Sex differences in the distribution and density of regulatory interneurons in the striatum.

Introduction: Dysfunction of the cortico-basal circuitry - including its primary input nucleus, the striatum - contributes to neuropsychiatric disorders, such as autism and Tourette Syndrome (TS). These conditions show marked sex differences, occurring more often in males than in females. Regulatory interneurons, such as cholinergic interneurons (CINs) and parvalbumin-expressing GABAergic fast spiking interneurons (FSIs), are implicated in human neuropsychiatric disorders such as TS, and ablation of these interneurons produces relevant behavioral pathology in male mice, but not in females. Here we investigate sex differences in the density and distribution of striatal interneurons. Methods: We use stereological quantification of CINs, FSIs, and somatostatin-expressing (SOM) GABAergic interneurons in the dorsal striatum (caudate-putamen) and the ventral striatum (nucleus accumbens) in male and female mice. Results: Males have a higher density of CINs than females, especially in the dorsal striatum; females have equal distribution between dorsal and ventral striatum. FSIs showed similar distributions, with a greater dorsal-ventral density gradient in males than in females. SOM interneurons were denser in the ventral than in the dorsal striatum, with no sex differences. Discussion: These sex differences in the density and distribution of FSIs and CINs may contribute to sex differences in basal ganglia function, particularly in the context of psychopathology.

Condom Failure Among HIV-Negative Men in Serodiscordant Relationships in Australia, Brazil, and Thailand.

Condoms continue to be used by many gay, bisexual, and other men who have sex with men (GBM) to reduce the risk of HIV transmission. However this is impacted by condom failure events, defined here as condom breakage and slippage. In a prospective, observational cohort study of 343 HIV serodiscordant male couples recruited through high HIV caseload clinics and hospitals between 2012 and 2016 in Australia, Brazil, and Thailand, condom failure rates and associated factors were analysed, including with the study partner versus other sexual partners. There were 717 reported instances of condom failure from an estimated total of 25,831 sex acts with condoms, from over 588.4 participant years of follow up. Of the HIV-negative partners (n = 343) in the study, more than a third (n = 117, 36.7%) reported at least one instance of condom failure with any partner type during study follow-up. Condom failure with their study partner was reported by 91/343 (26.5%) HIV-negative partners, compared with 43/343 (12.5%) who reported condom failure with other partners. In total, there were 86 events where the HIV-negative partner experienced ano-receptive condom failure with ejaculation, representing 12.0% of all failure events. In multivariable analysis, compared to Australia, HIV-negative men in Brazil reported a higher incidence risk rate of condom failure (IRR = 1.64, 95%CI 1.01-2.68, p = 0.046) and HIV-negative men who reported anal sex with other partners reported an increased risk of condom failure compared with men who only had sex with their study partner (IRR = 1.89, 95%CI 1.08-3.33, p = 0.025). Although at least one event of condom failure was reported by a significant proportion of participants, overall condom failure events represented a small proportion of the total condom protected sex acts.

Sex differences in sensitivity to fentanyl effects in mice: Behavioral and molecular findings during late adolescence.

PURPOSE: Sex differences play a crucial role in understanding vulnerability to opioid addiction, yet there have been limited preclinical investigations of this effect during the transition from adolescence to adulthood. The present study compared the behaviors of male and female rodents in response to fentanyl treatment and targeted molecular correlates in the striatum and medial prefrontal cortex. MATERIALS AND METHODS: Thirty adolescent C57BL/6J mice underwent a 1-week fentanyl treatment with an escalating dose. In addition to evaluating locomotor activity and anxiety-related parameters, we also assessed naloxone-induced fentanyl acute withdrawal jumps. We employed real-time quantitative PCR (qPCR) to assess overall gene expression of dopaminergic receptors (Drd1, Drd2, Drd4 and Drd5) and the µ-opioid receptor Oprm1. The levels of epigenetic base modifications including 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) were assessed on CpG islands of relevant genes. RESULTS: Females had higher locomotor activity than males after chronic fentanyl treatment, and they exhibited higher fentanyl withdrawal jumping behavior induced by naloxone. Females also presented lower Drd4 gene expression and DNA methylation (5mC + 5hmC) in the striatum. We found that locomotor activity and fentanyl withdrawal jumps were negatively correlated with Drd4 methylation and gene expression in the striatum, respectively. CONCLUSIONS: The findings suggested that female mice displayed heightened sensitivity to the effects of fentanyl treatment during the transition from adolescence to adulthood. This effect may be associated with molecular alterations related to the Drd4 gene.

