Sex Differences Research Articles

SPIN: sex-specific and pathway-based interpretable neural network for sexual dimorphism analysis.

Sexual dimorphism in prevalence, severity and genetic susceptibility exists for most common diseases. However, most genetic and clinical outcome studies are designed in sex-combined framework considering sex as a covariate. Few sex-specific studies have analyzed males and females separately, which failed to identify gene-by-sex interaction. Here, we propose a novel unified biologically interpretable deep learning-based framework (named SPIN) for sexual dimorphism analysis. We demonstrate that SPIN significantly improved the C-index up to 23.6% in TCGA cancer datasets, and it was further validated using asthma datasets. In addition, SPIN identifies sex-specific and -shared risk loci that are often missed in previous sex-combined/-separate analysis. We also show that SPIN is interpretable for explaining how biological pathways contribute to sexual dimorphism and improve risk prediction in an individual level, which can result in the development of precision medicine tailored to a specific individual's characteristics.

A Multinational Cohort Study Examining Sex Differences in Excess Risk of Death With Graft Function After Kidney Transplant.

Kidney transplant recipients show sex differences in excess overall mortality risk that vary by donor sex and recipient age. However, whether the excess risk of death with graft function (DWGF) differs by recipient sex is unknown. In this study, we combined data from 3 of the largest transplant registries worldwide (Scientific Registry of Transplant Recipient, Australia and New Zealand Dialysis and Transplant Registry, and Collaborative Transplant Study) using individual patient data meta-analysis to compare the excess risk of DWGF between male and female recipients of a first deceased donor kidney transplant (1988-2019), conditional on donor sex and recipient age. Among 463 895 individuals examined, when the donor was male, female recipients aged 0 to 12 y experienced a higher excess risk of DWGF than male recipients (relative excess risk 1.68; 95% confidence interval, 1.24-2.29); there were no significant differences in other age intervals or at any age when the donor was female. There was no statistically significant between-cohort heterogeneity. Given the lack of sex differences in the excess risk of DWGF (other than in prepubertal recipients of a male donor kidney) and the known greater excess overall mortality risk for female recipients compared with male recipients in the setting of a male donor, future study is required to characterize potential sex-specific causes of death after graft loss.

Sex differences in strength, functional capacity and mobility in patients with multiple sclerosis: An exploratory analysis

BackgroundPhysical exercise programs are commonly designed without consideration for sex differences. Nevertheless, disease progression exhibits sex-specific patterns, resulting in different functionality and strength performances. ObjectivesTo analyze sex differences in strength, functional capacity, and mobility, and to evaluate sex-dependent differences in leg strength in multiple sclerosis (MS) patients. MethodsA cross-sectional study was conducted with 35 participants (female: n = 19; Expanded Disability Status Scale (EDSS)= 3.0 ± 1.2, male: n = 16; EDSS= 3.3 ± 1.2). Body composition, maximal voluntary isometric contraction (MVIC), explosive strength (rate of force development, RFD), central activation ratio (CAR), functional capacity, and mobility were assessed. ResultsDifferences were observed between males and females (p = 0.001) in height, lean body mass and MVIC. No differences were observed in the other variables. Regarding the leg asymmetry, men showed higher values in the stronger leg for both MVIC (p < 0.001, d=large) and RFD, whereas women showed higher values only in RFD. Men with MS demonstrated a greater capacity to produce maximal strength than women with this disease. ConclusionsThe results found suggest that maximum strength differs between men and women in our sample of patients with multiple sclerosis. Furthermore, the weaker leg, regardless of sex, exhibits poorer results in explosive strength compared to the stronger leg. However, maximum strength only shows differences in men and not in women. Therefore, these findings should serve as a basis for rehabilitation professionals when planning training programs for this population.

#2526 Sex differences in chronic kidney disease-related complications and mortality across levels of glomerular filtration rate

