Found Sex Differences Research Articles

Characterizing cerebral hemodynamics across the adult lifespan with arterial spin labeling MRI data from the Human Connectome Project-Aging

Arterial spin labeling (ASL) magnetic resonance imaging (MRI) has become a popular approach for studying cerebral hemodynamics in a range of disorders and has recently been included as part of the Human Connectome Project-Aging (HCP-A). Due to the high spatial resolution and multiple post-labeling delays, ASL data from HCP-A holds promise for localization of hemodynamic signals not only in gray matter but also in white matter. However, gleaning information about white matter hemodynamics with ASL is challenging due in part to longer blood arrival times in white matter compared to gray matter. In this work, we present an analytical approach for deriving measures of cerebral blood flow (CBF) and arterial transit times (ATT) from the ASL data from HCP-A and report on gray and white matter hemodynamics in a large cohort (n = 234) of typically aging adults (age 36–90 years). Pseudo-continuous ASL data were acquired with labeling duration = 1500 ms and five post-labeling delays = 200 ms, 700 ms, 1200, 1700 ms, and 2200 ms. ATT values were first calculated on a voxel-wise basis through normalized cross-correlation analysis of the acquired signal time course in that voxel and an expected time course based on an acquisition-specific Bloch simulation. CBF values were calculated using a two-compartment model and with age-appropriate blood water longitudinal relaxation times. Using this approach, we found that white matter CBF reduces (ρ = 0.39) and white matter ATT elongates (ρ = 0.42) with increasing age (p < 0.001). In addition, CBF is lower and ATTs are longer in white matter compared to gray matter across the adult lifespan (Wilcoxon signed-rank tests; p < 0.001). We also found sex differences with females exhibiting shorter white matter ATTs than males, independently of age (Wilcoxon rank-sum test; p < 0.001). Finally, we have shown that CBF and ATT values are spatially heterogeneous, with significant differences in cortical versus subcortical gray matter and juxtacortical versus periventricular white matter. These results serve as a characterization of normative physiology across the human lifespan against which hemodynamic impairment due to cerebrovascular or neurodegenerative diseases could be compared in future studies.

Sex Differences in the Incidence of Obesity-Related Gastrointestinal Cancer.

Cancer is the second leading cause of death worldwide, with 9.6 million people estimated to have died of cancer in 2018. Excess body fat deposition is a risk factor for many types of cancer. Men and women exhibit differences in body fat distribution and energy homeostasis regulation. This systematic review aimed to understand why sex disparities in obesity are associated with sex differences in the incidence of gastrointestinal cancers. Cancers of the esophagus, liver, and colon are representative gastrointestinal cancers, and obesity is a convincing risk factor for their development. Numerous epidemiological studies have found sex differences in the incidence of esophageal, liver, and colorectal cancers. We suggest that these sexual disparities are partly explained by the availability of estrogens and other genetic factors regulating inflammation, cell growth, and apoptosis. Sex differences in gut microbiota composition may contribute to differences in the incidence and phenotype of colorectal cancer. To establish successful practices in personalized nutrition and medicine, one should be aware of the sex differences in the pathophysiology and associated mechanisms of cancer development.

(3α,5α)3-hydroxypregnan-20-one (3α,5α-THP) regulation of hypothalamic and extrahypothalamic corticotropin releasing factor (CRF): Sexual dimorphism and brain region specificity in Sprague Dawley rats

