Sex-specific effects of gut microbiome on shaping bile acid metabolism.

Gut microbiome is a group of microorganisms that plays important roles in contributing to health and diseases. These bacterial compositions have been demonstrated to impact bile acids (BAs) profiles, either by directly metabolizing primary BAs to secondary BAs or indirect ways through host metabolism by influencing BAs synthesis, transportation and conjugation in liver. It has been observed sexually dimorphic gut microbiome and bile acids composition, with variations in expression levels of bile acid metabolizing genes in the liver. However, associations between sex-specific differences in gut microbiome and BAs profiles are not well understood. This study aimed to investigate whether gut microbiome could influence BAs profiles in host in a sexspecific manner. We transplanted cecum feces of male and female C57BL/6 mice to male mice and measured BAs concentrations in feces, serum and liver samples 7 days after fecal transplantation. We found different BAs profiles between mice with male and female gut microbiome, including altering levels and proportions of secondary BAs. We also observed varied expression levels of genes related to bile acid metabolism in the liver and distal ileum. Our results highlight sex-specific effects of gut microbiome on shaping bile acid metabolism through gut bacteria and regulation of host genes.

Longitudinal sex-specific impacts of high-fat diet on dopaminergic dysregulation and behavior from periadolescence to late adulthood.

OBJECTIVES: Obesity is recognized for its adverse impact on brain health and related behaviors; however, the specific longitudinal effects of a high-fat diet (HFD) from juvenile stages of development through late adulthood remain poorly understood, particularly sex-specific outcomes. This study aimed to determine how prolonged exposure to HFD, commencing during periadolescence, would differentially predispose male and female mice to an elevated risk of dopaminergic dysregulation and associated behavioral deficits. METHODS: One-month-old C57BL/6J male and female mice were subjected to either a control diet or an HFD for 5 and 9 months. Muscle strength, motor skills, sensorimotor integration, and anxiety-like behaviors were assessed at the end of the 5th and 8th months. Key dopaminergic molecules, including dopamine (DA), dopamine receptor D2 (DRD2), dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT2), were quantified at the end of the 5th or 9th months. RESULTS: Behaviorally, male mice exposed to HFD exhibited more pronounced alterations in sensorimotor integration, anxiety-like behavior, and muscle strength after the 5th month of dietary exposure. In contrast, female mice displayed most behavioral differences after the 8th month of HFD exposure. Physiologically, there were notable sex-specific variations in the dopaminergic pathway response to HFD. Male mice exposed to HFD exhibited elevated tissue levels of VMAT2 and DRD2, whereas female mice showed reduced levels of DRD2 and DAT compared to control groups. DISCUSSION: These findings indicate a general trend of altered time course susceptibility in male mice to chronic HFD consumption compared to their female counterparts, with male mice impacted earlier than females.

Subregion-specific transcriptomic profiling of rat brain reveals sex-distinct gene expression impacted by adolescent stress.

Stress during adolescence clearly impacts brain development and function. Sex differences in adolescent stress-induced or exacerbated emotional and metabolic vulnerabilities could be due to sex-distinct gene expression in hypothalamic, limbic, and prefrontal brain regions. However, adolescent stress-induced whole-genome expression changes in key subregions of these brain regions were unclear. In this study, female and male adolescent Sprague Dawley rats received one-hour restraint stress daily from postnatal day (PD) 32 to PD44. Corticosterone levels, body weights, food intake, body composition, and circulating adiposity and sex hormones were measured. On PD44, brain and blood samples were collected. Using RNA-sequencing, sex-specific differences in stress-induced differentially expressed (DE) genes were identified in subregions of the hypothalamus, limbic system, and prefrontal cortex. Canonical pathways reflected well-known sex-distinct maladies and diseases, substantiating the therapeutic potential of the DE genes found in the current study. Thus, we proposed specific sex distinct, adolescent stress-induced transcriptional changes found in the current study as examples of the molecular bases for sex differences witnessed in stress induced or exacerbated emotional and metabolic disorders. Future behavioral studies and single-cell studies are warranted to test the implications of the DE genes identified in this study in sex-distinct stress-induced susceptibilities.

Maladaptive health factors as potential mediators for the association between posttraumatic stress disorder and cardiovascular disease: A sex-stratified analysis in the U.S. adult population.

