In the pursuit of mental and physical health, effective pain management stands as a cornerstone. Here, we examine a potential sex bias in pain management. Leveraging insights from psychological research showing that females\' pain is stereotypically judged as less intense than males\' pain, we hypothesize that there may be tangible differences in pain management decisions based on patients\' sex. Our investigation spans emergency department (ED) datasets from two countries, including discharge notes of patients arriving with pain complaints (N = 21,851). Across these datasets, a consistent sex disparity emerges. Female patients are less likely to be prescribed pain-relief medications compared to males, and this disparity persists even after adjusting for patients\' reported pain scores and numerous patient, physician, and ED variables. This disparity extends across medical practitioners, with both male and female physicians prescribing less pain-relief medications to females than to males. Additional analyses reveal that female patients\' pain scores are 10% less likely to be recorded by nurses, and female patients spend an additional 30 min in the ED compared to male patients. A controlled experiment employing clinical vignettes reinforces our hypothesis, showing that nurses (N = 109) judge pain of female patients to be less intense than that of males. We argue that the findings reflect an undertreatment of female patients\' pain. We discuss the troubling societal and medical implications of females\' pain being overlooked and call for policy interventions to ensure equal pain treatment.

In organisms with the XY sex-determination system, there is an imbalance in the inheritance and transmission of the X chromosome between males and females. Unlike an autosomal allele, an X-linked recessive allele in a female will have phenotypic effects on its male counterpart. Thus, genes located on the X chromosome are of particular interest to researchers in molecular evolution and genetics. Here we present a model for selection with two alleles of X-linkage to understand fitness components associated with genes on the X chromosome. We apply this model to the fitness analysis of an X-linked gene, OdsH (16D), in the fruit fly Drosophila melanogaster. The function of OdsH is involved in sperm production and the gene is rapidly evolving under positive selection. Using site-directed gene targeting, we generated functional and defective OdsH variants tagged with the eye-color marker gene white. We compare the allele frequency changes of the two OdsH variants, each directly competing against a wild-type OdsH allele in concurrent but separate experimental populations. After twenty generations, the two genetically modified OdsH variants displayed a 40% difference in allele frequencies, with the functional OdsH variant demonstrating an advantage over the defective variant. Using maximum likelihood estimation (MLE), we determined the fitness components associated with the OdsH alleles in males and females. Our analysis revealed functional aspects of the fitness determinants associated with OdsH, and that sex-specific fertility and viability consequences both contribute to selection on an X-linked gene.

Jumonji C domain-containing (JMJD) proteins are found in bacteria, fungi, animals, and plants. They belong to the 2-oxoglutarate-dependent oxygenase superfamily and are endowed with various enzymatic activities, including demethylation of histones and hydroxylation of non-histone proteins. Many JMJD proteins are involved in the epigenetic control of gene expression, yet they also modulate a myriad other cellular processes. In this review we focus on the 33 human JMJD proteins and their established and controversial catalytic properties, survey their epigenetic and non-epigenetic functions, emphasize their contribution to sex-specific disease differences, and highlight how they sense metabolic changes. All this underlines not only their key roles in development and homeostasis, but also that JMJD proteins are destined to become drug targets in multiple diseases.

Compared with lowlander migrants, native Tibetans have a higher reproductive success at high altitude though the underlying mechanism remains unclear. Here, we compared the transcriptome and histology of full-term placentas between native Tibetans and Han migrants. We found that the placental trophoblast shows the largest expression divergence between Tibetans and Han, and Tibetans show decreased immune response and endoplasmic reticulum stress. Remarkably, we detected a sex-biased expression divergence, where the male-infant placentas show a greater between-population difference than the female-infant placentas. The umbilical cord plays a key role in the sex-biased expression divergence, which is associated with the higher birth weight of the male newborns of Tibetans. We also identified adaptive histological changes in the male-infant placentas of Tibetans, including larger umbilical artery wall and umbilical artery intima and media, and fewer syncytial knots. These findings provide valuable insights into the sex-biased adaptation of human populations, with significant implications for medical and genetic studies of human reproduction.

Rheumatoid arthritis (RA) is considered a multifactorial condition where interaction between the genetic and environmental factors lead to immune dysregulation causing autoreactivity. While among the various genetic factors, HLA-DR4 and DQ8, have been reported to be the strongest risk factors, the role of various environmental factors has been unclear. Though events initiating autoreactivity remain unknown, a mucosal origin of RA has gained attention based on the recent observations with the gut dysbiosis in patients. However, causality of gut dysbiosis has been difficult to prove in humans. Mouse models, especially mice expressing RA-susceptible and -resistant HLA class II genes have helped unravel the complex interactions between genetic factors and gut microbiome. This review describes the interactions between HLA genes and gut dysbiosis in sex-biased preclinical autoreactivity and discusses the potential use of endogenous commensals as indicators of treatment efficacy as well as therapeutic tool to suppress pro-inflammatory response in rheumatoid arthritis.

