Assessing the causal relationship between frailty and sex hormone-binding globulin or insulin-like growth factor-1 levels: A sex-stratified bidirectional Mendelian Randomization study.

BACKGROUND: The association between frailty and sex hormone-binding globulin (SHBG) or insulin-like growth factor-1(IGF-1) levels demonstrates sex differences with inconsistent conclusions. This study aims to explore the causal relationship between frailty and SHBG or IGF-1 levels through bidirectional Mendelian randomization (MR). METHODS: We conducted two-sample bidirectional sex-stratified MR analyses using summary-level data from genome-wide association studies (GWASs) to examine the causal relationship between frailty and IGF-1 or SHBG levels, as measured by frailty index (FI) and frailty phenotype (FP). We use the random-effects inverse-variance weighted (IVW), weighted median, MR-Egger, MR-Egger intercept, and leave-one-out approaches. RESULT: The relationship between frailty and SHBG or IGF-1 levels is inversely related, with a significant decrease in SHBG levels in females. Specifically, SHBG levels significantly decrease with FI (ß = -5.49; 95 % CI: -9.67 to -1.32; FDR = 0.02) and more pronounced with FP (ß = -10.14; 95 % CI: -16.16 to -4.13; FDR = 0.01), as determined by the IVW approach. However, reverse analysis shows no significant effect of IGF-1 or SHBG levels on either FI or FP (p > 0.05). CONCLUSION: Our study indicates a negative correlation between frailty and the levels of SHBG and IGF-1. It is suggested that further research is required to establish cut-off values for SHBG and IGF-1 levels in the frailty population. This is particularly important for females at higher risk, such as those undergoing menopause, to enable comprehensive assessment and early prevention efforts. While the findings imply that reduced IGF-1 and SHBG levels may not directly contribute to frailty, it is important not to overlook the underlying mechanisms through which they may indirectly influence frailty.

ASPG and DAD1 are potential placental-derived biomarkers for ASD-like symptom severity levels in male/female offspring.

INTRODUCTION: An early evaluating system for autism spectrum disorder (ASD) severity is crucial. Questionnaire survey is challenging for accurately assessing the severity levels for ASD in children. METHODS: Offspring with ASD-like phenotypes were induced by treating pregnant mice with Poly (I:C) at GD12.5 and the placentae corresponding to the offspring were obtained by caesarean. The autism severity composite score (ASCS) for offspring was calculated through behavioral tests. HE staining and immunohistochemistry were used to observe the morphology of placenta. Candidate biomarkers were identified by weighted protein co-expression network analysis (WPCNA) combined with machine learning and further validated by ELISA. Sperman's was used to analyze the correlation between biomarkers and metabolome. RESULTS: The placental weight and mean vascular area of male offspring with ASD-like phenotypes were significantly decreased compared with typical mice. According to the WPCNA, four modules were identified and significantly correlated with ASCS of offspring. Two biomarkers (ASPG and DAD1) with high correlation with ASCS in offspring were identified. DISCUSSION: VEGF pathway may contribute to sexual dimorphism in placental morphology within mice with ASD-like phenotypes in term. The placental ASPG and DAD1 levels could reflect ASD-like symptom severity levels in male/female mice offspring.

Differences between males and females in infectious diseases notifications in the EU/EEA, 2012 to 2021.

BackgroundThere are differences between males and females for most diseases both for exposure and course of illness, including outcome. These differences can be related to biological sex or gender i.e. socio-cultural factors that may impact exposure and healthcare access.AimWe aimed to quantify differences between males and females in infectious disease notifications in Europe and identify countries with these differences significantly different from the European Union and European Economic Area (EU/EEA) average.MethodsNotifiable infectious disease surveillance data are reported by EU/EEA countries to ECDC. We retrieved surveillance data for 2012-2021. Using a cut-off median of annual disability-adjusted life years above 1 per 100,000 population, we included 16 infectious diseases. We calculated median male proportion and interquartile range by disease, year, country and age group and used boxplots to identify outliers.ResultsFor campylobacteriosis, acute hepatitis B, Legionnaires' disease, malaria and HIV and AIDS, all countries had male proportion above 50%. Most countries had a male proportion below 50% for pertussis (25/28 countries), STEC infection (21/28 countries) and Chlamydia trachomatis infection (16/24 countries). Chlamydia trachomatis infection and listeriosis showed the greatest dispersion of male proportion across age groups. Most outliers were countries reporting few cases.ConclusionWe observed important differences in male proportion across infectious disease notifications in EU/EEA countries. For some diseases with high male proportions in all countries, such as HIV and hepatitis B, behaviours play a role in disease transmission. Screening offered to specific populations may explain differences across countries for example for C. trachomatis infection.