Abstract Background and Aims Chronic kidney disease (CKD) is a growing global health concern. In recent years, studies have increasingly focused on the differential risk profile of diseases between men and women. Current evidence suggests that sex-linked biological and behavioral differences may play a key role in influencing the incidence, prevalence, and outcomes of diseases. Similarly, previous studies have demonstrated a differential risk profile in the prevalence, progression, and outcomes of CKD between men and women. Recent research has indicated sex disparities in CKD-related complications, yet the impact of sex differences on critical kidney function levels that trigger these complications and mortality remains inadequately documented. Method We investigated sex-specific disparities in CKD-related complications and mortality according to eGFR levels. We analyzed NHANES data spanning from 1999 to 2018, including adult participants with an eGFR of 15-150 ml/min per 1.73 m². The outcomes were CKD-related complications (hypertension, anemia, CV diseases, acidosis, hyperphosphatemia, hyperparathyroidism) and all-cause and cause-specific mortality (CV mortality and non-CV mortality). Sex-stratified multivariable logistic and Cox regression models yielded odds ratios (ORs) and hazard ratios (HRs) for the relationship between eGFR categories and outcomes. Sex-stratified natural splines were used to explore the relationship between continuous eGFR and outcomes and identified eGFR thresholds of statistical significance. Values of eGFR over which the log-odds (for CKD-related complications outcomes) or log-hazard (for all-cause and cause-specific mortality outcomes) was found to be significantly different from zero (i.e., 95% CI for the smooth term did not contain zero) were identified as thresholds of statistical significance. Results The study included 49, 562 participants (50.31% women, 49.68% men). Multivariable logistic regression demonstrated a significant eGFR association with all CKD-related complications, exhibiting a linear trend across eGFR categories. Modeling eGFR as a natural spline revealed varied significance thresholds between sexes for anemia and hyperparathyroidism. We found a significantly (P &amp;lt; 0.05) higher proportion of women with anemia downstream an eGFR cut-off of 69 mL/min per 1.73 m2, which was lower than the cut-off in men; a significantly higher proportion of men with anemia was observed downstream an eGFR cut-off of 76 mL/min per 1.73 m2. However, the relationship was more pronounced in women than in men; thus, at an eGFR cut-off of 41 mL/min per 1.73 m2, the proportion of women with anemia was significantly higher (P &amp;lt; .05) (Figure). Similarly, a higher proportion of women with hyperparathyroidism were observed downstream an eGFR cut-off of 73 mL/min per 1.73 m2, which was lower than in men; a significantly higher proportion of men (P &amp;lt; .05) was observed downstream an eGFR cut-off of 89 mL/min per 1.73 m2 (Figure). Furthermore, although no sex differences were observed in terms of eGFR thresholds for hyperphosphatemia, a more pronounced relationship was observed in men. Thus, at an eGFR cut-off of 38 mL/min per 1.73 m2, the proportion of men with hyperphosphatemia was significantly higher (P &amp;lt; .05) than that of women (Figure). We observed substantial but not statistically significant differences between men and women in the thresholds of statistical significance for CV (significance appeared at a higher eGFR in men) and non-CV mortality (significance appeared at a higher eGFR Conclusion Research shows sex disparities in most CKD-related complications. Men develop anemia and hyperparathyroidism earlier, women show steeper anemia increase. Men have higher CV mortality risk. As eGFR decreased, men faced a higher risk of CV mortality at a higher eGFR threshold than women.

Transcriptomic sex differences in postmortem brain samples from patients with psychiatric disorders.

Many psychiatric disorders exhibit sex differences, but the underlying mechanisms remain poorly understood. We analyzed transcriptomics data from 2160 postmortem adult prefrontal cortex brain samples from the PsychENCODE consortium in a sex-stratified study design. We compared transcriptomics data of postmortem brain samples from patients with schizophrenia (SCZ), bipolar disorder (BD), and autism spectrum disorder (ASD) with transcriptomics data of postmortem control brains from individuals without a known history of psychiatric disease. We found that brain samples from females with SCZ, BD, and ASD showed a higher burden of transcriptomic dysfunction than did brain samples from males with these disorders. This observation was supported by the larger number of differentially expressed genes (DEGs) and a greater magnitude of gene expression changes observed in female versus male brain specimens. In addition, female patient brain samples showed greater overall connectivity dysfunction, defined by a higher proportion of gene coexpression modules with connectivity changes and higher connectivity burden, indicating a greater degree of gene coexpression variability. We identified several gene coexpression modules enriched in sex-biased DEGs and identified genes from a genome-wide association study that were involved in immune and synaptic functions across different brain cell types. We found a number of genes as hubs within these modules, including those encoding SCN2A, FGF14, and C3. Our results suggest that in the context of psychiatric diseases, males and females exhibit different degrees of transcriptomic dysfunction and implicate immune and synaptic-related pathways in these sex differences.

Sex and Age Differences in Atypical Chief Complaints for Acute Decompensated Heart Failure in Emergency Department Visits.