Purpose: To quantify the Medicare reimbursement disparity between female and male vitreoretinal surgeons. Methods: Reimbursement reports were obtained from the US Center for Medicare and Medicaid Services from 2013 through 2020, which detail all Medicare Part B services. A vitreoretinal surgeon was defined as any provider with at least 10 charges of a Healthcare Common Procedure Coding System code related to vitrectomy or retinal detachment repair. Providers were grouped by sex, and the average total reimbursement rate and additional secondary statistics to quantify the reimbursement disparity were identified. Results: On average, female vitreoretinal surgeons were reimbursed 65% that of their male counterparts in 2020, $1.66 million to $2.56 million. The percentage of the average male vitreoretinal specialist\'s total reimbursement that the average female vitreoretinal specialist received decreased 8.8% from 2013 to 2020, from 73.8% to 65.0%. Conclusions: The reimbursement that the average female vitreoretinal surgeon receives from Medicare is only two thirds that of the average male vitreoretinal surgeon. In addition, there was no identifiable improvement in this disparity over the study period. Further efforts must be taken to establish concerted efforts to improve the reimbursement disparity and to identify the systematic inequities that led to its presence in the first place.

Commensal microbes have the capacity to affect development and severity of autoimmune diseases. Germ-free (GF) animals have proven to be a fine tool to obtain definitive answers to the queries about the microbial role in these diseases. Moreover, GF and gnotobiotic animals can be used to dissect the complex symptoms and determine which are regulated (enhanced or attenuated) by microbes. These include disease manifestations that are sex biased. Here, we review comparative analyses conducted between GF and Specific-Pathogen Free (SPF) mouse models of autoimmunity. We present data from the B6;NZM-Sle1NZM2410/AegSle2NZM2410/AegSle3NZM2410/Aeg-/LmoJ (B6.NZM) mouse model of systemic lupus erythematosus (SLE) characterized by multiple measurable features. We compared the severity and sex bias of SPF, GF, and ex-GF mice and found variability in the severity and sex bias of some manifestations. Colonization of GF mice with the microbiotas taken from B6.NZM mice housed in two independent institutions variably affected severity and sexual dimorphism of different parameters. Thus, microbes regulate both the severity and sexual dimorphism of select SLE traits. The sensitivity of particular trait to microbial influence can be used to further dissect the mechanisms driving the disease. Our results demonstrate the complexity of the problem and open avenues for further investigations.

Biological sex is an important variable that influences the immune system\'s susceptibility to infectious and non-infectious diseases and their outcomes. Sex dimorphic features in innate and adaptive immune cells and their activities may help to explain sex differences in immune responses. T lymphocytes in the adaptive immune system are essential to providing protection against infectious and chronic inflammatory diseases. In this review, T cell responses are discussed with focus on the current knowledge of biological sex differences in CD8+ T cell mediated adaptive immune responses in infectious and chronic inflammatory diseases. Future directions aimed at investigating the molecular and cellular mechanisms underlying sex differences in diverse T cell responses will continue to underscore the significance of understanding sex differences in protective immunity at the cellular level, to induce appropriate T cell-based immune responses in infection, autoimmunity, and cancer. This article is categorized under: Immune System Diseases > Molecular and Cellular Physiology Infectious Diseases > Molecular and Cellular Physiology.

OBJECTIVE: Biological factors and mechanisms that drive higher prevalence of insomnia in females are poorly understood. This study focused on the neurological consequences of X-chromosome functional imbalances between sexes.
METHODS: Benefited from publicly available large-scale genetic, transcriptional and epigenomic data, we curated and contrasted different gene lists: (1) X-liked genes, including assignments for X-chromosome inactivation patterns and disease associations; (2) sleep-associated genes; (3) gene expression markers for the suprachiasmatic nucleus.
RESULTS: We show that X-linked markers for the suprachiasmatic nucleus are significantly enriched for clinically relevant genes in the context of rare genetic syndromes and brain waves modulation.
CONCLUSIONS: Considering female-specific patterns on brain transcriptional programs becomes essential when designing health care strategies for mental and sleep illnesses with sex bias in prevalence.

UNASSIGNED: Prior work has demonstrated that women have been historically underrepresented across various research fields, including neuropsychology. Given these disparities, the goal of this study was to systematically evaluate the inclusion of women as participants in neuropsychology research. The current study builds upon previous research by examining articles from eight peer-reviewed neuropsychology journals published in 2019.
UNASSIGNED: Empirical articles examining human samples were included in the current review if they were available in English. Eligible articles were examined to glean whether the main topic of the article was related to a gender issue, how gender was categorized, the gender distribution of the sample, whether gender was considered in analyses, whether gender was addressed in the discussion, and what age categories the study examined.
UNASSIGNED: There was a relatively even distribution of men (51.76%) and women (48.24%) in neuropsychological research studies reviewed. There were twice as many studies that included only men compared to only women (16 vs. 8 studies), and nearly twice as many studies consisted of ≥ 75% men (16.6%) compared to ≥75% of women (8.5%). Gender-focused research was limited (3%). Furthermore, gender was frequently disregarded in analyses (58%) and often not addressed in the discussion (75%).
UNASSIGNED: The current study highlights the limitations within neuropsychology related to the representation of women in research. Although it is encouraging that neuropsychological research is generally inclusive of women participants, future research should aim to more comprehensively investigate how gender may influence cognitive risk and resilience factors across different clinical presentations. Recommendations to begin addressing this challenge and to move toward more gender-equitable research are provided.