Search Results (1,934)

(1) This cross-sectional study aims to elucidate the association between the XPO5 gene polymorphism (rs11544382) and colon cancer (CC). (2) Genotyping of XPO5 (rs11544382) was performed in 120 individuals (60 CC patients and 60 controls) using real-time PCR (qPCR). Logistic regression and Chi-square (χ²) tests were used for statistical analysis. (3) Evaluation of the XPO5 gene polymorphism in CC and control groups revealed no statistically significant association between the mutant (GG) genotype and either the wild-type (AA) or heterozygous (AG) genotypes (χ² = 2.07, p = 0.151). The AG genotype was predominant in both patients (86.7%) and controls (91.7%). Smoking and alcohol consumption showed significant associations with CC (p < 0.05). Although the rs11544382 polymorphism was not associated with CC risk, this is a cross-sectional study. In light of these findings, larger and more comprehensive studies with increased sample size are required to clarify the relationship between the XPO5 gene polymorphism (rs11544382) and CC. Full article

Atopic eczema and asthma frequently co-occur, forming a distinct complex phenotype that likely arises from shared genetic pathways and early-life environmental influences. We aimed to investigate whether variants in TNS1 and NRXN1—previously identified in a genome-wide interaction study—influence susceptibility to atopic eczema and the asthma–eczema phenotype and whether early-life environmental tobacco smoke (ETS) exposure modifies these genetic effects. A total of 188 Caucasian children under 2 years at recruitment were prospectively followed up to 6 years of age. Eligibility of all participants for the study or control group was based on a questionnaire and a physician-confirmed diagnosis of eczema and asthma. Early-life ETS exposure was assessed by parental questionnaire. All participants were genotyped for TNS1 and NRXN1 SNPs. The TNS1 rs918949 [T] allele was associated with the combined asthma–eczema phenotype but not with eczema alone. Synergistic gene–environment interactions were identified for both TNS1 and NRXN1, with the highest risk of the combined asthma–eczema phenotype observed among ETS-exposed carriers of risk alleles. Our findings provide the first independent replication of evidence suggesting that TNS1 and NRXN1 may contribute to the asthma–eczema comorbidity through mechanisms that could be substantially modified by early-life ETS exposure. Full article

Background/Objectives: The variation in the treatment outcomes of extended-release naltrexone (XR-NTX) including the potential role of genetic factors are poorly understood. This study aimed to explore the potential association between the catechol-O-methyltransferase (COMT) rs4680 and mu-opioid receptor (OPRM₁) rs1799971 genotypes and XR-NTX treatment outcomes in patients with opioid use disorder (OUD) specifically focusing on treatment retention, relapse to opioids, number of days of opioid use, and opioid cravings. Methods: This was a 24-week, open-label clinical prospective, exploratory study involving patients with OUD who chose treatment with monthly injections of intramuscular XR-NTX. Men and women aged 18–65 years with OUD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, were included. The participants were interviewed using the European Addiction Severity Index. Survival analyses and linear mixed models were used to analyze the data. Results: Of the 162 participants included in this study, 138 (21% female) initiated treatment with XR-NTX, with 88 genotyped for COMT rs4680 and 86 for OPRM₁ rs1799971. Heterozygous Met/Val carriers of COMT rs4680 were less likely to relapse to opioids compared with those with the COMT rs4680 Met/Met genotype. No significant association was observed for the OPRM₁ polymorphism. Conclusions: Patients with the COMT rs4680 Met/Val genotype exhibit a reduced risk of relapse to opioids and may therefore derive greater benefit from XR-NTX treatment compared with those with the COMT rs4680 Met/Met genotype. Future studies should be conducted with a larger number of participants and possibly include other genetic variants and treatment outcomes. The trial is registered at ClinicalTrials.gov (#NCT03647774) and the EU Clinical Trial Register (#2017-004706-18). Full article

