Specific differences and novel key regulatory genes of sex in influencing exceptional longevity phenotypes.

BACKGROUND AND AIMS: Although the life expectancy of women systematically and robustly exceeds that of men, specific differences and molecular mechanisms of sex in influencing longevity phenotypes remain largely unknown. Therefore, we performed transcriptome sequencing of peripheral blood samples to explore regulatory mechanisms of healthy longevity by incorporating sex data. METHODS: We selected 34 exceptional longevity (age: 98.26 ± 2.45 years) and 16 controls (age: 52.81 ± 9.78) without advanced outcomes from 1363 longevity and 692 controls recruited from Nanning of Guangxi for RNA sequencing 1. The transcriptome sequencing 1 data of 50 samples were compared by longevity and sex to screen differentially expressed genes (DEGs). Then, 121 aging samples (40-110 years old) without advanced outcomes from 355 longevity and 294 controls recruited from Dongxing of Guangxi were selected for RNA sequencing 2. The genes associated with aging from the transcriptome sequencing 2 of 121 aging samples were filtered out. Finally, the gender-related longevity candidate genes and their possible metabolic pathways were verified by cell model of aging and a real-time polymerase chain reaction (RT-PCR). RESULTS: Metabolism differs between male and female and plays a key role in longevity. Moreover, the principal findings of this study revealed a novel key gene, UGT2B11, that plays an important role in regulating lipid metabolism through the peroxisome proliferator activated receptor gamma (PPARG) signalling pathway and ultimately improving lifespan, particularly in females. CONCLUSION: The findings suggest specific differences in metabolism affecting exceptional longevity phenotypes between the sexes and offer novel therapeutic targets to extend lifespan by regulating lipid homeostasis.

Gender Differences in Achilles Tendon Ruptures - a Retrospective Study and a Review of the Literature.

Achilles tendon ruptures are common injuries typically sustained during sport with higher incidence in men, though little is understood regarding sex-specific risk factors or outcomes following injury management. This cross-sectional clinical study and systematic review aimed to examine sex-specific Achilles tendon rupture incidence and outcomes following intervention. This study included patients who sustained a rupture between 2011-2021, were ≥18 years old, and who had a minimum follow-up of at least six months, and evaluated age, sex, sport involvement, mechanism of injury, and postoperative complications and revision. Separately, a systematic literature review in the PubMed, EMBASE, and Cochrane databases was performed. A total of 705 male and 158 female patients were included in this retrospective study. 71.1% of men and 52.5% of women sustained a sports-related rupture (p< 0.001), with sport involvement demonstrating a positive correlation with revision rate (coefficient=0.09, p=0.02). A total of 21 studies with 250,907 patients (87,514 male, 35,792 female) were included in the systematic review. All studies revealed an increased incidence of ATR in men. Functional outcomes were worse in women, and female sex was an independent risk factor for postoperative complications and need for revision surgery. This study demonstrated a higher incidence of sports-related ATR in men than women, likely related to their higher ball sport participation. Although the retrospective analysis did not find a significant difference in complication or revision rates, the systematic review demonstrates poorer functional outcomes, with increased likelihood for postoperative complication and revision surgery in women as compared to men. LEVEL OF CLINICAL EVIDENCE: Level III.

Characteristics and variations in young adults with cutaneous melanoma: A national cancer database analysis.

BACKGROUND AND OBJECTIVES: Many cancers in young adulthood differ in terms of biology, histologic variation, and prognosis compared to cancer in other older age groups. Differences in cutaneous melanoma among young adults compared to other older age groups, as well as between sexes in young adults are not well studied. METHODS: The National Cancer Database was queried for patients diagnosed with cutaneous melanoma between 2004 and 2017. Patient characteristics, disease factors, and treatment were stratified by age-based cohorts and compared using standard univariate statistics. The Kaplan-Meier method and log-rank tests were used to evaluate overall survival (OS) between age-based cohorts and young adult sexes. RESULTS: Of the 329 765 patients identified, 10.5% were between 18 and 39 years of age at diagnosis. Compared with other older age groups, young adult patients were more likely to be female and uninsured with higher proportions of superficial spreading melanoma, melanoma of the trunk and extremities, and earlier-stage disease. Young adults had improved OS compared to other older age groups. Young male patients had a greater proportion of no insurance, nodular melanoma, higher-stage disease, and decreased OS compared to young female patients. Additionally, while the 5-year OS difference was statistically significant across all stages of disease between young males and females, the clinical significance is likely limited to later stages. CONCLUSIONS: Age and sex-specific differences in cutaneous melanoma highlight distinct patterns and characteristics, emphasizing the need for tailored approaches to screening, diagnosis, and treatment.