CRF is the main activator of the hypothalamic-pituitary-adrenal (HPA) axis in response to stress. CRF neurons are found mainly in the hypothalamus, but CRF positive cells and CRF1 receptors are also found in extrahypothalamic structures, including amygdala (CeA), hippocampus, NAc and VTA. CRF release in the hypothalamus is regulated by inhibitory GABAergic interneurons and extrahypothalamic glutamatergic inputs, and disruption of this balance is found in stress-related disorders and addiction. (3α,5α)3-hydroxypregnan-20-one (3α,5α-THP), the most potent positive modulator of GABAA receptors, attenuates the stress response reducing hypothalamic CRF mRNA expression and ACTH and corticosterone serum levels. In this study, we explored 3α,5α-THP regulation of hypothalamic and extrahypothalamic CRF mRNA and peptide expression, in male and female Sprague Dawley rats, following vehicle or 3α,5α-THP administration (15 mg/kg). In the hypothalamus, we found sex differences in CRF mRNA expression (females +74%, p < 0.01) and CRF peptide levels (females −71%, p < 0.001). 3α,5α-THP administration reduced hypothalamic CRF mRNA expression only in males (−50%, p < 0.05) and did not alter CRF peptide expression in either sex. In hippocampus and CeA, 3α,5α-THP administration reduced CRF peptide concentrations only in the male (hippocampus −29%, p < 0.05; CeA −62%, p < 0.01). In contrast, 3α,5α-THP injection increased CRF peptide concentration in the VTA of both males (+32%, p < 0.01) and females (+26%, p < 0.01). The results show sex and region-specific regulation of CRF signals and the response to 3α,5α-THP administration. This data may be key to successful development of therapeutic approaches for stress-related disorders and addiction.

Sex-specific associations of serum insulin-like growth factor-1 with bone density and risk of fractures in Chinese patients with type 2 diabetes.

The objective was to investigate the associations of serum insulin-like growth factor-1 (IGF-1) with bone mineral density (BMD) and risk of fractures in Chinese patients with type 2 diabetes (T2D) in each gender. This was a cross-sectional, retrospective study that included men over 50 years and postmenopausal women with T2D without medical conditions or medications known to significantly affect BMD or serum IGF-I levels. Data of IGF-1, bone metabolism markers, lumbar spine (LS), femoral neck (FN), and total hip (TH) BMD were obtained; 10-year probability of major osteoporotic fractures (MOFs) and hip fractures (HFs) was calculated and modified with rheumatoid arthritis, femoral neck T-score, and age. Correlations of IGF-1 levels with bone metabolism and risk of fractures were statistically analyzed in men and women, respectively. A total of 391 patients, including 226 men and 165 women, were included. The age, serum fasting C-peptide, glycosylated hemoglobin (HbA1c), bone formation marker, and all three modified 10-year probabilities of MOFs and HFs were higher in women than those in men (all p < 0.05). The levels of 25 hydroxyvitamin D (25OHD), IGF-1, and BMD were lower in women than those in men (all p < 0.05). In men, IGF-1 was positively correlated with FN and TH BMD (FN BMD: r = 0.267, p < 0.001; TH BMD: r = 0.235, p < 0.001) and negatively correlated with all three modified 10-year probabilities of MOFs (RA-modified MOFs: r = - 0.289, p < 0.001; age-modified MOFs: r = - 0.237, p < 0.001; FN T-score-modified MOFs: r = - 0.280, p < 0.001) and HFs (RA-modified HFs: r = - 0.291, p < 0.001; age-modified HFs: r = - 0.271, p < 0.001; FN T-score-modified HFs: r = - 0.270, p < 0.001), while no significant correlations were found between serum IGF-I and BMD and three modified 10-year probability in women. According to this study, we found sex differences in the associations of serum IGF-1 with BMD and risk of fractures in Chinese patients with T2D. These results suggested that increasing serum IGF-1 might be a clinical target for protecting fractures in T2D, especially in men.

