Search Results (6,743)

Male fetuses generally grow faster in utero and are heavier at birth than females, whereas the rates of perinatal mortality and morbidity are often higher in boys than in girls. Sexual dimorphism in placental function is believed to contribute to these differences. However, evidence for sex-specific differences in placental function remains limited. We hypothesized that placental nutrient-sensing signaling activity, amino acid transport capacity, and mitochondrial respiration are higher in male than female placentas. Placentas were collected from 46 women (BMI 18.5–29.9 kg/m²) with uncomplicated pregnancies delivering appropriate-for-gestational-age infants (n = 23 female; n = 23 male). In homogenates of male placentas, the phosphorylation of S6RP (Ser235/236) was increased and total 4E-BP1 protein expression was reduced compared with female placentas, indicating enhanced mTORC1 signaling. In vitro System A amino acid transport activity was also greater in microvillous plasma membranes isolated from male placentas. Placental mitochondrial respiratory capacity was assessed in villous tissue using high-resolution respirometry with carbohydrate and lipid substrate–uncoupler–inhibitor titration (Carb SUIT and Lipid SUIT) protocols on the Oroboros O2k platform. Male placentas exhibited greater maximal oxidative phosphorylation capacity, enhanced complex II-linked respiration, and higher maximal electron transport system capacity compared with female placentas under both carbohydrate- and lipid-supported respiratory conditions. Although placental weight did not differ between sexes, the birth weight-to-placental weight ratio was significantly higher in male pregnancies, consistent with greater placental functional efficiency. In conclusion, placental mTORC1 signaling activity, System A amino acid transport activity, and mitochondrial respiratory capacity are greater in male than female placentas and are associated with greater placental functional efficiency and fetal growth in male pregnancies. Full article

Glioblastoma (GBM) exhibits marked sex differences in incidence, outcome, and molecular regulation, yet the mechanisms underlying these disparities remain poorly defined. ZEB1 is a neurodevelopmental transcription factor implicated in GBM progression and cellular plasticity, but its prognostic and functional relevance may differ by sex. Here, we analyzed TCGA-GBM transcriptomic and clinical data to assess the relationship between ZEB1 expression, patient sex, and survival and to identify sex-specific transcriptional programs associated with ZEB1. Patients were stratified by ZEB1 expression and sex, followed by differential expression analysis, functional enrichment, and survival modeling. High ZEB1 expression was associated with improved overall survival in female patients but not in male patients. Sex-stratified transcriptomic analysis revealed distinct ZEB1-associated gene expression signatures, with enrichment of chromatin-modifying and demethylase-related pathways among male–female comparisons. Candidate Y-linked epigenetic regulators, including KDM5D and UTY, were differentially expressed in ZEB1-high male tumors. qPCR validation in male and female patient-derived GBM cell lines supported sex-dependent regulation of these candidates and showed that KDM5D and UTY expression was reduced following ZEB1 knockdown in male cells. Together, these findings identify a sex-dependent prognostic role for ZEB1 in GBM and suggest that ZEB1 interacts with sex-chromosome-linked epigenetic regulators to shape tumor transcriptional states. Full article

Hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis D virus (HDV), together with HIV and bacterial sexually transmitted infections (STIs), account for a rising toll of more than one million deaths annually and overlap within shared behavioral and social networks, yet are still diagnosed through separate, pathogen-specific pathways. This narrative review synthesizes contemporary evidence on the convergence between viral hepatitis, HIV, and high-risk STI groups—men who have sex with men, pre-exposure prophylaxis (PrEP) users, people practicing chemsex, people who inject drugs, incarcerated populations, and migrants from endemic regions—and characterizes the diagnostic technologies and linkage-to-care models available to address it. Despite effective antivirals, the diagnostic cascade remains the principal bottleneck: most people with chronic HCV are undiagnosed, and HDV—with a pooled anti-HDV seroprevalence of approximately 4.5% among HBsAg-positive individuals—is its clearest expression, as most carriers are never tested. Reflex algorithms, multiplex panels, point-of-care assays, dried blood spots, and electronic health record alerts are validated but unevenly implemented. We argue that, alongside persistent resource, political, and equity-related constraints, a substantial share of the remaining barriers is operational rather than purely technological, and propose a practical, STI-clinic-centered framework integrating reflex testing, population-specific periodicity, and explicit linkage pathways toward the WHO 2030 elimination targets. Full article