Around one million United States emergency department (ED) visits annually are due to acute decompensated heart failure (ADHF) symptoms. Characterizing ED symptom presentation of ADHF patients may improve clinical care, yet sex and age differences in ED chief complaints have not been thoroughly investigated. This paper aims to describe differences in chief complaints and comorbid conditions for ED patients with a ADHF diagnosis, stratified by sex and age. Retrospective analysis of adults presenting to North Carolina EDs in NC DETECT, a statewide syndromic surveillance system, between 2010 and 2016 with a diagnosis of ADHF. Frequencies of chief complaint categories for ED visits and comorbid conditions, stratified by sex and age, were evaluated and standardized differences computed. Top chief complaints were dyspnea (19.1%), chest pain (13.5%), and other respiratory complaints (13.4%). In the 18-44 age group, females when compared to males reported more nausea/vomiting (6.7% versus 4.1%) and headache (4.2% versus 2.0%). In those 45-64 and 65+ years old, complaints were similar by sex. When stratified by age group alone, the 18-44 and 45-64 age groups had more complaints of chest pain, whereas balance issues, weakness, and confusion were more common in the 65+ age group. Sex and age differences in atypical ADHF symptoms were seen in in ED patients with ADHF. Characterizing variation of ADHF symptoms in ED patients can inform the identification of ED patients with ADHF and the management of ADHF-related symptoms.

#1740 Survival of native arteriovenous fistulas in elderly patients

Abstract Background and Aims Current guidelines recommend native arteriovenous fistulas (nAVF) as the first-choice vascular access for hemodialysis. However, the patient's age may make its indication doubtful. The aim of our study was to know the association between primary survival (PS), defined as the time to the first reparation, and secondary survival (SS), defined as the end of the working life of a nAVF, with the patient's age. Method We conducted a prospective observational study based on a historical database including 795 nAVF from incident patients, both treated in an in-hospital dialysis unit (HDU) and an out-of-hospital dialysis center (DC), made between 1998 and 2022 and followed-up until June 2023. We performed Kaplan Meier survival curves to estimate PS and SS of the nAVF for each age group (≤ 50, 50-70 and ≥ 70 years) and a multivariate logistic regression analysis of PS and SS adjusted by comorbidity (Charlson's Comorbidity Index without age (CCI)), sex, nAVF indication at end stage kidney disease (ESKD) clinics, location of the nAVF, in-hospital dialysis unit or out-of-hospital dialysis center treated patient and initial laboratory parameters (albumin, hemoglobin and phosphorus). Results The medium age of the patients included was 63.4 years; 68% were males, 34% had diabetes and 63.3% had a CCI ≥ 3 at the time de nAVF was made. 53.5% of all the nAVF were indicated at the ESKD clinics; 57.9% of them were radiocephalics, 33.4% brachiocephalics and 8.8% brachiobasilics. Almost 40% of the fistulas had an in-hospital use. In the survival study we didn't find statistically significant differences for age or sex, but both PS and SS were lower for patients with a CCI ≥ 3, and SS was significantly better for the first nAVF of the patient and for radio-cephalic nAVF, as shown in Fig. 1. These results were concordant to the univariant analysis, in which we didn't find differences for age group or sex, but both PS and SS were worse in patients with a CCI ≥ 3 (HR 1.32, p 0.037). Patients with lower albumin levels at the time the nAVF was made had a lower PS (HR 0.62, p &amp;lt; 0.001); and SS also had a statistically significant association with being treated at an out-of-hospital dialysis center (HR 0.69, p 0.024) and the indication of the nAVF at the ESKD clinics (HR 0.71, p 0.036). Nevertheless, in the multivariate logistic regression analysis we only found significant differences, both for PS and SS, regarding the albumin levels at the time the nAVF was made (HR 0.62, p 0.001). Conclusion The survival of a native arteriovenous fistula, both primary and secondary, does not correlate to the patient's age, sex, comorbidity, indication at the ESKD clinics or the location of the fistula.

#1230 Comparative analysis of vitamin D status between patients with advanced chronic kidney disease and those on dialysis