Background/Objectives: Prostate cancer is the most frequent male malignancy. The incidence of disease varies among different ethnic groups. CYP3A polymorphisms are candidates for prostate cancer susceptibility studies. The aim of the present study is to investigate the ethnicity-related clinical impact of CYP3A4 variants on prostate cancer risk. Methods: A systematic literature search and meta-analysis were conducted according to PRISMA guidelines. A total of 10 eligible studies, including 3116 prostate cancer cases and 3008 healthy controls, were analyzed. We evaluated the association between the CYP3A4*1B (rs2740574, −392 A > G) variant and prostate cancer risk in European Caucasians. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using six genetic models. Data were analyzed using fixed and random-effects models based on the I2 value of heterogeneity magnitude. Funnel plots and Egger’s linear regression tests were used to assess publication bias. Results: CYP3A4*1B was associated with prostate cancer susceptibility in the allele (G vs. A: OR = 1.32, CI = 0.91–1.93), dominant (AG + GG vs. AA OR = 1.41, CI = 0.95–2.09), recessive (GG vs. AA + AG, OR = 1.82, CI = 1.26–2.63), homozygous (GG vs. AA, OR = 1.92, CI = 1.32–2.77), heterozygous model (AG vs. AA, OR = 1.31, CI = 0.89–1.93) and co-dominant model (AG vs. AA + GG; OR = 1.27, CI = 0.88–1.85). Significant heterogeneity characterized the allele, as well as the dominant model (I2 = 84.1%, I2 = 80.0%). Egger’s tests (p < 0.05) and funnel plots did not identify publication bias. Conclusions: The present meta-analysis indicates that the G allele and GG genotype might affect prostate cancer susceptibility in European Caucasians; however, the validity and reliability of the results need to be examined in future research. Full article

Objective: This study aimed to investigate the functional connectivity (FC) of three amygdala subregions—the laterobasal amygdala (LBA), centromedial amygdala (CMA), and superficial amygdala (SFA)—with large-scale brain networks in individuals with schizophrenia (SCZ) compared to healthy controls (HC). Methodology: Resting-state functional magnetic resonance imaging (rs-fMRI) data were obtained from 100 participants (50 SCZ, 50 HC) with balanced age and gender distributions. FC between amygdala subregions and target functional networks was assessed using a region-of-interest (ROI)-to-ROI approach implemented in the CONN toolbox. Result: Connectivity patterns of the LBA, CMA, and SFA differed between SCZ and HC groups. After false discovery rate (FDR) correction (p < 0.05), SCZ patients exhibited significantly increased FC between the left CMA and both the default mode network (DMN) and the visual network (VN). In contrast, decreased FC was observed between the right LBA and the sensorimotor network (SMN) in SCZ compared with HC. Conclusions: These findings reveal novel FC alterations linking amygdala subregions with large-scale networks in schizophrenia. The results underscore the importance of examining the amygdala as distinct functional subregions rather than as a single structure, offering new insights into the neural mechanisms underlying SCZ. Full article

Background: Ischemic stroke remains a leading cause of mortality and long-term disability worldwide. Reperfusion therapies, such as intravenous thrombolysis and mechanical thrombectomy, are crucial for restoring cerebral blood flow but may also trigger ischemia–reperfusion injury and systemic inflammatory activation, associated with poorer clinical outcomes. Methods: We retrospectively analyzed medical records of 8833 patients hospitalized for acute ischemic stroke between January 2014 and May 2025. Of these, 2242 (25.38%) underwent reperfusion therapy (mechanical thrombectomy ± intravenous thrombolysis), and 6591 (74.62%) were treated conservatively. Laboratory parameters, including leukocyte count, C-reactive protein (CRP), and albumin, and composite inflammatory indices (e.g., neutrophil-to-lymphocyte ratio (NLR), systemic immune–inflammation index (SII), systemic-inflammation response index (SIRI), and neutrophil percentage-to-albumin ratio (NPAR)), were assessed at admission. Clinical outcomes included in-hospital mortality and functional scale results (e.g., National Institutes of Health Stroke Scale, modified Rankin score (mRS), Barthel scale, and Glasgow Coma Scale (GCS)). Results: Patients treated with reperfusion therapy had higher inflammatory indices (white blood cells, CRP, NLR, SII, and NPAR) compared to patients treated conservatively. In multiple regression analysis, these indices were significantly determined only by GCS and mRS scores, but age, gender, comorbidities, biochemical determinations, and type of ischemic stroke treatment (reperfusion or conservative) remained non-statistically significant. Conclusions: Patients with acute ischemic stroke undergoing reperfusion therapy exhibited a stronger inflammatory response and higher in-hospital mortality than those treated conservatively. However, multivariate analysis showed that a stronger inflammatory response following reperfusion therapy results more from the severity of the patients’ state than the kind of therapy. Full article