OBJECTIVES: This study examined sex differences for health risk factors as potential mediators in the association between posttraumatic stress disorder (PTSD) and cardiovascular disease (CVD). METHODS: Secondary data from the 2012-2013 National Epidemiological Survey on Alcohol and Related Conditions Wave 3 was used. This cross-sectional survey contains a nationally representative sample of 36,309 U.S. adults (nfemales = 20,447, Mage = 47.16, 95% CI = [46.74, 47,57]; nmales = 15,682, Mage = 45.88, 95% CI = [45.42, 46.34]). Natural effect models and logistic regression analyses were conducted to evaluate health risk factors (smoking, substance use, low physical activity, high body mass index [BMI], binge eating, and multiple health risk factors) as potential mediators for the PTSD-CVD relationship in females and males. RESULTS: High BMI (indirect AOR = 1.05, 95% CI = [1.02, 1.07]) and substance use (indirect AOR = 0.93, 95% CI = [0.88, 0.98], p = 0.005) were potential mediators in females and males respectively. Binge eating, smoking, and low physical activity were not mediators in either sex. The number of health risk factors was also a potential mediator in females (indirect AOR = 1.12, 95% CI = [1.07, 1.19], p = <0.001) though not males (indirect AOR = 1.09, 95% CI = [1.00, 1.19], p = .059). CONCLUSIONS: The results inform prevention strategies, such as screening for health risk factors to mitigate the adverse effect of PTSD on CVD risk. Findings also inform important directions for future longitudinal research to establish causal pathways.

Sex-specific differences in SLE - Significance in the experimental setting of inflammation and kidney damage in MRL-Faslpr mice.

Animal models are an important tool in the research of chronic autoimmune diseases, like systemic lupus erythematosus (SLE). MRL-Faslpr mice are one of different lupus models that develop spontaneously an SLE-like disease with autoantibodies and immune complex deposition that leads into damage of different organs. In contrast to human SLE, both sexes of MRL-Faslpr mice develop a similar autoimmune disease. Due to the sex bias in human and the delayed disease progression in male MRL-Faslpr mice, the majority of studies have been performed in female mice. To determine the suitability of male MRL-Faslpr mice for SLE research, especially with regard to the 3 R-principle and animal welfare, analyses of phenotype, inflammation and damage with focus on kidney and spleen were performed in mice of both sexes. Female mice developed lymphadenopathy and skin lesions earlier as males. At an age of 3.5 month, more immune cells infiltrated kidney and spleen in females compared to males. At the age of 5 months, however, substantially less sex-specific differences were detected. Since other studies have shown differences between both sexes on other manifestations like autoimmune pancreatitis and Sjögren syndrome in MRL-Faslpr mice, the use of male mice as part of 3 R-principle and animal welfare must be carefully considered.

Prenatal and childhood air pollution exposure, cellular immune biomarkers, and brain connectivity in early adolescents.

Introduction: Ambient air pollution is a neurotoxicant with hypothesized immune-related mechanisms. Adolescent brain structural and functional connectivity may be especially vulnerable to ambient pollution due to the refinement of large-scale brain networks during this period, which vary by sex and have important implications for cognitive, behavioral, and emotional functioning. In the current study we explored associations between air pollutants, immune markers, and structural and functional connectivity in early adolescence by leveraging cross-sectional sex-stratified data from the Adolescent Brain Cognitive Development℠ Study®. Methods: Pollutant concentrations of fine particulate matter, nitrogen dioxide, and ozone were assigned to each child's primary residential address during the prenatal period and childhood (9-10 years-old) using an ensemble-based modeling approach. Data collected at 11-13 years-old included resting-state functional connectivity of the default mode, frontoparietal, and salience networks and limbic regions of interest, intracellular directional and isotropic diffusion of available white matter tracts, and markers of cellular immune activation. Using partial least squares correlation, a multivariate data-driven method that identifies important variables within latent dimensions, we investigated associations between 1) pollutants and structural and functional connectivity, 2) pollutants and immune markers, and 3) immune markers and structural and functional connectivity, in each sex separately. Results: Air pollution exposure was related to white matter intracellular directional and isotropic diffusion at ages 11-13 years, but the direction of associations varied by sex. There were no associations between pollutants and resting-state functional connectivity at ages 11-13 years. Childhood exposure to nitrogen dioxide was negatively correlated with white blood cell count in males. Immune biomarkers were positively correlated with white matter intracellular directional diffusion in females and both white matter intracellular directional and isotropic diffusion in males. Lastly, there was a reliable negative correlation between lymphocyte-to-monocyte ratio and default mode network resting-state functional connectivity in females, as well as a compromised immune marker profile associated with lower resting-state functional connectivity between the salience network and the left hippocampus in males. In post-hoc exploratory analyses, we found that the PLSC-identified white matter tracts and resting-state networks related to processing speed and cognitive control performance from the NIH Toolbox. Conclusions: We identified novel links between childhood nitrogen dioxide and cellular immune activation in males, and brain network connectivity and immune markers in both sexes. Future research should explore the potentially mediating role of immune activity in how pollutants affect neurological outcomes as well as the potential consequences of immune-related patterns of brain connectivity in service of improved brain health for all.

