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23 pages, 1943 KB  
Article
The Impact of GAGs, Cross-Link Maturity and Telopeptides on the Formation of a Porcine Collagen-Based Hydrogel
by Monika Šupová, Šárka Rýglová, Tomáš Suchý, Margit Žaloudková and Martin Braun
Gels 2025, 11(9), 695; https://doi.org/10.3390/gels11090695 (registering DOI) - 1 Sep 2025
Abstract
Collagen hydrogels serve as biomimetic scaffolds that closely resemble the natural extracellular matrix, thus providing an ideal 3D biocompatible environment for cells. However, based on our previous experience, not all collagen isolates are capable of gelling, which appears to depend on the type, [...] Read more.
Collagen hydrogels serve as biomimetic scaffolds that closely resemble the natural extracellular matrix, thus providing an ideal 3D biocompatible environment for cells. However, based on our previous experience, not all collagen isolates are capable of gelling, which appears to depend on the type, origin, species, age and sex of the source animal and the collagen isolation method applied. We therefore decided to evaluate porcine collagen-rich materials isolated from two different porcine genotypes applying two different specific isolation methods, and to analyse other main components, i.e., lipids and glycosaminoglycans, as well as amino acid composition and structural and morphological properties. While all the collagen isolates obtained were subjected to the gelling process, only one of them successfully gelled. In addition, the gelling ability of this isolate was confirmed repeatedly on collagens that were isolated from other pigs of the same porcine genotype. The results revealed that the gelling process proceeds via cooperation between the composition and the structure of the collagen isolate. With respect to the composition, one of the most important factors in terms of the success of the gelation process of collagen isolates concerns elevated glycosaminoglycan contents. The structural factors that characterise collagen isolates, i.e., cross-links (immature and mature) and their mutual ratio, as well as the presence of telopeptides, strongly impact the progress of the gelling process and the resulting character of the hydrogel structure. All these factors are influenced by the isolation procedure. Full article
(This article belongs to the Special Issue Advances in Hydrogels for Regenerative Medicine)
20 pages, 678 KB  
Article
Association of Single-Nucleotide Polymorphisms on FURIN and EPHA2 Genes with the Risk and Prognosis of Undifferentiated Nasopharyngeal Cancer
by Seddam Hares, Kamel Hamizi, Hamza Rahab, Maewa Hibatouallah Bounneche, Souhila Aouidane, Leila Mansoura, Manel Denni, Wissem Mallem and Ghania Belaaloui
Int. J. Mol. Sci. 2025, 26(17), 8486; https://doi.org/10.3390/ijms26178486 (registering DOI) - 1 Sep 2025
Abstract
The undifferentiated nasopharyngeal cancer (NPC) is a multifactorial disease mainly due to Epstein-Barr Virus (EBV) infection. The transmembrane tyrosine kinase ‘EphA2’ and the protease ‘Furin’ are implicated in the EBV entry into epithelial cells and other physiological processes. To gain insights into the [...] Read more.
The undifferentiated nasopharyngeal cancer (NPC) is a multifactorial disease mainly due to Epstein-Barr Virus (EBV) infection. The transmembrane tyrosine kinase ‘EphA2’ and the protease ‘Furin’ are implicated in the EBV entry into epithelial cells and other physiological processes. To gain insights into the association of single-nucleotide polymorphisms (SNPs) rs4702 and rs6603883 (FURIN and EPHA2 genes, respectively) with the risk and prognosis of the NPC, the genotypes of 471 individuals (228 cases and 243 controls) were assessed alongside risk cofactors (sex, tobacco, alcohol, occupation, and recurrent Ear, Nose and Throat infections) and prognosis cofactors (Tumor stage, local invasion, lymph node involvement, and metastasis) using multivariable logistic regression. We found that only the rs4702 AG/GG genotypes were statistically significantly associated with a reduced risk of cancer, both in the overall population and in men (approximately 50% reduction). The rs4702 GG genotype was also associated with a low frequency of local tumor invasion in the whole population (OR = 0.382, p = 0.017, co-dominant model, and OR = 0.409, p = 0.02, recessive model), but heterozygous women were associated with a higher lymph node involvement (OR = 3.53, p = 0.031, co-dominant model, and OR = 3.62, p = 0.02, overdominant model). The rs6603883 GG genotype was associated, in the dominant model, with distant metastasis in the whole population (OR = 2.5, p = 0.024), with advanced clinical stage in men (OR = 2.22, p = 0.034), and with advanced clinical stage and distant metastasis in patients under 49 years (OR = 3.13, p = 0.009, and OR = 5.15, p = 0.011, respectively). Additionally, men having the rs6603883 GA genotype were associated with lymph node invasion (OR = 2.22, p = 0.027, overdominant model). Our study is the first to demonstrate that FURIN and EPHA2 germline gene polymorphisms are associated with NPC risk (for rs4702) and prognosis (for both rs4702 and rs6603883), with sex-specific differences. These results need to be replicated and further investigated in other populations. Full article
(This article belongs to the Section Molecular Oncology)
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17 pages, 6375 KB  
Article
Sex-Specific Metabolic, Immunologic, and Behavioral Effects of Perfluorooctane Sulfonic Acid (PFOS) in BTBR-mtB6 Mice
by Danielle Qiu Yun Jiang, Fatma Eldefrawy, Jarissa Isabel Navarro and Tai L. Guo
Sci 2025, 7(3), 118; https://doi.org/10.3390/sci7030118 - 1 Sep 2025
Abstract
Perfluorooctane sulfonate (PFOS), a member of the per- and polyfluoroalkyl substance (PFAS) family, has been associated with adverse health effects, including potential links to autism spectrum disorder (ASD). This study investigates the impact of PFOS on metabolic, immunologic and behavioral profiles in BTBR-mt [...] Read more.