Background: BTB and CNC homology 1 (Bach1) are transcriptional regulators involved in the oxidative response and inflammation. Although its biological functions are well characterized, the clinical impact of Bach1 gene polymorphisms (rs2300301, rs1153285, and rs2070401) on respiratory outcomes in preterm infants remains unclear. Methods: This multicenter study included 212 Japanese preterm infants born at <32 weeks of gestation with birth weights <1250 g. Three Bach1 single-nucleotide polymorphisms (SNPs; rs2300301, rs1153285, and rs2070401) were genotyped using TaqMan polymerase chain reaction (PCR). The requirements for home oxygen therapy (HOT) were compared across genotypes. Logistic regression analyses were performed after adjusting for the gestational age, sex, birth weight, and histological chorioamnionitis status. Results: Infants requiring HOT had a significantly lower gestational age (26 ± 1.7 weeks vs. 27 ± 2.2 weeks, p = 0.015) and lower birth weight (774 ± 235 g vs. 818 ± 233 g, p = 0.043) than those who did not. Histological chorioamnionitis was more prevalent in the HOT group (p = 0.022). rs2300301 was associated with HOT in univariate analysis (OR = 1.78, 95% CI: 1.20–2.04, p = 0.015). However, this association did not remain statistically significant after adjustment for gestational age, sex, birth weight, and histological chorioamnionitis (OR = 2.48, 95% CI: 0.90–6.80, p = 0.079). The rs1153285 and rs2070401 SNPs were not significantly associated with HOT expression. Conclusions: Our findings suggest a potential association between the Bach1 rs2300301 polymorphism and prolonged oxygen requirement in preterm infants. Although the adjusted analysis did not confirm the statistical significance, this SNP may serve as a candidate genetic marker for respiratory morbidity. Further studies are required to validate these findings. Full article

Background/Objectives: Knee osteoarthritis (KOA) is a multifactorial and degenerative disease. Growth differentiation factor 5 (GDF5) polymorphism rs143384 G > A is associated with reduced gene expression and musculoskeletal pathologies. This study aimed to evaluate the association between this functional polymorphism and clinical variability and disease severity among patients with KOA in an admixed population. Methods: This cross-sectional observational study enrolled 224 Brazilian patients with KOA, who were evaluated and classified according to disease severity. Results: The median age was 64 (44–84) years; 75.9% of the patients were female, 50.9% were shorter than 1.60 m, and 67.4% were obese or morbidly obese. The disease severity distribution was 64.7% grades I–III and 35.3% IV–V. Patients with KOA who were over 70 years had significantly more advanced grades (OR = 9.3; 95% CI = 3.4–26), in either female group (OR = 8.2; 95% CI = 2.6–26). The minor allele frequency of the GDF5 rs143384 A variant was 41.7% in the overall KOA case group, increasing with disease severity (39.7% in grades I–III versus 45.6% in IV–V). After adjusting for the confounding factors (age and BMI) the GDF5 GA + AA genotype was significantly associated with higher KOA severity IV–V in female patients (OR = 2.5; 95% CI = 1.2–5.3). Additionally, the mean height of female KOA patients with the GDF5 GA + AA genotype (1.56 ± 0.07 m) was significantly shorter than that of patients with the GG genotype (1.59 ± 0.08 m). Conclusions: The GDF5 rs143384 polymorphism was associated with greater KOA severity and shorter stature in female patients. These results suggest that this variant may contribute to phenotypic variability in patients with knee osteoarthritis, helping to refine clinical characterization and stratification in this population, contributing to personalized diagnoses and guiding future changes in treatment guidelines for knee osteoarthritis. Full article

Background/Objectives: To explore the predictive value of pericardial fat tissue (PFT) radiomics for left ventricular (LV) involvement and major adverse cardiac events (MACE) in arrhythmogenic right ventricular cardiomyopathy (ARVC). Methods: In this retrospective multicenter study, LV involvement was assessed using cardiac magnetic resonance (CMR). A radiomic score (RS) derived from PFT was developed to predict LV involvement. The predictive accuracy of the RS was evaluated through receiver operating characteristic (ROC) analysis. Additionally, multivariable Cox regression analysis was employed to assess the prognosis across the entire dataset. Kaplan–Meier survival curves were used to evaluate the association between RS and MACE. Results: A total of 122 patients (mean age, 44 years ± 17; 76 male) were included, 90 for a development set and 32 for an external test set. The RS demonstrated good predictive performance for LV involvement in both the development and external test sets, with area under the curve (AUC) values of 0.771 and 0.785, respectively. Moreover, a high RS (≥−0.38) was independently associated with MACE during a median follow-up of 5 years (hazard ratio, 3.452; p < 0.001). Based on the right ventricular ejection fraction (RVEF) and RS, a simplified risk score was developed to categorize patients into three groups: high-risk (RVEF ≤ 40%, RS ≥ −0.38), intermediate-risk (RVEF ≤ 40%, RS < −0.38 or RVEF > 40%, RS ≥ −0.38), and low-risk (RVEF > 40%, RS < −0.38). Conclusions: The PFT radiomics can predict LV involvement and be associated with MACE in ARVC patients. Full article