Sex-specific associations between prolonged serum uric acid levels and risk of major adverse cardiovascular events.

Background: While hyperuricemia has been correlated with cardiovascular (CV) diseases, further evidence is required to evaluate the implications of stable serum uric acid (sUA) levels, especially concerning low sUA. This study aimed to investigate prolonged stable sUA levels and CV events/mortality. Methods: We conducted a retrospective cohort study at a medical center using electronic medical records linked with the national claims database. Patients with at least two sUA measurements, with intervals ranging from 6 months to 4 years, were included. The mean of the first two eligible sUA measurements were analyzed, stratified by sex. Outcomes of interest comprised major adverse cardiovascular events (MACE), heart failure hospitalization, CV and all-cause mortality. Results: This study included 33,096 patients (follow-up: men 6.6 years, women 6.4 years). After multivariable adjustment, cubic spline models showed that long-term high sUA levels were consistently associated with a higher risk of MACE, heart failure hospitalization, CV and all-cause mortality. A U-shaped association was observed between sUA levels and all-cause mortality in both sexes and between sUA levels and CV mortality in women. The impact of sUA, especially lower levels, on CV events and mortality was more pronounced in women than in men. Conclusion: Long-term high sUA levels are consistently associated with increased risk of CV events and mortality. A U-shaped association between sUA levels and all-cause mortality was observed in both men and women and was pronounced in women. The findings underscore the importance of considering sUA levels, especially in women, when assessing CV risk.

Multigenerational effects of glyphosate-based herbicide and emamectin benzoate insecticide on the reproduction and gene expression of the copepod Pseudodiaptomus annandalei (Sewell, 1919).

This study investigates the effects of glyphosate-based herbicide (GLY) and pure emamectin benzoate (EB) insecticide on the brackish copepod Pseudodiaptomus annandalei. The 96h median lethal concentration (96 h LC50) was higher in the GLY exposure (male: 3420.96 ± 394.67 µg/L; female: 3093.46 ± 240.67 µg/L) than in the EB (male: 79.10 ± 7.30 µg/L; female: 6.38 ± 0.72 µg/L). Based on the result of 96h LC50, we further examined the effects of GLY and EB exposures at sub-lethal concentrations on the naupliar production of P. annandalei. Subsequently, a multigenerational experiment was conducted to assess the long-term impact of GLY and EB at concentrations 375 µg/L, and 0.025 µg/L respectively determined by sub-lethal exposure testing. During four consecutive generations, population growth, clutch size, prosome length and width, and sex ratio were measured. The copepods exposed to GLY and EB showed lower population growth but higher clutch size than the control group in most generations. Gene expression analysis indicated that GLY and EB exposures resulted in the downregulation of reproduction-related (vitellogenin) and growth-related (myosin heavy chain) genes, whereas a stress-related gene (heat shock protein 70) was upregulated after multigenerational exposure. The results of the toxicity test after post-multigenerational exposure indicated that the long-term GLY-exposed P. annandalei displayed greater vulnerability towards GLY toxicity compared to newly-exposed individuals. Whereas, the tolerance of EB was significantly higher in the long-term exposed copepod than in newly-exposed individuals. This suggests that P. annandalei might have greater adaptability towards EB toxicity than towards GLY toxicity. This study reports for the first time the impacts of common pesticides on the copepod P. annandalei, which have implications for environmental risk assessment and contributes to a better understanding of copepod physiological responses towards pesticide contaminations.