Perfluorooctane sulfonate (PFOS), a member of the per- and polyfluoroalkyl substance (PFAS) family, has been associated with adverse health effects, including potential links to autism spectrum disorder (ASD). This study investigates the impact of PFOS on metabolic, immunologic and behavioral profiles in BTBR-mtB6 mice, a mouse strain that models ASD, to provide insights into the role of PFOS in ASD development and related health concerns. Three-month-old male and female BTBR-mtB6 mice were divided into two groups (n = 6) and received daily administration of either 1 mg/kg PFOS or vehicle over a three-month period by gavage. Metabolic assessments included measurements of body weight and weekly blood glucose levels, glucose and insulin tolerance tests, organ weights, and body compositions (free fluid, fat and lean tissue). Immune profiling was conducted via flow cytometric analysis of splenic leukocytes, while behavioral evaluations included grooming, sniffing, and three-chamber social interaction tests. PFOS exposure disrupted glucose homeostasis, with both sexes exhibiting elevated blood glucose levels. Male mice showed impaired glucose tolerance, delayed glucose level recovery, and increased insulin resistance, while females displayed decreased insulin resistance. Additionally, PFOS exposure led to liver enlargement in both sexes. Behavioral assessments revealed heightened grooming in PFOS-treated males, commonly interpreted as stress- or ASD-related repetitive behaviors, whereas females exhibited reduced grooming, reflecting altered behavioral responses to exposure. Immune alterations were also sex specific. PFOS-treated males exhibited decreased granulocytes, increased macrophages, and enhanced surface expressions of B220 and CD40L. PFOS-treated females showed increased macrophages, B-cells, cytotoxic T-cells and CD25+ T-cell subsets, with enhanced surface expression of B220 and CD8, and reduced surface expression of Mac-3. In addition, PFOS exposure reduced spleen weight in females. Taken together, PFOS exposure induced significant physiological and behavioral changes in BTBR-mtB6 mice, with sex-specific differences observed. These results raise concern that PFASs may contribute to the development or exacerbation of metabolic, immune and neurodevelopmental disorders, highlighting the need for sex-specific human risk assessment in environmental toxicology. Full article
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10 pages, 217 KB  
Article
Sex- and Sport-Specific Differences in Jump Strategies: Key Qualities for Jump Performance
by Jing-Hong Lin, Shayna Goldstein and E. Todd Schroeder
Sports 2025, 13(9), 292; https://doi.org/10.3390/sports13090292 - 1 Sep 2025
Abstract
This study investigated countermovement jump (CMJ) strategies among NCAA Division 1 athletes and explored key variables associated with jump height. A total of 69 athletes (38 male, 31 female) from basketball and volleyball teams completed three or more CMJ trials on force plates [...] Read more.
