Search Results (10,603)

Diabetic retinopathy (DR), recognized as a progressive neurovascular and microvascular complication of diabetes, remains one of the leading causes of visual disability worldwide, within the context of a sustained increase in ophthalmic diseases and retinal vascular disorders that compromise vision. This study aimed to characterize the progression of diabetic retinopathy in a streptozotocin (STZ)-induced Wistar rat model. A single dose of 65 mg/kg body weight was administered, with follow-up periods at 2, 4, 8, and 10 weeks, compared to healthy controls. STZ-induced rats exhibited reduced weight gain compared to the control group. They also showed markedly variable hyperglycemia, with glucose concentrations ranging from 250 to 530 mg/dL. Histological analysis of retinal tissue at week 4 revealed early signs of vascular compromise, including early indications of a microenvironment conducive to neovascularization and edema. By week 8, retinal damage had progressed to hemorrhage, persistent edema, and layer-specific vascular disruption. At week 10, intensified neovascularization and exacerbated edema indicated advanced microvascular deterioration. Immunofluorescence analysis demonstrated a temporal accumulation of CD8⁺ T cells in the retina, correlating with photoreceptor degeneration. The coordinated dynamics of CD4⁺ and CD8⁺ T cells suggested transient immune activation during STZ-induced retinal degeneration. Gene expression profiling revealed a proinflammatory and pro-oxidative retinal microenvironment, characterized by the overexpression of angiogenic pathways and proliferative signals. Simultaneously, the antioxidant response appeared partially impaired. Collectively, these findings provide mechanistic perspective on the multifactorial nature of diabetic retinopathy. Oxidative stress, inflammation, and angiogenesis converge to disrupt retinal homeostasis. This experimental model may serve as a reliable platform for future studies aimed at elucidating disease pathophysiology, identifying novel therapeutic targets, and evaluating emerging ophthalmic antidiabetic interventions. Full article

Background/Objectives: Seasonal waves of respiratory viruses—including SARS-CoV-2, influenza A virus (IAV), and respiratory syncytial virus (RSV)—continue to pose a global health burden and highlight the need for antiviral agents that are effective, safe, broadly active, affordable, and widely accessible. Current interventions are limited by the need for their early administration, the risk of resistance, their costs, and the restricted availability in large parts of the world. For certain natural products, such as European black elderberry (Sambucus nigra L.) fruit extract (ElderCraft^®; EC) and the seaweed-derived sulfated polymer iota-carrageenan (IC), antiviral activities against respiratory viruses, particularly IAV and SARS-CoV-2, have previously been shown. Here, we assessed the antiviral activity of IC and an anthocyanin-standardized EC extract against SARS-CoV-2, IAV, and RSV, either as monotherapy or in multiple-dose combinations. Methods: MDCKII cells were infected with IAV_PR8, human Calu-3 lung epithelial cells with the SARS-CoV-2 Omicron variant, and HEp-2 cells with RSV (A2 strain). Inhibitors were administered either by pre-incubation of cell-free virions prior to infection or, in separate time-of-addition experiments, during or post-infection. Viral replication was quantified by qRT-PCR or intracellular immunostaining. Cytotoxicity was evaluated using a neutral red uptake assay. Results: Most intriguingly, both EC and IC are able to neutralize virions derived from SARS-CoV-2, IAV, or RSV extracellularly in a dose-dependent manner. Notably, EC and IC alone exhibited strong anti-RSV activity, which was not reported previously. Most importantly, combined treatment with IC and EC caused a pronounced synergistic antiviral effect against the tested viruses, as confirmed by the Bliss independence model, without any detectable impact on cell viability. Finally, solutions prepared from matrix-standardized mono- or combi-lozenges, containing IC and/or EC in high or low doses, reproduced the antiviral and synergistic combination effects observed with the pure compounds. Conclusions: In summary, these findings support further development of EC and IC as a topically accessible, virion-neutralizing combination (e.g., lozenges) to provide additional protection against major respiratory viruses and potentially strengthen pandemic preparedness. Full article

