Epigenomic landscape of the human dorsal root ganglion: sex differences and transcriptional regulation of nociceptive genes.

Gene expression is influenced by chromatin architecture via controlled access of regulatory factors to DNA. To better understand regulation of gene expression in the human dorsal root ganglion (hDRG) we used bulk and spatial transposase-accessible chromatin technology followed by sequencing (ATAC-seq). We detected a total of 3005 differentially accessible chromatin regions (DARs) between sexes using bulk ATAC-seq. DARs in female hDRG mapped mainly to the X chromosome. In males, DARs were found in autosomal genes. We also found differential transcription factor binding motifs within DARs. EGR1/3 and SP1/4 were abundant in females, and JUN, FOS and other AP-1 family members in males. With the aim of dissecting the open chromatin profile in hDRG neurons, we used spatial ATAC-seq. Consistent with our bulk ATAC-seq data, most of the DARs in female hDRG were located in X chromosome genes. Neuron cluster showed higher chromatin accessibility in GABAergic, glutamatergic, and interferon-related genes in females, and in Ca2+-signaling-related genes in males. Sex differences in open chromatin transcription factor binding sites in neuron-proximal barcodes were consistent with the bulk data, having EGR1 transcription factor activity in females and AP-1 family members in males. Accordingly, we showed higher expression of EGR1 in female hDRG compared to male with in-situ hybridization. Our findings point to epigenomic sex differences in the hDRG that likely underlie divergent transcriptional responses that determine mechanistic sex differences in pain.

Do emergency medical dispatchers choose the same response to serious injury in men and women - a qualitative study.

BACKGROUND: Recent research has indicated that sex is an important determinant of emergency medical response in patients with possible serious injuries. Men were found to receive more advanced prehospital treatment and more helicopter transportation and trauma centre destinations and were more often received by an activated trauma team, even when adjusted for injury mechanism. Emergency medical dispatchers choose initial resources when serious injury is suspected after a call to the emergency medical communication centre. This study aimed to assess how dispatchers evaluate primary responses in trauma victims, with a special focus on the sex of the victim. METHODS: Emergency medical dispatchers were interviewed using focus groups and a semistructured interview guide developed specifically for this study. Two vignettes describing typical and realistic injury scenarios were discussed. Verbatim transcripts of the conversations were analysed via systematic text condensation. The findings were reported in accordance with the Consolidated Criteria for Reporting Qualitative Studies (COREQ) checklist. RESULTS: The analysis resulted in the main category "Tailoring the right response to the patient", supported by three categories "Get an overview of location and scene safety", "Patient condition" and "Injury mechanism and special concerns". The informants consistently maintained that sex was not a relevant variable when deciding emergency medical response during dispatch and claimed that they rarely knew the sex of the patient before a response was implemented. Some of the participants also raised the question of whether the Norwegian trauma criteria reliably detect serious injury in women. CONCLUSIONS: The results indicate that the emergency medical response is largely based on the national trauma criteria and that sex is of little or no importance during dispatch. The observed sex differences in the emergency medical response seems to be caused by other factors during the emergency medical response phase.

Isolating a culture of son preference among Armenian, Georgian and Azeri Parents in Soviet-era Russia.

A basic hypothesis is that cultural evolutionary processes sustain differences between groups, these differences have evolutionary relevance and they would not otherwise occur in a system without cultural transmission. The empirical challenge is that groups vary for many reasons, and isolating the causal effects of culture often requires appropriate data and a quasi-experimental approach to analysis. We address this challenge with historical data from the final Soviet census of 1989, and our analysis is an example of the epidemiological approach to identifying cultural variation. We find that the fertility decisions of Armenian, Georgian and Azeri parents living in Soviet-era Russia were significantly more son-biased than those of other ethnic groups in Russia. This bias for sons took the form of differential stopping rules; families with sons stopped having children sooner than families without sons. This finding suggests that the increase in sex ratios at birth in the Caucasus, which began in the 1990s, reflects a cultural preference for sons that predates the end of the Soviet Union. This result also supports one of the key hypotheses of gene-culture coevolution, namely that cultural evolutionary processes can support group-level differences in selection pressures that would not otherwise occur in a system without culture.