Costs and cost drivers of comprehensive sexual reproductive health services to female sex workers in Kenya.

BACKGROUND: Comprehensive sexual reproductive health (SRH) programs for female sex workers (FSW) offering clinical, behavioural, and structural interventions have contributed to declining rates of HIV in this population. However, data on costs and cost drivers is needed to support programs and their donors to better allocate resources, make an investment case for continued funding, and to identify areas of improvement in program design and implementation. We aimed to estimate the annual per-FSW costs of comprehensive services for a standalone FSW program in Kenya. METHODS: We implemented a top-bottom and activity-based costing study of comprehensive FSW services at two drop-in centres (DICs), Mtwapa and Kilifi town, in Kilifi County, Kenya. Service costs were obtained from routinely collected patient data during FSW scheduled and unscheduled visits using Kenyan Ministry of Health records. Costing data were from the program and organization's expenditure reports, cross checked against bank documents and supported by information from in-depth interviews. Data were collected retrospectively for the fiscal year 2019. We obtained approval from the AMREF Research Ethics Committee (AMREF-ESRC P862/2020). RESULTS: In 2019, the unit cost of comprehensive services was 105.93 USD per FSW per year, roughly equivalent to 10,593 Kenya shillings. Costs were higher at Mtwapa DICs compared to Kilifi town DIC; 121.90 USD and 89.90 USD respectively. HIV counselling and testing cost 63.90 USD per person, PrEP was 34.20 USD and family planning was 9.93 USD. Of the total costs, staff salaries accounted for about 60%. Adjusted for inflation, costs in 2024 would be approximately 146.60. CONCLUSION: Programs should strive to maximize the number of FSW served to benefit from economies of scale. Given that personnel costs contribute most to the unit costs, programs should consider alternative designs which reduce personnel and other costs.

The effect of endothelin a receptor inhibition and biological sex on cutaneous microvascular function in non-Hispanic Black and White young adults.

The purpose of this study was to investigate whether endothelin-A receptor (ETAR) inhibition in non-Hispanic Black (NHB) and White (NHW) young adults depends on biological sex. We recruited females during low hormone (n = 22) and high hormone (n = 22) phases, and males (n = 22). Participants self-identified as NHB (n = 33) or NHW (n = 33). Participants were instrumented with two microdialysis fibers: (1) lactated Ringer's (control) and (2) 500 nM BQ-123 (ETAR antagonist). Local heating was used to elicit cutaneous vasodilation, and an infusion of 20 mM L-NAME to quantify NO-dependent vasodilation. At control sites, NO-dependent vasodilation was lowest in NHB males (46 ± 13 %NO) and NHB females during low hormone phases (47 ± 12 %NO) compared to all NHW groups. Inhibition of ETAR increased NO-dependent vasodilation in NHB males (66 ± 13 %NO), in both groups of females during low hormone phases (NHW, control: 64 ± 12 %NO, BQ-123: 85 ± 11 %NO; NHB, BQ-123: 68 ± 13 %NO), and in NHB females during high hormone phases (control: 61 ± 11 %NO, BQ-123: 83 ± 9 %NO). There was no effect for ETAR inhibition in NHW males or females during high hormone phases. These data suggest the effect of ETAR inhibition on NO-dependent vasodilation is influenced by biological sex and racial identity.

Frequency of and sex differences in cancer treatment-related cardiac dysfunction in trastuzumab-treated patients with salivary gland cancer: a retrospective cohort study.