Children with Autism Spectrum Disorder (ASD) frequently exhibit marked impairments in nonverbal communication, particularly in eye contact, which serves as a foundational element for social interaction and relational development. This study evaluated the effectiveness of an early intervention program utilizing interactive games supported by Augmented Reality (AR) technology to enhance eye contact behaviors, specifically initiation and maintenance, in children with autism. Using a multiple baseline across participants single-case experimental design, four boys (aged 5–7 years) diagnosed with ASD participated in an 8-week intervention at a specialized center in Saudi Arabia. The intervention featured tablet-based, gamified AR tasks incorporating real-time visual feedback, graduated difficulty levels, and reinforcement mechanisms designed to elicit social gaze and sustained eye contact. Eye contact duration and frequency were measured during structured social interactions via systematic direct observation. The results demonstrated significant improvements across all participants, with the mean duration of eye contact increasing from a baseline of 2.0 s to 5.8 s post-intervention. Visual analysis revealed robust treatment effects, further supported by substantial Tau-U effect sizes (range = 0.89–0.96; M = 0.93). Follow-up data collected three weeks post-intervention confirmed the maintenance of gains for three of the four participants. These findings suggest that AR-based interventions provide an effective and culturally responsive approach for enhancing specific nonverbal communication behaviors among children with autism in Middle Eastern contexts. Implications for clinical practice and directions for future research are discussed. Full article

Background: Gut microbiome-derived metabolites, particularly short-chain fatty acids (SCFA) and tryptophan derivatives, are central mediators of the gut–brain axis. This ex vivo study assessed how nutritional interventions impact such metabolites during early life, a critical period for neurodevelopment. Methods: The effects of galacto-oligosaccharides (GOS), nutrient blends (vitamins, minerals and amino acids) and their combinations were evaluated in the gut microbiomes of infants (2–4 months, n = 6) and young children (2–3 years old, n = 6) using the ex vivo SIFR^® technology. Results: Baseline microbiome composition was age-dependent, with infants displaying lower α-diversity and greater interpersonal variability. After ex vivo incubation, nutrient blends increased the propionate/butyrate ratio and branched-chain fatty acids in young children and elevated several B-vitamins and amino acid-derived metabolites, including indole-3-carboxaldehyde, imidazoleacetic acid and pipecolinic acid. Combining nutrient blends with GOS exhibited potential synergistic effects on propionate (infants) and 2-hydroxyisocaproic acid (HICA, both age groups). GOS strongly stimulated Bifidobacteriaceae and increased metabolites linked to bifidobacterial metabolism like acetate, HICA, N-acetylated amino acids, aromatic lactic acids and acetylagmatine; in young children, butyrate and γ-aminobutyric acid (GABA) also increased. Conclusions: Combinations of GOS with nutrient blends impacted microbiome-derived metabolites associated with the gut–brain axis, with potential synergistic increases of metabolites with emerging roles in neurodevelopment, including GABA, acetylagmatine and HICA. Despite shared bifidogenic effects, differences between age groups indicate that microbiome maturity may influence responses to nutritional intervention. Future clinical studies are needed to determine whether these metabolite changes translate into neurodevelopmental benefits in vivo. Full article