Sex difference alters the behavioral and cognitive performance in a rat model of schizophrenia induced by sub-chronic ketamine.

Schizophrenia is a complex neuropsychiatric disorder with positive, negative, and cognitive symptoms. In rats, sub-chronic administration of ketamine is used for the induction of schizophrenia model. Increased locomotor activity is one of the most important features of psychotic-like symptoms in rodents. On the other hand, risperidone is a potent antipsychotic medication that is approved for the treatment of schizophrenia and bipolar disorder. In the present research, we aimed to investigate the effect of sub-chronic treatment of ketamine on cognitive and behavioral functions, and brain-derived neurotrophic factor (BDNF) expression level in the prefrontal cortex. Also, we assessed the efficacy of risperidone on cognitive and behavioral impairments induced by ketamine. Possible sex differences were also measured. Ketamine was intraperitoneally injected at the dose of 30 mg/kg for five consecutive days. Risperidone was also intraperitoneally injected at the dose of 2 mg/kg. Novel object recognition memory, pain threshold, locomotor activity, rearing behavior, and BDNF level were evaluated. The results showed that ketamine injection for five consecutive days impaired the acquisition of long-term recognition memory and decreased BDNF level in the prefrontal cortex in both sexes. Also, it decreased pain threshold in females, increased rearing behavior in males, and induced hyperlocomotion with greater effect in females. On the other hand, risperidone restored or attenuated the effect of ketamine on all the behavioral effects and BDNF level. In conclusion, we suggested that there were sex differences in the effects of ketamine on pain perception, locomotion, and rearing behavior in a rat model of schizophrenia.

Systemic administration of Resolvin D1 reduces cancer-induced bone pain in mice: Lack of sex dependency in pain development and analgesia.

AIMS: Bone cancer produces severe pain that is treated with opioids, but serious side effects limit opioid utilization. There is therefore a need to develop effective and safe non-opioid alternatives. The lipid mediator, Resolvin D1 (RvD1), could be a prospective candidate for cancer pain treatment. To assess RvD1 and other potential candidates, appropriate animal models that recapitulate clinical features must be used. Although several preclinical models of cancer pain have been developed, the influence of sex on the development of cancer pain and the effectiveness of RvD1 have not been studied. RESULTS: Using a mouse model of fibrosarcoma growth in and around the calcaneus bone, we demonstrated that the mechanical hyperalgesia in the tumor-bearing hind paw develops independently of sex, except that it developed a little sooner in female mice. A single intravenous injection of RvD1 (0.001-10 µg/kg) decreased hyperalgesia in both sexes with similar potency (ED50 = 0.0015 µg/kg) and efficacy. Repeated daily administration of 10 µg/kg RvD1 prolonged the analgesic effect and completely abolished hyperalgesia. This was also independent of sex. CONCLUSION: In this preclinical mouse model of bone cancer pain, the development of pain and the analgesic effectiveness of RvD1 are not influenced by sex.