BACKGROUND: Trastuzumab treatment for salivary gland, gastric, and breast cancer commonly causes cancer treatment-related cardiac dysfunction (CTRCD). CTRCD incidence by sex has not been well studied. METHODS: This retrospective cohort study investigated frequency of and sex differences in CTRCD in patients with salivary gland cancer treated with trastuzumab at our hospital from April 2017 to March 2022. All patients underwent echocardiography at baseline and after the first, third, and sixth trastuzumab courses. We measured changes in global and regional longitudinal strain (LS) after trastuzumab administration. CTRCD was defined by left ventricular ejection fraction (LVEF) or global LS (GLS). The results were compared by sex. RESULTS: We recorded clinical data of 49 patients (median age [IQR], 65 [55-71] years; males [75.5%]). The median follow-up period after the sixth trastuzumab course was 120 (111-128) days. One female patient and no male patient had CTRCD defined by LVEF, and two female patients (16.7%) and seven male patients (18.9%) had CTRCD, defined by GLS. The Kaplan-Meier curves showed no significant difference in CTRCD frequency, defined by GLS (log-rank, p = 0.88), between female and male patients. In the univariate analysis, sex was not associated with CTRCD, defined by GLS. A significant difference in apical LS was observed between baseline and the third follow-up results of male patients. CONCLUSIONS: In this study, CTRCD incidence was not significantly different between male and female patients with salivary gland cancer treated with trastuzumab. Although most previous studies have looked at female patients with breast cancer, a male patient may be found to be at similar risk of myocardial damage.

Prenatal and childhood air pollution exposure, cellular immune biomarkers, and brain connectivity in early adolescents.

Introduction: Ambient air pollution is a neurotoxicant with hypothesized immune-related mechanisms. Adolescent brain structural and functional connectivity may be especially vulnerable to ambient pollution due to the refinement of large-scale brain networks during this period, which vary by sex and have important implications for cognitive, behavioral, and emotional functioning. In the current study we explored associations between air pollutants, immune markers, and structural and functional connectivity in early adolescence by leveraging cross-sectional sex-stratified data from the Adolescent Brain Cognitive Development℠ Study®. Methods: Pollutant concentrations of fine particulate matter, nitrogen dioxide, and ozone were assigned to each child's primary residential address during the prenatal period and childhood (9-10 years-old) using an ensemble-based modeling approach. Data collected at 11-13 years-old included resting-state functional connectivity of the default mode, frontoparietal, and salience networks and limbic regions of interest, intracellular directional and isotropic diffusion of available white matter tracts, and markers of cellular immune activation. Using partial least squares correlation, a multivariate data-driven method that identifies important variables within latent dimensions, we investigated associations between 1) pollutants and structural and functional connectivity, 2) pollutants and immune markers, and 3) immune markers and structural and functional connectivity, in each sex separately. Results: Air pollution exposure was related to white matter intracellular directional and isotropic diffusion at ages 11-13 years, but the direction of associations varied by sex. There were no associations between pollutants and resting-state functional connectivity at ages 11-13 years. Childhood exposure to nitrogen dioxide was negatively correlated with white blood cell count in males. Immune biomarkers were positively correlated with white matter intracellular directional diffusion in females and both white matter intracellular directional and isotropic diffusion in males. Lastly, there was a reliable negative correlation between lymphocyte-to-monocyte ratio and default mode network resting-state functional connectivity in females, as well as a compromised immune marker profile associated with lower resting-state functional connectivity between the salience network and the left hippocampus in males. In post-hoc exploratory analyses, we found that the PLSC-identified white matter tracts and resting-state networks related to processing speed and cognitive control performance from the NIH Toolbox. Conclusions: We identified novel links between childhood nitrogen dioxide and cellular immune activation in males, and brain network connectivity and immune markers in both sexes. Future research should explore the potentially mediating role of immune activity in how pollutants affect neurological outcomes as well as the potential consequences of immune-related patterns of brain connectivity in service of improved brain health for all.

Effect of temperature on gonadal differentiation and growth of Leporinus friderici.

