Search Results (20,646)

Polycyclic aromatic hydrocarbons (PAHs) are widespread, persistent pollutants that can be sequestered within human adipose tissue due to their lipophilic nature. While this accumulation poses toxicological risks depending on dose and individual susceptibility, the specific morphological impact of chronic PAH storage on tissue architecture remains poorly defined. Here, we performed a histopathological and morphometric analysis on human subcutaneous adipose tissue samples characterized by high pyrene levels. We evaluated tissue organization, collagen distribution, the presence of inflammatory, neural, and vascular alterations and adipocyte morphometry to assess the structural response to PAH sequestration. Despite high pyrene concentrations, PAH-positive tissues maintained preserved overall architecture with normal collagen distribution, absence of lymphocytic infiltration, low macrophages, unaltered nerve fiber patterns, without evidence of vascular remodeling. Morphometry revealed smaller adipocyte area in PAH-positive samples, although not statistically significant. Our experimental data indicate that high PAH accumulation does not necessarily induce subcutaneous adipose tissue remodeling, suggesting that biochemical or metabolic alterations might occur even in the absence of evident histological changes. Further studies, with a broadened cohort, are needed to define the threshold at which PAHs’ presence translates into permanent tissue damage. Full article

Copy number variants (CNVs) are genomic rearrangements that carry a substantial risk for neurodevelopmental and neuropsychiatric disorders. Among these, recurrent deletions and duplications at the 16p11.2 locus are robustly associated with autism spectrum disorders, schizophrenia, epilepsy, and related conditions, yet also display marked variability in penetrance and phenotypic expression. Accumulating evidence indicates that 16p11.2 gene dosage influences multiple stages of brain development, from early progenitor dynamics and neuronal migration to synaptic formation, refinement, and plasticity. However, how disruptions across these processes are integrated over time, and how they relate to the observed variability and incomplete penetrance, remains poorly understood. In this review, we summarize the current evidence on the impact of 16p11.2 CNVs on brain development, focusing on cellular and circuit-level processes that shape neural connectivity. We discuss how gene dosage imbalance influences early developmental trajectories, synaptic formation and pruning, interneuron maturation, and activity-dependent plasticity, and consider how these processes interact across developmental stages. We suggest a conceptual framework wherein 16p11.2 CNVs do not impose fixed pathogenic outcomes, but rather they contribute towards developmental constraints that shape the timing and stability of neural circuit development. Consequently, these constraints increase vulnerability to neurodevelopmental and psychiatric outcomes in a context-dependent manner. Full article

Background: Distal radius fractures (DRFs) are common fragility fractures often associated with underlying osteoporosis. Objective: To evaluate the effect of nutraceutical supplementation in addition to pulsed electromagnetic field (PEMF) therapy on pain and early fracture healing. Methods: Sixty female patients were randomized into two groups: Group A received PEMF therapy alone, while Group B received PEMF plus nutraceutical supplementation. The primary outcome was pain reduction (NRS). Secondary outcomes included biochemical markers and ultrasound-based callus formation. Results: At T1, Group B showed a trend toward greater pain reduction compared with Group A (mean difference −0.57; p = 0.007) and higher bone alkaline phosphatase levels (p = 0.0002). A higher proportion of patients reached minimal clinically important difference (MCID) in Group B (60% vs. 30%, p = 0.02). Conclusions: Nutraceutical supplementation in addition to PEMF was associated with improved short-term outcomes; however, due to the absence of a non-PEMF control group, the independent effect of PEMF cannot be determined. Full article