Gene regulatory networks reveal sex difference in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) has been observed to have significant sex differences in incidence, prognosis, and response to therapy. However, the molecular mechanisms responsible for these disparities have not been investigated extensively. METHODS: Sample-specific gene regulatory network methods were used to analyze RNA sequencing data from non-cancerous human lung samples from The Genotype Tissue Expression Project (GTEx) and lung adenocarcinoma primary tumor samples from The Cancer Genome Atlas (TCGA); results were validated on independent data. RESULTS: We found that genes associated with key biological pathways including cell proliferation, immune response and drug metabolism are differentially regulated between males and females in both healthy lung tissue and tumor, and that these regulatory differences are further perturbed by tobacco smoking. We also discovered significant sex bias in transcription factor targeting patterns of clinically actionable oncogenes and tumor suppressor genes, including AKT2 and KRAS. Using differentially regulated genes between healthy and tumor samples in conjunction with a drug repurposing tool, we identified several small-molecule drugs that might have sex-biased efficacy as cancer therapeutics and further validated this observation using an independent cell line database. CONCLUSIONS: These findings underscore the importance of including sex as a biological variable and considering gene regulatory processes in developing strategies for disease prevention and management.

Lung adenocarcinoma (LUAD) is a disease that affects males and females differently. Biological sex not only influences chances of developing the disease, but also how the disease progresses and how effective various therapies may be. We analyzed sex-specific gene regulatory networks consisting of transcription factors and the genes they regulate in both healthy lung tissue and in LUAD and identified sex-biased differences. We found that genes associated with cell proliferation, immune response, and drug metabolism are differentially targeted by transcription factors between males and females. We also found that several genes that are drug targets in LUAD, are also regulated differently between males and females. Importantly, these differences are also influenced by an individual's smoking history. Extending our analysis using a drug repurposing tool, we found candidate drugs with evidence that they might work better for one sex or the other. These results demonstrate that considering the differences in gene regulation between males and females will be essential if we are to develop precision medicine strategies for preventing and treating LUAD.

Gender Disparities in the Association Between Educational Attainment and Cardiovascular-Kidney-Metabolic Syndrome: Cross-Sectional Study.

Background: Cardiovascular-kidney-metabolic (CKM) health is affected by social determinants of health, especially education. CKM syndrome has not been evaluated in Chinese population, and the association of education with CKM syndrome in different sexes and its intertwined relation with lifestyles have not been explored. Objective: We aimed to explore the association between educational attainment and the prevalence of CKM syndrome stages in middle-aged and older Chinese men and women as well as the potential role of health behavior based on Life's Essential 8 construct. Methods: This study used data from the nationwide, community-based REACTION (Risk Evaluation of Cancers in Chinese diabetic individuals: a longitudinal study). A total of 132,085 participants with complete information to determine CKM syndrome stage and education level were included. Educational attainment was assessed by the self-reported highest educational level achieved by the participants and recategorized as low (elementary school or no formal education) or high (middle school, high school, technical school/college, or above). CKM syndrome was ascertained and classified into 5 stages according to the American Heart Association presidential advisory released in 2023. Results: Among 132,085 participants (mean age 56.95, SD 9.19 years; n=86,675, 65.62% women) included, most had moderate-risk CKM syndrome (stages 1 and 2), and a lower proportion were at higher risk of CKM (stages 3 and 4). Along the CKM continuum, low education was associated with 34% increased odds of moderate-risk CKM syndrome for women (odds ratio 1.36, 95% CI 1.23-1.49) with a significant sex disparity, but was positively correlated with high-risk CKM for both sexes. The association between low education and high-risk CKM was more evident in women with poor health behavior but not in men, which was also interactive with and partly mediated by behavior. Conclusions: Low education was associated with adverse CKM health for both sexes but was especially detrimental to women. Such sex-specific educational disparity was closely correlated with health behavior but could not be completely attenuated by behavior modification. These findings highlight the disadvantage faced by women in CKM health ascribed to low education, underscoring the need for public health support to address this inequality.

Bidirectional negative relationship between thyrotropin and kidney function during alcohol intoxication in males.