This study aimed to investigate the effect of temperature on gonadal differentiation, growth, survival, and sex ratio of Leporinus friderici reared at 25 °C or 29 °C from 50 to 240 days after eclosion (DAE) in a water recirculation system. A total of 110 fish at 50 DAE (6.7 ± 0.1 cm and 6.1 ± 0.3 g) were equally and randomly distributed in 10 boxes (90 L) (11 fish/box, 5 boxes/temperature). One fish from each experimental unit was randomly sampled at 50, 70, 90, 110, 130, 150, 170, 190, 210 and 240 DAE. Female gonadal differentiation started at 150 DAE (11.4 ± 0.0 cm and 16.4 ± 0.0 g) at 25 °C and at 170 DAE (10.7 ± 0.7 cm and 27.7 ± 8.5 g) at 29 ºC, while testes differentiation only occurred at 29 °C from 190 DAE (12.1 ± 0.0 cm and 38.0 ± 0.0 g). Of 50 fishes sampled in each condition, 17 (12 females and five males) and three (three females) displayed gonadal differentiation at 29 °C and 25 °C, respectively. Final biometric values at 29 °C were twice those obtained at 25 °C, reaching 13.9 ± 0.65 cm and 57.3 ± 10.12 g versus 11.2 ± 0.39 cm and 28.5 ± 2.95 g, respectively. While temperature clearly influenced gonadal differentiation and growth, it had inconclusive effects on sex ratio. The higher temperature (29 °C) has direct implications for the production of this species, as it accelerates growth without causing mortality.

A matter of sex-persistent predictive value of MECKI score prognostic power in men and women with heart failure and reduced ejection fraction: a multicenter study.

Background: A sex-based evaluation of prognosis in heart failure (HF) is lacking. Methods and results: We analyzed the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score registry, which includes HF with reduced ejection fraction (HFrEF) patients. A cross-validation procedure was performed to estimate weights separately for men and women of all MECKI score parameters: left ventricular ejection fraction (LVEF), hemoglobin, kidney function assessed by Modification of Diet in Renal Disease, blood sodium level, ventilation vs. carbon dioxide production slope, and peak oxygen consumption (peakVO2). The primary outcomes were the composite of all-cause mortality, urgent heart transplant, and implant of a left ventricle assist device. The difference in predictive ability between the native and sex recalibrated MECKI (S-MECKI) was calculated using a receiver operating characteristic (ROC) curve at 2 years and a calibration plot. We retrospectively analyzed 7,900 HFrEF patients included in the MECKI score registry (mean age 61 ± 13 years, 6,456 men/1,444 women, mean LVEF 33% ± 10%, mean peakVO2 56.2% ± 17.6% of predicted) with a median follow-up of 4.05 years (range 1.72-7.47). Our results revealed an unadjusted risk of events that was doubled in men compared to women (9.7 vs. 4.1) and a significant difference in weight between the sexes of most of the parameters included in the MECKI score. S-MECKI showed improved risk classification and accuracy (area under the ROC curve: 0.7893 vs. 0.7799, p = 0.02) due to prognostication improvement in the high-risk settings in both sexes (MECKI score >10 in men and >5 in women). Conclusions: S-MECKI, i.e., the recalibrated MECKI according to sex-specific differences, constitutes a further step in the prognostic assessment of patients with severe HFrEF.

Understanding symptom contribution to sex inequality in bladder and renal cancer stage at diagnosis.

Background: Understanding sex-specific factors contributing to advanced-stage diagnosis can guide interventions to reduce sex inequality in patients with urological cancers. Method: We used linked primary care and cancer registry data to examine associations between symptoms and advanced-stage in 1151 bladder cancer and 440 renal cancer patients diagnosed between January 2012 and December 2015 in England. We performed logistic regression, adjusting for sex, age, deprivation and routes to diagnosis, including interaction terms between symptoms and sex and symptoms and age. Results: Female sex (OR vs. men 1.89 [1.28-2.79]; p = 0.001) and patients presenting with urinary tract infections (OR 2.22 [1.34-3.69]) and abdominal symptoms (OR 2.19 [1.30-3.70]) were associated with increased odds of advanced-stage bladder cancer (vs. haematuria, p = 0.016 for both). Women with haematuria and men with abdominal symptoms (compared with the opposite sex with the same presenting symptom) were more likely to have advanced-stage bladder cancer. Neither sex nor symptom associations were observed for renal cancer. Conclusion: Non-haematuria symptoms are associated with higher risk of advanced-stage bladder cancer. Greater risk of advanced-stage bladder cancer in women may reflect biological differences in haematuria onset and sex differences during diagnostic process. Identifying higher risk women with haematuria may reduce sex inequalities in bladder cancer outcomes.