Decapod Iridescent Virus 1 (DIV1) causes severe economic losses in Macrobrachium rosenbergii farming. Serum metabolic biomarkers are valuable tools for disease-resistant breeding, yet most existing studies employ mixed-sex samples, and the impact of sexual dimorphism on screening reliability remains poorly quantified. In this study, non-targeted serum metabolomics was performed on 28 healthy M. rosenbergii (14 females and 14 males), which were divided into marginally resistant and susceptible groups after DIV1 challenge. We compared results from mixed-sex and sex-specific screening strategies, and separately analyzed the overlap of upregulated and downregulated differential metabolites. Significant basal sexual dimorphism was observed in serum metabolism. Mixed-sex analysis identified 247 differential metabolites, while male-specific and female-specific analyses identified 121 and 161, respectively. Only 26 metabolites showed consistent directional changes across all three comparisons, accounting for 10.5% of total mixed-sex differential metabolites. Nearly 90% of mixed-sex results were either sex-specific signals or independent of sex. Analyses that do not account for sex introduce a large number of sex-unrelated differential markers and mask sex-specific metabolic features, and sex-specific screening is a necessary strategy to obtain reliable metabolic biomarkers for crustacean disease-resistant breeding. Full article

The aim of this study was to provide the first characterization of selected components of innate immunity (lysozyme and complement component C3) and adaptive humoral immunity (immunoglobulin Y) in seven Italian autochthonous chicken breeds and two turkey breeds. A total of 70 chickens (10 animals per breed) and 20 turkeys (10 animals per breed), equally distributed by sex, were sampled. The concentrations of immune traits were determined using avian-specific ELISA kits. In chickens, significant breed effects were detected for all traits, whereas sex influenced lysozyme and complement component C3 levels. Males generally showed greater lysozyme and complement component C3 levels than females. Higher lysozyme levels were found in Bionda Piemontese (920.8 ng/mL) and Bianca di Saluzzo (766.5 ng/mL), while the highest complement component C3 values were observed in Bionda Piemontese (315.2 µg/mL) and Bianca di Saluzzo roosters (287.4 µg/mL) and in Siciliana hens (329.1 µg/mL). Immunoglobulin Y showed limited variation among breeds and sexes. In turkeys, only lysozyme levels differed between breeds. Overall, these preliminary results, obtained from a limited number of individuals, reveal measurable differences in immune traits among Italian autochthonous poultry breeds, particularly for innate immune parameters, suggesting that genetic background may contribute to variation in immune responsiveness. These findings provide baseline data to support genetic conservation strategies and sustainable breeding programs for resilient poultry systems. Full article

Background: Chronic rhinosinusitis (CRS) impairs the quality of life (QoL), but its impact and risk factors remain unknown among Iraqis, including medical students. We aim to assess the QoL using the Sino-Nasal Outcome Test-22 (SNOT-22) in CRS-affected Iraqi medical students, categorize impairment severity, and identify associated correlates via multivariable analysis. Methods: We surveyed 435 Iraqi undergraduates with CRS to identify QoL correlates, SNOT-22 severity strata, associated symptoms, seasonality, and treatment history. Data analysis, including multivariable models, was conducted in IBM SPSS version 27. Results: Among 435 surveyed individuals, 76.6% had impaired QoL. Binary logistic regression identified key correlates: immune disturbances (OR = 2.68; p = 0.028), family history (OR = 2.12; p = 0.003), chronic comorbidities (OR = 2.07; p = 0.037), and pre-clinical (basic) educational level (OR = 1.95; p = 0.007). In sex-stratified models, chronic comorbidities predominated in females (OR = 4.64; p < 0.001) and immune disturbances in males (OR = 3.89; p = 0.014). Ordinal regression confirmed immune disturbances (β = 0.65; p = 0.017), chronic comorbidities (β = 0.58; p = 0.023), and family history (β = 0.57; p = 0.003). Logistic and ordinal regression exhibited good model fitting (p > 0.05) and showed comparable statistical accuracy (76.8% vs. 76.1%). Conclusions: Impaired QoL was common among CRS-affected medical students, with immune disturbances and family history as the strongest correlates. Sex-specific differences existed. Findings highlight the need for personalized management of high-risk groups. Full article