Abstract Background and Aims Decreased plasma concentration of 1,25-dihydroxy-vitamin D3 or calcitriol, the most active biological form of vitamin D3, in patients with advanced chronic kidney disease (ACKD) and on dialysis, is almost universal. In addition, 25-50% of these patients also have decreased levels of 25-hydroxy-vitamin D3 (calcidiol or calcifediol). The main cause of calcitriol deficiency is decreased hydroxylation in the kidney, both due to intrinsic renal damage and hyperphosphataemia. Calcifediol deficiency is directly related to decreased intake and sun exposure. We already know that this calcifediol deficiency is associated with ACKD, but we do not know if there are differences between ACKD patients and dialysis patients. The aim of this study is to analyse whether there are differences in calcifediol levels between ACKD and dialysis patients. Method An observational, analytical, ambispective, multicentre, analytical study was carried out with the participation of five Centres in Spain, under conditions of routine clinical practice. As study subjects, we included patients with ACKD and on haemodialysis from the University Hospitals of Virgen del Rocío, La Paz and Nuestra Señora de Candelaria, and the dialysis centres: Avericum, Quironsalud Tenerife. We selected demographic variables and also included serum levels of calcifediol, calcium, phosphorus and PTH; treatment with: phosphorus binders, erythropoietin synthesis analogues (ESA), ferrotherapy, calcimimetics, active vitamin D, native vitamin D. Data are organised and analysed with SPSS Statistics v22. In all analyses, the significance level is set for a P value &amp;lt; 0.05. Multivariate logistic regression analysis was also performed. Results A total of 161 patients were included. Both groups were homogeneous in the presence of diabetes, calcium levels and treatment with iron, native vitamin D, active vitamin D and calcimimetics. There were significant differences in sex, age, phosphorus levels, PTH, phosphate binders, ESA treatment. There are no significant differences in calcifediol levels or vitamin D status between the two comparison groups. Conclusion In our study, within a general context of hypovitaminosis D, patients with ACKD have a vitamin D status similar to dialysis patients.

#2458 Factors associated with cytomegalovirus infection in kidney transplant patients: analysis from a nationwide registry data

Abstract Background and Aims Cytomegalovirus (CMV) has had a significant impact on solid organ transplantation. It can affect allograft function and increase patient morbidity and mortality. We have made several efforts to prevent CMV infection after kidney transplantation (KT), but we have not yet been able to prevent it satisfactorily. Drugs were used as preventive therapy or preemptive therapy, but they did not completely prevent the diseases. Therefore, it will be possible to reduce CMV infection by taking actions against factors that can easily cause CMV infection. We investigated factors that make CMV infection more likely and explored the effects of CMV infection using The Korean Organ Transplantation Registry (KOTRY) datasets. Method We used the data from the KOTRY datasets. A total of 7545 KT recipients were analysed. Results The mean age of the subjects was 49.7 ± 11.5 years (range, 19-80). Among the 7545 subjects, 58.6% were male. Three hundred and twenty-four (4.2%) subjects had CMV infection (CMV group). There were 4827 (64%) living donors, 2717 (36%) cadaveric donors, and 1338 (17.3%) ABO incompatible donors. Of the total, 95% were transplanted from positive to positive CMV IgG, and 1.9% were from positive to negative. Although preventive treatment is performed in the second cases, in most cases preemptive therapy is performed. The age was 49.6 ± 11.5 in the no CMV group and 51.4 ± 12.6 in the CMV group (P = 0.013). There was no difference in sex, weight and BMI in both cases. The causes of end stage renal disease were glomerulonephritis, DM, and hypertension in that order, and there was no difference in the rates of diabetes and hypertension between the two groups. There was no difference in the desensitization rate at 24% in the no CMV group and 23% in the CMV group. At the time of discharge after surgery, the tacrolimus dose was 6.4 mg/d±3.6 in the no CMV group and 6.3 ± 3.8 mg/d in the CMV group (P = 0.89). Tacrolimus concentration (C0) was 8.0 ± 2.6 ng/ml in the no CMV group and 8.9 ± 2.4 ng/ml in the CMV group. It was higher in the CMV group (P = 0.002). When divided into 3 tertiles based on C0, the break points were 6.7 and 8.9 ng/ml. There was a higher incidence of CMV in the third tertile group compared to the first and second tertiles, but there was no difference between the first and second groups. When the metabolic rate (tacrolimus concentration divided by dose) was divided into three groups, CMV occurred more frequently in the group with the lower metabolic rate, at 3.9% in the group with the lowest tertile and 2.3% in the highest tertile (P = 0.046). At 6 months, tacrolimus dose was 4.3 ± 2.4 mg/d in the no CMV group and 3.9 ± 2.3 mg/d in the CMV group, which was lower in the CMV group (P = 0.005). Tacrolimus concentration was 6.8 ± 2.4 ng/ml in the no CMV group and 6.4 ± 2.3 ng/ml in the CMV group, which was lower in the CMV group (P = 0.004). There was no difference according to metabolic rate. At discharge (62.5 ± 25.7 vs. 54.5 ± 26.5), at 6 month (56.0 ± 22.3 vs. 47.9 ± 19.0), and at 1 year (57.2 ± 20.0 vs. 48.8 ± 19.6 mL/min/1.73 m2), eGFR in the No CMV group was higher than that in the CMV group (P &amp;lt; 0.005). One thousand two hundred and sixty-four (16.8%) patients showed acute rejection within 1 year. Acute rejection occurred within 1 year in 36.4% of the CMV group and 15.9% of the no CMV group (P &amp;lt; 0.001). Delayed graft function occurred in 4.6% of the CMV group and 5.5% of the no CMV group (P &amp;lt; 0.001). Conclusion CMV was more common in older people, those with higher tacrolimus concentrations, and those with lower tacrolimus metabolic rates. The risk increases when the concentration exceeds 8.9 ng/ml, and after reducing the dose, the dose and concentration were lower in the CMV group at 6 month and 1 year. Although the dose was later reduced in the CMV group, more acute rejections occurred within 1 year, which suggests that CMV infection can trigger rejections. Delayed graft function occurred less frequently in the CMV group, which may be related to the higher concentration of tacrolimus.