Sex Differences in the Expression of Cardiac Remodeling and Inflammatory Cytokines in Patients with Obstructive Sleep Apnea and Atrial Fibrillation.

Although there is a link between obstructive sleep apnea (OSA) and atrial fibrillation (AF) and numerous investigations have examined the mechanism of AF development in OSA patients, which includes cardiac remodeling, inflammation, and gap junction-related conduction disorder, there is limited information regarding the differences between the sexes. This study analyzes the impact of sex differences on the expression of cardiac remodeling, inflammatory cytokines, and gap junctions in patients with OSA and AF. A total of 154 individuals diagnosed with sleep-related breathing disorders (SRBDs) were enrolled in the study and underwent polysomnography and echocardiography. Significant OSA was defined as an apnea-hypopnea index (AHI) of ≥15 per hour. Exosomes were purified from the plasma of all SRBD patients and incubated in HL-1 cells to investigate their effects on inflammatory cytokines and GJA1 expression. The differences in cardiac remodeling and expression of these biomarkers in both sexes were analyzed. Of the 154 enrolled patients, 110 patients were male and 44 patients were female. The LA sizes and E/e' ratios of male OSA patients with concomitant AF were greater than those of control participants and those without AF (all p < 0.05). Meanwhile, female OSA patients with AF had a lower left ventricular ejection fraction than those OSA patients without AF and control subjects (p < 0.05). Regarding the expression of inflammatory cytokines and GJA1, the mRNA expression levels of GJA1 were lower and those of IL-1ß were higher in those male OSA patients with AF than in those male OSA patients without AF and control subjects (p < 0.05). By contrast, mRNA expression levels of HIF-1α were higher in those female OSA patients with and without AF than in control subjects (p < 0.05). In conclusion, our study revealed sex-specific differences in the risk factors and biomarkers associated with AF development in patients with OSA.

Sex-specific outcomes and left atrial remodeling following catheter ablation of persistent atrial fibrillation: results from the DECAAF II trial.

BACKGROUND: Catheter ablation is recognized as an effective treatment for atrial fibrillation (AF). Despite its effectiveness, significant sex-specific differences have been observed, which influence the outcomes of the procedure. This study explores these differences in a cohort of patients with persistent AF. We aim to assess sex differences in baseline characteristics, symptoms, quality of life, imaging findings, and response to catheter ablation in patients with persistent AF. METHODS: This post hoc analysis of the DECAAF II trial evaluated 815 patients (161 females, 646 males). Between July 2016 and January 2020, participants were enrolled and randomly assigned to receive either personalized ablation targeting left atrial (LA) fibrosis using DE-MRI in conjunction with pulmonary vein isolation (PVI) or PVI alone. In this analysis, we aimed to compare female and male patients in the full cohort in terms of demographics, risk factors, medications, and outcomes such as AF recurrence, AF burden, LA volume reduction assessed by LGE-MRI before and 3 months after ablation, quality of life assessed by the SF-36 score, and safety outcomes. Statistical methods included t-tests, chi-square, and multivariable Cox regression. RESULTS: Females were generally older with more comorbidities and experienced higher rates of arrhythmia recurrence post-ablation (53.3% vs. 40.2%, p < 0.01). Females also showed a higher AF burden (21% vs. 16%, p < 0.01) and a smaller reduction in left atrial volume indexed to body surface area post-ablation compared to male patients (8.36 (9.94) vs 11.35 (13.12), p-value 0.019). Quality of life scores were significantly worse in females both pre- and post-ablation (54 vs. 66 pre-ablation; 69 vs. 81 post-ablation, both p < 0.01), despite similar improvements across sexes. Safety outcomes and procedural parameters were similar between male and female patients. CONCLUSION: The study highlights significant differences in the outcomes of catheter ablation of persistent AF between sexes, with female patients showing worse quality of life, higher recurrence of AF and AF burden after ablation, and worse LA remodeling.

Sex-Specific Analysis of Mid-Term Outcomes of Atherectomy-Assisted Endovascular Treatment in Severe Peripheral Arterial Disease.