This study investigated countermovement jump (CMJ) strategies among NCAA Division 1 athletes and explored key variables associated with jump height. A total of 69 athletes (38 male, 31 female) from basketball and volleyball teams completed three or more CMJ trials on force plates during their regular neuromuscular monitoring. Using repeated-measures correlation analysis, we examined the relationships between various force–time variables and jump height across different sports and sexes. The results demonstrated very strong correlations between concentric peak velocity and jump height across all groups (r > 0.987). In addition, female athletes exhibited higher correlations between force-related parameters (concentric peak force, relative concentric peak force, and relative concentric mean force) and jump height compared to male athletes. Furthermore, no significant differences in force asymmetry were observed between sports or sexes. These findings indicate that concentric peak velocity serves as a key indicator of jump performance while emphasizing the importance of considering the interaction between force, time, and velocity, rather than focusing solely on peak force production. This research provides valuable insights for developing sport-specific training programs and monitoring jump performance in collegiate athletes, highlighting the necessity of individualized assessment and training approaches rather than assuming specific physical qualities are associated with particular populations. Full article
16 pages, 1128 KB  
Article
CK2α Overexpression in Colorectal Cancer: Evidence for Sex- and Age-Linked Differences
by Jana Romy Friedrich, Clara Meier, Guido Plotz, Stefan Zeuzem, Angela Brieger and Sarah J. Overby
Cancers 2025, 17(17), 2857; https://doi.org/10.3390/cancers17172857 (registering DOI) - 30 Aug 2025
Abstract
Background/Objectives: Colorectal cancer (CRC) remains a leading cause of cancer-related deaths, with notable sex-specific differences in its incidence, diagnosis, and outcomes. Our previous work identified casein kinase 2 alpha (CK2α) as being capable of impairing DNA mismatch repair (MMR) via phosphorylation of MLH1, [...] Read more.
Background/Objectives: Colorectal cancer (CRC) remains a leading cause of cancer-related deaths, with notable sex-specific differences in its incidence, diagnosis, and outcomes. Our previous work identified casein kinase 2 alpha (CK2α) as being capable of impairing DNA mismatch repair (MMR) via phosphorylation of MLH1, thereby increasing the tumor mutational burden. This study aimed to investigate sex-specific differences in CK2α protein expression in CRC. Methods: Immunohistochemical (IHC) analysis was performed on 161 CRC tumors and adjacent normal tissues to quantify the CK2α protein levels. A multi-cohort meta-analysis of proteomic and clinical data was conducted to validate our findings and assess the correlations with age, sex, and relevant signaling pathways. Results: Female CRC patients exhibited significantly higher CK2α expression than male patients, which was confirmed in two independent cohorts. Additionally, CK2α expression was positively correlated with age in female but not male patients. Cross-cohort correlation analyses linked CK2α levels with key proteins involved in estrogen receptor signaling and aging, including DEAD-box helicase 5 (DDX5), histone deacetylase 1 (HDAC1), proliferating cell nuclear antigen (PCNA), prohibitin-2 (PHB2), H/ACA ribonucleoprotein complex subunit 2 (NHP2), and dual-specificity mitogen-activated protein kinase kinase 3 (MAP2K3). Conclusions: CK2α is significantly overexpressed in the tumor tissue of female CRC patients and shows a strong age-related correlation. These findings suggest a sex- and age-specific regulatory mechanism potentially influenced by estrogen signaling or menopause. Such dimorphisms underscore the need for sex-specific strategies in CRC biomarker development and therapy. Full article
(This article belongs to the Section Cancer Immunology and Immunotherapy)
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17 pages, 1749 KB  
Article
Frequency-Dependent Modulation of Short-Term Neuronal Dynamics in the Female and Male Dorsal and Ventral Rat Hippocampus
by Athina Miliou, Giota Tsotsokou, Michaela Tsouka, Andriana Koutsoumpa and Costas Papatheodoropoulos
Int. J. Mol. Sci. 2025, 26(17), 8424; https://doi.org/10.3390/ijms26178424 - 29 Aug 2025
Viewed by 177
Abstract
Short-term synaptic plasticity (STSP) and short-term neuronal dynamics (STND) are fundamental properties of neural circuits, essential for information processing and brain function. Emerging evidence suggests that biological sex may influence these properties, yet sex-related differences in STSP and STND remain underexplored. This study [...] Read more.