Type 2 diabetes mellitus (T2DM) is a major driver of chronic kidney disease and cardiovascular morbidity worldwide. Extracellular vesicles (EVs), particularly exosomes, carry microRNAs (miRNAs) that reflect the pathophysiological state of their parent cells and represent promising non-invasive biomarkers. This review comprehensively examines the diagnostic and mechanistic roles of EV-derived miRNAs in diabetic nephropathy (DN) and cardiovascular diseases (CVDs) associated with T2DM. A PRISMA-guided literature search of PubMed, Scopus, Web of Science, and Embase identified 847 articles published between January 2020 and June 2026, of which 152 studies met the inclusion criteria. Several urinary exosomal miRNAs demonstrated significant diagnostic performance for DN, including miR-4534 (AUC = 0.786), miR-136-5p (sensitivity 72.2%, specificity 78.4%), and miR-142-3p. A meta-analysis of circulating miRNAs in diabetic kidney disease reported a pooled AUC of 0.79. In the cardiovascular setting, exosomal miR-155-5p (AUC = 0.901), miR-15a-3p (AUC = 0.874), and a four-miRNA panel (miR-433-3p/let-7b/miR-30-5p/miR-122-5p; AUC = 0.833) demonstrated strong diagnostic performance for ischemic heart disease and carotid atherosclerosis in T2DM. Mechanistically, key EV-associated miRNAs, including miR-21, miR-192, and the anti-fibrotic miR-29 family, participate in fibrosis, inflammation, oxidative stress, endothelial dysfunction, and cardiac remodeling pathways. EV-derived miRNAs therefore represent highly promising non-invasive biomarkers for the early diagnosis and monitoring of diabetic renal and cardiovascular complications. However, clinical translation requires standardized EV isolation and miRNA detection protocols, together with validation in large multicenter prospective cohorts. This review highlights the considerable diagnostic and translational potential of EV-derived miRNAs for precision medicine and liquid biopsy applications in T2DM complications. Full article

Background/Objectives: COVID-19, caused by the SARS-CoV-2 virus, can lead to widespread neurological and cognitive complications, even in the absence of significant structural brain abnormalities. Understanding the evolving health concerns in the context of viral infections is critical to service member readiness, fitness, and mission completion. The potential neuroprotective effects of SARS-CoV-2 vaccination remain underexplored. Methods: Using a cross-sectional, non-human primate model (female cynomolgus macaques), we employed magnetoencephalography (MEG) to assess resting-state brain activity following vaccination with escalating doses of a novel psoralen-inactivated SARS-CoV-2 vaccine (PsIV) or a combination of PsIV and a DNA vaccine (prime boost), and subsequent challenge with the Delta variant (SARS-CoV-2 B.1.617.2). MEG scans were acquired 41 days after inoculation. Source series were constructed for 42 regions of interest for each subject, and band power was computed. Results: Band power demonstrated substantial preservation of neural activity across multiple brain regions in vaccinated subjects compared to unvaccinated controls following viral challenge. Significantly lower power was observed across the brain at all bandwidths in the unvaccinated group relative to the prime boost group. As PsIV concentration increased, spectral power increased, with the prime boost group having the greatest power. Conclusions: This approach not only underscores the role of vaccination in mitigating neuropathology but also highlights the capability of MEG to detect subtle yet significant changes in brain function that may be overlooked by other imaging modalities. These findings advance our understanding of vaccine-induced neuroprotection and establish MEG as a powerful tool for monitoring brain function in the context of viral infections. Full article

Background: Creating antibiograms solely for adults may overestimate resistance of antimicrobials for certain pathogens in children. The Canadian Paediatric Society comments that areas with no cephalosporin-resistant Streptococcus pneumoniae cases should consider ceftriaxone or cefotaxime monotherapy for meningitis, despite most experts recommending adding vancomycin. The present study created age-specific antibiograms using LifeLabs data to report incidences of resistant bacterial meningitis pathogens at the regional level to determine the need for duo-coverage. Methods: Data of common bacterial meningitis pathogen susceptibility was collected from 1 January 2023 to 31 December 2024, in the LifeLabs community laboratory on Vancouver Island. Results: Most Streptococcus pneumoniae isolates (78/83) were susceptible to ceftriaxone using the meningitis breakpoint; the remaining five isolates showed intermediate susceptibility to ceftriaxone. There was a significant difference when comparing S. pneumoniae susceptibility using penicillin-meningitis and penicillin-non-meningitis breakpoints (82% vs. 99%, respectively; p < 0.05). There was a significant difference between the three age groups (<18 years, 18–50 years, >50 years) when analyzing ciprofloxacin susceptibility of isolates [82% (n = 462), 77% (n = 2452), 75% (n = 8352), respectively, p < 0.05]. Conclusions: Ceftriaxone should remain the drug of choice for community-acquired bacterial meningitis and might be sufficient as a monotherapy for pneumococcal meningitis on Vancouver Island. The age-specific differences in E. coli susceptibilities to ciprofloxacin showed the importance of age-specific antibiograms. Full article