Background: Endovascular treatment of lower-extremity peripheral disease (PAD) is associated with higher complication rates and suboptimal outcomes in women. Atherectomy has shown favourable outcomes in calcified lesions, minimising the incidence of stent placement caused by recoil or flow-limiting dissection. To date, there are no published mid-term outcomes evaluating the performance of atherectomy differentiated by sex. This study aims to evaluate sex-specific outcomes and prognostic factors affecting the results of atherectomy-assisted endovascular treatment in severe PAD. Methods: A retrospective analysis was conducted at a single centre in Germany, initiated by physicians and not sponsored by industry, on patients presenting with Rutherford categories ranging from III to V and featuring de novo occlusive or stenotic lesions of the superficial femoral (SFA) and/or popliteal arteries. The intervention involved rotational atherectomy-assisted angioplasty utilising the Jetstream (Boston, US®) device. The point of interest of this study was postinterventional clinical improvement as well as mid-term outcomes, including primary patency, over a targeted 2-year follow-up period. Statistical analysis utilised Cox regression (survival analysis) to calculate hazard ratios according to sex category. Comparative survival analysis was performed using the log-rank test and visually represented through Kaplan-Meier curves. Risk factors associated with absence of clinical improvement were examined across both sex groups utilising the chi-square or Fisher exact test, as appropriate. Results: A total of 98 patients (103 limbs) were initially included, with >75% having moderate-to-severe lesion calcification (>50%). A total of 84 patients (97 limbs, 62 male and 35 female) proceeded to a 2-year follow-up (mean 16.4 months for males and 16.1 for females) after a successful index procedure. Age distribution, Rutherford class, diabetes, chronic kidney disease (CKD), target vessel, lesion type, and length were balanced among both groups. Similar primary patency rates, of 89% among female and 91% among male limbs, were observed (p = 0.471). Female patients exhibited a lower rate of clinical improvement based on the Rutherford scale in comparison to males (80.6% vs. 94.5%, p = 0.048). CDK was the only significant prognostic factor across pooled data (odds ratio for CKD: 15.15, p < 0.001). Conclusions: Rotational atherectomy showed comparably high rates of mid-term primary patency, with low rates of bailout stent placement. These findings highlight the beneficial use of atherectomy in female patients who are per se at risk for higher rates of complications during and after endovascular interventions.

Selective effect of winter weather on a songbird's morphology depends on individual sex and winter condition.

Knowledge of the effect of harsh weather on the phenotypic traits of organisms is essential for understanding the environmental influence on phenotype evolution and holds implications for predicting how species respond to current climate change. For many birds, harsh weather in winter often imposes a strong selective effect on their survival, and only the individuals with certain phenotypes may survive. However, whether the selective effect on phenotype varies with winter weather conditions has been poorly investigated. Here, we explored the selective effect of winter weather on black-throated tit's (Aegithalos concinnus) morphological traits under winters with and without severe snowstorms. We found that for males, the sizes of their bills, heads and wings significantly affected their overwinter survival, but the effects varied with winter conditions. In relatively benign winters, males with smaller bill depths, smaller bill surface areas, and greater head lengths survived better; whereas, in winters with severe snowstorms, a reverse pattern was found. This phenomenon was likely driven by selection pressures from heat retention and foraging requirements, with their relative importance depending on winter conditions. Additionally, wing length was positively correlated with male survival and the relationship was stronger in harsher winters, which was probably due to longer wings' higher flight efficiency in adverse weather. By contrast, we found no correlation between morphological traits and survival in females. These results suggest a sex-specific and condition-dependent selective effect of environment on bird phenotypes, implying complicated interactions between different selection pressures and phenotype evolution.

Weather Variability and COPD: A Risk Estimation Identified a Vulnerable Sub-population in Hungary.

BACKGROUND/AIM: Chronic obstructive pulmonary disease (COPD) is a major public health concern, affecting over 200 million people worldwide in 2019. The prevalence of COPD has risen by 40% from 1990 to 2010 and continued to increase by 13% from 2010 to 2019, causing over 3 million deaths globally in 2019, ranking it as the third leading cause of death. This study explored how daily weather changes relate to the number of COPD-related emergency department (ED) visits. MATERIALS AND METHODS: We collected data on daily COPD-related ED visits in 2017 in Pécs along with corresponding meteorological data to analyze this connection. RESULTS: High diurnal temperature range (DTR) and day-to-day variability in dew point were linked to a 4.5% increased risk of more COPD-related ED visits. Notably, DTR had a stronger impact on males, contributing to a 6.3% increase, while dew point variability significantly affected males with an odds ratio (OR) of 1.083. (OR=1.083). Stratifying by age revealed heightened risks for those aged 30-39 (43.5% increase) and 50-59 (7.6% increase). Females aged 30-39 and 50-59 faced elevated risks of 42.7% and 9.1%, respectively, whereas males aged 60-69 showed a 9.8% increase. CONCLUSION: Our findings highlight the influence of weather variations on COPD-related ED visits, with nuanced effects based on age and sex.