Introduction: Despite a well-established direct toxic effect of alcohol on renal cells, there is a salutary dose-dependent effect of alcohol consumption on common laboratory parameters related to kidney performance. Alcohol also impacts thyroid hormones, while thyroid status modulates kidney function. The modulation of kidney parameters with thyrotropin (TSH) and thyroid status indicates a possible interaction between alcohol, kidney, and thyroid functions. This retrospective study was conducted to test the hypothesis that the positive effect of alcohol use on the estimated glomerular filtration rate (eGFR) is mediated by alcohol's effect on thyroid hormones. Methods: We reviewed the electronic medical records of 767 hospitalized adult patients free of thyroid disorders who received medical care in the Mayo Clinic Health System from June 2019 through June 2022 and had blood alcohol concentration (BAC), serum TSH, and serum creatinine measured during the hospitalization. We calculated the eGFR using both the re-expressed Modification of Diet in Renal Disease (MDRD II) study equation and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine equation. Results: We found a significant relationship of BAC with eGFR (CKD-EPI) and TSH in males only. BAC had a positive association with eGFR (b = 0.24, p = 0.0001) and negative with TSH (b=-0.17, p = 0.006). The covariance between the two outcomes (eGFR and TSH) was negative (b = -0.12, p = 0.049). The path analyses using the eGFR MDRD II equation were not significant in males, whereas females had no significant path analyses with either of the eGFR equations. Discussion: We observed that BAC influences both eGFR and TSH, whereas eGFR and TSH influence each other. After considering important covariates (e.g., age, body mass index, diabetes mellitus, cardiovascular disease, chronic kidney disease, and chronic liver disease) and the negative bidirectional effect of TSH and eGFR, a positive impact of BAC on eGFR was observed in males.

SexAnnoDB, a knowledgebase of sex-specific regulations from multi-omics data of human cancers.

BACKGROUND: Sexual differences across molecular levels profoundly impact cancer biology and outcomes. Patient gender significantly influences drug responses, with divergent reactions between men and women to the same drugs. Despite databases on sex differences in human tissues, understanding regulations of sex disparities in cancer is limited. These resources lack detailed mechanistic studies on sex-biased molecules. METHODS: In this study, we conducted a comprehensive examination of molecular distinctions and regulatory networks across 27 cancer types, delving into sex-biased effects. Our analyses encompassed sex-biased competitive endogenous RNA networks, regulatory networks involving sex-biased RNA binding protein-exon skipping events, sex-biased transcription factor-gene regulatory networks, as well as sex-biased expression quantitative trait loci, sex-biased expression quantitative trait methylation, sex-biased splicing quantitative trait loci, and the identification of sex-biased cancer therapeutic drug target genes. All findings from these analyses are accessible on SexAnnoDB ( https://ccsm.uth.edu/SexAnnoDB/ ). RESULTS: From these analyses, we defined 126 cancer therapeutic target sex-associated genes. Among them, 9 genes showed sex-biased at both the mRNA and protein levels. Specifically, S100A9 was the target of five drugs, of which calcium has been approved by the FDA for the treatment of colon and rectal cancers. Transcription factor (TF)-gene regulatory network analysis suggested that four TFs in the SARC male group targeted S100A9 and upregulated the expression of S100A9 in these patients. Promoter region methylation status was only associated with S100A9 expression in KIRP female patients. Hypermethylation inhibited S100A9 expression and was responsible for the downregulation of S100A9 in these female patients. CONCLUSIONS: Comprehensive network and association analyses indicated that the sex differences at the transcriptome level were partially the result of corresponding sex-biased epigenetic and genetic molecules. Overall, SexAnnoDB offers a discipline-specific search platform that could potentially assist basic experimental researchers or physicians in developing personalized treatment plans.

Sexual variations at the molecular level have a profound impact on cancer biology and outcomes, influencing drug responses that diverge between men and women exposed to the same drugs. Despite existing databases on sex differences in human tissues, our understanding of the regulations governing sex disparities in cancer is limited, lacking detailed mechanistic studies on sex-biased molecules. This study addresses this gap by conducting a comprehensive examination of molecular distinctions and regulatory networks across 27 cancer types, specifically focusing on sex-biased effects. The analyses led to the identification of 126 cancer therapeutic target sex-associated genes and shed light on the intricate relationship between sexual differences and cancer. Furthermore, the findings from these analyses are made accessible through SexAnnoDB, providing a specialized search platform. This platform has the potential to assist basic experimental researchers or physicians in developing personalized treatment plans based on a deeper understanding of sex-specific factors in cancer.

