Search Results (48,626)

Alzheimer’s disease (AD) continues to be one of the greatest challenges in public health due to its multifactorial and heterogeneous nature, involving multiple physiological axes that encompass a large number of genetic, metabolic, vascular, and inflammatory interactions. In current clinical practice, medical specialties, mainly neurology and psychiatry, still rely on targeted gene panels for genetic evaluation. Although these panels remain effective for certain predefined hypotheses, their restricted and predefined nature limits the detection of the broader spectrum of genetic variation that may contribute to the complex biological interactions underlying neurodegeneration. Whole-exome sequencing (WES) is, from our clinic-based perspective, one of the most comprehensive genomic approaches currently available, since it allows the analysis of the ~19,500 protein-coding regions, and depending on the library approximately 5500 additional clinically relevant genomic loci, including splice sites, untranslated regions, long non-coding RNAs (lncRNAs), pseudogenes, regulatory elements and mitochondrial DNA (mtDNA). It enables the identification of pathogenic variants and variants of uncertain significance (VUS) under the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) classification frameworks. It also expands biological interpretation to variants conventionally classified as benign, which, when interpreted collectively, may contribute to pathway-level contextualization within the hypothesis-generating theoretical framework proposed in this review without implying pathogenicity, causal inference, or immediate clinical actionability. Additionally, WES enables the identification of secondary and incidental findings that may provide clinically relevant information beyond the primary phenotype, thereby supporting preventive surveillance and clinical risk management. This review analyzes the use of WES as a strategic platform for personalized decision-making in contemporary practice given the multifactorial and heterogeneous complexity of AD. It also addresses the complexities and limitations of the ACMG/AMP recommendations for filtering and classification of variants, the lack of standardization between reports and platforms, and the need for physician training, which constitute a great challenge for the translation of data to therapeutic decision-making. While the clinical utility of whole-exome sequencing (WES) in genetic diagnosis and precision medicine is well established, this review additionally proposes a hypothesis-generating theoretical framework whereby variants conventionally classified as benign or of uncertain significance may contribute to pathway-level biological contextualization in Alzheimer’s disease. Full article

Background/Objectives: We investigated the associations of severe vision impairment (SVI) with SARS-CoV-2 infection and COVID-19 outcomes using the nationwide K-COV-N database, which links Korea Disease Control and Prevention Agency SARS-CoV-2 testing records with National Health Insurance Service data. Methods: Adults aged ≥20 years with laboratory-confirmed SARS-CoV-2 infection and matched controls who either tested negative or were untested but had no documented SARS-CoV-2 infection between 8 October 2020, and 31 December 2021, were included. Pre-existing SVI was defined using an inclusive algorithm based on either a best-corrected visual acuity <6/60 in the better-seeing eye in the health-checkup database or legal SVI recorded in the National Disability Registration System before the COVID-19 observation period. Propensity score matching (1:30) was used to evaluate SARS-CoV-2 test positivity in the overall cohort and severe COVID-19 outcomes among infected individuals. Results: The study included 560,182 SARS-CoV-2-positive individuals and 1,677,364 matched controls. After adjustment, SVI was associated with a trend toward higher SARS-CoV-2 test positivity (adjusted odds ratio [aOR], 1.09; 95% confidence interval [CI], 0.99–1.20). Among infected individuals, SVI was associated with increased odds of severe COVID-19 illness (aOR, 3.05; 95% CI, 2.59–3.58) and COVID-19-related death (aOR, 1.39; 95% CI, 1.13–1.71), with stronger associations during the Delta variant period. Conclusions: These findings suggest that SVI is associated with poorer COVID-19 outcomes and may increase susceptibility to SARS-CoV-2 infection. Full article