Long-term Health Outcomes Among Survivors Exposed to Sulfur Mustard in Iran

The prevalence and severity of long-term health complications after exposure to sulfur mustard are unknown. To investigate the long-term health outcomes among survivors exposed to sulfur mustard during the Iran-Iraq War. In this retrospective cohort study, late-onset health complications of 64 190 Iranian survivors exposed to sulfur mustard during the Iran-Iraq War from 1980 to 1988 were investigated using descriptive statistics. Data involving affected organs and symptom severity were extracted from the Veterans and Martyr Affair Foundation (VMAF) database from 1980 to 2019. Assessments were conducted across 3 groups depending on whether survivors were (1) evacuated and admitted (EA) to a hospital; (2) not evacuated or admitted (NEA) to a hospital; or (3) evacuation or admission status was not documented. Analysis of chronic symptom severity following exposure to sulfur mustard. Mild, moderate, or severe rankings of symptoms in lungs, eyes, and skin of survivors exposed to sulfur mustard using data from the VMAF database. Of 64 190 chemical survivors registered in the VMAF database, 60 861 met the inclusion criteria. Of the included survivors, 98.0% were male, and the mean (SD) age was 23.5 (7.7) years. Most survivors (53 675 [88.2%]) had no symptoms or mild lesions, and 7186 survivors (11.8%) had moderate or severe complications. Moderate to severe lung (6540 [10.7%]), eye (335 [0.6%]), or skin (725 [1.2%]) injuries were documented in the exposed population. The proportion of moderate plus severe late complications in eyes was 3 times as high in male survivors compared with female survivors (0.6% [95% CI, 0.53%-0.65%] vs 0.2% [95% CI, 0.09%-0.73%]; P < .001), whereas dermal complications were significantly more common in female survivors (3.9% [95% CI, 2.92%-5.11%] vs 1.14% [95% CI, 1.06%-1.23%]; P < .001). Mild lung lesions were more prevalent in the NEA group than in the EA group (73.9% [95% CI, 73.4%-74.4%] vs 11.0% [95% CI, 10.6%-11.3%]; P < .001). In the NEA group, 83.2% (n = 23 866) developed lung injuries that were mostly mild or moderate, whereas 77% (n = 24 766) of the EA group did not develop lung injuries (P < .001). The present study found sex differences in the frequencies of eye and skin complications following sulfur mustard exposure, and lung complications were more prevalent years after sulfur mustard exposure than soon after exposure. Mild lung lesions were observed more frequently among sulfur mustard-exposed survivors who had not been evacuated or hospitalized than among those who had been evacuated or hospitalized. These differences may be due to physiological response or dose of exposure. Close monitoring over an extended period may be required for detection of late pulmonary complications in individuals exposed to sulfur mustard.

Age-related DNA methylation changes are sex-specific: a comprehensive assessment

The existence of a sex gap in human health and longevity has been widely documented. Autosomal DNA methylation differences between males and females have been reported, but so far few studies have investigated if DNA methylation is differently affected by aging in males and females. We performed a meta-analysis of 4 large whole blood datasets, comparing 4 aspects of epigenetic age-dependent remodeling between the two sexes: differential methylation, variability, epimutations and entropy. We reported that a large fraction (43%) of sex-associated probes undergoes age-associated DNA methylation changes, and that a limited number of probes show age-by-sex interaction. We experimentally validated 2 regions mapping in FIGN and PRR4 genes and showed sex-specific deviations of their methylation patterns in models of decelerated (centenarians) and accelerated (Down syndrome) aging. While we did not find sex differences in the age-associated increase in epimutations and entropy, we showed that the number of probes having an age-related increase in methylation variability is 15 times higher in males compared to females. Our results can offer new epigenetic tools to study the interaction between aging and sex and can pave the way to the identification of molecular triggers of sex differences in longevity and age-related diseases prevalence.

Sex and cognition: Relationships with tau PET across the Alzheimer’s disease spectrum

AbstractBackgroundRecent evidence suggests that tau accumulates differently in the brains of men and women with Alzheimer’s disease (AD), with greater neurofibrillary tangles in women especially in the MCI stage. Women show a reserve in verbal memory but then more rapid decline in this domain once they are symptomatic. Since regional tau deposition is closely tethered to cognitive symptoms, we were interested in how relationships between tau distribution and cognition might differ by sex.MethodData were extracted from the AD Neuroimaging Initiative database for participants (136 women, 139 men) who were amyloid PET positive and had flortaucapir (“tau”) PET, across clinical diagnoses of normal cognition (NC), mild cognitive impairment (MCI) and AD. Vertex‐wise analyses were conducted in FreeSurfer, quantifying the vertices with above‐threshold SUVR and assessing regional distribution. We compared overall burden in men and women, and further investigated results by ApoE status and diagnosis and assessed how regional tau burden related to different cognitive scores.ResultsWomen and men did not differ on overall amount of tau PET uptake, but there was a sex by diagnosis interaction on overall tau SUVr. On further analysis (figure 1) this was driven by higher SUVr in women in the MCI stage (F(1, 85) = 7.313, p = .008). Furthermore, women with a higher tau burden scored worse across verbal memory measures, whereas men with higher tau burdens demonstrated worse performance on processing speed and executive measures. This was reflected in topological representation of the tau burden by cognitive test (figure 2).ConclusionSex differences in the expression of AD correspond to differences in tau especially at the MCI stage. Higher tau in women is reflected in reduced performance in verbal memory, while higher tau in men reflects worse performance on executive measures. These findings point to the differences in trajectories of tau deposition in men and women and the relationship of tau to sex differences in cognitive findings.