Background: Early childhood nutrition is strongly associated with neurodevelopmental outcomes, particularly in socially vulnerable settings. Limited evidence is available describing the relationship between nutritional status, food security, and neurodevelopment among preschool children in low-income urban areas of Colombia. This study aimed to evaluate nutritional status, household food insecurity, and neurodevelopmental outcomes in children attending early childhood centers in El Codito, Bogotá, and to explore the association between anthropometric indicators and neurodevelopmental performance. Methods: A cross-sectional study was conducted in children enrolled in community childcare centers. Nutritional status was assessed using anthropometric indicators according to World Health Organization growth standards, including weight for age, height for age, and body mass index for age. Neurodevelopment was evaluated using the Escala Abreviada de Desarrollo (EAD). Household food insecurity was measured through a validated questionnaire. Descriptive statistics were performed, and associations between variables were analyzed using correlation tests and group comparisons according to data distribution. Results: Most participants presented adequate nutritional status; however, a proportion of children showed risk of stunting or excess weight. Neurodevelopmental scores were generally within expected ranges, although variability was observed across developmental domains. Significant associations were identified between certain anthropometric indicators and neurodevelopmental outcomes. Moderate to severe household food insecurity was identified in 21.4% of participating households. Conclusions: Nutritional status and household food insecurity represent important contextual factors for child health in vulnerable urban populations. These findings highlight the importance of integrated nutritional and developmental monitoring strategies within early childhood programs. Further longitudinal studies are required to clarify causal pathways and to guide targeted public health interventions in similar contexts. Full article

Background and Objectives: Blood group antigens are well known for their importance in transfusion medicine and transplant compatibility; however, their biological role extends beyond these functions and includes associations with the risk of several diseases. In this study, we investigated the relationship between ABO blood groups and the circulating levels of 73 different molecules. Patients and Methods: Fifty-six healthy donors were enrolled, including 24 individuals with blood group O, 19 with blood group A, and 13 with blood group B. Blood samples were collected and analyzed in a single laboratory using Luminex fluorescent bead-based assay panels to determine the concentrations of 73 circulating molecules. Depending on data distribution, ANOVA or Kruskal–Wallis tests and Student’s t-test or Kolmogorov–Smirnov tests were applied to identify significant differences among groups. Associations were further assessed by binary logistic regression analysis. Results: Subjects with blood group A showed significantly higher circulating levels of IL-1R1, IL-13, IL-23, PDGF-BB, VEGF-A, VEGF-D, soluble VEGF-R2 (KDR), soluble VEGF-R3 (FLT-4), VLA-4, CD141, MMP-1, syndecan-1 (SDC-1), and mannose-binding lectin (MBL) compared with the other blood groups. In contrast, individuals with blood group B exhibited significantly higher levels of IL-22, IL-23, PDGF-BB, CD62P (P-selectin), and amyloid β1–42. Several significant associations were identified by logistic regression analysis. Conclusions: Our findings indicate that ABO blood groups are associated with distinct circulating molecular profiles, supporting the existence of biological differences that may contribute to variations in disease susceptibility among individuals with different blood types. Nevertheless, given the exploratory’s nature and limited sample size of this study, further investigations are required to validate these findings, confirm the observed associations, and clarify their potential clinical implications. Full article