Male proboscis monkey cranionasal size and shape is associated with visual and acoustic signalling

The large nose adorned by adult male proboscis monkeys is hypothesised to serve as an audiovisual signal of sexual selection. It serves as a visual signal of male quality and social status, and as an acoustic signal, through the expression of loud, low-formant nasalised calls in dense rainforests, where visibility is poor. However, it is unclear how the male proboscis monkey nasal complex, including the internal structure of the nose, plays a role in visual or acoustic signalling. Here, we use cranionasal data to assess whether large noses found in male proboscis monkeys serve visual and/or acoustic signalling functions. Our findings support a visual signalling function for male nasal enlargement through a relatively high degree of nasal aperture sexual size dimorphism, the craniofacial region to which nasal soft tissue attaches. We additionally find nasal aperture size increases beyond dental maturity among male proboscis monkeys, consistent with the visual signalling hypothesis. We show that the cranionasal region has an acoustic signalling role through pronounced nasal cavity sexual shape dimorphism, wherein male nasal cavity shape allows the expression of loud, low-formant nasalised calls. Our findings provide robust support for the male proboscis monkey nasal complex serving both visual and acoustic functions.

Somatometric Characteristics of the Grey Wolf&amp;nbsp;(Canis lupus) in Bulgaria

Grey wolf (Canis lupus Linnaeus 1758) is the largest representative of the Canidae family in Bulgaria. It inhabits almost the whole territory, most frequently the mountainous and hilly areas. The grey wolf is a hunting species in the country. Despite this, there is little information in the literature on its size. The aim of this work was to provide the first systematized data of the somatometric characteristics (weight &amp;ndash; P; total body length &amp;ndash; L; length of the body to the base of the tail &amp;ndash; Lb; tail length &amp;ndash; Lo and height at the withers &amp;ndash; Hb) of the grey wolf in Bulgaria and to establish what is the degree of their sexual dimorphism. We found that the adult males are 24.3% heavier than the females (t=4.46; p&lt;0.001). They also have a longer body by 8.8% (t = 3.66; p&lt;0.001) and a greater height by 6.5% (U=546; p=0.005). The smallest difference (6.2%) between the two sexes was observed in tail length (U=629.5; p=0.03). The results of our study support the clear sexual dimorphism established in other wolf populations. Further studies are needed to link the wolf &amp;rsquo;s body size data with prey type data in the respective areas for more clarity. This will be beneficial both for better wolf population management and for the accumulation of a database. &amp;nbsp;

Sexual Dimorphisms in Skeletal Muscle: Current Concepts and Research Horizons.

The complex compositional and functional nature of skeletal muscle makes this organ an essential topic of study for biomedical researchers and clinicians. An additional layer of complexity is added with the consideration of sex as a biological variable. Recent research advances have revealed sexual dimorphisms in developmental biology, muscle homeostasis, adaptive responses, and disorders relating to skeletal muscle. Many of the observed sex differences have hormonal and molecular mechanistic underpinnings, while others have yet to be elucidated. Future research is needed to investigate the mechanisms dictating sex-based differences in the various aspects of skeletal muscle. As such, it is necessary that skeletal muscle biologists ensure that both female and male subjects are represented in biomedical and clinical studies to facilitate the successful testing and development of therapeutics for all patients.