Sex differences in type of exercise associated with depression in South Korean adults

Exercise has been considered as treatment and a preventive modality to alleviate depressive symptoms, but sex differences regarding specific types of exercise in association with depression have not been clearly elucidated. Here, we investigated sex differences in the association between exercise type and depression in Korean adults. Data from the Korea National Health and Nutrition Examination Survey (KNHANES) were used for this study. A total of 13,914 participants who had filled in a Patient Health Questionnaire-9 (PHQ-9) were included. The subjects’ exercise status had been evaluated with questions on strength exercise and walking, and answers were analysed in the current study using multivariate logistic regression. Male participants who reported having done strength exercise more than once in a week were less likely to be depressed after adjusting for covariates assumed to affect depression levels [adjusted odds ratio (OR) 0.60, 95% CI 0.40–0.92]. In women, walking more than once during the previous week was associated with lower depression levels after covariate adjustments (adjusted OR 0.54, CI 0.34–0.87). This study identifies the relationship between exercise and the presence of depressive symptoms and finds sex differences in the types of exercise that correlate with depression in Korean adults.

Sex-biased Immune Responses Following SARS-CoV-2 Infection.

Males are disproportionately affected by severe disease and death from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In their recent article, Takahashi et al. found sex differences in immune responses to SARS-CoV-2 and the predictors of disease progression. These findings contribute to elucidating the mechanisms that underlie the male bias in severe disease and death from coronavirus disease 2019 (COVID-19).

Frequency of Recent Binge Drinking Is Associated With Sex-Specific Cognitive Deficits: Evidence for Condition-Dependent Trait Expression in Humans.

Evolutionary theory suggests that commonly found sex differences are largest in healthy populations and smaller in populations that have been exposed to stressors. We tested this idea in the context of men’s typical advantage (vs. women) in visuospatial abilities (e.g., mental rotation) and women’s typical advantage (vs. men) in social-cognitive (e.g., facial-expression decoding) abilities, as related to frequent binge drinking. Four hundred nineteen undergraduates classified as frequent or infrequent binge drinkers were assessed in these domains. Trial-level multilevel models were used to test a priori Sex × Group (binge drinking) interactions for visuospatial and social-cognitive tasks. Among infrequent binge drinkers, men’s typical advantage in visuospatial abilities and women’s typical advantage in social-cognitive abilities was confirmed. Among frequent binge drinkers, men’s advantage was reduced for one visuospatial task (Δ d = 0.29) and eliminated for another (Δ d = 0.75), and women’s advantage on the social-cognitive task was eliminated (Δ d = 0.12). Males who frequently engaged in extreme binges had exaggerated deficits on one of the visuospatial tasks, as did their female counterparts on the social-cognitive task. The results suggest sex-specific vulnerabilities associated with recent, frequent binge drinking, and support an evolutionary approach to the study of these vulnerabilities.

Sex and burrowing behavior and their implications with lytic activity in the sand-dwelling spider Allocosa senex.