Bisphenol A (BPA) is a non-persistent industrial chemical widely used in the production of polycarbonate plastics and epoxy resins. Due to its mass production and versatility, BPA is ubiquitous in environmental matrices, leading to human exposure through ingestion, dermal contact, and inhalation. As a known endocrine-disrupting chemical (EDC) with estrogenic activity, BPA exposure has been associated with reproductive, metabolic, immune, oncogenic, and developmental effects. Mechanistically, BPA is reported to exert its toxic effects via multiple pathways, including alterations in epigenetic microRNA (miRNA) expression. miRNAs are endogenous non-coding RNA molecules that regulate gene expression by targeting mRNAs, thereby influencing a wide range of cellular and metabolic pathways involved in development and disease. Importantly, this review consolidates evidence suggesting that the biological effects of BPA may, in part, be mediated through miRNA-driven epigenetic modifications, affecting numerous downstream proteins and signaling pathways. Altered miRNA expression induced by BPA exposure is implicated in diverse health outcomes, including reproductive dysfunction, oncogenesis, metabolic disorders, and neurodevelopmental abnormalities. Notably, BPA exposure predominantly results in the upregulation of specific miRNAs, such as miR-21 and miR-146a, although tissue-specific and sex-dependent variations are evident. In this review, we provide a comprehensive overview of human, in vivo, and in vitro studies investigating BPA-induced miRNA dysregulation and its associated biological effects. Full article

Background/Objectives: This study aimed to examine the association between a plant-based diet (PBD) and the incidence of total cardiovascular disease (CVD), coronary heart disease (CHD), and stroke in a meta-analysis of prospective cohort studies. Methods: We searched the PubMed, ISI Web of Science and Scopus databases up to February 2026 to identify prospective cohort studies assessing the association between a PBD and the incidence of total CVD, CHD, and stroke. Results: A total of twenty-two articles (nineteen cohort studies), including 846,589 subjects and 139,652 cases, were included in the meta-analysis. People with the highest adherence to overall PBD had a 10% lower risk of CVD than those with the lowest adherence (relative risk [RR] = 0.90, 95% CI: 0.85–0.95). Adherence to a healthful plant-based diet (hPBD) was inversely associated with CVD risk (RR = 0.83, 95% CI: 0.76–0.90), whereas adherence to an unhealthful plant-based diet (uPBD) was positively associated with CVD risk (RR = 1.13, 95% CI: 1.03–1.24). High compliance with overall and a healthful PBD was associated with a 9% (RR = 0.91, 95% CI: 0.85–0.96) and 23% lower risk (RR = 0.77, 95% CI: 0.72–0.84) of CHD development compared with low compliance, respectively. High compliance with a uPBD was associated with a 24% higher risk of CHD than low compliance. We found no significant association with stroke risk. Conclusions: This meta-analysis indicated that a PBD was inversely associated with the risk of CVD and CHD. A hPBD showed an inverse association, whereas a uPBD showed a positive association between cardiovascular health. Further well-designed interventions are needed to clarify these associations. Full article

Background/Objectives: Metabolic syndrome (MetS) and low socioeconomic status (SES) are each established drivers of coronary artery disease (CAD), a leading cause of acute cardiovascular presentations to emergency and acute care services. Whether SES modifies the long-term association between MetS and CAD in a universal health coverage setting is unclear. We examined the independent and joint associations of MetS and income-based SES with 20-year incident CAD. Methods: In this nationwide retrospective cohort study using the Korean National Health Insurance Service database, 489,521 adults aged 40–79 years who underwent a national health examination in 2005 and were free of CAD at baseline were followed through 31 December 2024 (up to 20 years). At baseline, the mean age was 54.1 ± 9.2 years, and 252,818 participants (51.6%) were men. MetS was defined by modified harmonized criteria, with body mass index (BMI) ≥ 25 kg/m² substituted for waist circumference. SES was measured by health insurance premium deciles and classified as high (deciles 8–10), middle (4–7), low income (1–3), and Medical Aid (decile 0). The outcome was incident CAD (myocardial infarction or angina pectoris). Multivariable Cox proportional hazards models were adjusted for age, sex, smoking, alcohol consumption, regular exercise, BMI, chronic kidney disease, alternate exposure, and estimated adjusted hazard ratios (aHRs); joint exposure and additive interaction (relative excess risk due to interaction, RERI) were assessed. Results: MetS prevalence was 30.6%. During follow-up, 48,428 participants (9.9%) developed CAD. MetS was independently associated with CAD (aHR 1.84; 95% CI 1.78–1.91), as was a graded socioeconomic gradient (Medical Aid vs. high SES aHR 1.62; 1.54–1.70). Incidence rates ranged from 3.13 (high-SES without MetS) to 11.40 (Medical Aid with MetS) per 1000 person-years. In the joint analysis, Medical Aid beneficiaries with MetS had the highest risk (aHR 2.92; 2.78–3.08 vs. high-SES without MetS; p for interaction < 0.001), with positive additive interaction (RERI 0.68). Conclusions: Over two decades, low SES amplified the CAD burden associated with MetS. Adults living in the most severe material deprivation who also had MetS constituted the highest risk group, of direct relevance to risk stratification and disparities in emergency and acute cardiovascular care. Full article