Taxonomic review of the genus Lemyra Walker (Erebidae: Arctiinae) from India

In the present manuscript, we review the genus Lemyra Walker, 1856 from India by examining the specimens collected freshly from different parts of India from 2016 to 2019 and from the National Zoological Collection of the Zoological Survey of India (NZCZSI). The revised status of Lemyra in India is presented by describing seven new species: Lemyra (Thyrgorina) rubripecta sp. nov., L. (T.) densimacula sp. nov., L. (T.) fortiorspina sp. nov., L. (T.) apatani sp. nov., L. (T.) adunca sp. nov., L. (T.) obsoleta sp. nov. and L. (T.) pinus sp. nov., synonymizing equal number of species: L. (T.) punctilinea (Moore, 1879), syn. nov. under L. (T.) flavalis (Moore, 1865), L. (T.) magnaproteus N. Singh &amp; Kirti, 2016, syn. nov. under L. (T.) proteus (De Joannis, 1928), Thanatarctia costalis Kaleka, 2012: 51, syn. nov., Thanatarctia collarlis Kaleka, 2012: 53, syn. nov., L. (T.) collarlis N. Singh, Kirti &amp; Kaleka, 2016: 15, syn. nov. (objective synonym of T. collarlis Kaleka, 2012), L. (T.) pseudocollarlis N. Singh, Kirti &amp; Kaleka, 2016: 16, syn. nov. under L. (T.) nigrescens (Rothschild, 1910) and L. (T.) angularis (Strand, 1919) under L. (T.) spilosomata (Walker, [1865]). The status of L. (T.) aurantiaca (Fang, 1985), a new record to India, is upgraded to species level. Additionally, two species i.e., L. (T.) kaikarisi Saldaitis et al., 2019 and L. (T.) persephone Saldaitis et al., 2020 are reported for the first time from India. An updated checklist of 117 species (including the nominotypical subspecies) and 10 subspecies of Lemyra is provided with 48 species (including the new records and new species described herein) from India. Of the 48 species from India, the systematics of 42 species is provided based on their voucher specimens. We could not study the rest of the six species with their voucher specimens. The detailed diagnoses with closely similar congeners, genitalia illustrations, distributions, individual variations and sexual dimorphism, if any, and bionomics is provided.

#2145 Sexual dimorphism in kidney regenerative capacity decline and in progressive tubular cell polyploidization during aging

Abstract Background and Aims Aging is characterized by a progressive kidney function decline, resulting in chronic kidney disease (CKD), which is steeper in men than in women. However, sex-related differences in mechanisms underpinning CKD development during aging still remain to be clarified. In most organs regenerative capacity declines overtime from a pool of resident stem cells leading to tissue aging. In the kidney, we have revealed that two adaptive responses co-exist to recover kidney function after injury. On one hand a population of renal progenitors (RPC), which is interspersed among parietal epithelial cells of Bowman's capsule and tubular cells (TC) of nephron segments, proliferate and generate new podocytes and TC to recover structural integrity during the regenerative processes occurring in glomerular and tubular diseases. On the other, TC enter the alternative cell cycles to become polyploid in order to increase their functional capacity and maintain the residual kidney function after injury. However, a continuous TC polyploidization comes with the long term trade-offs (fibrosis and senescence), driving CKD. Here, we aimed to investigate the role of sexual dimorphism in these two different adaptive responses during aging. Method To trace RPC (Pax2+cells) we used the inducible Pax2/Confetti or Pax2/mTmG mice (RPC are randomly labelled by one of the four fluorescent reporter genes or with GFP respectively). To study polyploid TC, we used the inducible Pax8/FUCCI2aR mice (polyploid TC are identified by expression of cell cycle fluorescent proteins in combination with DNA content analysis). Mice were analyzed at 2, 5, 12 and 20 months of age. scRNA sequencing was performed at 2 and 20 months of age. Results Pax2/Confetti mice revealed that the number of Pax2+RPC either of the Bowman's capsule or in tubules was higher in female than in male mice at all ages. Specifically, tracing analysis during aging showed that in females Pax2+RPC of the Bowman's capsule generated new podocytes, resulting in glomeruli with a better integrity of the slit-diaphragm compared with aged males. Moreover, tubular Pax2+RPC in females clonally expanded, generating a higher number of clones, which were longer than those in males. scRNAseq analysis on kidneys showed that females were endowed with a greater number of Pax2+RPC with a higher expression of Pax2 than males, suggesting that RPC in females kept a higher regenerative capacity than males during aging. Simultaneously, analysis of tubular polyploidy demonstrated that, whereas in females the polyploid fraction progressively increased, it was drastically reduced in males during aging. These results suggested that whereas in females the increase of polyploid TC provided a better maintenance of kidney function overtime, loss of polyploid response in males made them more susceptible to develop CKD. Indeed, aged male mice showed a higher percentage of polyploid TC undergoing further cycles of polyploidization, which were associated with fibrosis and senescence. In agreement with these findings, we observed a progressive kidney function decline along with an increase of glomerulosclerosis, interstitial fibrosis and blood pressure, which were significantly greater in males than in females. Conclusion Female mice showed a higher regenerative and polyploid response compared to male mice, aimed likely to cope kidney function decline during aging. These results reveal the intriguing role of a new kidney adaptive response, which may explain the higher susceptibility of males to develop a more premature CKD during aging.