Objectives: Cardiovascular diseases (CVDs) represent the main global burden of morbidity and mortality, with an accelerated epidemiological transition in regions such as Latin America. The university environment constitutes a period of critical vulnerability due to increased sedentary lifestyles and cardiometabolic risk factors. The objective of this study was to evaluate the cardiovascular risk profile in a university community in the central Andean region of Colombia using anthropometric, haemodynamic and biochemical indicators. Methods: A cross-sectional, observational, and analytical study was conducted on a sample of n = 143 participants (students, teachers, and administrators) aged between 18 and 80 years. Haemodynamic parameters (SBP, DBP, MAP), anthropometric parameters (BMI, % body fat, waist-to-height ratio [WC/W]) and lipid profile were evaluated. Statistical analysis included multiple linear regression models to determine predictors of systolic blood pressure (SBP). Results: Significantly higher levels of SBP were found in the older age groups compared with the younger age groups, reaching stage 1 hypertension levels in the sixth decade. The biochemical profile revealed metabolic deterioration with an atherogenic index (TC/HDL) consistently above the clinical threshold (>4.5) in all groups. The regression model BMI was identified as the statistical predictor with the strongest association with SBP variability in the sample (β = 1.18), followed by age (β = 0.28). A marked sexual dimorphism was observed, with men presenting early haemodynamic risk, while women experienced an accelerated post-menopausal tension and metabolic crisis. Conclusions: The university community presents latent cardiometabolic vulnerability closely linked to modifiable anthropometric factors. These findings underscore the urgency of implementing institutional preventive health policies and weight control intervention programmes to mitigate the future burden of chronic diseases on campus. Full article

Background/Objectives: Cognitive impairment is a major concern in aging populations. Early detection through validated neuropsychological tests is essential for dementia risk stratification and preventive interventions. This scoping review (PRISMA-ScR, 2013–2023, registration protocol: 10.17605/OSF.IO/8NHJF) evaluated cognitive testing trends in aging research and identified the most frequently used neuropsychological screening tests in Spanish populations. Methods: Searches in PubMed and Web of Science (March 2024) yielded 730 records; 156 were reviewed in full, and 15 met inclusion criteria for Spanish adults ≥65 years. Results: The Mini-Mental State Examination was the most-used test, followed by verbal fluency and Trail Making Test. No test covered all six DSM-5 cognitive domains, and social cognition was never assessed in any of the studies. The Montreal Cognitive Assessment was underused despite its superior sensitivity. Conclusions: Findings support developing a tailored, multidomain battery combining global and domain-specific tests. Social cognition assessments should be included to ensure a complete cognitive domain coverage. Full article

Background: Postoperative hemorrhage is a severe complication after pancreatic surgery. While bleeding related to pancreatic fistula is well characterized, hemorrhage secondary to biliary leakage remains poorly understood. This study investigates the incidence, associated factors, clinical course, and outcomes of hepaticojejunostomy insufficiency-associated arterial hemorrhage (HIAA). Methods: This retrospective single-center study included 1413 patients who underwent pancreatic surgery with hepaticojejunostomy between 2004 and 2014. Demographics, underlying disease, surgical procedures, postoperative complications, management strategies, and outcomes were analyzed. Results: HIAA occurred in 13 patients (0.9%), accounting for one third of all erosion-related hemorrhages. The median onset was 16 days postoperatively, and 77% were preceded by sentinel bleeding. Completion pancreatectomy and sepsis were significantly associated with HIAA. The right hepatic artery was the most frequent bleeding source. Primary interventional angiography achieved hemostasis in 62.5% of patients, while 61.5% required surgical revision. Thirty- and ninety-day mortality rates were 15.4% and 30.8%, respectively, compared with 2.1% and 3.7% in the overall cohort. Conclusions: HIAA is a rare but highly lethal complication after pancreatic surgery. It represents a distinct clinical entity characterized by delayed onset, frequent sentinel bleeding, an association with sepsis and completion pancreatectomy, and markedly increased mortality. Early recognition, prompt imaging, and an interventional-first strategy are essential to improve outcomes. Full article