Objective: This in vitro study evaluated the insertion torque characteristics of the KS 3 implant compared with the TSIII implant in standardized artificial bone models representing weak bone, extraction-socket-like reduced support, and maxillary sinus simulation conditions. Materials and Methods: A comparative in vitro study was performed using three models: a weak bone model, a standardized extraction-socket-like reduced-support model, and a maxillary sinus simulation model. Maximum and final insertion torque values were obtained from torque–depth curves. Torque–depth integrals were additionally calculated as exploratory secondary parameters. Statistical analyses were performed using Welch’s t-test and two-way ANOVA where appropriate, and the results were interpreted as exploratory because of the limited sample size. Results: The KS 3 implant showed higher maximum and/or final insertion torque values than the TSIII implant in the weak bone, extraction-socket-like, and maxillary sinus simulation models. In the maxillary sinus model, the torque values showed directional differences according to implant type and residual bone height under the tested fixed undersized drilling protocols for both CAS drilling and bone compaction drilling. Torque–depth integral analysis provided additional information regarding cumulative insertion resistance. Conclusions: Within the limitations of this controlled in vitro study, the KS 3 implant showed higher insertion torque values than the TSIII implant under the tested artificial bone conditions. These findings should be interpreted as in vitro insertion torque data under the tested artificial bone and drilling conditions, not as evidence of clinical superiority. In the maxillary sinus simulation model, the observed torque differences should be interpreted as the combined effect of implant macrodesign and the fixed undersized drilling protocol, rather than as an isolated macrodesign effect. Full article

Background: Viral vectors are indispensable tools in gene therapy and neural circuit mapping, offering promising therapeutic strategies for diverse genetic diseases and advancing neuroscience research. To achieve high transduction efficiency while mitigating impurity-induced immunogenicity, the development of viral vectors with improved purity and quality is essential. However, this critical requirement is often unmet by conventional purification methods such as ultracentrifugation, which are time-consuming and frequently result in limited product purity. The pseudorabies virus (PRV) is extensively employed as a viral tool for mapping neural circuits, where improved purity contributes to enhanced accuracy of neural tracing. PRV531 is a retrograde trans-synaptic tracer modified from the PRV Bartha strain, specifically designed to facilitate the precise visualization of hierarchical neural networks. Methods: In this study, we developed a method for the concentration and purification of PRV531 by integrating hollow fiber ultrafiltration (HF) with Capto^TM Core 700 (CC700) chromatography. Initially, to concentrate the viral supernatant, a 500 kDa HF membrane was employed, maintaining a feed flow rate of 80 mL/min, a shear rate ranging from 2000 to 6000 s⁻¹, and a transmembrane pressure (TMP) between 0.5 and 1 bar. Following concentration, the virus underwent purification through CC700 chromatography, operating at linear flow rates ranging from 100 to 300 cm/h. Results: Sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE) revealed distinct bands consistent with the expected sizes of major PRV structural proteins, each with molecular weights ranging from 25 kDa to 150 kDa, concurrently demonstrating a substantial reduction in host cell proteins (HCPs) contamination. The purified PRV531 achieved a high final infectious titer of 3.55 × 10⁹ PFU/mL, with an overall functional virus recovery of 8.88% from the crude supernatant to the final product. Conclusion: These data demonstrate that TFF combined with CC700 resin can efficiently purify retrograde trans-synaptic PRV tracer. Furthermore, this approach provides a promising strategy for purifying other viral-based tracers that traditionally rely on conventional centrifugation methods. Full article

Background/Objectives: Eating disorders (EDs) are among the most severe psychiatric conditions affecting young people, with increasing prevalence in the post-pandemic period. This study assessed the prevalence of ED risk and dysfunctional eating behaviors among Italian university students, a population poorly characterized with respect to ED risk, and examined associations with key socio-demographic and anthropometric variables. Methods: A cross-sectional online screening study was conducted between August 2023 and February 2026 with 401 Italian university students (306 women and 95 men). Participants completed the validated Italian versions of the Eating Attitudes Test-26 (EAT-26) and the Eating Disorder Examination Questionnaire 6.0 (EDE-Q 6.0), alongside self-reported anthropometric data. Multiple linear regression analyses were performed to identify predictors of ED risk scores. Results: A total of 37.9% of participants had BMI outside the normal range (19.7% underweight; 18.2% overweight or obese). EAT-26 scores exceeded the clinical cut-off in 28.4% of participants (women: 35.6%; men: 5.3%). EDE-Q 6.0 global scores exceeded the clinical cut-off in 21.0% (women: 25.8%; men: 5.3%). Only 45.4% showed no anthropometric or questionnaire-based screening risk indicators (i.e., scores above the clinical cut-off on the EAT-26 or EDE-Q 6.0). BMI was negatively associated with EAT-26 scores in the total sample and in women, while a positive association between BMI and EDE-Q 6.0 scores was observed in men. Conclusions: A substantial proportion of Italian university students, particularly women, presented screening-based indicators of ED risk. The combined use of anthropometric and questionnaire-based screening tools provides a more comprehensive risk assessment than either measure alone, highlighting the need for multidimensional screening programs. Full article