Recommendations to Improve Services and Supports for Domestically Sex Trafficked Persons Derived from the Insights of Health Care Providers.

Health care providers are highly likely to encounter persons who have been domestically sex trafficked and, therefore, possess valuable insights that could be useful in understanding and improving existing services and supports. In-depth interviews were conducted with 31 health care providers residing and working in Canada's largest province, Ontario. Results were analyzed using Braun and Clarke's analytical framework. Across providers, a key theme was identified: "Facilitators to improve care", which was comprised of two sub-themes, "Address needs in service provision" and "Center unique needs of survivors". From these results, eight wide-ranging recommendations to improve services and supports were developed (eg, Jointly mobilize an intersectoral, collaborative, and coordinated approach to sex trafficking service provision; Employ a survivor-driven approach to designing and delivering sex trafficking services). These recommendations hold the potential to enhance services in Canada and beyond by reducing barriers to access and care, facilitating disclosure, aiding in recovery, and empowering those who have been domestically sex trafficked.

The Health Narratives Research Group (HeNReG): A self-direction process offered to help decrease burnout in public health nurse practitioners.

Founded in accordance with 19th century sex roles and public health concerns, nursing evolved as other-directed, dependent on physician-focused diagnosis, prescription decisions, and public health advancements. The result of this other direction is that public health nurse practitioners have endured significant workplace stress resulting in burnout, especially during COVID-19. To help decrease their burnout, nurses require development of self-direction. The Health Narratives Research Group (HeNReG) has the potential to reduce burnout in nurse practitioners by encouraging the development of self-direction. The HeNReG process is presented through historically analyzed documents regarding reducing burnout in health researchers by developing self-direction including: (1) three years of archived year-end feedback results provided by participants, (2) archived participant responses to specific HeNReG-related writing prompts, and (3) a comparison of HeNReG results with the outcomes of resilience programs. The conclusion-the HeNReG offers an effective option for reducing burnout in health researchers that has the potential to decrease nurse practitioner burnout in a way that resilience programs do not. Tailoring the HeNReG process to public health nurses is discussed, inviting future research for reducing burnout in public health nurses.

Sex-specific analysis of hiking accidents in the Austrian Alps: a follow-up from 2015 to 2021.

Background: Hiking is one of the most popular leisure sport activities practiced in the Alps during the summer season, but bears the risk of mountain emergencies, accidents, and fatalities. This paper provides an updated analysis of hiking accidents for the years 2015 to 2021 in the Austrian Alps, thereby outlining fatal and non-fatal accident characteristics. Methods: For this retrospective analysis, mountain hiking accidents documented by the Austrian Alpine Police during a 7-year period were screened for potential exclusion criteria. The final sample size consisted of 7368 accidents and 7552 victims. The outcome measures were mainly specified by sex, age, injury degree, injury location, pathophysiological characteristics, and cause of injury. Results: The overall annual number of accidents showed a continuous increase from 428 in 2015 to 544 in 2021. In total, 7.1% of the total victims died during the 7-year period, with male hikers being significantly more affected than female hikers (m: 80.8%, f: 19.2%; p ≤ 0.001). The sex specific distribution for non-fatal hiking accidents was 55.9% in women and 44.1% in men. Male victims showed significantly more frequent cardiovascular events (m: 78.5%, f: 21.5%), multiple injuries (m: 60.2%, f: 39.8%), and wounds/blood loss (m: 57.4%, f: 42.6%) than female victims, whereas women showed more fractures (m: 31.5%, f: 68.5%) than men (p ≤ 0.001). Additionally, men were more likely to injure their abdomen/chest (3.7%), head (14.1%), and multiple body parts (26.5%), whereas women were more likely to injure their ankle or foot (42.3%). Finally, men were more likely to have an accident during the ascent (24.1%), whereas women during the descent (69.0%) (p ≤ 0.001). Conclusion: This paper provides the latest data and a deeper insight into sex-specific characteristics of mountain hiking accidents in the Austrian Alps.

Maximum tolerated dose and toxicity evaluation of orally administered docetaxel granule in mice.