Sex differences in large-scale brain network connectivity for mental rotation performance.

Mental rotation has emerged as an important predictor for success in science, technology, engineering, and math fields. Previous studies have shown that males and females perform mental rotation tasks differently. However, how the brain functions to support this difference remains poorly understood. Recent advancements in neuroimaging techniques have enabled the identification of sex differences in large-scale brain network connectivity. Using a classic mental rotation task with functional magnetic resonance imaging, the present study investigated whether there are any sex differences in large-scale brain network connectivity for mental rotation performance. Our results revealed that, relative to females, males exhibited less cross-network interaction (i.e. lower inter-network connectivity and participation coefficient) of the visual network but more intra-network integration (i.e. higher intra-network connectivity and local efficiency) and cross-network interaction (i.e. higher inter-network connectivity and participation coefficient) of the salience network. Across all participants, mental rotation performance was negatively correlated with cross-network interaction (i.e. participation coefficient) of the visual network, was positively correlated with cross-network interaction (i.e. inter-network connectivity) of the salience network, and was positively correlated with intra-network integration (i.e. local efficiency) of the somato-motor network. Interestingly, the cross-network integration indexes of both the visual and salience networks significantly mediated sex difference in mental rotation performance. The present findings suggest that large-scale brain network connectivity may constitute an essential neural basis for sex difference in mental rotation, and highlight the importance of considering sex as a research variable in investigating the complex network underpinnings of spatial cognition.

Sex-specific modulating role of social support in the associations between oxidative stress, inflammation, and telomere length in older adults.

Telomere length, a biomarker of human aging, is related to adverse health outcomes. Growing evidence indicates that oxidative stress and inflammation contributes to telomere shortening, whereas social support may protect from telomere shortening. Despite sex differences in telomere length and social support, little is known about whether there are sex differences in the relationship between oxidative stress/inflammation and telomere length, and sex-specific moderating roles of social support in older adults. Using data from the National Health and Nutrition Examination Survey (NHANES) 1999-2002, this study assessed whether the associations between oxidative stress/inflammation and telomere length vary with sex and explored social support as a moderator in these associations among 2289 older adults. Oxidative stress was measured based on serum Gamma-glutamyl transferase (GGT), and inflammation was measured based on C-reactive protein (CRP). After adjusting for the covariates, GGT was significantly associated with telomere length in females only (ß = - 0.037, 95% CI = - 0.070, - 0.005), while CRP was associated with telomere length in males only (ß = - 0.019, 95% CI = - 0.035, - 0.002). Moreover, high social support mitigated the negative association between GGT and telomere length, which was more evident in females. Furthermore, social support moderated the association between CRP and telomere length in males aged 70 and above. Our findings indicated that biological mechanisms related to telomere length may vary with sex, while social support plays a sex-specific moderating role.

Effective method for life-style modifications focused on dietary sodium intake in chronic kidney disease: sub-analysis of the FROM-J study.