Visceral leishmaniasis (VL) is a severe zoonotic disease characterized by high mortality and a pronounced systemic inflammatory response. Although Pentraxin 3 (PTX3) has been implicated in infectious and inflammatory disorders, its role in human VL remains poorly defined, and host-derived indicators that simultaneously reflect inflammatory and parasitic activity are limited. This study investigated the association between plasma PTX3 levels, parasite load, and PTX3 gene polymorphisms (rs1840680 and rs2305619) in patients with VL. An observational study was conducted between 2017 and 2021, including 36 patients with confirmed VL and 45 healthy controls matched by age and sex. Plasma PTX3 concentrations were determined by ELISA, parasite load by quantitative PCR (qPCR), and cytokines (IL-2, IL-6, IL-10, IL-17A, IFN-γ and TNF-α) by flow cytometry. PTX3 levels were significantly higher in VL patients than in controls (23.2 ng/mL vs. 0.80 ng/mL; p < 0.0001) and correlated positively with parasite load (r = 0.39; p = 0.02) and cytokines IL-6, IL-10 and IFN-γ. No associations were observed between PTX3 polymorphisms and disease susceptibility. These findings suggest that PTX3 reflects both inflammatory responses and parasitic burden in VL and may serve as a potential indicator of disease activity. Full article

Background/Objectives: Early-onset inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), frequently presents with a more severe clinical course. Genetic susceptibility, particularly involving the TGF-β signaling pathway, plays a key role in IBD pathogenesis. SMAD3 and LTBP3 encode crucial components of this pathway and have been implicated in IBD in previous genome-wide association studies. Methods: This study aimed to assess the clinical significance of the rs17293632 (SMAD3) and rs11545200 (LTBP3) polymorphisms in a pediatric IBD cohort. A total of 286 children (133 with UC and 153 with CD) were recruited from seven pediatric centers in Poland. Clinical data included age at diagnosis, inflammatory markers (CRP, albumin), growth indices (Z-scores for weight, height, and BMI), and treatment regimens. Results: The LTBP3 rs11545200 minor allele was significantly associated with a younger age at diagnosis, poorer nutritional status during disease flares, and a more frequent use of infliximab—particularly in patients with UC. In CD, the SMAD3 rs17293632 major homozygous genotype was associated with increased use of systemic corticosteroids, suggesting a more severe or treatment-resistant disease phenotype. Conclusions: The assessed polymorphisms in LTBP3 and SMAD3, both involved in TGF-β signaling, are associated with clinical characteristics of pediatric IBD. These findings support the potential role of genetic variants as biomarkers for disease severity and treatment tailoring, contributing to the development of personalised therapeutic strategies in children with IBD. Full article

Post-Traumatic Stress Disorder (PTSD) is consistently linked to multidimensional working memory (WM) impairments, encompassing deficits in sustained attention, verbal and visuospatial processing, and executive control, with inhibitory dysfunction emerging as a key feature. This scoping review synthesizes evidence from 39 studies examining neurobiological mechanisms, trauma-related factors, genetic and hormonal influences, gender differences, and task-specific variability. Findings indicated that PTSD is associated with altered activation and connectivity in the prefrontal cortex, hippocampus, and related neural networks, often resulting in compensatory but inefficient recruitment patterns. Emotional distraction and comorbidities such as depression, alcohol use, and traumatic brain injury can exacerbate cognitive deficits. Performance impairments are evident across both emotional and neutral WM tasks, with visuospatial and updating processes being particularly vulnerable. Risk factors include chronic trauma exposure, older age, APOE ε4 allele, and the BDNF Val66Met (rs6265) polymorphism, while modulators such as oxytocin, cortisol, and physical activity show potential cognitive benefits under specific conditions. Methodological heterogeneity and limited longitudinal data restrict generalizability. These findings underscore the importance of early screening, targeted cognitive interventions, and inclusion of underrepresented populations to refine prevention and treatment strategies for PTSD-related WM deficits. Full article