The immune response can be costly. Studies in several arthropod species have indicated a trade-off between immunity and other life-history traits, including reproduction. In sexually dimorphic species in which females and males largely differ in their life history strategies and related energetic demands, we can expect to find sex differences in immune functions. Sex differences in immunity are well documented in vertebrates; however, we largely lack data from invertebrate systems. Lytic activity, the immune system's ability to lysate bacteria and viruses, has been widely used as a proxy for the strength of the immune response in several invertebrates. With this in mind, we used the burrowing wolf spider Allocosa senex to test differences in lytic activity between females and males. We also studied whether digging behavior affects the immune responses in this species. While females of A. senex construct simple refuges where they stay during the day, males construct deep burrows, which they donate to females after copulation. In accordance with our hypothesis, females showed higher lytic activity compared with males, and those males who dug showed higher levels of lytic activity than those that did not dig. Furthermore, male body condition and lytic activity did not correlate with burrow length, a trait under female choice in this species. Our results show sexual dimorphism in lytic activity responses, which are likely related to differences in life-history strategies and energetic requirements of each sex in A. senex spiders.

Integration of microarray data and literature mining identifies a sex bias in DPP4+CD4+ T cells in HIV-1 infection.

HIV-1 infection exhibits a significant sex bias. This study aimed at identifying and examining lymphocyte associated sex differences in HIV-1 pathogenesis using a data-driven approach. To select targets for investigating sex differences in lymphocytes, data of microarray experiments and literature mining were integrated. Data from three large-scale microarray experiments were obtained from NCBI/GEO and screened for sex differences in gene expression. Literature mining was employed to identify sex biased genes in the microarray data, which were relevant to HIV-1 pathogenesis and lymphocyte biology. Sex differences in gene expression of selected genes were investigated by RT-qPCR and flowcytometry in healthy individuals and persons living with HIV-1. A significant and consistent sex bias was identified in 31 genes, the majority of which were related to immunity and expressed at higher levels in women. Using literature mining, three genes (DPP4, FCGR1A and SOCS3) were selected for analysis by qPCR because of their relevance to HIV, as well as, B and T cell biology. DPP4 exhibited the most significant sex bias in mRNA expression (p = 0.00029). Therefore, its expression was further analyzed on B and T cells using flowcytometry. In HIV-1 infected controllers and healthy individuals, frequencies of CD4+DPP4+ T cells were higher in women compared to men (p = 0.037 and p = 0.027). In women, CD4 T cell counts correlated with a predominant decreased in DPP4+CD4+ T cells (p = 0.0032). Sex differences in DPP4 expression abrogated in progressive HIV-1 infection. In conclusion, we found sex differences in the pathobiology of T cells in HIV-1 infection using a data-driven approach. Our results indicate that DPP4 expression on CD4+ T cells might contribute to the immunological sex differences observed in chronic HIV‑1 infection.

Determinants of health and well-being in adolescents : Review of sex differences with afocus on boys.

Awide variety of variables determine health and well-being in adolescence. How these variables may differ in relation to gender or sex is often not clear. In addition, research on sex differences often focuses on females rather than males. This review gives an overview on the literature with respect to possible gender/sex-specific determinants and correlates of health and well-being in adolescent boys. The search strategy used the approach of anarrative review, which led to 17papers being included. The data synthesis employed aqualitative and descriptive analysis approach. We found sex differences in three categories: clinical symptoms, health and well-being, and risk behavior. The results show avariety of determinants that lead to sex differences in health outcomes, such as peer relations, social economic status, physical activity and coping styles. Strengths and limitations of the literature and implications for future research are discussed.

Key role of the 5-HT1A receptor addressing protein Yif1B in serotonin neurotransmission and SSRI treatment