Conventional diagnosis of chronic kidney disease (CKD) relies predominantly on invasive blood-based examinations, limiting the scalability of kidney health screening in resource-constrained environments. This study presents embedded engineering framework for non-invasive, breath-based CKD staging framework supported by machine learning and implemented on a low-cost embedded platform. To account for physiological sex differences in baseline creatinine production, estimated glomerular filtration rate (eGFR) values and breath ammonia concentrations were derived from two independent clinical cohorts using sex-specific MDRD equations (incorporating the standard male formula and the $0.742$ female correction factor, respectively) and creatinine–BUN conversion models, with male- and female-parameterized algorithms developed in parallel. The resulting feature space was analyzed using four unsupervised clustering approaches to stratify subjects into five clinically meaningful kidney function stages. Stage-specific ammonia thresholds were implemented within an Arduino Nano-based prototype equipped with an MQ-137 gas sensor and OLED display, enabling real-time point-of-care classification. Dataset-level classification accuracy reached 82% for the male algorithm and 92% for the female algorithm. Hospital-based validation on 29 patients (22 male, 7 female) yielded a real-world testing accuracy of 90.5% ($20/22$) for male patients and 71.4% ($5/7$) for female patients, a discrepancy largely attributable to the small female sample size. Because the current evaluation lacks healthy control subjects and is constrained by sample size, these empirical results serve primarily to demonstrate hardware-software functional integration and real-world deployment feasibility rather than definitive clinical efficacy. Despite these preliminary, sample-limited clinical datasets, results suggest this approach holds promise as an accessible, non-invasive screening complement to conventional diagnostic pathways, particularly in low-resource healthcare settings. Full article

Background/Objectives: Pediatric solid tumors (PST) are a biologically distinct group of malignancies whose developmental origins and molecular drivers differ substantially from those of adult cancers, with direct implications for therapeutic strategy and clinical outcome. This review synthesizes current evidence on molecular pathogenesis, tumor microenvironment biology, and the structural conditions that shape access to care across select PST. Methods: A narrative review of peer-reviewed literature was conducted primarily using PubMed, supplemented by Google Scholar, covering publications from 2000 to 2025. Tumor types were selected based on their prevalence in the pediatric population and the availability of evidence addressing both molecular features and health disparities. Body: Across eight tumor types (neuroblastoma, Ewing sarcoma, pediatric brain tumors, rhabdomyosarcoma, Wilms tumor, retinoblastoma, osteosarcoma, and chondrosarcoma), recurrent molecular alterations including MYCN amplification, EWS-FLI1 fusions, PAX-FOXO1 rearrangements and IDH 1/2 mutations emerge as central determinants of disease behavior and eligibility for treatment. The tumor microenvironment manifests as a shared mediator of immune exclusion and therapeutic resistance across tumor types, with, but not limited to, tumor-associated macrophages, myeloid-derived suppressor cells, and checkpoint molecule expression, identified as recurrent features influencing treatment response. Immunotherapeutic strategies have shown variable efficacy across PST, with the most consistent clinical benefit established in neuroblastoma. A critical and underappreciated pattern stands out across tumor types: children carrying the most aggressive molecular subtypes are disproportionately those with the least access to therapies those subtypes demand, emphasizing an overlap of biological and structural disadvantage that is also amplified in low- and middle-income countries, where late-stage presentation, treatment abandonment and limited access to molecular diagnostics compound the biological disadvantage. Conclusions: Within the eight PST reviewed, the most aggressive molecular subtypes and the greatest structural disadvantages converge in the same children; those carrying MYCN amplification, PAX-FOXO1 fusions, or EWS-FLI1 fusions are disproportionately those with the least access to the therapies their biology demands. Genomic and immunologic advances will only reach their full clinical potential when paired with inclusive trial data, diversified genomic databases, and most importantly, equitable access to biomarker-specialized therapies across all populations. Full article