BACKGROUND: Lifestyle modifications by educational sessions are an important component of multidisciplinary treatment for chronic kidney disease (CKD). We attempted to identify the best method to teach these modifications in order to ensure their acceptance by patients and investigated its effectiveness in CKD practice. METHODS: This study is a post-hoc analysis of the FROM-J study. Subjects were 876 CKD patients in the advanced care group of the FROM-J study who had received lifestyle modification sessions every 3 months for 3.5 years. Two-hundred and ten males (32.6%) and 89 females (38.2%) showed success in sodium restriction. In this study, we examined factors affecting sodium restriction in these subjects. RESULTS: Subjects received three or more consecutive educational sessions about improvement of salt intake. The median salt-intake improvement maintenance period was 407 days. The number of dietary counseling sessions (OR 1.090, 95%CI: 1.012-1.174) in males and the number of dietary counseling sessions (OR 1.159, 95%CI: 1.019-1.318), CKD stage progression (OR 1.658, 95%CI: 1.177-2.335), and collaboration with a nephrologist (OR 2.060, 95%CI: 1.073-3.956) in females were identified as significant factors improving salt intake. The only factor contributing to the maintenance of improved salt intake was the continuation of dietary counseling (p = 0.013). CONCLUSION: An increased number of educational sessions was the only successful approach for males to implement and maintain an improved salt intake. Providing the resources for continuous counseling is beneficial for lifestyle modifications and their maintenance in the long-term management of CKD. Continuous counseling for lifestyle modifications is highly cost-effective. TRIAL REGISTRATION: The FROM-J study was registered in UMIN000001159 on 16/05/2008.

Early-life risperidone alters locomotor responses to apomorphine and quinpirole in adulthood.

An escalating trend of antipsychotic drug use in children with ADHD, disruptive behavior disorder, or mood disorders has raised concerns about the impact of these drugs on brain development. Since antipsychotics chiefly target dopamine receptors, it is important to assay the function of these receptors after early-life antipsychotic administration. Using rats as a model, we examined the effects of early-life risperidone, the most prescribed antipsychotic drug in children, on locomotor responses to the dopamine D1/D2 receptor agonist, apomorphine, and the D2/D3 receptor agonist, quinpirole. Female and male Long-Evans rats received daily subcutaneous injections of risperidone (1.0 and 3.0 mg/kg) or vehicle from postnatal day 14-42. Locomotor responses to one of three doses (0.03, 0.1, and 0.3 mg/kg) of apomorphine or quinpirole were tested once a week for four weeks beginning on postnatal day 76 and 147 for each respective drug. The locomotor activity elicited by the two lower doses of apomorphine was significantly greater in adult rats, especially females, administered risperidone early in life. Adult rats administered risperidone early in life also showed more locomotor activity after the low dose of quinpirole. Overall, female rats were more sensitive to the locomotor effects of each agonist. In a separate group of rats administered risperidone early in life, autoradiography of forebrain D2 receptors at postnatal day 62 revealed a modest increase in D2 receptor density in the medial caudate. These results provide evidence that early-life risperidone administration can produce long-lasting changes in dopamine receptor function and density.

Identification of Phosphodiesterase-7A (PDE7A) as a Novel Target for Reducing Ethanol Consumption in Mice.

BACKGROUND: Ethanol elicits a rapid stimulatory effect and a subsequent, prolonged sedative response, which are potential predictors of EtOH consumption by decreasing adenosine signaling; this phenomenon also reflects the obvious sex difference. cAMP (cyclic Adenosine Monophosphate)-PKA (Protein Kinase A) signaling pathway modulation can influence the stimulatory and sedative effects induced by EtOH in mice. This study's objective is to clarify the role of phosphodiesterase (PDE) in mediating the observed sex differences in EtOH responsiveness between male and female animals. METHODS: EtOH was administered i.p. for 7 days to identify the changes in PDE isoforms in response to EtOH treatment. Additionally, EtOH consumption and preference of male and female C57BL/6J mice were assessed using the drinking-in-the-dark and 2-bottle choice tests. Further, pharmacological inhibition of PDE7A heterozygote knockout mice was performed to investigate its effects on EtOH-induced stimulation and sedation in both male and female mice. Finally, Western blotting analysis was performed to evaluate the alterations in cAMP-PKA/Epac2 pathways. RESULTS: EtOH administration resulted in an immediate upregulation in PDE7A expression in female mice, indicating a strong association between PDE7A and EtOH stimulation. Through the pharmacological inhibition of PDE7A KD mice, we have demonstrated for the first time, to our knowledge, that PDE7A selectively attenuates EtOH responsiveness and consumption exclusively in female mice, whichmay be associated with the cAMP-PKA/Epac2 pathway and downstream phosphorylation of CREB and ERK1/2. CONCLUSIONS: Inhibition or knockdown of PDE7A attenuates EtOH responsivenessand consumption exclusively in female mice, which is associated with alterations in the cAMP-PKA/Epac2 signaling pathways, thereby highlighting its potential as a novel therapeutic target for alcohol use disorder.