Altered function of serotonin receptor 1A (5-HT1AR) has been consistently implicated in anxiety, major depressive disorder and resistance to antidepressants. Mechanisms by which the function of 5-HT1AR (expressed as an autoreceptor in serotonergic raphe neurons and as a heteroreceptor in serotonin [5-HT] projection areas) is altered include regulation of its expression, but 5-HT1AR trafficking may also be involved. We investigated the consequences of the lack of Yif1B (the 5-HT1AR trafficking protein) on 5-HT neurotransmission in mice, and whether Yif1B expression might be affected under conditions known to alter 5-HT neurotransmission, such as anxious or depressive states or following treatment with fluoxetine (a selective serotonin reuptake inhibitor) in humans, monkeys and mice. Compared with wild-type mice, Yif1B-knockout mice showed a significant decrease in the forebrain density of 5-HT projection fibres and a hypofunctionality of 5-HT1A autoreceptors expressed on raphe 5-HT neurons. In addition, social interaction was less in Yif1B-knockout mice, which did not respond to the antidepressant-like effect of acute fluoxetine injection. In wild-type mice, social defeat was associated with downregulated Yif1B mRNA in the prefrontal cortex, and chronic fluoxetine treatment increased Yif1B expression. The expression of Yif1B was also downregulated in the postmortem prefrontal cortex of people with major depressive disorder and upregulated after chronic treatment with a selective serotonin reuptake inhibitor in monkeys. We found sex differences in Yif1B expression in humans and monkeys, but not in mice under the tested conditions. These data support the concept that Yif1B plays a critical role in 5-HT1AR functioning and brain 5-HT homeostasis. The opposite changes in its expression observed in anxious or depressive states and after therapeutic fluoxetine treatment suggest that Yif1B might be involved in vulnerability to anxiety and depression, and fluoxetine efficacy.

DIFFERENCES IN PULSE WAVE VELOCITY BETWEEN TRANSPLANTED BOYS AND GIRLS: LONGITUDINAL ANALYSIS OF 4C-T STUDY

4C Study. Background: Mortality rates in children with end stage renal disease (ESRD) are higher in girls1. Cardiovascular complications are among the most common causes of death2. Pulse wave velocity (PWV), a measure of aortic stiffness, is associated with mortality in adults with ESRD. We investigated whether sex differences in aortic PWV were present in children who underwent tx in the 4C study. Method: Of 336 children undergoing RRT, 236 (156 boys) received tx and were longitudinally analyzed. PWV was normalized for sex and height; systolic and diastolic blood pressure (BP) for age, sex, and height. Results: Whereas PWV z-scores did not differ between girls and boys as they entered chronic kidney disease (CKD) stage 4 (boys=0.18±1.6 and girls=0.18±1.9), PWV was higher in girls at the last visit before start of RRT (0.45±1.9 vs. 0.25±1.5) and three years after tx (0.83±1.3 vs. 0.30±1.1). We did not find sex differences in the mean time between reaching eGFR ≤30 ml/min/1.73m2 to tx or the months on dialysis. At inclusion eGFR was similar (boys=24.3±8.7; girls=23.4±8.2 ml/min/1.73m2), but the current rate of eGFR loss at the last visit before RRT start was greater in girls than in boys (-0.42±0.48 vs -0.33±0.57 ml/min/1.73m2 per month). A stratified analysis of the time periods before and after tx disclosed an association of PWV increase with eGFR decline prior to RRT in girls (an average eGFR decline of -1 ml/min/1.73m2/month within the period before RRT start was associated with an increase of 0.58 PWV). Further independently associated factors contributing to higher PWV were increasing diastolic BP z-score (DBP), serum calcium, and HDL, whereas RAAS blockers had a protective effect. In the model after tx, the higher PWV in girls after transplantation was explained by the faster eGFR decline in girls prior to tx. Further factors associated with higher PWV were longer time after tx, higher DBP, larger cholesterol increase and higher PWV at last visit prior to RRT. Discussion: Girls with advanced CKD show more pronounced aortic stiffening when compared to boys, leading to a significant sex difference that persists after tx. This difference could explain the higher mortality rate seen in girls with ESRD.

Sex Differences in Salience Network Connectivity and its Relationship to Sensory Over-Responsivity in Youth with Autism Spectrum Disorder.