Oral delivery of chemotherapy drugs is the most favorable and preferred route of drug administration. However, because of poor solubility and/or permeability, most chemotherapy drugs are given by intravenous administration. Docetaxel (DTX) is a potent chemotherapy drug that inhibits microtubular depolymerization and is widely used to treat numerous cancers. DTX is highly lipophilic and insoluble in water; thus, 50% polysorbate 80, which may cause hypersensitivity reactions and reduce drug uptake by tumor tissue, is used in the commercial DTX injection to dissolve DTX. Maximum tolerated dose (MTD) and toxicity are important to determine parameters in preclinical studies and to predict human dose in clinical trials. However, MTD and toxicity of oral DTX formulations have not been studied although various oral DTX formulations have been reported. We have previously developed oral DTX granule and demonstrated its ability to inhibit tumor growth. In this study, we aimed to systemically measure MTD and tissue distribution and evaluate the toxicity of oral DTX granule in mice. Oral DTX granule showed sex differences in toxicity and absorption. The MTD of DTX granule was determined at 50 mg/kg for female mice and 25 mg/kg for male mice. However, female mice had higher tissue absorption than male mice. At a very high dose (400 mg/kg), oral DTX granule induced kidney damage but did not influence the liver and the lungs. The study provides the fundamental data for future preclinical studies and clinical application of oral DTX formulations for cancers.

Registering a proposed business reduces police stops of innocent people? Reconsidering the effects of strip clubs on sex crimes found in Ciacci & Sviatschi's study of New York City.

Ciacci & Sviatschi's (2021) 'The Effect of Adult Entertainment Establishments on Sex Crime: Evidence from New York City,' published in The Economic Journal, concluded that opening new adult entertainment businesses reduces sex crimes, with the most compelling finding that '[strip clubs, gentleman's clubs, and escort services] decrease sex crime by 13% per police precinct one week after the opening.' We contend that the study's conclusions speak beyond the data, which cannot support these findings because they do not measure the necessary variables. The study uses the date a business is registered with New York State as a proxy for its opening date, but the actual date of opening comes weeks or months later, after requirements such as inspections, licensure, and community board approval. The study then uses police Stop, Question and Frisk Reports as data about subsequent crimes. As reports created to memorialize forcible police stops based on less than probable cause, 94% of these reports document that the police had an unfounded belief in criminal activity, and the person stopped was innocent of any crime. In effect, what the study has done is measure changes in police encounters with innocent people in the week after an entity has filed the paperwork that will eventually allow it to open as a business. The study lacks construct validity, cannot reject the null hypothesis of its most important finding, and its methods fall short of the rigor necessary to permit replication.

Population dynamics and seasonal migration patterns of Spodoptera exigua in northern China based on 11 years of monitoring data.

Background: The beet armyworm, Spodoptera exigua (Hübner), is an important agricultural pest worldwide that has caused serious economic losses in the main crop-producing areas of China. To effectively monitor and control this pest, it is crucial to investigate its population dynamics and seasonal migration patterns in northern China. Methods: In this study, we monitored the population dynamics of S. exigua using sex pheromone traps in Shenyang, Liaoning Province from 2012 to 2022, combining these data with amigration trajectory simulation approach and synoptic weather analysis. Results: There were significant interannual and seasonal variations in the capture number of S. exigua, and the total number of S. exigua exceeded 2,000 individuals in 2018 and 2020. The highest and lowest numbers of S. exigua were trapped in September and May, accounting for 34.65% ± 6.81% and 0.11% ± 0.04% of the annual totals, respectively. The average occurrence period was 140.9 ± 9.34 days during 2012-2022. In addition, the biomass of S. exigua also increased significantly during these years. The simulated seasonal migration trajectories also revealed varying source regions in different months, primarily originated from Northeast China and East China. These unique insights into the migration patterns of S. exigua will contribute to a deeper understanding of its occurrence in northern China and provide a theoretical basis for regional monitoring, early warning, and the development of effective management strategies for long-range migratory pests.

Sex-based outcomes after thoracic endovascular aortic repair: a systematic review and meta-analysis.