Anxiolytic treatment of a trapped rat reduces helping and anxiogenic treatment increases helping: Evidence for emotional contagion in altruism.

The present experiment used the trapped rat model to explore whether pharmacological manipulation of distress affects the likelihood of helping behavior. 120 Sprague-Dawley rats (30 male pairs and 30 female pairs) completed 12 consecutive, daily trials assessing helping behavior. During an individual trial, a trapped rat was placed in a restrainer in the center of an open field, while its cagemate could move around freely and possibly open the restrainer by lifting a door. Trapped rats received an intraperitoneal injection of either 1) physiological saline, 2) the anxiolytic midazolam (1.5 mg/kg), or 3) the anxiogenic yohimbine (2.5 mg/kg) 30 min prior to the start of each trial. Dependent variables measured were: 1) door opening latency (sec), 2) percentage of trials in which a door opening occurred, and 3) the number of free rats classified as "openers." Based on emotional contagion theory, we predicted that 1) free rats paired with midazolam-subjects would show attenuated helping behavior (e.g., higher door opening latency) compared to controls, and conversely 2) free rats paired with yohimbine-subjects would show enhanced helping behavior. First, a significant sex-difference was observed, in that more females were classified as openers than males. This supports previous evidence that females express higher altruistic motivation and experience stronger emotional contagion than males. Second, midazolam-treatment significantly attenuated helping behavior. From trials 4-12, free rats paired with midazolam-subjects expressed slower door opening latencies compared to controls. Third, yohimbine-treatment significantly increased helping behavior (e.g., reduced door opening latencies) - but only on trials 1-3; by trials 9-12, this pattern was reversed. These results are consistent with emotional contagion theory and indicate that intensity of distress directly modulates altruistic motivation through vicarious state-matching.

Sex differences in body temperature and thermal perception under stable and transient thermal environments: A comparative study.

Sex difference stands as a crucial factor necessitating consideration in personalized thermal environment control, with the mechanisms of its emergence potentially differing across different thermal environments. However, a comparative analysis of sex differences regarding body temperature (skin and core body temperature) and thermal perception across different environments is lacking. A stable environmental experiment (comprising three conditions: 16 °C, 20 °C, and 24 °C) and a transient environmental experiment (involving a whole-body step-change from 19 °C to 35 °C and back to 19 °C) were conducted, with participation from 20 young males and 20 young females. Skin temperature and core body temperature were continuously recorded during the experiments, and three types of thermal perceptions were regularly collected. The results showed that: (1) The impact of thermal environment on females' skin temperature surpassed that on males, in stable environment, with every 1 °C rise in ambient temperature, the mean skin temperature increased by 0.28 °C for males and 0.35 °C for females respectively; in transient environment, females' mean skin temperature raise and fell at a faster rate. (2) Males exhibited stronger thermal regulation abilities than females, particularly evident during sudden increase in ambient temperature (from 19 °C to 35 °C), where the reduction magnitude of males' core body temperature was notably larger. (3) Whether in stable or transient environments, significant sex differences often occurred in skin temperature and thermal sensation at distal parts, particularly at the hand. (4) Males typically fed back higher levels of thermal comfort and thermal acceptability than females, suggesting that in addition to physiological sex differences, psychological sex distinctions also play a role. In summary, personalized design for stable thermal environment can focus on sex differences in skin temperature, while transient thermal environment requires consideration of both skin temperature and core body temperature. A comprehensive consideration of physiological and psychological sex differences aids in creating personalized thermal environments with greater precision.

Age and sex differences in the impact of common comorbidities on stroke and myocardial infarction: results from the China Patient-Centered Evaluative Assessment of Cardiac Events Million Persons Project.