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-1β 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.

#2057 Sex differences in bioimpedance-spectroscopy-derived fluid status and body composition of maintenance hemodialysis patients

Abstract Background and Aims Bioimpedance-spectroscopy-(BIS)-derived estimates of fluid status and body composition are associated with mortality in patients undergoing maintenance hemodialysis (HD). Previously, thresholds for improved survival were identified for volume overload (VO, &amp;lt;2.5 L), VO relative to extracellular water (VO/ECW, &amp;lt;15%), lean tissue index (LTI, 15-20 kg/m2) and fat tissue index (4-15 kg/m2). However, these thresholds did not distinguish between sexes. Considering current efforts to untangle differences between male and female kidney disease patients, we aimed to analyze BIS data stratified by sex. Method We retrospectively evaluated pre-HD BIS measurements using the whole-body “Body Composition Monitor” device (Fresenius Medical Care). Measurements were conducted at the “Vienna Dialysis-Center”, a large tertiary dialysis center in Vienna, Austria. Continuous variables were described as medians and interquartile ranges and compared between sexes using Wilcoxon tests. Differences in proportions of males and females within the above-mentioned target ranges of body composition parameters were tested using Chi-Square tests and Fisher's exact tests. Results In November 2022, the Vienna Dialysis-Center cared for 304 patients, 159 of whom underwent BIS measurements. A total of 137 patients remained for analysis after excluding erroneous results (62% male, 38% female). The median [interquartile range] age among analyzed male and female patients was 60.0 years [48.0; 72.0] and 65.5 years [57.8; 75.3], and the median dialysis vintage was 28.9 months [12.1; 52.7] and 27.2 months [14.8; 61.9], respectively. VO (2.7 vs 1.9 L, p = 0.025), LTI (13.4 vs. 11 kg/m2, p &amp;lt; 0.001) and FTI (11.1 vs. 14.2 kg/m2, p = 0.036) differed significantly between males and females but VO/ECW did not (14.3 vs. 12%, p = 0.4). 27.1% of males (n = 23) were within 15-20 kg/m2 LTI compared to 7.7% of females (n = 4, p = 0.007). Differences in the proportions of male and female patients within optimal ranges of VO (43.5% vs. 61.5%, p = 0.062) and FTI (67.9% vs. 50.0%, p = 0.058) were close to reaching statistical significance. Conclusion We discovered relevant differences in fluid status and body composition among patients undergoing maintenance HD not only in absolute numbers, but also in the proportion of patients within the optimal range of LTI. Considering sex differences in body composition but (on average) equal mortality among HD patients, optimum target ranges of BIS measurements may differ between sexes. Our findings from this relatively small cohort call for large-scale sex-specific analyses of fluid status, body composition and outcomes in maintenance HD patients.

Sex differences in cholinergic signaling affect functional outcomes for theta-gamma coordination in hippocampal subcircuits following experimental febrile status epilepticus.

Sex determines cognitive outcome in animal models of early life seizure, where males exhibit impaired hippocampal-dependent learning and memory compared with females. The physiological underpinnings of this sex effect are unclear. Cholinergic signaling is essential for the generation of hippocampal oscillations, and supplementation of cholinergic precursors prior to status epilepticus in immature male rats prevents subsequent memory deficits. We hypothesized that there are sex differences in acetylcholine circuits and their response to experimental febrile status epilepticus (eFSE). eFSE was induced in male and female rat pups. We transversed the hippocampus of postnatal day >60 control (CTL) and eFSE rats with a 64-channel laminar silicon probe to assay cholinergic-dependent theta oscillations under urethane anesthesia. Local field potential properties were compared during (1) baseline sensory stimulation, (2) pharmacological stimulation via acetylcholine reuptake blockade, and (3) sensory stimulation after muscarinic acetylcholine receptor block (atropine). In all groups, a baseline tail pinch could elicit theta oscillations via corticohippocampal synaptic input. Following atropine, a tail pinch response could no longer be elicited in CTL male, CTL female, or eFSE female rats. In contrast, induced slow theta power in eFSE males after atropine was not decreased to spontaneous levels. Analysis of oscillation bandwidths revealed sex differences in acetylcholine modulation of theta frequency and slow gamma frequency and power. This study also identified significant effects of both sex and eFSE on baseline theta-gamma comodulation, indicating a loss of coupling in eFSE males and a potential gain of function in eFSE females. There are differences in cholinergic modulation of theta and gamma signal coordination between male and female rats. These differences may underlie worse cognitive outcomes in males following eFSE. Promoting the efficacy of muscarinic acetylcholine signaling prior to or following early life seizures could elucidate a mechanism for the temporal discoordination of neural signals within and between hippocampus and neocortex and provide a novel therapeutic approach for improving cognitive outcomes.