Inhibition of WNT/ß-catenin signalling during sex-specific gonadal differentiation is essential for normal human fetal testis development.

Sex-specific gonadal differentiation is directed by complex signalling promoting development in either male or female direction, while simultaneously inhibiting the opposite pathway. In mice, the WNT/ß-catenin pathway promotes ovarian development and the importance of actively inhibiting this pathway to ensure normal testis development has been recognised. However, the implications of alterations in the tightly regulated WNT/ß-catenin signalling during human fetal gonad development has not yet been examined in detail. Thus, the aim of this study was to examine the consequences of dysregulating the WNT/ß-catenin signalling pathway in the supporting cell lineage during sex-specific human fetal gonad development using an established and extensively validated ex vivo culture model. Inhibition of WNT/ß-catenin signalling in human fetal ovary cultures resulted in only minor effects, including reduced secretion of RSPO1 and reduced cell proliferation although this was not consistently found in all treatment groups. In contrast, promotion of WNT/ß-catenin signalling in testes severely affected development and function. This included disrupted seminiferous cord structures, reduced cell proliferation, reduced expression of SOX9/AMH, reduced secretion of Inhibin B and AMH as well as loss of the germ cell population. Additionally, Leydig cell function was markedly impaired with reduced secretion of testosterone, androstenedione and INSL3. Together, this study suggests that dysregulated WNT/ß-catenin signalling during human fetal gonad development severely impairs testicular development and function. Importantly, our study highlights the notion that sufficient inhibition of the opposite pathway during sex-specific gonadal differentiation is essential to ensure normal development and function also applies to human fetal gonads.

Neonatal Chlamydia muridarum respiratory infection causes neuroinflammation within the brainstem during the early postnatal period.

Respiratory infections are one of the most common causes of illness and morbidity in neonates worldwide. In the acute phase infections are known to cause wide-spread peripheral inflammation. However, the inflammatory consequences to the critical neural control centres for respiration have not been explored. Utilising a well characterised model of neonatal respiratory infection, we investigated acute responses within the medulla oblongata which contains key respiratory regions. Neonatal mice were intranasally inoculated within 24 h of birth, with either Chlamydia muridarum or sham-infected, and tissue collected on postnatal day 15, the peak of peripheral inflammation. A key finding of this study is that, while the periphery appeared to show no sex-specific effects of a neonatal respiratory infection, sex had a significant impact on the inflammatory response of the medulla oblongata. There was a distinct sex-specific response in the medulla coincident with peak of peripheral inflammation, with females demonstrating an upregulation of anti-inflammatory cytokines and males showing very few changes. Microglia also demonstrated sex-specificity with the morphology of females and males differing based upon the nuclei. Astrocytes showed limited changes during the acute response to neonatal infection. These data highlight the strong sex-specific impact of a respiratory infection can have on the medulla in the acute inflammatory phase.

Sex-specific differences in the clinical profile among psychiatric patients with pulmonary Embolism: a hospital-based retrospective study.