Individuals with autism spectrum disorder (ASD) are significantly more likely to experience sensory over-responsivity (SOR) compared to neurotypical controls. SOR in autism has been shown to be related to atypical functional connectivity in the salience network (SN), a brain network thought to help direct attention to the most relevant stimuli in one's environment. However, all studies to date which have examined the neurobiological basis of sensory processing in ASD have used primarily male samples so little is known about sex differences in the neural processing of sensory information. This study examined the relationship between SOR and resting-state functional connectivity in the SN for 37 males and 16 females with autism, ages 8-17 years. While there were no sex differences in parent-rated SOR symptoms, there were significant sex differences in how SOR related to SN connectivity. Relative to females with ASD, males with ASD showed a stronger association between SOR and increased connectivity between the salience and primary sensory networks, suggesting increased allocation to sensory information. Conversely, for females with ASD, SOR was more strongly related to increased connectivity between the SN and prefrontal cortex. Results suggest that the underlying mechanisms of SOR in ASD are sex specific, providing insight into the differences seen in the diagnosis rate and symptom profiles of males and females with ASD. LAY SUMMARY: Sensory over-responsivity (SOR) is common in autism. Most research on the neural basis of SOR has focused on males, so little is known about SOR or its neurobiology in females with autism spectrum disorder. Here despite no sex differences in SOR symptoms, we found sex differences in how SOR related to intrinsic connectivity in a salience detection network. Results show sex differences in the neural mechanisms underlying SOR and inform sex differences seen in diagnosis rates and symptom profiles in autism. Autism Res 2020, 13: 1489-1500. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.

Sex differences in the acceptability and short‐term outcomes of a web‐based personalized feedback alcohol intervention for high school seniors

Despite the escalation of alcohol use through high school, the majority of research on school-based alcohol interventions has been conducted with junior high students or first and second year high school students. Preliminary research indicates a brief, web-based personalized feedback intervention developed for college students (eCHECKUP TO GO) may be a promising program for high school seniors. Although these studies demonstrate positive intervention effects, there is some evidence for greater program efficacy for females in this age group. The current study investigates sex differences in program acceptability of the eCHECKUP TO GO and its relationship to short-term alcohol outcomes among high school seniors (N = 135). Overall, the majority of students reported they found the program to be acceptable (i.e., user-friendly and useful). However, contrary to our hypothesis, results indicated that male students reported significantly higher perceptions of program acceptability than females. Although, we did not find sex differences in alcohol outcomes, program user-friendliness was related to reductions in alcohol use for males. Results of this study add to the literature supporting the eCHECKUP TO GO for high school seniors and highlight the importance of program user-friendliness for males. Implications for implementing the program as a school-based intervention are discussed.

Anxiety-like behaviour is regulated independently from sex, mating status and the sex peptide receptor in Drosophila melanogaster

Sex differences in anxiety-related behaviours have been documented in many animals and are notable in human populations. A major goal in behaviour research is to understand why and how sex differences in cognitive-emotional states like anxiety arise and are regulated throughout life. Anxiety allows individuals to detect and respond to threats. Mating is a candidate regulator for anxiety because threats are likely to change, often in sex-specific ways, when individuals shift to a postmating reproductive state. However, we know little about how mating mediates anxiety-related behaviour in males and females, or about how males might influence female anxiety via seminal proteins transferred during mating. To address this gap, we examined anxiety-related behaviour in the fruit fly Drosophila melanogaster , an emerging model animal for anxiety, with respect to sex, mating and sex peptide, a seminal protein known to modulate a host of female postmating responses in fruit flies. We assayed anxiety-like behaviour using the open-field assay to assess individual avoidance of the interior of an arena (‘wall-following’ behaviour). We found sex differences in activity level, but no evidence for sex differences in wall-following behaviour. We found no effects of mating in either sex, or of the presence of the sex peptide receptor in females, on wall following. Our results suggest that anxiety is not one of the cognitive-emotional states regulated by mating and sex peptide in fruit flies, and that researchers need an alternative model for sex differences in anxiety. • Many animals display anxiety, but few studies have compared males and females. • In fruit flies, we found no sex differences in anxiety-like behaviour. • Mating could modulate anxiety, directly or via male ejaculate proteins. • We found that anxiety was independent from mating and the sex peptide protein. • Anxiety is not part of the postmating behavioural shift in fruit flies.