Short-term synaptic plasticity (STSP) and short-term neuronal dynamics (STND) are fundamental properties of neural circuits, essential for information processing and brain function. Emerging evidence suggests that biological sex may influence these properties, yet sex-related differences in STSP and STND remain underexplored. This study investigates sex-specific differences in short-term synaptic plasticity (STSP) and neuronal dynamics (STND) along the dorsoventral axis of the rat hippocampus. Our findings reveal that both STSP and STND exhibit significant variation between female and male subjects. These differences are particularly pronounced in the ventral hippocampus, a region associated with affective and motivational processes. Given the role of short-term activity-dependent neuronal phenomena in modulating information processing and network function, these findings suggest potential functional implications for sex-specific cognitive and emotional regulation. The results highlight the importance of incorporating sex as a biological variable in studies of hippocampal physiology and its relation to behavior. Full article
(This article belongs to the Special Issue Advances in Synaptic Transmission and Plasticity)
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10 pages, 1709 KB  
Article
Comparative Analysis of Small Nerve Fiber Density in Fibromyalgia Syndrome and Small Fiber Neuropathy
by Pietro Falco, Eleonora Galosi, Caterina Maria Leone, Gianfranco De Stefano, Giuseppe Di Pietro, Giulia Di Stefano, Nicoletta Esposito, Enrico Evangelisti, Daniel Litewczuk, Cristina Mollica, Lars Arendt-Nielsen and Andrea Truini
Biomedicines 2025, 13(9), 2109; https://doi.org/10.3390/biomedicines13092109 - 29 Aug 2025
Viewed by 115
Abstract
Background/Objectives: Fibromyalgia syndrome is commonly associated with reduced intraepidermal nerve fiber density (IENFD), as assessed by skin biopsy, a finding referred to as small fiber pathology (SFP-FMG). The clinical significance of this abnormality, and how it relates to symptoms in fibromyalgia, remains uncertain. [...] Read more.
Background/Objectives: Fibromyalgia syndrome is commonly associated with reduced intraepidermal nerve fiber density (IENFD), as assessed by skin biopsy, a finding referred to as small fiber pathology (SFP-FMG). The clinical significance of this abnormality, and how it relates to symptoms in fibromyalgia, remains uncertain. Reduced IENFD also represents the defining feature of small fiber neuropathy (SFN). While previous observations suggest that IENFD reduction is generally less severe in SFP-FMG than in SFN, no study has directly confirmed this finding in a large cohort. This retrospective study aimed to compare the severity of IENFD reduction in patients with SFP-FMG and those with SFN. Methods: To account for age and sex differences, we used the age-and sex-adjusted axonal loss density (ALD), defined as the percentage reduction from normative IENFD values. We retrospectively analyzed skin biopsy data from 73 patients with SFP-FMG and 134 patients diagnosed with SFN. Results: We found that the reduction in IENFD was significantly milder in patients with SFP-FMG than in those with SFN both at distal and proximal sites. Receiver operating characteristic analysis indicated that an ALD threshold of 37.6% provided good specificity for distinguishing SFN from SFP-FMG. Conclusions: These findings indicate that small fiber damage in fibromyalgia syndrome is quantitatively mild compared to patients with SFN. This may explain the absence of detectable sensory deficits on clinical examination and suggests a limited contribution of peripheral nerve damage to the pathophysiology of fibromyalgia syndrome. Full article
(This article belongs to the Special Issue Advanced Research on Fibromyalgia (3rd Edition))
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17 pages, 1054 KB  
Article
Maternal Dietary Pattern in Pregnancy and Behavioral Outcomes at 4 Years of Age in the Piccolipiù Cohort: Potential Sex-Related Differences
by Letizia Leccese, Lorenza Nisticò, Martina Culasso, Costanza Pizzi, Vieri Lastrucci, Luigi Gagliardi and Sonia Brescianini
Nutrients 2025, 17(17), 2814; https://doi.org/10.3390/nu17172814 - 29 Aug 2025
Viewed by 162
Abstract
Background: The fetal period is critical for neurodevelopment, with maternal diet emerging as a key environmental factor influencing long-term child health. This study investigated the associations between maternal dietary patterns during pregnancy and neurocognitive and behavioral outcomes in 4-year-old children, with a [...] Read more.