Background/Objectives: In recent years, research on psychosis has increasingly focused on prevention, aiming to implement early interventions that mitigate or reduce its impact. Within this framework, the analysis of linguistic markers in individuals with at-risk mental states (ARMS) has proven valuable for identifying those at risk and predicting psychosis onset. Artificial intelligence tools, particularly natural language processing (NLP), have emerged as effective resources for detecting these language-based indicators. This study aims to synthesize the existing scientific evidence on linguistic markers analyzed through NLP techniques in individuals with ARMS. Methods: A systematic review following the PRISMA 2020 protocol was conducted. Three databases (PubMed, PsycInfo, and Scopus) were searched for published articles from their inception to October 2025. Rayyan software was used to manage references and article downloads. Out of ninety initial search results, fifteen studies involving 1313 participants from diverse groups were included in the review. Results: The findings indicated that alterations in semantic coherence, syntactic complexity, referential cohesion, and speech/content poverty differentiated ARMS individuals from healthy controls. Several of these markers, analyzed with NLP methods, predicted the onset of psychosis with accuracy levels ranging from 79% to 100%, although these findings should be interpreted with caution due to the significant methodological heterogeneity and variability in sample sizes across the included studies. Conclusions: NLP techniques offer a powerful approach for detecting language alterations that distinguish ARMS individuals and provide meaningful predictions of psychosis onset, highlighting their potential as a complement to traditional clinical assessments for early identification and prevention. Full article

Background and Clinical Significance: Dentinogenesis imperfecta is a hereditary dentin disorder that compromises tooth structure, esthetics, and function. Case Presentation: We report the case of a 1.5-year-old female presenting with generalized discoloration of the primary dentition and intermittent sensitivity to thermal stimuli. The diagnosis of dentinogenesis imperfecta was established based on characteristic clinical features, radiographic findings, and a positive family history. The patient was followed longitudinally from 2020 to 2025, with documentation of diagnostic findings, radiographic changes, therapeutic interventions, and outcomes. Management included placement of composite veneers on the maxillary incisors for esthetic rehabilitation and sealants on second primary molars as a preventive measure. Although various management approaches have been described in the literature, evidence regarding optimal strategies and long-term outcomes in the primary dentition remains limited. This case highlights the occurrence of asymptomatic periapical pathology and root resorption despite minimal clinical symptoms, underscoring the challenges of relying on symptom-based assessment alone. Conclusions: Early diagnosis, regular radiographic monitoring, and individualized, risk-based treatment planning are essential in managing dentinogenesis imperfecta. This case emphasizes the importance of recognizing asymptomatic disease progression and integrating psychosocial considerations into comprehensive care. Full article

Despite advances in surgical technique and perioperative care, pancreatic ductal adenocarcinoma (PDAC) remains associated with poor survival. Sarcopenia is highly prevalent in PDAC and is consistently associated with inferior survival and reduced tolerance of systemic therapy. However, interventions primarily aimed at increasing muscle mass through nutritional supplementation and resistance-based exercise have yielded limited improvements in clinically meaningful postoperative outcomes. This has prompted increasing interest in sarcopenia as a marker of broader biological vulnerability rather than isolated physical deconditioning. Emerging clinical, translational, and experimental evidence demonstrates that skeletal muscle and adipose tissue function as active immunometabolic organs, and that cancer-associated inflammatory pathways drive early muscle loss, immune dysfunction, and impaired physiological recovery. Across multiple clinical cohorts, sarcopenia is reproducibly associated with worse overall survival and failure to complete adjuvant therapy, but not consistently with increased postoperative complications, suggesting that its prognostic relevance lies in impaired recovery and oncological fitness rather than immediate surgical risk. Translational studies further indicate that sarcopenia identifies patients with reduced antitumor immune competence, particularly in early-stage disease. This review synthesizes current evidence linking sarcopenia, immune dysfunction, and surgical outcomes in PDAC and examines implications for perioperative care. We propose that immunometabolic-informed prehabilitation, integrated with existing nutritional and exercise strategies, may represent a more effective approach to improving recovery, treatment tolerance, and durable oncological outcomes following PDAC resection. Full article