Gender-Affirming Hormone Therapy Modifies the CpG Methylation Pattern of the ESR1 Gene Promoter After Six Months of Treatment in Transmen

BackgroundBrain sexual differentiation is a process that results from the effects of sex steroids on the developing brain. Evidence shows that epigenetics plays a main role in the formation of enduring brain sex differences and that the estrogen receptor α (ESR1) is one of the implicated genes. AimTo analyze whether the methylation of region III (RIII) of the ESR1 promoter is involved in the biological basis of gender dysphoria. MethodsWe carried out a prospective study of the CpG methylation profile of RIII (−1,188 to −790 bp) of the ESR1 promoter using bisulfite genomic sequencing in a cisgender population (10 men and 10 women) and in a transgender population (10 trans men and 10 trans women), before and after 6 months of gender-affirming hormone treatment. Cisgender and transgender populations were matched by geographical origin, age, and sex. DNAs were treated with bisulfite, amplified, cloned, and sequenced. At least 10 clones per individual from independent polymerase chain reactions were sequenced. The analysis of 671 bisulfite sequences was carried out with the QUMA (QUantification tool for Methylation Analysis) program. OutcomesThe main outcome of this study was RIII analysis using bisulfite genomic sequencing. ResultsWe found sex differences in RIII methylation profiles in cisgender and transgender populations. Cismen showed a higher methylation degree than ciswomen at CpG sites 297, 306, 509, and at the total fragment (P ≤ .003, P ≤ .026, P ≤ .001, P ≤ .006). Transmen showed a lower methylation level than trans women at sites 306, 372, and at the total fragment (P ≤ .0001, P ≤ .018, P ≤ .0107). Before the hormone treatment, transmen showed the lowest methylation level with respect to cisgender and transgender populations, whereas transwomen reached an intermediate methylation level between both the cisgender groups. After the hormone treatment, transmen showed a statistically significant methylation increase, whereas transwomen showed a non-significant methylation decrease. After the hormone treatment, the RIII methylation differences between transmen and transwomen disappeared, and both transgender groups reached an intermediate methylation level between both the cisgender groups. Clinical ImplicationsClinical implications in the hormonal treatment of trans people. Strengths & LimitationsIncreasing the number of regions analyzed in the ESR1 promoter and increasing the number of tissues analyzed would provide a better understanding of the variation in the methylation pattern. ConclusionsOur data showed sex differences in RIII methylation patterns in cisgender and transgender populations before the hormone treatment. Furthermore, before the hormone treatment, transwomen and transmen showed a characteristic methylation profile, different from both the cisgender groups. But the hormonal treatment modified RIII methylation in trans populations, which are now more similar to their gender. Therefore, our results suggest that the methylation of RIII could be involved in gender dysphoria.Fernández R, Ramírez K, Gómez-Gil E, et al. Gender-Affirming Hormone Therapy Modifies the CpG Methylation Pattern of the ESR1 Gene Promoter After Six Months of Treatment in Transmen. J Sex Med 2020;17:1795–1806.

"You Do It without Their Knowledge." Assessing Knowledge and Perception of Stealthing among College Students.

In recent years, the act of nonconsensual condom removal, termed stealthing, has become commonly discussed on social and print media; yet, little to no evidence exists on the current knowledge and perception of stealthing among young adults. As such, we assessed what college students know and feel regarding stealthing. We employed an exploratory mixed-method analysis where focus groups were followed by a quantitative survey. A qualitative assessment was conducted using grounded theory analyses and questions for a quantitative survey were developed based on emergent themes from focus groups. Quantitative data was analyzed using descriptive and bivariate analyses with alpha less than 0.05 to denote significance. Though limited knowledge exists, participants felt that stealthing was a violation of their privacy, trust, sexual consent, and their ability to make a health decision, and should be considered an assault. Participants noted stealthing may have become acceptable due to its popularity in social media and young adult culture, especially porn. We also found sex differences in the perception of stealthing being considered a sexual assault with lower rates among males as compared to females. Our results demonstrate that there is a need for health educators to assess the prevalence of such a behavior among college students and policy makers to assess the legal implications of nonconsensual condom removal.