Ebola alerts reveal the truth about preparedness. They show whether a health system can recognize danger early, protect health workers, isolate and care for patients, trace contacts, communicate clearly, and sustain public trust before fear replaces cooperation. In the Pandemic Agreement Era, this truth has become harder to ignore. The 2026 Bundibugyo virus disease outbreak in the Democratic Republic of the Congo and Uganda is a sharp reminder that the principles of pandemic prevention, preparedness, response, equity, and cooperation become meaningful only when they work where the first cases occur. In the absence of licensed vaccines and specific treatments for Bundibugyo virus disease, preparedness depends on the basic functions of public health: surveillance, diagnosis, infection prevention and control, referral, risk communication, community engagement, and operational coordination. These functions are often described as routine. They are not. During high-consequence infectious disease alerts, they serve as the primary protective infrastructure. Ebola also exposes a deeper ethical failure. Frontline countries and communities are expected to contain threats of global relevance, but international support often intensifies only after the risk becomes visible beyond the affected area. This reactive model is neither fair nor efficient. The WHO Pandemic Agreement defines a political direction for a more equitable and coordinated global response. Here, Ebola is not presented as a typical pandemic event but as an operational test of preparedness, solidarity, early support to affected settings, and international cooperation. Ebola alerts test whether that direction can become an operational reality before escalation. Digital tools, telemedicine, and artificial intelligence may strengthen this agenda but only when they make local systems faster, safer, more trusted, and more usable. Ebola preparedness is therefore not only a technical task. It is a test of responsibility. Full article

Background–Aim: Children represent a particularly susceptible population to endocrine-disrupting chemical (EDC) exposure; however, biomonitoring data in this population remain limited. To the best of our knowledge, this is the first study using hair biomonitoring to simultaneously assess the concentrations of phthalate metabolites (PMs), triclosan (TCS) and triclocarban (TCC) in children with obesity (OB), type 1 diabetes mellitus (T1D), and hypothalamic–pituitary-related diseases (HPRD), through hair biomonitoring. Methods: Liquid chromatography–mass spectrometry (LC-MS) was used to measure TCS, TCC and PM levels in head hair samples from 212 children, categorized into control, T1D, HPRD and OB groups. PMs and TCS levels were compared across groups and evaluated in relation to health issues, cosmetics exposure, dietary habits, cardiometabolic, and somatometric parameters. Results: Our hair biomonitoring results showed that the most commonly detected EDCs were MEHP, MBP, MiBP, and TCS, with detection frequencies of samples 95.3%, 84.4%, 79.7%, and 60.8%, respectively. Children with T1D had statistically significantly higher mean MEHP concentrations than the control group. Children with HPRD exhibited higher PM concentrations, primarily driven by elevated mean MEHP and MBP levels compared with the control group. In contrast, mean MiBP levels were lower in the OB group than in the control group. Regarding TCS levels, no statistically significant differences were observed across the disease groups compared with controls. TCS was inversely associated with somatometric parameters in the OB group. Subgroup analyses by age, sex, residence area, and maternal education were conducted to assess statistically significant differences in concentrations of PM and TCS. Conclusions: Overall, our biomonitoring results indicate group-specific concentration patterns of PMs and TCS among children with T1D, HPRD and OB groups compared to the control group. In particular, PM levels were higher in children with T1D and HPRD and lower in those with OB groups compared to the control group. As a result, this is the first study to assess PM and TCS concentrations in children across clinical groups, using hair matrix. Full article