Youth soccer performance is influenced by multiple factors, including age, body size, and physical capacities, but the relative contribution of these variables to aerobic and explosive performance remains unclear. Understanding these relationships can improve the interpretation of field tests and support individualized training prescription. This study was designed to examine the association of age category, body mass, and height with physical performance in youth soccer players by jointly considering aerobic and explosive capacities, in order to support the interpretation of field tests within training prescription. Forty-five male players (15 U16, 15 U17, 15 U19) from the same club were assessed across two standardised on-field testing sessions, including the 45–15 test (estimated maximal aerobic speed, MAS) and vertical jump tests (squat jump, SJ; countermovement jump, CMJ; countermovement jump with free arms, CMJ_FH). Performance variables (SJ, CMJ, CMJ_FH, MAS) were treated as outcomes, while category, body mass, and height were included as predictors. A multivariate analysis was performed, followed by univariate analyses for each indicator. Results showed a significant multivariate effect of age category on overall performance (p < 0.001; η²p = 0.482), whereas height and body mass were not significant (p > 0.05). In univariate analyses, age category was associated with all variables: SJ (p = 0.005; adj. R² = 0.160), CMJ (p < 0.001; adj. R² = 0.287), CMJ_FH (p = 0.004; adj. R² = 0.173), and MAS (p < 0.001; adj. R² = 0.352). Performance increased progressively from U16 to U17 to U19, with larger between-category differences in aerobic capacity. In conclusion, age category was more strongly associated with the performance profile than height and body mass when considered jointly; these findings should be interpreted in light of the observational design and the lack of biological maturation measures. Full article

Background/Objectives: Advancements in neuroscience and machine learning have increasingly enabled brain pattern recognition based on bio-signal measurements, such as electroencephalography (EEG). These developments support next-generation technologies, including brain–computer interfaces (BCIs) and AI-assisted systems. However, volume conduction (VC) effects remain a major source of contamination in EEG recordings, affecting both univariate analyses and functional connectivity estimation. Methods: In this work, we propose a VC mitigation method that explicitly models and suppresses VC components in the observed functional networks. Specifically, the observed functional network is decomposed into a matrix capturing only VC-related components (i.e., components attributed to volume conduction) and a residual matrix, where the residual is regarded as a proxy for a VC-mitigated functional network that better reflects the underlying functional interactions. The VC component matrix is modeled using a decay function parameterized by the inter-electrode distance matrix, capturing the dominant spatial bias induced by VC. To estimate these parameters, we introduce supervised channel importance, quantified as the mutual information between experimental labels and channel signals, as a proxy for task-relevant neural activity. The parameters are optimized such that the unsupervised node importance derived from the VC-mitigated functional network, defined as the average node strength, aligns with the supervised channel importance. Results: Evaluation results using a deep-learning framework demonstrate that, compared with the observed functional network, the VC-mitigated functional network improves classification performance in brain pattern recognition tasks. Full article

Not all sleep loss is equal, and overlooking this limits progress in sleep and neurological disease research. We compared nine rodent sleep deprivation paradigms, gentle handling, multiple platform variants, disk-over-water, the Unpredictable Chronic Sleep Deprivation (UCSD) paradigm, novel object introduction, curling prevention by water, automated systems, and head-lifting, evaluating stress confounds, sleep stage specificity, chronicity, and neurobiological outcomes. Effects included hippocampal plasticity, prefrontal chemistry, glymphatic clearance, neuroinflammation, oxidative stress, neurogenesis, and circadian regulation, linked to Alzheimer’s, Parkinson’s, and psychiatric comorbidities. UCSD with caffeine produced antioxidant depletion, serotonin reduction, acetylcholinesterase upregulation, and synaptophysin loss, early neurodegeneration markers. We propose a disease-targeted framework with six translational priorities and reporting standards. Full article