Background/Objectives: Individuals with autism spectrum disorder (ASD) represent a special population whose characteristics may adversely affect both their own and their families’ quality of life. These characteristics include poor oral health, sensory hypersensitivity, restrictive and repetitive behaviours, communication difficulties, medication-related adverse effects, and associated comorbidities. This scoping review aimed to evaluate the oral health-related quality of life (OHRQoL) of children and adolescents with ASD, as perceived by their parents/caregivers, and to identify the factors associated with these outcomes. Methods: Literature searches were conducted in the MEDLINE/PubMed, Scopus, Web of Science, Embase, and Google Scholar databases. Studies published between 2016 and May 2026 were considered for inclusion. Results: Of the 799 records identified, 23 studies met the eligibility criteria. Among these, 15 used the Parental-Caregiver Perceptions Questionnaire (P-CPQ), an instrument specifically developed for children with cognitive impairments. Most studies reported statistically significant associations between poorer OHRQoL and dental caries experience, lower household income, older age, male sex, and lower parental oral health literacy. Conversely, preventive interventions and comprehensive dental rehabilitation performed under general anaesthesia were associated with improvements in the quality of life of both children and their families. Parents of children with ASD also reported a greater emotional burden, primarily related to responsibility for toothbrushing, dental attendance, the child’s general health status, and the family’s financial situation. Conclusions: The majority of the included studies indicate that, according to parental reports, children and adolescents with ASD experience poor OHRQoL, particularly in the domains of emotional well-being, social well-being, functional limitations, and oral symptoms. These findings highlight the need for targeted preventive strategies and multidisciplinary interventions aimed at improving both oral health and overall quality of life in this vulnerable population. Full article

Background/Objectives: Obesity has been linked to a distinct non-allergic, late-onset, neutrophilic asthma phenotype for more than two decades, yet whether obesity should be regarded as a cause of that phenotype rather than a coexisting comorbidity remains unresolved because randomised allocation to obesity is neither feasible nor ethical. This review asks whether the evidence accumulated between 1995 and 2026 supports a causal interpretation. Methods: A structured narrative synthesis was undertaken. PubMed/MEDLINE, Scopus and Web of Science were searched from January 1995 to June 2026 (the synthesis emphasises the 2020–2026 evidence while drawing on the full window for landmark studies) for cohort, cross-sectional, Mendelian randomisation (MR), interventional, mechanistic and pharmaco-epidemiological studies; landmark earlier work was retained where it remains the primary source for a given viewpoint. The retrieved evidence was mapped onto Sir Austin Bradford Hill’s nine viewpoints (1965) and triangulated using E-values for unmeasured confounding, GRADE, directed acyclic graphs and MR. Results: All nine viewpoints were satisfied to varying degrees. Strength: effect estimates 1.4–6.8, E-values 4.8–13.1, MR summary risk ratio 1.05 per 1 kg/m². Consistency: replication across four continents, both sexes and multiple study designs. Temporality: prospective cohort and life-course MR evidence. Biological gradient: body mass index dose–response for TNFα, IL-17A and Th17 frequency. Plausibility: a twelve-layer architecture from adipose dysfunction to bronchial epithelium. Coherence, experimental evidence (bariatric surgery, lifestyle weight loss, GLP-1 receptor agonists, murine and in vitro models) and analogy were also supported; specificity was met at the phenotype level. Conclusions: The cumulative evidence strongly supports a causal contribution of obesity to the development of the late-onset, non-allergic asthma phenotype while falling short of definitive proof (GRADE: moderate certainty), with implications for primary prevention, endotype-targeted therapy and longitudinal research. Phenotype-stratified MR remains the principal missing element of the causal argument. Full article