Background: Direct evidence linking meal timing to cardiovascular disease (CVD) remains limited. This study examined the associations of meal timing and temporal eating patterns with prevalent CVD among Chinese older adults. Methods: From September 2021 to October 2025, 1386 community-dwelling adults aged ≥60 years from various socioeconomic regions of China were interviewed face-to-face. Meal timing (breakfast, lunch, and dinner timing) and sleep–wake schedules (wake-up and bedtime) were collected using standardized questionnaires. Four temporal eating parameters were calculated: wake-up to breakfast interval, eating window, dinner to bedtime interval, and the interval from eating midpoint to awake midpoint. Latent profile analysis (LPA) was used to identify temporal eating patterns. Prevalent CVD was assessed by questionnaires and verified with medical records. Results: Among 1305 eligible participants (mean [SD] age, 69.6 [6.9] years; 54.6% female), 196 (15.0%) had prevalent CVD. Compared with participants who had breakfast at ≤6:00, those who had breakfast at >7:00 had 75% higher odds of prevalent CVD (95% CI: 1.02, 2.99). Compared with dinner at ≤17:00, dinner at >18:00 had higher odds of prevalent CVD (OR = 2.61, 95% CI: 1.54, 4.43). Three temporal eating patterns were identified: typical eating pattern (58.1%), early-phase eating pattern (10.9%), and late-phase eating pattern (31.0%). Compared with the typical eating pattern, the late-phase eating pattern was associated with 56% higher odds of prevalent CVD (95% CI: 1.08, 2.26), whereas the early-phase eating pattern was associated with 45% lower odds of prevalent CVD (95% CI: 0.28, 1.07), although this association did not reach statistical significance. Conclusions: Late-phase eating pattern, particularly delayed breakfast and dinner timing, was associated with increased likelihood of prevalent CVD. Temporal eating patterns may represent a modifiable behavioral target for cardiovascular health in older adults. Full article

Severe pulmonary diseases, including atelectasis, pneumonia, and meconium aspiration syndrome, are major causes of neonatal respiratory distress, weaning difficulties, ventilator or oxygen dependence, prolonged oxygen requirements, extended hospitalization, and poor prognosis. The lack of simple and effective treatment strategies seriously endangers the survival and health of newborns, particularly premature infants. Recent advances in lung ultrasound (LUS) technology have made LUS-guided non-fiberobronchoscopic bronchoalveolar lavage (NFB-BAL) a promising solution. This approach addresses the limitations of conventional BAL in neonates by enabling accurate diagnosis, precise lesion localization, and dynamic procedural monitoring, hence reducing complications. Based on international expert consensus, these guidelines were developed to improve knowledge and promote the application of this technology and enhance operational standardization to ensure its effectiveness and safety. These guidelines contain 17 recommendations on 13 key clinical issues for reference and implementation in clinical practice. The wide application of these guidelines is expected to help significantly improve the prognosis of critically ill newborns with atelectatic pulmonary diseases. Full article

Foot-and-mouth disease (FMD) causes significant losses for livestock farmers in affected countries and regions, including Southeast Asia, where several countries are progressing through different stages of the Progressive Control Pathway (PCP) under diverse resource settings. The PCP, developed by the World Organization for Animal Health and the Food and Agriculture Organization of the United Nations, is an outcome-oriented strategy designed to support progress toward the elimination of FMD. In this review paper, we propose an evidence-based framework linking epidemiological tools to each PCP stage requirements based on studies conducted in eight Southeast Asian countries through peer-reviewed research and gray literature. The findings indicate that Stage 1 progression is supported through risk-factor analyses, seroprevalence studies, and participatory epidemiology, while Stage 2 relies on spatial analyses and evaluations of control strategies. Progression to Stage 3 requires evidence of active surveillance systems for rapid detection of new viral incursions, whereas later stages depend on risk assessment, sustained surveillance, and restricting transboundary animal movement. Regional challenges include underreporting, surveillance-system deficiencies, and inconsistent vaccination monitoring. The framework proposed herein provides a practical approach for aligning the generation of evidence with PCP requirements. Ultimately, strengthened regional collaboration that coordinates transboundary risk management is crucial for progress toward sustainable FMD control in Southeast Asia. Full article