Acute effects of atrazine on the immunoexpressions of sertoli and germ cells molecular markers, cytokines, chemokines, and sex hormones levels in mice testes and epididymides.

Atrazine is currently one of the most commonly used agrochemicals in the United States and elsewhere. Here, we studied the immunoexpression of molecular markers of mammalian testicular functions: androgen receptor (AR), promyelocytic leukemia zinc finger (PLZF), GDNF family receptor alpha-1 (GFRA1), VASA/DDX4 (DEAD-Box Helicase 4) as well as the levels of intratesticular and intra-epididymal estradiol (E2) and dihydrotestosterone (DHT), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukins (IL-1ß and IL-6, IL-10) and testicular chemokines (CXCL-1, CCL-2 and CCL3) in BalB/c mice after a sub-acute gavage treatment with a gonado-toxin, atrazine (50 mg/kg body wt.) for three days. We found high numbers of AR immunopositive Sertoli cells and low numbers of GFRA1, PLZF and VASA/DDX4-positive germ cells in the seminiferous tubule regions of the testes. While TNF-α level in the testes fell and remained unchanged in the epididymides, IFN-γ levels in the testes remained constant but increased in the epididymides. E2 and DHT concentrations remained unaltered in the testes but were changed in the epididymides. There were no significant changes in the levels of interleukins in the testis and epididymis. Intratesticular chemokines were also not significantly altered, except for CCL-4, which was increased in the testis. Light microscopy of the epididymis showed detached epithelium and some detached cells in the lumen. It is concluded that atrazine changed the inflammatory status of the gonads and highlighted Sertoli and undifferentiated spermatogonia as important targets for atrazine's toxic effects in the testis of mice. Concerning the epididymis, atrazine altered the epididymal hormonal concentrations and promoted histopathological modifications in its parenchyma.

Health literacy and falls among community-dwelling older people in China: is there a sex difference?

BACKGROUND: Health literacy is one of the important determinants of healthy aging, yet few studies have focused on the association between health literacy and falls. AIMS: This study aims to explore the relationship between health literacy and falls, with a focus on sex differences among older people in China. METHODS: This cross-sectional study enrolled 2,144 older people aged ≥ 60 years from Shandong Province, China in 2021. We used general health literacy screening scale to assess health literacy, and collected the incidence of falls in the past year. Logistic regression models were employed to analyze the relationship between health literacy and falls. We investigated the sex differences by subgroup analyses. RESULTS: The prevalence of adequate health literacy and falls was 21.7% (95% CI: 20.0-23.5%) and 25.4% (95% CI: 23.6-27.3%), respectively. In a fully-adjusted model, adequate health literacy was associated with a lower prevalence of falls in older adults (OR = 0.71, 95%CI: 0.52-0.96). Subgroup analysis revealed sex differences in this relationship (Pfor interaction <0.05). Specifically, the female group showed no significant relationship between health literacy and falls (OR = 0.92, 95% CI: 0.59-1.44); however, the male group demonstrated a robust and significant relationship (OR = 0.58, 95% CI: 0.37-0.90). CONCLUSIONS: Older people with adequate health literacy have lower prevalence of falls, which appears to differ by sex. This relationship was significant among men but not among women. These findings emphasize the need for policymakers and healthcare providers to consider sex differences when designing and implementing programs aimed at improving health literacy and preventing falls in the older population. Improving health literacy among older women could be a strategic component in bridging sex inequality in falls.