Background: The fetal period is critical for neurodevelopment, with maternal diet emerging as a key environmental factor influencing long-term child health. This study investigated the associations between maternal dietary patterns during pregnancy and neurocognitive and behavioral outcomes in 4-year-old children, with a particular focus on sex-related differences. Methods: We used data from the Piccolipiù Italian birth cohort, including 2006 mother/child pairs. Maternal dietary intake during pregnancy was assessed via a questionnaire and categorized into distinct patterns using Principal Component Analysis (PCA). Child neurodevelopment was evaluated at age 4 using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) and the Child Behavior Checklist (CBCL 1.5–5). Linear and logistic regression models were employed, adjusting for potential confounders and stratifying by child sex. Results: Two major maternal dietary patterns were identified: “Processed and high-fat foods” and “Fresh foods and fish”. Higher maternal adherence to the “Processed and high-fat foods” pattern was associated with increased externalizing behaviors in offspring (β = 0.88; 95%CI 0.28–1.49; p = 0.004). In males, this pattern was associated with an increased clinical risk of Attention Deficit Hyperactivity Disorder (ADHD) (OR (Odds Ratio) = 1.13; 95%CI: 1.02–1.26; p = 0.021). Conclusions: Our findings indicate that maternal consumption of a diet rich in processed and high-fat foods during pregnancy is associated with increased behavioral problems in children, with sex-specific vulnerabilities: slightly higher externalizing behaviors in girls and an increased risk of ADHD in boys. These results underscore the importance of promoting healthy maternal dietary patterns during pregnancy as a targeted early prevention strategy for supporting child neurodevelopment. Full article
(This article belongs to the Special Issue The Role of Nutrients in Child Neurodevelopment)
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19 pages, 4239 KB  
Article
Sex-Specific Differences in the Revascularization of Grafted Pancreatic Islets
by Selina Wrublewsky, Annika Valerie Widmann, Caroline Bickelmann, Alex Rafacho, Leticia Prates Roma, Matthias W. Laschke and Emmanuel Ampofo
Cells 2025, 14(17), 1344; https://doi.org/10.3390/cells14171344 - 29 Aug 2025
Viewed by 108
Abstract
Islet transplantation can improve glycemic control in a subset of patients with type 1 diabetes mellitus (T1DM). This therapeutic approach is often limited by scarcity of adequate donor islets and an insufficient revascularization capacity of grafted islets. Recent findings reveal that sex is [...] Read more.
Islet transplantation can improve glycemic control in a subset of patients with type 1 diabetes mellitus (T1DM). This therapeutic approach is often limited by scarcity of adequate donor islets and an insufficient revascularization capacity of grafted islets. Recent findings reveal that sex is an important determinant for the outcome of islet transplantation. However, it is still unknown how the biological sex of islet donors and recipients affects the revascularization of the grafts during the initial ischemic post-transplantation phase. In this study, we observed in a mouse dorsal skinfold chamber model a higher revascularization capacity of female islets transplanted in female or male recipient mice when compared to male islets transplanted in female or male recipients. To mimic the ischemic in vivo conditions ex vivo, we subjected isolated female and male islets to oxygen-glucose deprivation. Under these conditions female islets expressed and secreted significantly more glucagon (GCG). By a panel of functional angiogenesis assays, we could further demonstrate that GCG exhibits a strong pro-angiogenic function. This effect was pronounced in blood vessels as well as endothelial cells and pericytes of female origin due to a higher expression of GCG receptor. Taken together, these results not only confirm the clinical observation that transplantation of female islets improves the outcome of islet transplantation but also indicate that this is mediated by an accelerated GCG-driven islet engraftment. Full article
(This article belongs to the Special Issue New Insights into Vascular Biology in Health and Disease)
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13 pages, 231 KB  
Article
Norepinephrine Versus Dopamine as a First-Line Vasopressor in Dogs with Hypotension: A Pilot Study
by Bridget Lyons, Rebecka Hess and Deborah C. Silverstein
Vet. Sci. 2025, 12(9), 832; https://doi.org/10.3390/vetsci12090832 (registering DOI) - 29 Aug 2025
Viewed by 134
Abstract
Norepinephrine (NE) and dopamine (DA) are vasopressors used to treat vasodilatory shock for decades, and norepinephrine is considered the preferred first-line vasopressor in human patients. However, there is a dearth of evidence to support specific treatment recommendations for the management of hypotensive, non-anesthetized, [...] Read more.