Cardiovascular disease is the leading cause of death in Poland, and alcohol is among the principal modifiable determinants of cardiovascular health there. The view of light-to-moderate drinking as cardioprotective has been challenged by bias-corrected synthesis, Mendelian randomisation, and the 2023 World Health Organization position that no level of alcohol consumption is safe. We synthesised the primary epidemiological and modelling evidence on alcohol and cardiovascular mortality in Poland and the wider Central and Eastern European region. PubMed/MEDLINE and ClinicalTrials.gov were searched on 18 June 2026 from 1998 onward; 107 studies were included. Risk of bias was assessed with the Newcastle–Ottawa Scale and AMSTAR-2 and certainty with GRADE. Heterogeneity precluded meta-analysis, so the evidence was synthesised without meta-analysis (SWiM). The review was registered in PROSPERO (CRD420261427480) and follows PRISMA 2020. Excess cardiovascular and all-cause mortality tracked high average intake and alcohol use disorder rather than occasional intake. Polish data showed dose-graded rises in blood pressure, and stronger alcohol-control policy in the Baltic states and Poland was associated with lower mortality. The lower mortality of moderate drinkers relative to abstainers is consistent with sick-quitter bias rather than cardioprotection. Certainty was low to very low. The evidence does not support promoting any level of alcohol consumption for cardiovascular protection. Full article

Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic pathogen that causes substantial livestock losses and a range of severe human illnesses, including hemorrhagic disease, hepatitis, retinitis, vision loss, and delayed encephalitis. Despite its public health and One Health importance, no approved RVFV-specific antiviral therapy or licensed human vaccine is available. Therapeutic development is challenged by the progression of RVFV disease from acute viremia and hepatic injury to delayed neurologic and ocular complications, highlighting the need for countermeasures that protect both systemic organs and CNS tissues. This review examines RVFV antiviral development in the context of neuroinvasive disease. We summarize evidence on RVFV neuroinvasion and central nervous system injury, including route-dependent entry, blood–brain barrier interactions, immune responses, neuroinflammation, and neuronal damage. We then evaluate major antiviral strategies by mechanism, treatment timing, tissue exposure, and central nervous system relevance. Finally, we propose that future RVFV therapeutics are assessed not only by survival, viremia, and hepatic viral-load endpoints, but also by blood–brain barrier penetration, brain pharmacokinetics, efficacy in neuroinvasive models, delayed-treatment activity, and protection against encephalitis-associated injury. This framework may help prioritize antivirals that control both acute systemic disease and delayed neurological complications. Full article

Human sarcocystosis is a neglected zoonotic infection caused by protozoa of the genus Sarcocystis. Although sporadic cases and outbreaks have been reported worldwide, the global burden of human infections has not been comprehensively synthesized. This study aimed to estimate the pooled prevalence and global distribution of Sarcocystis infections in humans. A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines and registered with PROSPERO (CRD420251159944). PubMed, Scopus, Web of Science, Ovid, Nursing & Allied Health Premium, and Google Scholar were used for retrieving relevant studies. Observational studies published from 2000 onward reporting human Sarcocystis infections confirmed by microscopic and/or molecular methods were included. A random-effects model was used to estimate pooled prevalence. Heterogeneity was assessed using the I² statistic. Subgroup analyses and meta-regression were performed to explore sources of heterogeneity. Seventeen studies comprising 66,329 participants met the inclusion criteria. The pooled prevalence of human Sarcocystis infection was 0.85% (95% confidence interval [CI]: 0.33–2.19), with substantial heterogeneity (I² = 98.2%). Prevalence estimates showed marked variation across continents, countries, participant groups, diagnostic methods, Sarcocystis species, and clinical forms of sarcocystosis. Although human Sarcocystis infection appears relatively rare, its prevalence is geographically heterogeneous across studies published between 2000 and 2024. The robustness of the pooled prevalence estimate is limited by the small number of studies, uneven geographical coverage, and substantial heterogeneity. Differences in diagnostic approaches, study populations, infecting species, and disease phenotypes likely contributed to this variability. Enhanced surveillance and standardized application of sensitive molecular diagnostics are essential to better define the epidemiology, burden, and public health significance of human sarcocystosis. Full article