Prevalence of depressive disorders among the very old in the 21st century.

BACKGROUND: The aim of this study is to explore the prevalence of depressive disorders in very old adults over time, in rural/urban environments, between men/women, as well as to explore other factors associated with depressive disorders. METHODS: This study was conducted utilizing the GERDA-database data, which consists of four cohorts of 85, 90 and 95+ year olds living in Northern Sweden. Participants could reside independently or in residential care. Data collections took place between 2000 and 2017. Descriptive data and logistic regression models were utilized to explore data. RESULTS: The prevalence of depressive disorders increased between 2000/02 and 2015/17 in all age groups, with the highest percentages observed in the 95+ age group, reaching 53.6 % in 2015/17. The prevalence varied from 20.3 % in those without dementia to 65.1 % in those with dementia. Sex or living in an urban/rural environment was not associated with an increased risk of depression in the fully adjusted models. Dementia and reduced capacity in activities of daily living were associated with depressive disorders among 85 and 90-year-olds, while living alone was associated with depressive disorders in the 95+ age group. LIMITATIONS: Potentially limited generalizability, as this study took place in northern Sweden. CONCLUSIONS: The prevalence of depressive disorders among very old adults increases with age and the prevalence also increases throughout cohorts and time. These alarming rates of depressive disorders among the very old require immediate measures and further investigation. Future studies are needed to explore and monitor trends and to plan and design tailored interventions.

Sex differences in self-harm and suicide in young autistic adults.

INTRODUCTION: Both suicide and self-harm are disproportionately common in autistic people. Sex differences in risk of self-harm and suicide are observed in the general population, but findings are mixed for autistic people. Self-cutting may be a particularly risky self-harm behaviour for suicide in autistic people. We aimed to explore sex differences and differences in method of self-harm in the association between self-harm and suicide in autistic and non-autistic adolescents and young adults. METHODS: We used a total population register of 2.8 million Swedish residents. Participants were followed from age 12 until December 2021 for medical treatment because of self-harm, and death from suicide. We used Cox proportional hazard regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of death from suicide following self-harm, and Relative Excessive Risk due to Interaction (RERI) to explore the interaction between self-harm and autism in females and males. RESULTS: We identified 85,143 autistic individuals (31,288 female; 53,855 male) and 2,628,382 non-autistic individuals (1,286,481 female; 1,341,901 male) aged 12-37 years. Incidence of suicide following self-harm was higher in autistic males (incidence per 100,000 risk-years = 169.0 [95% CI 135.1, 211.3]) than females (125.4 [99.4, 158.3]). The relative risk was higher for autistic females (HR 26.1 [95% CI 20.2, 33.7]) than autistic males (12.5 [9.9, 15.8]). An additive effect of both autism and self-harm was observed in both females (RERI = 9.8) and males (2.0). Autistic individuals who self-harmed through cutting were at greatest risk of death from suicide (HR 25.1 [17.9, 35.2]), compared to other methods. CONCLUSION: Autistic males and females are at increased risk of death from suicide following severe self-harm, particularly self-cutting.

Protective role of macrophages from maternal-fetal interface in unvaccinated coronavirus disease 2019 pregnant women.

Pregnant women represent a high-risk population for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection. The presence of SARS-CoV-2 has been reported in placenta from infected pregnant women, but whether the virus influences placenta immune response remains unclear. We investigated the properties of maternal-fetal interface macrophages (MFMs) in a cohort of unvaccinated women who contracted coronavirus disease 2019 (COVID-19) during their pregnancy. We reported an infiltration of CD163+ macrophages in placenta from COVID-19 women 19 whereas lymphoid compartment was not affected. Isolated MFMs exhibited nonpolarized activated signature (NOS2, IDO1, IFNG, TNF, TGFB) mainly in women infected during the second trimester of pregnancy. COVID-19 during pregnancy primed MFM to produce type I and III interferon response to SARS-CoV-2 (Wuhan and δ strains), that were unable to elicit this in MFMs from healthy pregnant women. COVID-19 also primed SARS-CoV-2 internalization by MFM in an angiotensin-converting enzyme 2-dependent manner. Activation and recall responses of MFMs were influenced by fetal sex. Collectively, these findings support a role for MFMs in the local immune response to SARS-CoV-2 infection, provide a basis for protective placental immunity in COVID-19, and highlight the interest of vaccination in pregnant women.