BACKGROUND: Pulmonary embolism (PE) is a severe and life-threatening complication of venous thromboembolism. However, there is a lack of systematic studies on differences between female and male PE patients. This paper aimed to compare the sex-specific differences in clinical characteristics and laboratory indicators in psychotic patients with PE. METHODS: This retrospective study enrolled psychiatric patients with PE from June 2018 to June 2022 at Shenzhen Kangning Hospital (Shenzhen Mental Health Center). Demographic characteristics, factors associated with PE, and laboratory indices were collected to assess sex-specific differences. RESULTS: Of the 168 patients, 87 (51.8%) were female and 81 (48.2%) were male, with a mean age of 58 years for females and 46 years for male patients. The male group had higher ratio of hyperprolactinemia, more patients using antipsychotic medications, higher D-dimer levels at PE onset, greater D-dimer difference, and a higher rate of D-dimer elevation than the female group (p < 0.05). Female patients were significantly older, exhibited a higher prevalence of diabetes, and had a greater number of patients taking antidepressants and hypnotics/sedatives than male patients (p < 0.05). Schizophrenia spectrum disorders were more prevalent in male patients, while female patients had a higher incidence of mood disorders (p < 0.05). Among patients aged < 45 years, the male group had higher D-dimer levels at PE onset and greater D-dimer difference (p < 0.05). Among all 112 patients aged ≥ 45 years, male patients were more likely than female patients to have respiratory tract infections, higher D-dimer levels at PE onset, greater D-dimer difference, and a higher rate of D-dimer elevation (p < 0.05). The multiple linear regression analysis indicated that hyperprolactinemia and the use of first-generation antipsychotics (FGAs) were associated with D-dimer levels at PE onset in male patients, while the time of PE onset and protective restraints were associated with D-dimer levels at PE onset in female patients (p < 0.05). CONCLUSION: PE-associated clinical features differ between male and female patients. These differences may imply that the processes and mechanisms of PE onset are sex specific. Male patients are more likely to have respiratory tract infections and higher D-dimer levels at PE onset than female patients. The use of FGAs may be associated with increased D-dimer in male psychiatric patients, while protective restraints may be associated with increased D-dimer in female psychiatric patients.

Unmarried Status Effect on Stage at Presentation and Treatment Patterns in Non-Metastatic Upper Tract Urothelial Carcinoma Patients.

BACKGROUND: Unmarried status has been associated with higher proportions of locally advanced stage and lower treatment dose intensification rates in several urological and non-urological malignancies. However, no previous investigators focused on the association between unmarried status and advanced stage (T3-4N0-2) at presentation and lower nephroureterectomy (RNU) and systemic therapy (ST) rates in non-metastatic upper tract urothelial carcinoma (UTUC) patients. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database 2000-2020, all non-metastatic UTUC patients were identified. Multivariable logistic regression models (LRMs) tested for differences in stage at presentation and treatment (RNU and ST) according to marital status (married vs unmarried), in a sex-specific fashion. RESULTS: Of all 8544 non-metastatic UTUC patients, 4748 (56%) were male vs 3190 (44%) were female. Of all 4748 male UTUC patients, 1191 (25%) were unmarried. Of all 3190 female UTUC patients, 1608 (50%) were unmarried. In multivariable LRMs predicting RNU, unmarried status was an independent predictor of lower RNU rates in male (Odds Ratio [OR]: 0.56; P < .001), but not in female (OR: 0.81; P = .1) non-metastatic UTUC patients. In multivariable LRMs predicting ST exposure, unmarried status was an independent predictor of lower ST rates in both male (OR:0.73; P = .03) and female (OR:0.64; P < .001) UTUC patients. In multivariable LRMs predicting locally advanced stage (T3-4N0-2), unmarried status was not associated with an increased risk of locally advanced stage at presentation in either male (OR: 0.95; P = .5) or female (OR: 0.99; P = .9) UTUC patients. CONCLUSIONS: Unmarried male UTUC patients appear at risk of less being able to access RNU, relative to their married counterparts. Moreover, unmarried UTUC patients appear to less benefit from ST, regardless of sex. Conversely, unmarried status was not associated with an increased risk of locally advanced stage at presentation in either male or female UTUC patients.

Sex-Specific Associations between Maternal Thyroid Peroxidase Antibodies and Cognitive Development in Preschool Children: A Prospective Cohort Study.