The increasing prevalence of childhood obesity has been accompanied by an increase in consumption of ultra-processed foods (UPF), characterized by high energy density and low nutritional quality. Emerging evidence suggests that dietary patterns rich in UPF may contribute to low-grade systemic inflammation and early metabolic dysfunction in children and adolescents. Objective: This systematic review aimed to evaluate the association between UPF consumption and markers of inflammation and metabolic health in pediatric populations. Methods: A systematic literature search was conducted on PubMed in accordance with PRISMA guidelines. Observational and interventional studies evaluating UPF intake or diet-related inflammatory potential in children and adolescents (≤18 years) were included. Outcomes of interest included inflammatory biomarkers (e.g., C-reactive protein, interleukins, tumor necrosis factor-α) and metabolic parameters (e.g., insulin resistance, lipid profile, glucose metabolism). Results: A limited number of studies have directly assessed UPF consumption using the NOVA classification. Overall, these studies suggest a potential association between increased UPF intake and adverse metabolic outcomes, although findings on inflammatory markers remain inconsistent. A larger body of indirect evidence, including studies assessing dietary inflammatory indices and related dietary patterns, consistently supports a link between pro-inflammatory diets and increased inflammation and metabolic dysregulation in pediatric populations. Conclusions: Although direct evidence on UPF consumption remains limited, the available findings, supported by complementary indirect evidence, suggest a plausible relationship between UPF-rich diets, inflammation, and metabolic health in children and adolescents. Further well-designed studies are needed to clarify causality and improve the standardization of dietary assessment methods. Full article

Background: Women with atrial fibrillation experience a higher lifetime risk of ischemic stroke, greater stroke severity, and worse functional outcomes than men. Preventive strategies focused on AF detection may therefore miss critical opportunities for early intervention in women. Methods: We developed a decision-analytic Markov model using real-world primary care data from Catalonia (Spain) to evaluate an artificial intelligence (AI) enabled strategy for upstream thromboembolic risk detection. The intervention combined electronic health record–based risk prediction, targeted digital rhythm screening, and individualized anticoagulation. Lifetime clinical and economic outcomes were estimated for adults aged ≥65 years, with pre-specified sex-stratified analysis. Results: Compared with usual care, the AI-enabled strategy reduced ischemic stroke, major adverse cardiovascular events, and long-term disability. Absolute reductions in stroke and disability were greater in women, reflecting higher baseline thromboembolic risk. Per 1000 high-risk women, the strategy prevented more strokes and generated larger quality-adjusted life-year gains than in men. From both healthcare payer and societal perspectives, the intervention was cost-saving in women, driven by reductions in stroke-related disability and long-term care. Conclusions: AI-enabled upstream thromboembolic risk detection may deliver particularly important benefits for older women and represents a promising approach to reduce sex-based inequities in stroke prevention. Full article

Background: Metabolic syndrome is associated with early impairments in cellular bioenergetics that are not fully captured by conventional body composition measures. Molecular hydrogen, produced endogenously through gut microbial fermentation and measurable in breath, has been implicated in redox and mitochondrial regulation. Whether breath hydrogen relates to preservation of intracellular, metabolically active tissue in metabolic syndrome remains unclear. Objectives: To examine the association between breath hydrogen concentration and an integrated cellular bioenergetic phenotype derived from intracellular body composition indices in sedentary adults with metabolic syndrome. Methods: Twenty-eight sedentary, middle-aged adults (51.2 ± 7.9 years, 19 females) with metabolic syndrome underwent fasting breath hydrogen assessment and multifrequency bioelectrical impedance analysis. A composite cellular bioenergetic phenotype was derived using principal component analysis of body cell mass, intracellular water, total body potassium, and glycogen. Associations between breath hydrogen and the composite phenotype were evaluated using Spearman correlation with bootstrapped confidence intervals, Theil-Sen regression, and Bayesian linear regression adjusted for age, sex, and waist circumference. Sensitivity analyses included fat-free mass. Results: A single principal component explained 98.6% of the variance across intracellular variables, indicating a highly coherent cellular bioenergetic phenotype. Breath hydrogen concentration was positively associated with this phenotype (ρ = 0.43, p = 0.021; BCa 95% CI 0.07–0.70). Theil-Sen regression confirmed a robust positive association (β = 0.017 per ppm hydrogen; 95% CI 0.002–0.046). Bayesian models showed posterior distributions centered on positive effect sizes, independent of central adiposity. In contrast, the association with fat-free mass alone was borderline. Conclusions: Breath hydrogen concentration reflects an integrated intracellular bioenergetic phenotype in sedentary adults with metabolic syndrome, tracking cellular quality rather than lean mass quantity. Breath hydrogen may serve as a non-invasive biomarker of cellular bioenergetic integrity and a potential tool for phenotype-guided metabolic interventions. Full article