A Qualitative Content Analysis of Perceived Individual and Relational Consequences of Sexual Compliance and Their Contributors.

Sexual compliance (i.e., consensually engaging in sex despite a lack of desire for it) is common in committed intimate relationships, but the consequences of compliance for the well-being of the individual and the relationship are poorly understood. We investigated the perceived consequences of sexual compliance and perceptions of factors contributing to negative/positive consequences by applying qualitative content analysis to free-text retrospective survey responses from 107 (mostly) Finnish adults. We identified five themes of personal consequences (emotions and mood, sexual experience, sexual desire, pressure and violations, and physical pain), four of relational consequences (relationship satisfaction, partner's response, relationship interaction, and value alignment), and nine of possible factors contributing to negative/positive consequences (communication, self-esteem, motives for sex, relationship factors, agency and self-knowledge, mental health and stress, psychological flexibility, societal norms, and past negative experiences). Perceived consequences varied widely across individuals, both in terms of whether any positive or negative consequences were experienced and whether compliance was perceived as improving or worsening specific domains of well-being. We discuss the themes identified in relation to previous theories of sexuality and intimate relationships and offer hypotheses that can be tested in future quantitative studies.

Effect of methadone maintenance therapy on sexual disorders in males: a systematic review and meta-analysis.

INTRODUCTION: Methadone maintenance treatment (MMT) is a popular method of treating opioid use disorder. However, the majority of drug-using males experience sexual dysfunction. OBJECTIVES: This systematic review and meta-analysis examined the possible impact of MMT on sexual dysfunction in drug-using males. METHODS: Cochrane, Web of Science, ProQuest, PubMed, and Google Scholar are the international databases that we used in this study. There were neither temporal nor regional limitations on the search. Stata version 14 (StataCorp) was used for data analysis. RESULTS: When compared with the control group, the MMT group, as measured by the International Index of Erectile Function (IIEF), exhibited significantly greater levels of intercourse satisfaction disorders (standardized mean difference [SMD], -0.52; 95% CI, -0.71 to -0.32), decreased sexual desire/drive (SMD, -0.44; 95% CI, -0.87 to -0.01), lower overall satisfaction (SMD, -0.27; 95% CI, -0.43 to -0.11), and reduced total IIEF score (SMD, -0.69; 95% CI, -0.92 to -0.47). According to the Arizona Sexual Experiences Scale, the MMT group was substantially more satisfied with orgasm than the control group (SMD, 0.58; 95% CI, 0.31-0.86). As determined by the Sexual History Form, MMT was linked to a statistically significant increase in orgasmic dysfunction in comparison with the control group (SMD, 0.65; 95% CI, 0.10-1.20). The Arizona Sexual Experiences Scale revealed a significant decrease in men reporting sexual disorder following MMT as compared with their pretreatment levels. CONCLUSION: As compared with control, MMT increased disorders of intercourse satisfaction, sexual desire/drive, and overall satisfaction according to the IIEF. MMT was also associated with a statistically significant decrease in various aspects of male sexual function as compared with pretreatment levels-including erectile function, intercourse satisfaction, orgasmic function, sexual desire/drive, and overall satisfaction. These findings highlight the importance of including sexual dysfunction screening in the routine care of male patients undergoing MMT.

Maternal APOE ε2 as a possible risk factor for elevated prenatal Pb levels.