Background: Motor competence (MC) is defined as the ability to perform a wide range of motor skills with proficiency and control. The present quasi-experimental study design examines the impact of two structured intervention programs on MC in children who practiced athletics at the same club, aged 6 to 10 years, implemented over 12 weeks. Methods: The sample consisted of 64 children, assigned to two intervention groups: Intervention Group A (IG_A) composed of 15 male and 17 female children (9.57 ± 0.86 years) and Intervention Group B (IG_B), of 14 male and 18 female children (9.08 ± 1.33 years). IG_A received athletics-based training exclusively, three times per week, while IG_B undertook two weekly athletics sessions and one complementary activity session, such as handball, gymnastics, swimming, and motor games. MC was assessed using the modified Körperkoordinationstest für Kinder (KTK3+). The KTK3+ consists of three original KTK tasks, [Backward Balance (BB), Sideways Moving (MS), and Jumping Sideways (JS)] and an additional Eye–Hand Coordination (EHC) task. For statistical analysis, ANOVA repeated measures 2 × 2 was used. Results: In relation to JS, the performance on this test did not change with the intervention programs in either of the two groups. For BB and MS, both groups improved their performances in a similar way through the program implementation. Differently, for EHC, results showed that only IG_B improved its performance significantly (p < 0.001) with the program’s intervention, with a large Cohen’s d effect size (0.84). Finally, as a general analysis, the KTK3+ raw results (RS) and results translated to Global Motor Quotient (GQM), revealed significant differences between IG_A and IG_B post-intervention, with p < 0.001 for both variables’ comparison and with large Cohen’s d effect sizes for both (1.581 for RS and 1.595 for GQM), favoring IG_B. Conclusions: Both programs led to improvements in the various KTK3+ battery tasks. However, only the program that combined athletics training with multiactivity training led to significant improvements in the EHC test and in the overall KTK3+ results of the children involved. Full article

Background: Acute coronary syndrome (ACS) is a major cardiovascular emergency influenced by environmental and genetic factors. Thrombophilic variants such as prothrombin G20210A (rs1799963) and factor V Leiden G1691A (rs6025) may influence thrombin generation and has been reported to show associations with coronary events. Methods: This case–control study included 100 ACS patients and 131 age and sex-matched healthy controls. Genotyping of rs1799963 and rs6025 was performed using polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) analysis. Results: The GG genotype was markedly more common among ACS patients for both variants. For rs1799963, carriers of the A allele (GA + AA) were less common in ACS (2.0%) than controls (9.2%; p = 0.039), corresponding to an 8.6-fold higher odds of ACS in GG carriers (OR = 8.624; 95% CI: 1.757–42.345; p = 0.008). For rs6025, A allele carriers (9.0%) were also reduced in ACS versus controls (18.3%; p = 0.049), and GG homozygotes exhibited a 2.6-fold higher risk (OR = 2.635; 95% CI: 1.104–6.290; p = 0.029). Age was independently associated with higher ACS risk (OR = 1.047; 95% CI: 1.029–1.066; p < 0.001). Conclusions: Our findings indicate that the rs1799963 and rs6025 variants were independently associated with ACS, together with advancing age. Both the GG genotype and older age were associated with higher odds of ACS, whereas A-allele carriers appeared less common among ACS cases. Full article

Background: Immune-regulatory genes such as CTLA-4, FOXO-3, and PTPN-22 influence immune tolerance and metabolic adaptation, but their interaction with environmental factors in type 1 diabetes (T1DM) remains unclear. Methods: In this observational associated study, we analyzed CTLA-4 (rs3087243, rs231775), FOXO-3 (rs2802292, rs9400239), and PTPN-22 (rs12730735) polymorphisms in 277 adults with T1DM, assessing associations with probiotic and vitamin D use, self-reported dietary patterns, metabolic control, autoimmune thyroid disease (AITD), and metabolic dysfunction-associated steatotic liver disease (MASLD). Results: Across the cohort, CTLA-4 rs3087243 G and FOXO-3 rs2802292 T alleles were associated with higher AITD risk (p = 0.016–0.03), significant in both dominant and additive models. The effect persisted by sex: CTLA-4 in women and FOXO-3 in men. Stratified analyses revealed metabolic advantages for CTLA-4 G and FOXO-3 T carriers (vegetarian diet, lower HbA1c, stress adaptation). FOXO-3 rs9400239 T was linked to MASLD (p ≈ 0.037–0.041), with similar trends for CTLA-4 rs231775, stronger in men. Vitamin D supplementation showed protective trends, particularly in FOXO-3 rs2802292 GG and CTLA-4 GG/AG carriers. Conversely, probiotic use was associated with higher AITD in FOXO-3 rs2802292 GT and CTLA-4 rs3087243 GG genotypes. Conclusions: CTLA-4, FOXO-3, and PTPN-22 variants may modulate the metabolic and autoimmune response to environmental factors including nutrients in T1DM. Full article