Background: Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by amyloid-β aggregation, tau hyperphosphorylation, oxidative stress, and mitochondrial dysfunction. Emerging evidence indicates that the gut microbiota plays a critical role in modulating neuroinflammatory, and metabolic pathways involved in AD pathogenesis through the microbiota-gut-brain axis. Objective: This systematic review aims to comprehensively evaluate the role of the microbiota-gut-brain axis in Alzheimer’s disease, with a particular focus on its mechanistic links to oxidative stress, mitochondrial dysfunction, and amyloid pathology, as well as its therapeutic potential. Methodology: A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science databases, focusing on studies evaluating gut microbiota composition, metabolomic changes, oxidative stress markers, mitochondrial activity, and therapeutic interventions in AD models and patients. Results: Altered gut microbial composition in AD is associated with increased pro-inflammatory taxa (Escherichia-Shigella, Bacteroides) and depletion of short-chain fatty acid (SCFA) producing bacteria (Faecalibacterium, Roseburia). Dysbiosis contributes to systemic inflammation, disrupted intestinal permeability, and microglial activation, leading to oxidative damage and mitochondrial impairment in neurons. Preclinical and clinical studies indicate that probiotics, prebiotics, and fecal microbiota transplantation can restore redox balance, reduce neuroinflammation, and improve cognitive outcomes. Multi-omics and AI-based models are emerging as tools for identifying microbiome-derived biomarkers for early AD detection. Conclusion: The gut microbiota-mitochondria-oxidative stress axis represents a promising therapeutic target in Alzheimer’s disease. Future research should focus on longitudinal human studies, standardized microbial profiling, and personalized microbiome-based interventions to translate these mechanistic insights into clinical benefit. Full article

Background and Objectives: Visceral artery aneurysms (VAAs) are rare but potentially catastrophic vascular abnormalities, particularly in pregnant patients or women of childbearing age. Rupture is often fatal for both mother and fetus, with mortality rates exceeding 70% in some series. While most VAAs are found incidentally, a subset may present acutely with nonspecific abdominal or flank pain, making early recognition and appropriate referral essential. This review article aims to provide General Practitioners (GPs) and emergency department (ED) clinicians with a practical approach to the recognition, investigation, initial management, and escalation pathways for VAAs. Results: Physiological and hormonal adaptations in pregnancy heighten aneurysm rupture risk. Despite this, imaging is frequently delayed. Computed tomography angiography (CTA) remains the gold standard for diagnosis and is safe in pregnancy when clinically justified, with fetal radiation exposure well below teratogenic thresholds. Guidelines from major vascular societies uniformly recommend repairing VAAs in pregnancy or women planning pregnancy irrespective of aneurysm size, and treating pseudoaneurysms urgently in all patients. Endovascular intervention is first-line where anatomy permits, while open or hybrid approaches remain essential in unstable presentations. The manuscript outlines practical steps for ED and GP settings, including haemodynamic stabilization, early obstetric involvement, transfer considerations for rural environments, reproductive counselling, and post-repair surveillance. Conclusions: With an increasing number of abdominal scans being performed in primary and tertiary settings, there is an associated increased volume of incidental findings that require work-up. This article outlines a practical investigation and management strategy for clinicians presented with VAAs, including in high-risk cohorts, emphasizing early imaging, inter-specialty coordination, and guideline-supported thresholds for intervention. Full article