Norepinephrine (NE) and dopamine (DA) are vasopressors used to treat vasodilatory shock for decades, and norepinephrine is considered the preferred first-line vasopressor in human patients. However, there is a dearth of evidence to support specific treatment recommendations for the management of hypotensive, non-anesthetized, fluid-replete dogs. The objective of this study was to compare the effects of NE and DA on systolic blood pressure (SBP), heart rate, and shock index (SI) when used as first-line vasopressors for the treatment of vasodilatory shock in dogs. Twenty-four client-owned canine patients of similar age, sex, and weight with hypotension necessitating vasopressor therapy were randomized to receive NE or DA; attending clinicians were blinded. Twenty-two dogs were included in the final analysis (10 in the NE group and 12 in the DA group). Seventy-seven percent of all dogs achieved normotension. In both groups, SBP increased significantly compared to baseline (p = 0.0004 in the NE group and p = 0.006 in the DA group). The SI also decreased in both groups compared to baseline values (p = 0.01 in the NE group and p = 0.01 in the DA group). The heart rate in the NE group was higher than in the DA group at timepoints 6–10 (p = 0.023). Both NE and DA cause an increase in blood pressure and a decrease in SI in dogs with vasodilatory hypotension. Further investigation is warranted to determine if there are differences between NE and DA or the requirement for a second vasopressor, occurrence of arrhythmias, length of stay, and survival. Full article
13 pages, 1448 KB  
Article
The Diagnostic Value of Signal-to-Cutoff Ratios in Architect and Alinity HIV Screening Assays: A 10-Year Experience in a Pandemic-Affected, Low-Prevalence Setting
by İmran Sağlık, Melda Payaslıoğlu, Hatice Ortaç and Hülya Ayma Rüzgar
Viruses 2025, 17(9), 1179; https://doi.org/10.3390/v17091179 - 29 Aug 2025
Viewed by 309
Abstract
Early and accurate diagnosis of HIV remains a cornerstone of public health strategies. This study aimed to evaluate the predictive value of signal-to-cutoff (S/CO) ratios from two fourth-generation HIV screening assays (Abbott Architect and Alinity) and to analyze diagnostic trends across pre-pandemic, pandemic, [...] Read more.
Early and accurate diagnosis of HIV remains a cornerstone of public health strategies. This study aimed to evaluate the predictive value of signal-to-cutoff (S/CO) ratios from two fourth-generation HIV screening assays (Abbott Architect and Alinity) and to analyze diagnostic trends across pre-pandemic, pandemic, and post-pandemic periods in a low-prevalence setting. We retrospectively analyzed 197,642 unique HIV screening tests conducted at Bursa Uludağ University Hospital from 2015 to 2024. Receiver operating characteristic (ROC) analysis was used to determine optimal S/CO thresholds for distinguishing true-positive results. Of the 197,642 samples screened, the overall HIV prevalence was 0.5%, with 196 cases (0.1%) confirmed as new diagnoses. The Architect assay showed an optimal S/CO threshold of ≥11.8 (sensitivity 98.3%, specificity 97.3%). The Alinity assay demonstrated 100% sensitivity and specificity at an S/CO threshold of ≥19.1. Although a temporary decline in test volume occurred in 2020, there was no statistically significant difference in confirmation rates across years. During the pandemic, newly diagnosed individuals were significantly older and had lower CD4 counts, indicating delayed diagnosis (p = 0.026 and 0.008, respectively). Men who have sex with men (MSM)-related transmission significantly increased post-pandemic (p = 0.032). S/CO ratio–guided interpretation enhances diagnostic accuracy and may reduce unnecessary confirmatory testing, especially in low-prevalence and resource-limited regions. Selecting the optimal threshold can help to ensure a timely diagnosis and optimize HIV screening algorithms. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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13 pages, 765 KB  
Article
Acute L-Carnitine Supplementation Does Not Improve CrossFit® Performance: A Randomized, Double-Blind, Placebo-Controlled Crossover Study
by Asli Devrim-Lanpir, Lucero Salazar Velasco, Fanny Guadalupe Ramirez Lara, Azucena Ojeda Sanchez, Rachel Kimble, Reza Zare, Fatma Esra Gunes, Beat Knechtle, Katja Weiss, Thomas Rosemann and Katie Heinrich
Nutrients 2025, 17(17), 2784; https://doi.org/10.3390/nu17172784 - 27 Aug 2025
Viewed by 593
Abstract
Background: L-carnitine supplementation is thought to enhance exercise performance, particularly in moderate and high-intensity activities, but evidence supporting this is mixed. This study aimed to assess whether acute L-carnitine tartrate supplementation could improve CrossFit® performance, specifically during the “Cindy” workout, a high-intensity [...] Read more.