Background/Objectives: The hemoglobin–albumin–lymphocyte–platelet (HALP) score combines routine laboratory measures into an index of systemic immune–nutritional status. Its relationship with graded diabetic retinopathy (DR) severity is not fully established. We compared HALP between patients with DR and ophthalmology controls without documented diabetes and examined its association with retinopathy stage and proliferative disease. Methods: This prospective single-center case–control study enrolled 209 consecutive adults: 105 patients with DR and 104 controls. DR was recorded across eight ordered stages and additionally classified as non-proliferative DR (NPDR) or proliferative DR (PDR). Between-group tests, Spearman correlation, logistic regression, and receiver operating characteristic analysis were used. Results: HALP was lower in the DR group than in controls (47.47 [26.44] vs. 52.67 [31.83], p = 0.048) and in PDR than in NPDR (45.98 [17.62] vs. 52.90 [42.49], p = 0.008). HALP declined modestly with increasing stage (rho = −0.260, p = 0.007). In an exploratory age- and sex-adjusted model, each 10-unit increase in HALP was associated with lower odds of case-group membership (OR = 0.850, 95% CI: 0.750–0.963; p = 0.011). Within the DR cohort, HALP was not significantly associated with PDR after adjustment for age, sex, and HbA1c (OR = 0.809, 95% CI: 0.640–1.023; p = 0.077). Discrimination between cases and controls was limited (AUC = 0.579); a threshold of ≤52.09 provided 62.9% sensitivity and 53.8% specificity. Conclusions: Lower HALP values accompanied DR case status and greater retinopathy severity, but the adjusted association with PDR was not significant. Because diabetes status differed between groups, the case–control finding may reflect systemic effects of diabetes as well as retinal involvement. Full article

Background: Commencing peritoneal dialysis (PD) with a lower dose (incremental PD) is a common strategy to improve patient acceptance and reduce treatment burden. However, specific dietary protein recommendations for incremental PD are lacking. Methods: An interim analysis of the I-COPE PD study cohort aimed to assess one-year changes in serum albumin, body mass index (BMI), and metabolic parameters in a cohort of patients on incremental PD. Following local protocols, patients were categorized into two groups according to protein diet prescription: protein diet (PrD) ≤ 0.6 and PrD > 0.6 g/kg/day. Longitudinal changes at baseline, 6 and 12 months were analyzed using mixed-effects models adjusted for age, sex, diabetes, residual kidney function and serum albumin at baseline. Results: We included 205 patients (mean age 63.3 ± 14.2 years; 66% male; 30% diabetes; 92.2% CAPD) and in 45.4% a PrD ≤ 0.6 g/kg/day was prescribed. Baseline demographic, clinical, lab and therapeutic characteristics were well-balanced between the two diet groups. After one year of follow-up, the prevalence of patients persisting in incremental PD was not different between the two dietary groups (59.1% in PrD ≤ 0.6 vs. 63.3% in PrD > 0.6, log-rank test = 0.759), and both groups showed a similar trend in serum albumin, characterized by an initial decline followed by stabilization (p = 0.647), with no significant differences in BMI (p = 0.461). Despite comparable dialysis adequacy, patients on PrD ≤ 0.6 exhibited significantly lower serum urea, phosphate, and potassium levels over time compared to the PrD > 0.6 group. Conclusions: In patients starting incremental PD, the prescription of a lower protein diet could be associated with better control of uremic toxins, while serum albumin levels over time remain comparable to those observed in patients under a higher-protein diet. Full article