Investigating the Correlation between Frustration and Values with an Emphasis on Gender

This research paper investigates the correlation between individuals’ reactions to frustration and their values, with an emphasis on sex differences. Frustration is an arbitrary emotional response to obstacles or unmet expectations, although social values carry beliefs and principles that guide behavior within a societal context. Getting a gist of how sex influences these aspects can shed light on societal dynamics and inform interventions aimed at promoting psychological well-being and social harmony. The study undergoes a quantitative approach to the data, through different scales using SPSS to analyze data and gather comprehensive insights. Results reveal new patterns in how individuals of different genders perceive and respond to frustration in relation to their value system, Enlightening the need for gender-sensitive works in addressing emotional regulation and socialization processes.

Sex Differences in Athletic Performance Response to the Imagery and Mental Toughness of Elite Middle- and Long-Distance Runners.

This study aimed to determine whether there is a difference between the levels of imagery and mental toughness in the context of sports performance in male and female athletes. A total of 344 track and field athletes, 205 male (59.6%, 23.3 ± 4.0 years) and 139 female (40.4%, 22.9 ± 4.0 years), voluntarily participated in the study. Imagery Inventory and Mental Toughness Inventory in Sport were used as data collection tools in the study. In the evaluation of athletic performance, athletes were asked about their ranks in the years 2020, 2021, and 2022 and were categorized according to the scoring tables specified by the International Association of Athletics Federation. A MANOVA analysis was used to determine whether there was a difference between low (-2% to +5%), medium (+6 to +11%), and high (+12 to +17%) performers among male and female athletes, and a post hoc analysis was used to determine the source of the difference. According to the present findings, there was no significant difference between the imagery and mental toughness levels of athletes with high, medium, and low performance among male athletes. On the contrary, a significant difference was detected between the imagery and mental toughness levels of female athletes with medium and high performances, showing that athletes in the high-performance range had higher levels of imagery (Eta2 = 8) and mental toughness (Eta2 = 10) than athletes in the medium- and low-performance ranges. The findings of this study show that imagery and emotional intelligence are important factors for sports performance. In this context, coaches and sports psychologists can include these parameters in their training programs to achieve the optimal performance range.

#1668 The 60:40 conundrum: are women with CKD discriminated against after referral to a nephrology clinic?

Abstract Background and Aims The representation of women in kidney medicine clinical trials has diffused the belief that women are discriminated although epidemiological data suggest that chronic kidney disease (CKD) is more prevalent among females than males. We aimed to test whether sex distribution varies at nephrology referral, inclusion in a clinical study or at the starting of dialysis. Method This was a retrospective, monocentric study conducted in a large non-university hospital in central France. We exploited data from patients included in the PRO-RE-RE-PRO study on the effect of diet on the progression of CKD. We evaluated patients’ characteristics and gender at the time of the first consultation in the Unit for the Care of Advanced CKD (UIRAV), at the inclusion in the PRO-RE-RE-PRO study and at the beginning of the kidney replacement therapy. Results 866 patients were included in this study as they were referred to the UIRAV, 59% males and 41% females. Female patients were older but less comorbid and were referred at the same eGFR than males. The same proportion of males/females was observed in patients included in the PRO-RE-RE-PRO study. No sex differences were observed at dialysis start. Survival was significantly higher in females. Overall, distribution across sex remained stable over time. Conclusion The main result of this study is the stability of the approximately 35-40% female to 60-65% male ratio from start of follow-up in all subsets of cases: patients referred to the unit dedicated to advanced CKD, patients recruited in the observational study, patients not included, or who refused to participate, patients on follow-up at the completion of the database. Furthermore, the same distribution is observed in dialysis patients, from dialysis start to the most recent update. Our data suggest that if a gender-selection bias exists in nephrology, it should be sought before the first nephrology referral. However, further studies are needed to ensure health equity.