Lead (Pb) is a global contaminant associated with multiple adverse health effects. Humans are especially vulnerable during critical developmental stages. During pregnancy, exposure to Pb can occur through diet and release from maternal bones. Apolipoprotein E gene (APOE) variants (ɛ2, ɛ3, ɛ4 alleles) may influence sex steroid hormones, bone metabolism, and Pb kinetics. We examined the interplay among maternal APOE (mAPOE) genotypes, fetal sex, parity, and Pb in maternal and cord blood (mB-Pb, CB-Pb) using linear regression models. Our study involved 817 pregnant women and 772 newborns with measured adequate levels of zinc and selenium. We compared carriers of the ε2 and ε4 alleles to those with the ε3/ε3 genotype. The geometric means (range) of mB-Pb and CB-Pb were 11.1 (3.58-87.6) and 9.31 (1.82-47.0) ng/g, respectively. In cases with female fetuses, the maternal mAPOE ε2 allele was associated with higher, while the mAPOE ε4 allele was associated with lower mB-Pb and CB-Pb levels. Nulliparity increased the strength of the observed associations. These findings highlight the significance of mAPOE genetics, fetal sex, and parity in prenatal Pb kinetics. Notably, the maternal ε2 allele may increase the risk of Pb exposure.

Gender differences in gliomas: From epidemiological trends to changes at the hormonal and molecular levels.

Gender plays a crucial role in the occurrence and development of cancer, as well as in the metabolism of nutrients and energy. Men and women display significant differences in the incidence, prognosis, and treatment response across various types of cancer, including certain sex-specific tumors. It has been observed that male glioma patients have a higher incidence and worse prognosis than female patients, but there is currently a limited systematic evaluation of sex differences in gliomas. The purpose of this study is to provide an overview of the association between fluctuations in sex hormone levels and changes in their receptor expression with the incidence, progression, treatment, and prognosis of gliomas. Estrogen may have a protective effect on glioma patients, while exposure to androgens increases the risk of glioma. We also discussed the specific genetic and molecular differences between genders in terms of the malignant nature and prognosis of gliomas. Factors such as TP53, MGMT methylation status may play a crucial role. Therefore, it is essential to consider the gender of patients while treating glioma, particularly the differences at the hormonal and molecular levels. This approach can help in the adoption of an individualized treatment strategy.

An integrated approach to identifying sex-specific genes, transcription factors, and pathways relevant to Alzheimer's disease.

BACKGROUND: Age represents a significant risk factor for the development of Alzheimer's disease (AD); however, recent research has documented an influencing role of sex in several features of AD. Understanding the impact of sex on specific molecular mechanisms associated with AD remains a critical challenge to creating tailored therapeutic interventions. METHODS: The exploration of the sex-based differential impact on disease (SDID) in AD used a systematic review to first select transcriptomic studies of AD with data regarding sex in the period covering 2002 to 2021 with a focus on the primary brain regions affected by AD - the cortex (CT) and the hippocampus (HP). A differential expression analysis for each study and two tissue-specific meta-analyses were then performed. Focusing on the CT due to the presence of significant SDID-related alterations, a comprehensive functional characterization was conducted: protein-protein network interaction and over-representation analyses to explore biological processes and pathways and a VIPER analysis to estimate transcription factor activity. RESULTS: We selected 8 CT and 5 HP studies from the Gene Expression Omnibus (GEO) repository for tissue-specific meta-analyses. We detected 389 significantly altered genes in the SDID comparison in the CT. Generally, female AD patients displayed more affected genes than males; we grouped said genes into six subsets according to their expression profile in female and male AD patients. Only subset I (repressed genes in female AD patients) displayed significant results during functional profiling. Female AD patients demonstrated more significant impairments in biological processes related to the regulation and organization of synapsis and pathways linked to neurotransmitters (glutamate and GABA) and protein folding, Aß aggregation, and accumulation compared to male AD patients. These findings could partly explain why we observe more pronounced cognitive decline in female AD patients. Finally, we detected 23 transcription factors with different activation patterns according to sex, with some associated with AD for the first time. All results generated during this study are readily available through an open web resource Metafun-AD (https://bioinfo.cipf.es/metafun-ad/). CONCLUSION: Our meta-analyses indicate the existence of differences in AD-related mechanisms in female and male patients. These sex-based differences will represent the basis for new hypotheses and could significantly impact precision medicine and improve diagnosis and clinical outcomes in AD patients.