Background: Attention-deficit/hyperactivity disorder (ADHD) is associated with cognitive, behavioral, emotional, and social difficulties that may increase vulnerability to bullying during childhood and adolescence. Although previous studies have examined different aspects of this relationship, the available evidence remains limited and heterogeneous, particularly regarding associated factors, profiles of bullying involvement, and implications for prevention and intervention. Objective: To analyze the available evidence regarding bullying involvement in children and adolescents with ADHD, focusing on victimization, perpetration, bully–victim profiles, associated factors, psychological consequences, and implications for prevention and intervention. Methods: A narrative review was conducted using studies identified in PubMed, Scopus, and Web of Science between January and March 2026, with no publication date restrictions. The search was performed in three independent and consecutive stages and included observational studies evaluating the relationship between ADHD and bullying in children and adolescents. Narrative reviews, systematic reviews, meta-analyses, editorials, and studies conducted exclusively in adults were excluded. Results: Seventeen studies were included. The evidence consistently showed that children and adolescents with ADHD have greater involvement in bullying than their peers without ADHD. Victimization was the most consistently reported outcome, although increased perpetration, bully–victim profiles, and cyberbullying were also identified. Bullying involvement appeared to be influenced by multiple interacting factors, including ADHD symptoms, emotional dysregulation, impulsivity, comorbidities, peer relationships, family characteristics, and school-related factors. Victimization was consistently associated with increased anxiety and depressive symptoms, emotional difficulties, and poorer quality of life. Emerging evidence also suggests sex-specific patterns of bullying involvement and bidirectional longitudinal relationships between ADHD symptoms and bullying experiences. Conclusions: Children and adolescents with ADHD may have greater involvement in multiple forms of bullying; however, this relationship appears to be multifactorial rather than solely explained by core ADHD symptoms. Family, peer, and school environments may play important protective roles, highlighting the need for comprehensive prevention and intervention strategies that address both individual and contextual factors. Full article

Countries face interconnected policy challenges: population aging, fertility change, migration, urbanization, labor transitions, food and water security, climate risk, health-system demand, school planning, housing pressure, consumption planning, and spatial inequality. Yet planning evidence is often fragmented across ministries, statistical offices, surveys, administrative systems, research projects, and dashboards. This paper proposes the Population-Based Systems Model, or PopSyM, as a country-owned analytical infrastructure that places population dynamics at the center of integrated policy planning. PopSyM begins with a demographic spine by age, sex, location, year, and scenario, then links that spine to modules for health, education, food, labor, housing, social protection, environment, and local infrastructure. Its purpose is not projection for its own sake, but the measurement and improvement of population well-being: longer and healthier lives, adequate material conditions, skills, meaningful work, security, dignity, and country-specific dimensions of a good life. Nepal is used as a motivating example, but the proposed architecture is general. The paper argues that the population should be treated not only as a denominator for indicators but also as the organizing framework through which countries understand future demand, vulnerability, consumption needs, policy trade-offs, and feedback between people and systems. Full article

Heart rate variability (HRV) is a non-invasive marker of cardiac autonomic regulation that reflects the dynamic interaction between sympathetic and parasympathetic influences on the sinoatrial node. Reduced HRV is a hallmark of autonomic dysfunction and has been consistently associated with adverse outcomes across a wide range of cardiovascular conditions, particularly heart failure (HF). HRV is markedly reduced in HF, reflecting profound autonomic imbalance characterized by vagal withdrawal, impaired baroreflex sensitivity, and altered cardiorespiratory coupling. In heart failure with reduced ejection fraction (HFrEF), lower global HRV, particularly reduced SDNN, is consistently associated with mortality, sudden cardiac death, and disease progression. In heart failure with preserved ejection fraction (HFpEF), emerging observational evidence suggests that HRV alterations may accompany early autonomic dysregulation and may be associated with sex-specific patterns, although their mechanistic and prognostic significance remains incompletely defined. In acute HF, HRV assessed during hospitalization may provide additional prognostic information, although current evidence remains limited and heterogeneous. Pharmacological therapies, cardiac resynchronization therapy, exercise training, and lifestyle interventions have variably modulated HRV across studies, but the evidence is heterogeneous and changes in HRV should not be assumed to translate directly into improved clinical outcomes. Despite persistent challenges related to methodological standardization and clinical implementation, emerging technologies and multimodal approaches may refine the feasibility of integrating HRV into risk assessment frameworks. This narrative review aims to summarize the physiological basis of HRV, critically evaluate its alterations across different HF phenotypes, and discuss its prognostic associations, therapeutic modulation, and current practical limitations in clinical application. Full article