Background: An association between maternal thyroid dysfunction throughout pregnancy and the subsequent risk of neurodevelopmental abnormalities in offspring has been demonstrated. However, the potential effects of maternal thyroid autoimmunity on neurodevelopment in the absence of maternal hypothyroidism remain unclear. Therefore, in this study, we explored the association between maternal thyroid peroxidase antibody (TPOAb) positivity and cognitive development in preschool children. Methods: A total of 1849 mother-child pairs were recruited from the Ma'anshan Birth Cohort (MABC) Study. During the follow-up period, an electrochemiluminescence immunoassay was used to retrospectively measure serum TPOAb levels in pregnant women. The cognitive development of preschool children was evaluated by using the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition (WPPSI-IV). A growth mixture model was used to fit the trajectory of TPOAb. Multiple linear regression and logistic regression models were used to explore the associations between the developmental trajectory of TPOAb-positivity at different gestational periods and the cognitive development of preschool children by sex. Results: A total of 1849 mother-child pairs (mean [SD] age: 26.7 [3.6] years) were enrolled in the final study. Maternal TPOAb positivity in the first trimester was associated with a risk of below-average processing speed index in girls (OR: 2.07; 95% CI 1.06 to 4.01) and below-average full-scale intelligence quotient (FSIQ) in boys (OR: 2.36; 95% CI: 1.10 to 5.05). Maternal TPOAb positivity in the third trimester (T3) was associated with below-average working memory index (WMI) (OR: 2.51; 95% CI: 1.02 to 6.20) in girls. In girls, the WMI (ß = -3.17, 95% CI: -5.82 to -0.52), fluid reasoning index (FRI) (ß = -4.49, 95% CI: -7.18 to -1.80), and FSIQ score (ß = -2.43, 95% CI: -4.77 to -0.08) decreased, whereas in mothers, the level of log-transformed thyroid peroxidase antibody (lgTPOAb) increased during pregnancy. Conclusions: Positive maternal TPOAb levels during pregnancy may be associated with poorer cognitive development in preschool children. These findings require independent confirmation in other populations.

Understanding desiccation tolerance and sex-specific responses in Bryum argenteum: insights from phenological phases and physiological analyses.

BACKGROUND AND AIMS: Desiccation tolerance (DT) is crucial for survival in arid environments, where organisms develop strategies in reproduction, maintenance and defence to cope with water scarcity. Therefore, investigating the relationship between reproduction and DT is essential to understand the ecology and adaptive strategies of species. This study explores the connection between the development of male and female gametangia in the moss Bryum argenteum and the decrease in DT during the progression of phenological phases in gametangia and protonema. METHODS: Samples collected from a dry tropical forest in Brazil were cultivated, cloned and subjected to desiccation. Subsequently, the physiological parameters of shoots and protonemata were analysed. Shoot and protonema regeneration were monitored for 28 d after the physiological analyses. Both phases were subjected to control and desiccation treatments. KEY RESULTS: Significant effects of desiccation and sex on the physiological parameters and regeneration capacity of shoots and protonemata were found. Male shoots generally exhibited lower values of Fv/Fm (quantum efficiency of photosystem II) and ϕPSII (effective quantum yield of photosystem II), while females demonstrated higher values and better recovery after desiccation. Protonemata also showed variation in Fv/Fm over time and with sex, with no significant differences in ϕPSII between them. Desiccated male shoots had higher mortality rates and produced fewer new shoots. For females, the regeneration patterns varied between the desiccation-exposed groups and the control, with decreased shoot production, and some protonemata growing into filaments without forming shoots. CONCLUSION: These findings improve our understanding of the ecological responses of bryophytes to desiccation stress and provide insights into their adaptive strategies in challenging environments, such as the possible rarity of males in dioicous moss populations.

Maternal Diet High in Linoleic Acid Alters Renal Branching Morphogenesis and mTOR/AKT Signalling Genes in Rat Fetal Kidneys.

Linoleic acid (LA), an n-6 polyunsaturated fatty acid (PUFA), is obtained from the maternal diet during pregnancy, and is essential for normal fetal growth and development. A maternal high-LA (HLA) diet alters maternal and offspring fatty acids, maternal leptin and male/female ratio at embryonic (E) day 20 (E20). We investigated the effects of an HLA diet on embryonic offspring renal branching morphogenesis, leptin signalling, megalin signalling and angiogenesis gene expression. Female Wistar Kyoto rats were fed low-LA (LLA; 1.44% energy from LA) or high-LA (HLA; 6.21% energy from LA) diets during pregnancy and gestation/lactation. Offspring were sacrificed and mRNA from kidneys was analysed by real-time PCR. Maternal HLA decreased the targets involved in branching morphogenesis Ret and Gdnf in offspring, independent of sex. Furthermore, downstream targets of megalin, namely mTOR, Akt3 and Prkab2, were reduced in offspring from mothers consuming an HLA diet, independent of sex. There was a trend of an increase in the branching morphogenesis target Gfra1 in females (p = 0.0517). These findings suggest that an HLA diet during pregnancy may lead to altered renal function in offspring. Future research should investigate the effects an HLA diet has on offspring kidney function in adolescence and adulthood.