OBJECTIVE: As it remains unclear whether there are sex-based differences in clinical outcomes after thoracic endovascular aortic repair (TEVAR), this meta-analysis aimed to evaluate differences in early outcomes and overall survival between female and male patients who underwent TEVAR. METHODS: PubMed, Embase, Web of Science, and Cochrane Central databases were searched for eligible studies published through June 10, 2023, that reported sex-based differences in clinical outcomes after TEVAR. The primary outcome was operative mortality; second outcomes included stroke, spinal cord ischemia (SCI), acute kidney injury (AKI), hospital length of stay (LOS), and overall survival. Patient characteristics, operative data, and early outcomes were aggregated using the random-effects model, presenting pooled risk ratio (RR) or standardized mean difference (SMD) along with their corresponding 95% confidence intervals (CIs). Overall survival was assessed by reconstructing individual patient data to generate sex-specific pooled Kaplan-Meier curves. This study was registered in PROSPERO (CRD42023426069). RESULTS: Out of the 1785 studies retrieved, 14 studies met all eligibility criteria, encompassing a total of 17374 patients, comprising 5026 females and 12348 males. Female patients were older, had a smaller maximum aortic diameter, had lower rates of smoking and coronary artery disease, and had higher rates of anemia. Intraoperatively, females were more likely to use iliac conduits and require blood transfusions. There were no sex-based differences in operative mortality (RR: 1.12, 95% CI: 0.90-1.40; p=0.309), stroke (RR: 1.14, 95% CI: 0.95-1.38; p=0.165), SCI (RR: 1.33, 95% CI: 0.83-2.14; p=0.234), AKI (RR: 0.78, 95% CI: 0.52-1.17; p=0.228), and hospital LOS (SMD: 0.09, 95% CI: -0.03 to 0.20; p=0.141). Pooled Kaplan-Meier estimates showed a worse overall survival in female patients compared with male patients (87.2% vs. 89.8% at 2-year, log-rank p=0.001). CONCLUSIONS: Among patients treated by TEVAR, female sex was not associated with increased risk of operative mortality or major morbidity. However, females exhibited a lower overall survival after TEVAR compared with males.

The effect of age, sex, and eastern cooperative oncology group performance status on the efficacy and safety of immune checkpoint inhibitors in patients with hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND: The effect of age, sex, and eastern cooperative oncology group performance status (ECOG PS) on the efficacy and safety of immune checkpoint inhibitor (ICI) therapy among hepatocellular carcinoma (HCC) patients remains elusive. Thus, a meta-analysis was conducted to evaluate whether such effects exist. RESEARCH DESIGN AND METHODS: Eligible studies in PubMed, Embase, and Cochrane Library databases were retrieved. RESULTS: One-hundred-and-eleven studies involving 14,768 HCC patients were included. The findings indicated that the ECOG PS didn't have a significant effect on the ORR and PFS in ICI-treated HCC patients (higher ECOG PS vs. lower ECOG PS: ORR: OR = 0.78, 95%CI = 0.55-1.10; PFS: HR = 1.15, 95%CI = 0.97-1.35), while those patients with a higher ECOG PS may have a worse OS (HR = 1.52, 95% CI = 1.26-1.84). There is no significant evidence of the effect of age (older vs. younger) or sex (males vs. females) on the efficacy of ICI therapy in HCC. CONCLUSION: ICI therapy in HCC should not be restricted strictly to certain patients in age or sex categories, while HCC patients with higher ECOG PS may require closer medication or follow-up strategy during ICI therapy. PROSPERO REGISTRATION: CRD42024518407.

MicroRNA in cardiometabolic health and disease: The perspectives of sex, gender and personalised medicine.

BACKGROUND: Personalized medicine represents a novel and integrative approach that focuses on an individual's genetics and epigenetics, precision medicine, lifestyle and exposures as key players of health status and disease phenotypes. METHODS: In this narrative review, we aim to carefully discuss the current knowledge on gender disparities in cardiometabolic diseases, and we consider the sex- specific expression of miRNAs and their role as promising tool in precision medicine. RESULTS: Personalised medicine overcomes the restricted care of patient based on a binomial sex approach, by enriching itself with a holistic and dynamic gender integration. Recognized as a major worldwide health emergency, cardiometabolic disorders continue to rise, impacting on health systems and requiring more effective and targeted strategies. Several sex and gender drivers might affect the onset and progression of cardiometabolic disorders in males and females at multiple levels. In this respect, distinct contribution of genetic and epigenetic mechanisms, molecular and physiological pathways, sex hormones, visceral fat and subcutaneous fat and lifestyle lead to differences in disease burden and outcomes in males and females. CONCLUSIONS: Sex and gender play a pivotal role in precision medicine because the influence the physiology of each individual and the way they interact with environment from intrauterine life.