OBJECTIVES: This study aims to evaluate the age- and sex-specific associations of comorbidities with stroke and MI and further calculate the population-attributable fractions (PAFs) of five comorbid diseases for stroke and myocardial infarction (MI) by age and sex. STUDY DESIGN: This is a prospective cohort study. METHODS: This study leveraged data from a sub-cohort of the China Patient-Centered Evaluative Assessment of Cardiac Events (PEACE) Million Persons Project. Participants aged 35-75 years without a prevalent stroke and MI were enrolled from January 2016 to December 2020, with follow-up through December 2021. Five common comorbidities were collected at baseline, and the study outcome was hospitalization for stroke and MI identified from the Inpatients Registry. RESULTS: Of 100,873 participants, the mean age was 54.2 (±10.2) years, 34.2% were ≥60 years old, and 60.8% were women. After a median follow-up of 3.52 years, 4156 participants had stroke/MI. The strengths of the associations between hypertension, diabetes, and obesity with stroke/MI were higher in younger individuals than in seniors, and obesity had a more hazardous impact on stroke/MI in men than in women. The five comorbidities collectively explained a higher population attributable fraction (PAF) for stroke/MI in the young group (51.5[46.9, 55.7] %) than in the senior group (41.3[37.0, 45.4] %), in men (45.6[40.9, 49.9] %) than in women (41.1[36.1, 45.7] %). CONCLUSIONS: Most of the common comorbidities were significantly associated with stroke and MI. Several age and sex differences in the impacts of comorbidities on stroke/MI were observed, highlighting the importance of age- and sex-specific preventive strategies to reduce premature stroke and MI.

What characterizes device-related thrombosis following LAAC, if ejection fraction fails to shine?

Cardiac compartmental size depends on sex, with smaller values found in (healthy) women compared to a matched group of men. Various types of heart disease may cause dilation of the affected chamber. For example, atrial fibrillation (AF) is associated with enlarged left atrial (LA) size, often also implying increased left ventricular (LV) size. Sex-specific differences appear to persist during disease states. Thus, chamber volumes depend on both sex and the severity of the underlying disorder, and require quantification to evaluate the effect of interventions. Often, we rely on the popular performance metric ejection fraction (EF) which refers to the ratio of the minimum and maximum LV or LA volumetric values observed during the cardiac cycle. Here we discuss a sex stratified analysis of LVEF and LAEF in AF patients as treated by LA appendage closure, while comparing those with or without device-related thrombosis. Also, an alternative analysis based on primary data is presented while emphasizing its attractiveness. In any event, age- and sex-specific reference values as broadly documented for various imaging modalities should be applied to LA and LV.

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

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

Relationship between sex differences in drinking, smoking, and exercising and the incidence of malignancies and medical procedures: a cross-sectional study of 21,916 participants in China.

Objectives: The unresolved issue of the relationship between sex differences in tea, coffee, and beverage consumption and malignancy risk prompted our study in 2022. Methods: Logistic proportional hazards models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) in our investigation of the associations between cancer risk and tea, coffee, and beverage consumption. Results: Our findings revealed that frequent consumption of white tea significantly reduced the occurrence of malignant tumours, but this effect was detected only in the fully adjusted model for males (OR: 0.736, 95% CI: 0.095-5.704). The amount of sugar added to coffee was associated with an increased risk of malignancy in a dose-dependent manner (P for trend = 0.001), with significance observed for both men (P for trend = 0.049) and women (P for trend = 0.005) in the final model. Notably, individuals who consumed more than 2100 ml of sugary beverages daily had a statistically significant reduction in malignancy risk (OR: 0.219, 95% CI: 0.052-0.917). Interestingly, the intake of sugary beverages had a protective effect on cancer incidence, with a significant effect on males (P for trend = 0.031) but not females (P for trend = 0.096) in the final model. Conclusions: Our study highlights the substantial impact of regular white tea consumption on reducing the risk of malignant tumours in males. This study first reported that the potential protective effect of consuming sugary beverages is predominantly observed in males, and a correlation between the amount of sugar added to coffee and a heightened risk of malignancy.