Background: L-carnitine supplementation is thought to enhance exercise performance, particularly in moderate and high-intensity activities, but evidence supporting this is mixed. This study aimed to assess whether acute L-carnitine tartrate supplementation could improve CrossFit® performance, specifically during the “Cindy” workout, a high-intensity exercise protocol. Methods: In a randomized, double-blind, placebo-controlled crossover design, 20 trained male recreational CrossFit® athletes completed the “Cindy” workout within a 20 min period after ingesting either 3 g of L-carnitine tartrate or a placebo 90 min before exercise. Performance was measured by total repetitions completed. Secondary outcomes included ratings of perceived exertion (RPE), gastrointestinal issues, and blood pressure (BP) measurements. Results: The results showed that L-carnitine supplementation did not significantly affect the number of repetitions performed (202.4 ± 69.9 vs. 204.5 ± 78.8, p = 0.810) compared to the placebo. There were also no significant differences in RPE (6.3 ± 1.5 vs. 6.9 ± 1.4, p = 0.180) or BP changes between groups. However, 10% of participants reported difficulty sleeping after L-carnitine supplementation. Conclusions: The findings suggest that 3 g of L-carnitine tartrate does not enhance CrossFit® performance in recreational athletes. Further research is needed to clarify its potential benefits, especially with larger samples and consideration of factors like sex and carbohydrate co-ingestion. Full article
(This article belongs to the Special Issue Nutritional Supplements and Diet in Athletic Performance)
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16 pages, 538 KB  
Article
Clinical Relevance of Peripheral Interleukins in Drug-Naive First-Episode Psychosis: Symptom-Specific Associations from the PANSS Dimensions
by Iva Binic, Jovana Petrovic, Olivera Zikic, Suzana Tosic Golubovic, Vladimir Djordjevic, Marko Stevanovic, Dane Krtinic and Marija Andjelkovic Apostolovic
Brain Sci. 2025, 15(9), 932; https://doi.org/10.3390/brainsci15090932 (registering DOI) - 27 Aug 2025
Viewed by 231
Abstract
Background/Objectives: Emerging evidence suggests a role of immune–inflammatory mechanisms in the pathophysiology of schizophrenia, particularly in the early stages of the illness. Cytokines, as key mediators of inflammation, may affect brain function and clinical presentation. Drug-naive patients with first-episode psychosis (FEDN) offer [...] Read more.
Background/Objectives: Emerging evidence suggests a role of immune–inflammatory mechanisms in the pathophysiology of schizophrenia, particularly in the early stages of the illness. Cytokines, as key mediators of inflammation, may affect brain function and clinical presentation. Drug-naive patients with first-episode psychosis (FEDN) offer a unique opportunity to investigate these associations free from confounding pharmacological effects. Methods: This study included 38 patients with drug-naive first episode psychosis and 22 age- and sex-matched healthy controls. Serum concentrations of IL-1β, IL-2, IL-6, and IL-10 were measured using ELISA. Clinical symptoms were assessed using the PANSS scale. Statistical analyses included Mann–Whitney U tests, Spearman’s correlations, and ROC curve analysis. Results: Significantly elevated serum levels of IL-1β, IL-2, and IL-10 were observed in the FEDN group compared to the controls (p < 0.01), while IL-6 levels did not differ significantly. IL-2 exhibited the highest discriminatory power in differentiating the patients from the controls (AUC = 0.917; 95% CI: 0.759–1000.0; p < 0.001). IL-1β levels positively correlated with negative and general psychopathology symptoms, including hostility and grandiosity. IL-10 was associated with volitional disturbance and overall PANSS severity. Conclusions: Our findings underscore the relevance of immune dysregulation in the early stages of psychosis and highlight the potential of specific cytokines, particularly IL-2 and IL-1β, as peripheral biomarkers. Their diagnostic utility and correlation with symptom dimensions suggest a promising role in the development of precision psychiatry approaches, including early detection strategies and individualised therapeutic targeting. Longitudinal studies are needed to validate these findings and to assess their prognostic significance. Full article
(This article belongs to the Section Neuropsychiatry)
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14 pages, 6375 KB  
Article
Sex Differences in the Initiation and Progression of Necroptosis Following Kidney Ischemia–Reperfusion Injury
by Minh H. Tran, Colby L. Parris, Catherin Liu, Andrea Oropeza, Carlos Esquivel, Alka Rani, Yingxiang Fan, Liying Fu, Jacentha Buggs and Lei Wang
Biomedicines 2025, 13(9), 2085; https://doi.org/10.3390/biomedicines13092085 - 27 Aug 2025
Viewed by 291
Abstract
Background: Ischemia–reperfusion injury (IRI) is a major contributor to acute kidney injury (AKI). While the precise mechanisms of AKI are still incompletely defined, extensive evidence highlights tubular cell injury and death as key factors in its development. Necroptosis has recently emerged as a [...] Read more.