T cells in obesity-associated inflammation: The devil is in the details.

Obesity presents a significant health challenge, affecting 41% of adults and 19.7% of children in the United States. One of the associated health challenges of obesity is chronic low-grade inflammation. In both mice and humans, T cells in circulation and in the adipose tissue play a pivotal role in obesity-associated inflammation. Changes in the numbers and frequency of specific CD4+ Th subsets and their contribution to inflammation through cytokine production indicate declining metabolic health, that is, insulin resistance and T2D. While some Th subset alterations are consistent between mice and humans with obesity, some changes mainly characterize male mice, whereas female mice often resist obesity and inflammation. However, protection from obesity and inflammation is not observed in human females, who can develop obesity-related T-cell inflammation akin to males. The decline in female sex hormones after menopause is also implicated in promoting obesity and inflammation. Age is a second underappreciated factor for defining and regulating obesity-associated inflammation toward translating basic science findings to the clinic. Weight loss in mice and humans, in parallel with these other factors, does not resolve obesity-associated inflammation. Instead, inflammation persists amid modest changes in CD4+ T cell frequencies, highlighting the need for further research into resolving changes in T-cell function after weight loss. How lingering inflammation after weight loss affecting the common struggle to maintain lower weight is unknown. Semaglutide, a newly popular pharmaceutical used for treating T2D and reversing obesity, holds promise for alleviating obesity-associated health complications, yet its impact on T-cell-mediated inflammation remains unexplored. Further work in this area could significantly contribute to the scientific understanding of the impacts of weight loss and sex/hormones in obesity and obesity-associated metabolic decline.

Who's Worried? Memory, Worries About Dementia, and Marital Strain in Midlife Same- and Different-Sex Marriages: A Dyadic Perspective.

OBJECTIVES: Prior scholarship has highlighted the importance of marriage for cognition. However, little research has considered how cognition-related concerns may impact marriage. In this study, we examine how aging couples view each other's memory and worry about their potential development of dementia in the future. Additionally, we investigate whether these cognition-related concerns may strain marriage, and how these dynamics differ for men and women in same- and different-sex marriages. METHODS: We used two waves of dyadic data from the Health and Relationships Project (HARP; 2015-2022), including 594 respondents from 297 same- and different-sex married couples (aged 41-71 at Time 2). We employed the Actor- Partner Interdependence Model (APIM) to explore associations between actor and partner reports of memory and dementia worry with marital strain. RESULTS: Men and women in same- and different-sex marriages were equally likely to report worries about their own potential development of dementia. However, women reported more concerns about their spouse developing dementia in the future than men did, regardless of whether they were married to a man or a woman. Both partners' reports of memory and dementia worry played a complex role in influencing marital strain, with variations observed across couple types. DISCUSSION: Concerns about cognitive decline and dementia are common in older populations, and for married couples, spouses have concerns about their own memory as well as that of their partner. Our findings identified the significance of concerns about a spouse's memory on marital dynamics among aging couples.

Sex-Specific Susceptibility Loci Associated With Coronary Artery Aneurysms in Patients With Kawasaki Disease.

BACKGROUND AND OBJECTIVES: Kawasaki disease (KD) is an acute vasculitis that primarily affects children under age 5 years. Approximately 20-25% of untreated children with KD and 3-5% of those treated with intravenous immunoglobulin therapy develop coronary artery aneurysms (CAAs). The prevalence of CAAs is much higher in male than in female patients with KD, but the underlying factors contributing to susceptibility to CAAs in patients with KD remain unclear. This study aimed to identify sex-specific susceptibility loci associated with CAAs in KD patients. METHODS: A sex-stratified genome-wide association study (GWAS) was performed using previously obtained GWAS data from 296 KD patients and a new replication study in an independent set of 976 KD patients by comparing KD patients without CAA (controls) and KD patients with aneurysms (internal diameter ≥5 mm) (cases). RESULTS: Six male-specific susceptibility loci, PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ (odds ratios [ORs], 2.25-9.98; p=0.00204-1.96×10-6), and 2 female-specific susceptibility loci, SMAD3 (OR, 4.59; p=0.00016) and IL1RAPL1 (OR, 4.35; p=0.00026), were significantly associated with CAAs in patients with KD. In addition, the numbers of CAA risk alleles additively contributed to the development of CAAs in patients with KD. CONCLUSIONS: A sex-stratified GWAS identified 6 male-specific (PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ) and 2 female-specific (SMAD3 and IL1RAPL1) CAA susceptibility loci in patients with KD.

