosis (TB) progression cohort. At immune steady state >4 years after infection and disease resolution, we found that, after accounting for significant effects of age, sex, season and genetic ancestry on T cell composition, a polyfunctional type 17 helper T (TH17) cell-like effector state was reduced in abundance and function in individuals who previously progressed from Mycobacterium tuberculosis (M.tb) infection to active TB disease. These cells are capable of responding to M.tb peptides. Deconvoluting this state-uniquely identifiable with multimodal analysis-from public data demonstrated that its depletion may precede and persist beyond active disease. Our study demonstrates the power of integrative multimodal single-cell profiling to define cell states relevant to disease and other traits.