Characterization of 35 novel NR5A1/SF-1 variants identified in individuals with atypical sexual development: The SF1next study.

CONTEXT: Steroidogenic factor 1 (NR5A1/SF-1) is a nuclear receptor that regulates sex development, steroidogenesis and reproduction. Genetic variants in NR5A1/SF-1 are common among differences of sex development (DSD) and associate with a wide range of phenotypes, but their pathogenic mechanisms remain unclear. OBJECTIVE: Novel, likely disease-causing NR5A1/SF-1 variants from the SF1next cohort of individuals with DSD were characterized to elucidate their pathogenic effect. METHODS: Different in silico tools were used to predict the impact of novel NR5A1/SF-1 variants on protein function. An extensive literature review was conducted to compare and select the best functional studies for testing the pathogenic effect of the variants in a classic cell culture model. The missense NR5A1/SF-1 variants were tested on the promoter luciferase reporter vector -152CYP11A1_pGL3 in HEK293T cells and assessed for their cytoplasmic/nuclear localization by Western blot. RESULTS: Thirty-five novel NR5A1/SF-1 variants were identified in the SF1next cohort. Seventeen missense NR5A1/SF-1 variants were functionally tested. Transactivation assays showed reduced activity for 40% of the variants located in the DNA binding domain and variable activity for variants located elsewhere. Translocation assessment revealed three variants (3/17) with affected nuclear translocation. No clear genotype-phenotype, structure-function correlation was found. CONCLUSIONS: Genetic analyses and functional assays do not explain the observed wide phenotype of individuals with these novel NR5A1/SF-1 variants. In nine individuals, additional likely disease-causing variants in other genes were found, strengthening the hypothesis that the broad phenotype of DSD associated with NR5A1/SF-1 variants may be caused by an oligogenic mechanism.

Sex-associated differences in cardiac ageing: Clinical aspects and molecular mechanisms.

Despite the extensive clinical and scientific advances in prevention, diagnostics and treatment, cardiovascular diseases (CVD) remain the leading cause of morbidity and mortality worldwide for people aged 65 and over. Of all ageing-related diseases, CVD are responsible for almost one-third of deaths in the elderly, being above all cancers combined. Age is an independent and unavoidable risk factor contributing to the impairment of heart and blood vessels. As the average age of the population in industrialized countries has doubled in the last century, and almost a fifth of the world's population is predicted to be over 65 in the next decade, we can assume that the burden of CVD will fall primarily on the elderly. Evidence from basic and clinical science has shown that sex significantly influences the onset and severity of CVD. In women, CVD usually develop later than in men and with atypical symptomatology. After menopause, however, the incidence and severity of CVD increase in women, reaching equality in both sexes. Although intrinsic sexual dimorphism in cardiovascular ageing may contribute to the sex differences in CVD progression, the molecular mechanisms associated with cardiovascular ageing and their clinical value are not known in detail. In this review, we discuss the scientific knowledge available, focusing on structural, hormonal, genetic/epigenetic and inflammatory pathways, seeking to transfer these findings to the cardiovascular clinic in terms of prevention, diagnosis, prognosis and management of these pathologies and proposing possible validation of target specifics.

Evidence for 3-hydroxyhexan-2-one as a shared pheromone component for 12 South American species of cerambycid beetles.