Sex-based Differences in Heart Failure Biomarkers.

PURPOSE OF REVIEW: Differences in HF biomarker levels by sex may be due to hormonal, genetic, and fat distribution differences. Knowledge of these differences is scarce, and it is not well established whether they may affect their usefulness in the management of HF. RECENT FINDINGS: The different biomarker profiles in women and men have been confirmed in recent studies: in women, markers of cardiac stretch and fibrosis (NP and galectin-3) are higher, whereas in men, higher levels of markers of cardiac injury and inflammation (cTn and sST2) are found. The use of new biomarkers, together with growing evidence that a multimarker approach can provide better risk stratification, raises the question of building models that incorporate sex-specific diagnostic criteria. More and more research are being devoted to understanding sex-related differences in HF. The aim of this review is to review the dynamics of HF biomarkers according to sex and in different situations, to learn whether these sex differences may affect their use in the diagnosis and follow-up of HF patients.

Identification of the Sex Pheromone of the Asparagus Moth, Parahypopta Caestrum (Lepidoptera, Cossidae).

Chemical, electrophysiological, and field trapping experiments were carried out to identify the female-produced sex pheromone of the asparagus moth, Parahypopta caestrum, a very serious pests of asparagus cultivations in southern Europe. Gas chromatography coupled with mass spectrometry and electroantennogram detection (GC-MS-EAD) analysis of hexane and solid-phase microextraction (SPME) extracts of sex pheromone glands of calling females consistently detected four compounds eliciting EAG responses in male moth antennae. According to their GC retention times, mass spectra, and comparative EAG analyses with reference standards, these EAD-active compounds were identified as (Z)-9-tetradecenol (Z9-14:OH), (Z)-5-tetradecenyl acetate (Z5-14:Ac), (Z)-7-tetradecenyl acetate (Z7-14:Ac), and (Z)-9-tetradecenyl acetate (Z9-14:Ac), respectively. In the SPME extracts from the head-space of individual abdominal tips, Z9-14:Ac, Z5-14:Ac, Z7-14:Ac, and Z9:14 OH were detected in the ratio of 82:9:5:4. In EAG dose-response experiments, Z9-14:Ac was the strongest antennal stimulant at different doses tested. In field trapping experiments, Z9-14:Ac, Z7-14:Ac, and Z5-14:Ac proven to be essential for male attraction and a their 85:5:10 blend loaded onto green rubber septum dispensers was significantly more effective than single-, two-, and any other three-component blend of these compounds. The addition of Z9-14:OH to the optimal blend resulted in a significant reduction of male catches. The attractive blend here identified allowed for an effective and accurate monitoring of P. caestrum flight activity in southern Italy.

Sexual activity and respiratory disease: A systematic review.

CONTEXT: Sex and gender are related concepts, but they have distinct meanings and implications. Respiratory diseases are a major driver of morbi-mortality. It is frequent that respirologists, primary care doctors, or other specialists, when dealing with respiratory patients, and aiming for a holistic management of their patients, they all skip any question or matter associated with sexual activity or behavior. OBJECTIVES: To review how sexual activity is explored in respiratory patients. METHODS: To conduct this review, we endorse PRISMA guidance for reporting systematic reviews, and also the sex and gender equity in research (SAGER) guidelines. RESULTS: Compared to other conditions such as heart disease, mental disorders, Alzheimer's, or even COVID-19, to date there is no review focused on sexual activity and respiratory health and disease. Asthma, COPD and other respiratory patients can have their sexual activity and behaviors affected by their disease, but also limitations in sex might be the sentinel event of an incident respiratory disease. Asking on sexual desire and related sex issues should not be considered taboo in any respiratory consultation. Importantly, any marketed stereotypes on cigarettes after any sexual activity should be counteracted. Many clinical trials of respiratory drugs keep recruiting few or no women, so research on women's sexual desire and satisfaction lags behind that of men's. By using the available objective tools and validated questionnaires summarized in this review, these important domains of respiratory patients and their partners can be properly identified and managed. CONCLUSIONS: Sexual activity, depending on age and individual specific conditions, is a fundamental driver of overall health, and therefore of lung health.