Sexual dimorphism is a fundamental feature of aging, yet the liver-centric mechanisms underlying sex-specific aging trajectories remain incompletely understood. SIRT6, a NAD⁺-dependent deacetylase, is a master regulator of genome stability, metabolic homeostasis, and longevity. However, its cell-type- and sex-specific functions in aging have not been fully characterized. Here, we generated hepatocyte-specific Sirt6 knockout (HKO) mice of both sexes and evaluated longitudinal lifespan, comprehensive metabolic profiling, hepatic histopathology, and transcriptomic profiles. Female HKO mice exhibited an acceleration of aging and a 17.60% reduction in median lifespan, characterized by severe systemic gerometabolic decline, visceral adiposity, and advanced metabolic-associated fatty liver disease (MAFLD). In stark contrast, aged male HKO mice displayed an enhanced catabolic state and lipid-clearing phenotype via the compensatory reprogramming. Mechanistically, hepatic Sirt6 deficiency in females exclusively hyperactivated the expression of estrogen sulfotransferase SULT1E1, resulting in reduced circulating estradiol levels. This hormonal collapse triggered a self-amplifying pathological triad of de novo lipogenesis, genomic instability, and cellular senescence. Crucially, pharmacological SIRT6 activation using the small-molecule activator MDL-800 suppressed Sult1e1 expression, restored estrogen homeostasis, and successfully rescued the gerometabolic phenotypes in aged female mice. Collectively, these findings demonstrate that hepatic SIRT6 regulates female lifespan and healthspan by safeguarding estrogen homeostasis, defining the druggable SIRT6-SULT1E1 axis as a sex-stratified therapeutic target against age-related metabolic decline. Full article

This study examines the long-term associations between ambient air pollutants and the burden of major respiratory and infectious diseases in this geographically sensitive region. A retrospective analysis was conducted using ICD-10-coded hospital records of patients diagnosed with asthma, chronic obstructive pulmonary disease (COPD), bronchitis, and tuberculosis from January 2020 to June 2026. These data were integrated with in situ air quality measurements, including PM₁₀, PM_2.5, and SO₂, as well as satellite-derived Aerosol Optical Depth (AOD) from MODIS. Disease incidence was stratified by year, sex, and age groups (0–85+ years) to assess demographic susceptibility patterns. Respiratory diseases constituted a substantial public health burden over the study period. Asthma showed a marked female predominance (≈29,700 females vs. ≈16,000 males) and a bimodal age distribution with peaks in early childhood (0–5 years) and mid-adulthood (35–50 years). COPD was predominantly observed in males (≈8300 males vs. ≈5500 females), with a higher median age range (≈67–70 years). Bronchitis exhibited a similar bimodal pattern, disproportionately affecting both pediatric and elderly populations, while overall case numbers declined over time. Tuberculosis incidence was approximately threefold higher in males than females, with notable age-related divergence, affecting younger females (≈30–32 years) and middle-aged males (≈42–45 years). The findings suggest a spatial–temporal correspondence between elevated pollutant concentrations and respiratory disease prevalence in the Iğdır Basin. The observed sex- and age-specific disparities underscore the potential value of region-specific environmental health strategies, strengthened air quality management, and continuous epidemiological surveillance in enclosed basin environments. Full article