3-Hydroxyhexan-2-one (3-C6-ketol) has emerged as the most conserved pheromone structure within the beetle family Cerambycidae. In this study, we report the sex-specific production of this compound by males of 12 species of South American cerambycid beetles. Males of Chrysoprasis chalybea Redtenbacher and Mallosoma zonatum (Sahlberg) (Tribe Dichophyiini), and Ambonus lippus (Germar), Eurysthea hirta (Kirby), Pantonyssus nigriceps Bates, Stizocera plicicollis (Germar), and Stizocera tristis (Guérin-Méneville) (Elaphidiini) produced 3R-C6-ketol as a single component, whereas males of Neoclytus pusillus (Laporte & Gory) (Clytini), Aglaoschema concolor (Gounelle), Orthostoma abdominale (Gyllenhal) (Compsocerini), Dorcacerus barbatus (Olivier), and Retrachydes thoracicus thoracicus (Olivier) (Trachyderini) produced 3R-C6-ketol, along with lesser amounts of other compounds. In field trials testing 8 known cerambycid pheromone compounds, C. chalybea, E. hirta, and R. t. thoracicus were attracted in significant numbers to traps baited with 3-C6-ketol. A second field experiment provided support for the strategy of using the attraction of cerambycid species to test lures as a method of providing leads to their likely pheromone components. Because both sexes are attracted to these aggregation-sex pheromones, live beetles can be obtained from baited traps to verify they produce the compound(s) to which they were attracted, that is, that the compounds are indeed pheromone components.

Comparison of the effect of tea shoots during different seasons in Arma chinensis (Hemiptera: Pentatomidae) reared on Ectropis grisescens (Lepidoptera: Geometridae) pupae.

In this study, we compared the growth, development, and fecundity of Arma chinensis (Fallou) reared on pupae of the geometrid Ectropis grisescens Warren fed on tea shoots during different seasons of the year. The raw data on life history were analyzed using the age-stage, 2-sex life table. When reared on spring or winter geometrid pupae, the duration of the immature stage of A. chinensis was significantly longer than in those produced during the summer or autumn. The survival rate of immature A. chinensis reared on autumn geometrid pupae was significantly lower compared to other treatments. Reproductive diapause was observed in adult A. chinensis reared on winter geometrid pupae. The adult preoviposition period (APOP), total preoviposition period (TPOP), and total longevity were significantly longer in A. chinensis reared on winter pupae than in the other treatments. The fecundity of A. chinensis reared on spring geometrid pupae was significantly lower than in the other treatments. The higher intrinsic rate of increase of the A. chinensis reared on summer pupae (r = 0.0966 day-1) and autumn pupae (r = 0.0983 day-1) resulted in higher fecundity, shorter immature duration, and shorter TPOP compared to the winter and spring populations. These findings can be utilized to enhance and sustain biological control of E. grisescens in tea plantations.

Recruitment of hippocampal and thalamic pathways to the central amygdala in the control of feeding behavior under novelty.

It is adaptive to restrict eating under uncertainty, such as during habituation to novel foods and unfamiliar environments. However, sustained restrictive eating can become maladaptive. Currently, the neural substrates of restrictive eating are poorly understood. Using a model of feeding avoidance under novelty, our recent study identified forebrain activation patterns and found evidence that the central nucleus of the amygdala (CEA) is a core integrating node. The current study analyzed the activity of CEA inputs in male and female rats to determine if specific pathways are recruited during feeding under novelty. Recruitment of direct inputs from the paraventricular nucleus of the thalamus (PVT), the infralimbic cortex (ILA), the agranular insular cortex (AI), the hippocampal ventral field CA1, and the bed nucleus of the stria terminals (BST) was assessed with combined retrograde tract tracing and Fos induction analysis. The study found that during consumption of a novel food in a novel environment, larger number of neurons within the PVTp and the CA1 that send monosynaptic inputs to the CEA were recruited compared to controls that consumed familiar food in a familiar environment. The ILA, AI, and BST inputs to the CEA were similarly recruited across conditions. There were no sex differences in activation of any of the pathways analyzed. These results suggest that the PVTp-CEA and CA1-CEA pathways underlie feeding inhibition during novelty and could be potential sites of malfunction in excessive food avoidance.

The estrogen signaling pathway reprograms prostate cancer cell metabolism and supports proliferation and disease progression.