Identification and functional analysis of a rare variant of gene DHX37 in a patient with 46,XY disorders of sex development.

BACKGROUND: 46,XY sex reversal 11 (SRXY11) [OMIM#273250] is characterized by genital ambiguity that may range from mild male genital defects to gonadal sex reversal in severe cases. DHX37 is an RNA helicase that has recently been reported as a cause of SRXY11. So far, a total of 21 variants in DHX37 have been reported in 58 cases with 46,XY disorders of sex development (DSD). METHODS: Whole exome sequencing (WES) was conducted to screen for variations in patients with 46,XY DSD. The subcellular localization of mutant DHX37 proteins was detected by immunofluorescence. And the levels of mutant DHX37 proteins were detected via Western blotting. RESULTS: A novel pathogenic variant of DHX37 was identified in a patient with 46,XY DSD c.2012G > C (p.Arg671Thr). Bioinformatics analysis showed that the protein function of the variant was impaired. Compared with the structure of the wild-type DHX37 protein, the number of hydrogen bonds and interacting amino acids of the variant protein were changed to varying degrees. In vitro assays revealed that the variant had no significant effect on the intracellular localization of the protein but significantly reduced the expression level of the protein. CONCLUSIONS: Our finding further expands the spectrum of the DHX37 variant and could assist in the molecular diagnosis of 46,XY DSD patients.

Women Are Also Disadvantaged in Accessing Transplant Outside the United States: Analysis of the Spanish Liver Transplantation Registry.

Sex inequities in liver transplantation (LT) have been documented in several, mostly US-based, studies. Our aim was to describe sex-related differences in access to LT in a system with short waiting times. All adult patients registered in the RETH-Spanish Liver Transplant Registry (2000-2022) for LT were included. Baseline demographics, presence of hepatocellular carcinoma, cause and severity of liver disease, time on the waiting list (WL), access to transplantation, and reasons for removal from the WL were assessed. 14,385 patients were analysed (77% men, 56.2 ± 8.7 years). Model for end-stage liver disease (MELD) score was reported for 5,475 patients (mean value: 16.6 ± 5.7). Women were less likely to receive a transplant than men (OR 0.78, 95% CI 0.63, 0.97) with a trend to a higher risk of exclusion for deterioration (HR 1.17, 95% CI 0.99, 1.38), despite similar disease severity. Women waited longer on the WL (198.6 ± 338.9 vs. 173.3 ± 285.5 days, p < 0.001). Recently, women's risk of dropout has reduced, concomitantly with shorter WL times. Even in countries with short waiting times, women are disadvantaged in LT. Policies directed at optimizing the whole LT network should be encouraged to guarantee a fair and equal access of all patients to this life saving resource.

Epidemiology and outcome of out-of-hospital cardiac arrest in Salt Lake City: Sex-based investigations.

Objectives: Prior research indicates sex disparities in the incidence and outcomes of out-of-hospital cardiac arrest (OHCA). This study investigates the presence of such differences in Salt Lake City, Utah. Methods: We analyzed data from the Salt Lake City Fire Department (2008‒2023). We included adults with non-traumatic OHCA. We calculated the annual incidence of OHCA and examined sex-specific survival outcomes using multivariable logistic regression, adjusting for OHCA characteristics known to be associated with survival. Results: The annual incidence of OHCA was 76 per 100,000 person-years. Among the 894 OHCA cases included in the analysis, 67.5% were males, 37.3% achieved return of spontaneous circulation (ROSC), and 13.6% survived hospital discharge. Unadjusted analysis revealed that males had significantly higher OHCA in public locations (43.9% vs. 28.6%), witnessed arrests (54.5% vs. 47.8%), and shockable rhythms (33.3% vs. 22.9%). Males also showed higher rates of ROSC (37.5% vs. 36.9%), hospital discharge survival (14.5% vs. 11.7%), and neurologically intact survival. After adjusting for the OHCA characteristics, there was no significant differences between males and females in ROSC, survival to hospital discharge, and favorable neurological function with adjusted odds ratios (male vs. female) of 0.92 (95% confidence interval [CI] 0.73‒1.16), 0.85 (95% CI 0.59‒1.22), and 0.92 (95% CI 0.62‒1.40), respectively. Conclusion: Approximately, 128 adults suffer OHCA in Salt Lake City annually. Males initially showed higher crude survival rates, but after adjusting for OHCA characteristics, no significant sex differences in survival outcomes were found. Enhancing OHCA characteristics could benefit both sexes. Investigations into the relationship between sex- and region-specific factors influencing OHCA outcomes are needed.

Impact of sex of bystanders who perform cardiopulmonary resuscitation on return of spontaneous circulation in out-of-hospital cardiac arrest patients: A retrospective, observational study.

Background: The impact of the sex of bystanders who initiate cardiopulmonary resuscitation (CPR) on out-of-hospital cardiac arrest (OHCA) patients has not been fully elucidated. This study aims to investigate the association between the sex of bystanders who perform CPR and the clinical outcomes of OHCA patients in real-world clinical settings. Methods: We conducted a retrospective, observational study using data from the Okayama City Fire Department in Japan. Patients were categorized based on bystanders' sex. Our primary outcomes were return of spontaneous circulation (ROSC). Our secondary outcome was 30-day survival and 30-day favorable neurological outcome, defined as Cerebral Performance Category score of 1 or 2. Multivariable logistic regression analysis was used to examine the association between these groups and outcomes. Results: The study included 3,209 patients with a comparable distribution of male (1,540 patients: 48.0%) and female bystanders (1,669 patients: 52.0%) between the groups. Overall, 221 (6.9%) ROSC at hospital arrival, 226 (7.0%) patients had 30-day survival, and 121 (3.8%) patients had 30-day favorable neurological outcomes. Bystander sex (female as reference) did not contribute to ROSC at hospital arrival (adjusted OR [aOR] 1.11, 95% CI: 0.76-1.61), 30-day survival (aOR 1.23, 95% CI: 0.83-1.82), or 30-day favorable neurological outcomes (aOR 0.66, 95% CI: 0.34-1.27). Basic life support education experience was a bystander factor positively associated with ROSC. Patient factors positively associated with ROSC were initial shockable rhythm and witness of cardiac arrest. Conclusion: There were no differences in ROSC, 30-day survival, or 30-day neurological outcomes in OHCA patients based on bystander sex.

Experiences of child sex trafficking identification among Ontario pediatric emergency department healthcare providers: A qualitative study.

BACKGROUND AND OBJECTIVE: More than 60 % of people exposed to sex trafficking access hospital emergency departments (ED), making the ED a critical setting for child sex trafficking identification. Children exposed to sex trafficking (CEST) do not always recognize that they are being exploited. With many ED leaders confirming that there are no formal processes or assessment tools to screen for human trafficking in EDs, it is especially challenging for healthcare providers to identify CEST. Accordingly, the following study sought to examine healthcare providers' child sex trafficking identification practices in Ontario pediatric EDs. METHODS: We conducted interviews with healthcare providers (N = 12) who work in an Ontario pediatric ED and have provided services to CEST. Thematic analysis and intersectionality theory guided our analytic approach. RESULTS: Participants underscored the key role of Registered Nurses for identifying presentations of child sex trafficking in Ontario pediatric EDs. Although white, feminine presenting youth are the predominantly identified demographic of CEST in Ontario pediatric EDs, healthcare providers also described key intersections between race, poverty, child welfare agency system involvement, and adverse childhood life experiences as factors that heightened vulnerability to child sex trafficking. Common presentations to the ED were for non-specific concerns, injuries, following a sexual assault, or for mental health concerns. Suggested methods for identification varied but were centred around the principles of trauma- and violence-informed care. CONCLUSION: Identifying child sex trafficking in Ontario pediatric EDs is a complex practice, requiring human trafficking training and education for healthcare providers. The interrelated indicators of child sex trafficking, including the sociodemographic and clinical profile of the patient, must be considered jointly, using a trauma- and violence-informed approach.

Expression profiling of cochlear genes uncovers sex-based cellular function in mouse cochleae.

Sex is a pivotal biological factor that significantly impacts tissue homeostasis and disease susceptibility. In the auditory system, sex differences have been observed in cochlear physiology and responses to pathological conditions. However, the underlying molecular mechanisms responsible for these differences remain elusive. The current research explores the differences in gene expression profiles in the cochlea between male and female mice, aiming to understand the functional implication of sex-biased gene expression in each sex. Using RNA-sequencing analysis on cochlear tissues obtained from male and female mice, we identified a significant number of genes exhibiting sex-biased expression differences. While some of these differentially expressed genes are located on sex chromosomes, most are found on autosomal chromosomes. Further bioinformatic analysis revealed that these genes are involved in several key cellular functions. In males, these genes are notably linked to oxidative phosphorylation and RNA synthesis and processing, suggesting their involvement in mitochondrial energy production and regulatory control of gene expression. In contrast, sex-biased genes are associated with mechano-transduction and synaptic transmission within female cochleae. Collectively, our study provides valuable insights into the molecular differences between the sexes and emphasizes the need for future research to uncover their functional implications and relevance to auditory health and disease development.

Prevalence and Risk Factors for HPV Seropositivity and Anogenital DNA-Positivity among Men Who Have Sex With Men: A Repeated Cross-Sectional Study.

OBJECTIVES: To assess associations of potential risk factors with HPV seropositivity among men who have sex with men (MSM), and compare these to risk factors for anal and penile HPV DNA-positivity in the same study population. METHODS: Seropositivity and anal and penile HPV DNA-positivity were determined for 7 high-risk HPV genotypes for MSM aged 16-24 years participating in PASSYON 2009-2021. Logistic regression models were conducted to assess risk factors for seropositivity, anal and penile HPV DNA-positivity. RESULTS: 1,019 MSM were included. HPV-16 and -18 were most common for serology, and anal and penile HPV DNA-positivity. Although no clear similarities were observed for most risk factors for HPV seropositivity and anal or penile DNA-positivity, receptive anal intercourse (RAI) was the strongest associated risk factor for both seropositivity (RAI ever aOR 3.50, 95%CI 1.56-7.88; RAI previous 6 mos. aOR 2.17, 95%CI 1.44-3.26) and anal DNA-positivity (RAI previous 6 mos. aOR 1.67, 95%CI 1.09-2.56). CONCLUSIONS: Our study is suggestive of site-specific immune response after HPV infection; RAI might lead to anal HPV infections and consequently to seroconversion. Finally, as the two genotypes that are most oncogenic and preventable by all HPV vaccines were most common, our results underline the importance of gender-neutral vaccination.

Adolescent intermittent ethanol (AIE) sensitized fever in male Sprague Dawley rats exposed to poly I:C in adulthood.

Fever plays an indispensable role in host defense processes and is used as a rapid index of infection severity. Unfortunately, there are also substantial individual differences in fever reactions with biological sex, immunological history, and other demographic variables contributing to adverse outcomes of infection. The present series of studies were designed to test the hypothesis that a history of adolescent alcohol misuse may be a latent experiential variable that determines fever severity using polyinosinic:polycytidylic acid (poly I:C), a synthetic form of double-stranded RNA that mimics a viral challenge. Adult male and female Sprague Dawley rats were injected with 0 (saline) or 4 mg/kg poly I:C to first establish sex differences in fever sensitivity in Experiment 1 using implanted radiotelemetry devices for remote tracking. In Experiments 2 and 3, adolescent males and females were exposed to either water or ethanol (0 or 4 g/kg intragastrically, 3 days on, 2 days off, ∼P30-P50, 4 cycles/12 exposures total). After a period of abstinence, adult rats (∼P80-96) were then challenged with saline or poly I:C, and fever induction and maintenance were examined across a prolonged time course of 8 h using implanted probes. In Experiments 4 and 5, adult male and female subjects with a prior history of adolescent water or adolescent intermittent ethanol (AIE) were given saline or poly I:C, with tissue collected for protein and gene expression analysis at 5 h post-injection. Initial sex differences in fever sensitivity were minimal in response to the 4 mg/kg dose of poly I:C in ethanol-naïve rats. AIE exposed males injected with poly I:C showed a sensitized fever response as well as enhanced TLR3, IκBα, and IL-1ß expression in the nucleus of the solitary tract. Other brain regions related to thermoregulation and peripheral organs such as spleen, liver, and blood showed generalized immune responses to poly I:C, with no differences evident between AIE and water-exposed males. In contrast, AIE did not affect responsiveness to poly I:C in females. Thus, the present findings suggest that adolescent binge drinking may produce sex-specific and long-lasting effects on fever reactivity to viral infection, with preliminary evidence suggesting that these effects may be due to centrally-mediated changes in fever regulation rather than peripheral immunological mechanisms.

A positive affect intervention alters leukocyte DNA methylation in sexual minority men with HIV who use methamphetamine.

OBJECTIVE: This epigenomics sub-study embedded within a randomized controlled trial examined whether an evidenced-based behavioral intervention model that decreased stimulant use altered leukocyte DNA methylation (DNAm). METHODS: Sexual minority men with HIV who use methamphetamine were randomized to a five-session positive affect intervention (n = 32) or an attention-control condition (n = 21), both delivered during three months of contingency management for stimulant abstinence. All participants exhibited sustained HIV virologic control - an HIV viral load less than 40 copies/mL at baseline and six months post-randomization. The Illumina EPIC BeadChip measured leukocyte methylation of cytosine-phosphate-guanosine (CpG) sites mapping onto five a priori candidate genes of interest (i.e., ADRB2, BDNF, FKBP5, NR3C1, OXTR). Functional DNAm pathways and soluble markers of immune dysfunction were secondary outcomes. RESULTS: Compared to the attention-control condition, the positive affect intervention significantly decreased methylation of CpG sites on genes that regulate ß2 adrenergic and oxytocin receptors. There was an inconsistent pattern for the direction of the intervention effects on methylation of CpG sites on genes for glucocorticoid receptors and brain-derived neurotrophic factor. Pathway analyses adjusting for the false discovery rate (padj < 0.05) revealed significant intervention-related alterations in DNAm of Reactome pathways corresponding to neural function as well as dopamine, glutamate, and serotonin release. Positive affect intervention effects on DNAm were accompanied by significant reductions in the self-reported frequency of stimulant use. CONCLUSIONS: There is an epigenetic signature of an evidence-based behavioral intervention model that reduced stimulant use, which will guide the identification of biomarkers for treatment responses.

The single-cell chromatin landscape in gonadal cell lineage specification.

Gonad development includes sex determination and divergent maturation of the testes and ovaries. Recent advances in measuring gene expression in single cells are providing new insights into this complex process. However, the underlying epigenetic regulatory mechanisms remain unclear. Here, we profiled chromatin accessibility in mouse gonadal cells of both sexes from embryonic day 11.5 to 14.5 using single-cell assay for transposase accessible chromatin by sequencing (scATAC-seq). Our results showed that individual cell types can be inferred by the chromatin landscape, and that cells can be temporally ordered along developmental trajectories. Integrative analysis of transcriptomic and chromatin-accessibility maps identified multiple putative regulatory elements proximal to key gonadal genes Nr5a1, Sox9 and Wt1. We also uncover cell type-specific regulatory factors underlying cell type specification. Overall, our results provide a better understanding of the epigenetic landscape associated with the progressive restriction of cell fates in the gonad.

Challenging assumptions about the demographics of eosinophilic gastrointestinal diseases: A systematic review.

Background: The demographic characteristics of patients with eosinophilic gastrointestinal diseases (EGIDs) are poorly understood. Population-based assessments of EGID demographics may indicate health disparities in diagnosis. Objectives: We aimed to characterize the demographic distribution of EGIDs and evaluate the potential for bias in reporting patient characteristics. Methods: We conducted a systematic review, extracting data on age, sex, gender, race, ethnicity, body mass index, insurance, and urban/rural residence on EGID patients and the source population. Differences in proportions were assessed by chi-square tests. Demographic reporting was compared to recent guidelines. Results: Among 50 studies that met inclusion/exclusion criteria, 12 reported ≥1 demographic feature in both EGID and source populations. Except for age and sex or gender, demographics were rarely described (race = 4, ethnicity = 1, insurance = 1) or were not described (body mass index, urban/rural residence). A higher proportion of male subjects was observed for EoE or esophageal eosinophilia relative to the source population, but no difference in gender or sex distribution was observed for other EGIDs. "Sex" and "gender" were used interchangeably, and frequently only the male proportion was reported. Reporting of race and ethnicity was inconsistent with guidelines. Conclusion: Current data support a male predominance for EoE only. Evidence was insufficient to support enrichment of EGIDs in any particular racial, ethnic, or other demographic group. Population-based studies presenting demographics on both cases and source populations are needed. Implementation of guidelines for more inclusive reporting of demographic characteristics is crucial to prevent disparities in timely diagnosis and management of patients with EGIDs.