Background: Ischemia–reperfusion injury (IRI) is a major contributor to acute kidney injury (AKI). While the precise mechanisms of AKI are still incompletely defined, extensive evidence highlights tubular cell injury and death as key factors in its development. Necroptosis has recently emerged as a critical pathway in the pathogenesis of ischemia–reperfusion-induced AKI (IR-AKI). Although sex differences in susceptibility to IR-AKI have been reported, it remains unclear whether there are sex differences in necroptosis dynamics and whether these differences underlie the observed sexual dimorphism in kidney IRI. This study aimed to address these questions. Methods: male and female C57BL/6 J mice were subjected to AKI via ischemia induced by bilateral renal pedicle clamping for 18 min at 37 °C. Plasma, urine, and kidney samples were collected at 0 h, 3 h, 6 h, 12 h, 24 h, 48 h, and 72 h post-reperfusion. Kidney injury and function were assessed by measuring plasma creatinine (PCr), blood urea nitrogen (BUN) levels, and histological damage (PAS and cleaved caspase3 staining). Necroptosis activation was assessed by quantifying phosphorylated forms of key markers: p-RIPK1 and p-MLKL. To explore the role of sex hormones in regulating necroptosis dynamics, ovariectomized female mice were subjected to the same IR-AKI protocol, and their kidney injury and functional outcomes were compared with those of intact counterparts. Results: The PCr was 0.35 ± 0.04 and 0.32 ± 0.06 mg/dL for males and females, respectively, at 3 h of IR. The levels exponentially increased to 2.05 ± 0.18 at 48 h post-reperfusion in the males but only gradually to 0.94 ± 0.13 mg/dL in females. Necroptosis activation began as early as 3 h post-IR in males but was delayed until ~6 h in females. Males exhibited stronger and more sustained necroptosis activation than females, showing elevated phosphorylation levels of pRIPK1 and pMLKL in Western blot. Female sex hormone deficiency exacerbated the female response to IR-induced injury, which reduced the sex difference in the dynamic of the necroptotic activation and subsequent kidney injury. To our knowledge, this is the first study to characterize sex differences in the initiation and progression of necroptosis and subsequent injury in a mouse model of IR-AKI. Conclusions: Our findings reveal distinct temporal patterns of programmed cell death between sexes. Necroptosis-targeted therapies require early intervention in males, which can be delayed in females after IR-AKI, highlighting the need for sex-specific therapeutic windows. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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Article
Sex and Age Disparities in Water Polo-Related Skills
by Francisco Noronha, Sofia Canossa, Diogo D. Carvalho, Ana Sofia Monteiro, José Afonso, Flávio Castro and Ricardo Fernandes
Appl. Sci. 2025, 15(17), 9381; https://doi.org/10.3390/app15179381 - 26 Aug 2025
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Abstract
Existing research points to sex-specific biological and physiological differences, but the effects of sex and age on water polo-specific motor skills have not yet been sufficiently investigated. The current study investigated sex- and age-related disparities in in-water vertical jump, change of direction ability, [...] Read more.
Existing research points to sex-specific biological and physiological differences, but the effects of sex and age on water polo-specific motor skills have not yet been sufficiently investigated. The current study investigated sex- and age-related disparities in in-water vertical jump, change of direction ability, sprint performance, aerobic fitness and shot velocity, hypothesising that these variables are related to the players’ specific motor performance. Sixty-six players (47 males, 19 females) were split into an adult and a young group (each with n = 33). Two-way (sex and age as factors) analysis of variance and Tukey’s post hoc test were employed to evaluate the influence of sex and age on specific water polo skill performance. The male players’ in-water vertical jump (135.4 ± 8.1 vs. 121.5 ± 6.1 cm), shot velocity with previous displacement (68.3 ± 6.4 vs. 51.0 ± 2.5 km·h−1) and without displacement (68.5 ± 5.7 vs. 52.2 ± 2.9 km·h−1), 10 m sprint (5.6 ± 0.9 vs. 6.6 ± 0.4 s), aerobic fitness (311.7 ± 92.1 vs. 235.7 ± 70.3 m) and change of direction (3.3 ± 0.4 vs. 3.9 ± 0.4 s) scores were superior to those of female players. No significant age-related differences were observed in shot velocity with previous displacement (F (1,53) = 2.124, p = 0.151, η2p = 0.039) or 10 m sprint performances (F(1,62) = 0.935, p = 0.337, η2p = 0.015). Male players outperformed females in most water polo-specific motor skills, while age-related differences were limited. Full article
(This article belongs to the Special Issue Applied Biomechanics and Sports Sciences)
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