Just as the androgen receptor (AR), the estrogen receptor α (ERα) is expressed in the prostate and is thought to influence prostate cancer (PCa) biology. Yet, the incomplete understanding of ERα functions in PCa hinders our ability to fully comprehend its clinical relevance and restricts the repurposing of estrogen-targeted therapies for the treatment of this disease. Using two human PCa tissue microarray cohorts, we first demonstrated that nuclear ERα expression was heterogeneous among patients, being only detected in half of tumors. Positive nuclear ERα levels were correlated with disease recurrence, progression to metastatic PCa, and patient survival. Using in vitro and in vivo models of the normal prostate and PCa, bulk and single-cell RNA-Seq analyses revealed that estrogens partially mimic the androgen transcriptional response and induce specific biological pathways linked to proliferation and metabolism. Bioenergetic flux assays and metabolomics confirmed the regulation of cancer metabolism by estrogens, supporting proliferation. Using cancer cell lines and patient-derived organoids, selective estrogen receptor modulators, a pure anti-estrogen, and genetic approaches impaired cancer cell proliferation and growth in an ERα-dependent manner. Overall, our study revealed that, when expressed, ERα functionally reprograms PCa metabolism, is associated with disease progression, and could be targeted for therapeutic purposes.

Acute stress differentially alters reward-related decision making and inhibitory control under threat of punishment.

Acute stress has various effects on cognition, executive function and certain forms of cost/benefit decision making. Recent studies in rodents indicate that acute stress differentially alters reward-related decisions involving particular types of costs and slows choice latencies. Yet, how stress alters decisions where rewards are linked to punishment is less clear. We examined how 1 h restraint stress, followed by behavioral testing 10 min later altered action-selection on two tasks involving reward-seeking under threat of punishment in well-trained male and female rats. One study used a risky decision-making task involving choice between a small/safe reward and a large/risky one that could coincide with shock, delivered with a probability that increased over blocks of trials. Stress increased risk aversion and punishment sensitivity, reducing preference for the larger/risky reward, while increasing decision latencies and trial omissions in both sexes, when rats were teste. A second study used a "behavioral control" task, requiring inhibition of approach towards a readily available reward associated with punishment. Here, food pellets were delivered over discrete trials, half of which coincided with a 12 s audiovisual cue, signalling that reward retrieval prior to cue termination would deliver shock. Stress exerted sex- and timing-dependent effects on inhibitory control. Males became more impulsive and received more shocks on the stress test, whereas females were unaffected on the stress test, and were actually less impulsive when tested 24 h later. None of the effects of restraint stress were recapitulated by systemic treatment with physiological doses of corticosterone. These findings suggest acute stress induces qualitatively distinct and sometimes sex-dependent effects on punished reward-seeking that are critically dependent on whether animals must either choose between different actions or withhold them to obtain rewards and avoid punishment.

Discriminatory experiences among gay, bisexual, and other men who have sex with men, and transgender and non-binary individuals: a cross sectional analysis.

Background: Several systems of oppression combine in complex ways to impact the lives of minority populations. Following an intersectionality framework, we assessed the frequency and perceived reasons for discrimination among gay, bisexual, and other cisgender men who have sex with men (MSM) and transgender and non-binary individuals (TGNB), stratified by race. Methods: Online survey among MSM and TGNB ≥18 years living in Brazil, between November/2021 and January/2022. We used the 18-item Explicit Discrimination Scale to assess day-to-day experiences of differential treatment, and perceived discrimination. For each item, participants indicated their perceived reasons for differential treatment using 14 pre-defined options. Negative binomial regression models assessed if race was a significant predictor of discrimination. Subsequent models, stratified by race, examined associations of perceived reasons and number of reasons with perceived discrimination. Findings: Of 8464 MSM and TGNB, 4961 (58.6%) were White, 2173 (25.7%) Pardo (Brazil's official term for admixed populations), and 1024 (12.1%) Black. Black participants' scores for perceived discrimination (mean, standard deviation) were higher (10.2, 8.8) [Pardo (6.5, 6.8), White (5.2, 5.7)], and race was both the main reason for and the strongest predictor of perceived discrimination. The number of reasons participants used to interpret their discriminatory experiences was also a predictor of discrimination score among White, Pardo, and Black participants. Interpretation: LGBTQIA+phobia was highly prevalent among all participants. Additionally, our results indicated that Black MSM and TGNB participants were more frequently discriminated against than other racial groups, with racial discrimination uniquely contributing these experiences. Funding: Fundação Oswaldo Cruz, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro.