Search Results (3,306)

Pediatric asthma is a multifactorial and heterogeneous disease determined by the dynamic interplay of genetic susceptibility, environmental exposures, and immune dysregulation. Recent advances have highlighted the pivotal role of epigenetic mechanisms, in particular, DNA methylation, histone modifications, and non-coding RNAs, in the regulation of inflammatory pathways contributing to asthma phenotypes and endotypes. This review examines the role of respiratory viruses such as respiratory syncytial virus (RSV), rhinovirus (RV), and other bacterial and fungal infections that are mediators of infection-induced epithelial inflammation that drive epithelial homeostatic imbalance and induce persistent epigenetic alterations. These alterations lead to immune dysregulation, remodeling of the airways, and resistance to corticosteroids. A focused analysis of T2-high and T2-low asthma endotypes highlights unique epigenetic landscapes directing cytokines and cellular recruitment and thereby supports phenotype-specific aspects of disease pathogenesis. Additionally, this review also considers the role of miRNAs in the control of post-transcriptional networks that are pivotal in asthma exacerbation and the severity of the disease. We discuss novel and emerging epigenetic therapies, such as DNA methyltransferase inhibitors, histone deacetylase inhibitors, miRNA-based treatments, and immunomodulatory probiotics, that are in preclinical or early clinical development and may support precision medicine in asthma. Collectively, the current findings highlight the translational relevance of including pathogen-related biomarkers and epigenomic data for stratifying pediatric asthma patients and for the personalization of therapeutic regimens. Epigenetic dysregulation has emerged as a novel and potentially transformative approach for mitigating chronic inflammation and long-term morbidity in children with asthma. Full article

Municipal wastewaters pose a severe risk to the environment and human health when discharged untreated. This is due to their high content of pathogens, such as viruses and bacteria, which can cause diseases like cholera. Herein, the research and development of porphyrin-modified polyethersulfone (PES) ultrafiltration (UF) membranes was conducted to improve bacterial inactivation in complex municipal wastewater and enhance the fouling resistance and filtration performance. The synthesis and fabrication of porphyrin nanofillers and the resultant membrane characteristics were studied. The incorporation of porphyrin-based nanofillers improved the membrane’s hydrophilicity, morphology, and flux (247 Lm⁻² h⁻¹), with the membrane contact angle (CA) decreasing from 90° to ranging between 58° and 50°. The membrane performance was monitored for its flux, antifouling properties, reusability potential, municipal wastewater, and humic acid. The modified membranes demonstrated an effective application in wastewater treatment, achieving notable antibacterial activity, particularly under light exposure. The In-BP@SW/PES membrane demonstrated effective antimicrobial photodynamic effects against both Gram-positive S. aureus and Gram-negative E. coli. It achieved at least a 3-log reduction in bacterial viability, meeting Food and Drug Administration (FDA) standards for efficient antimicrobial materials. Among the variants tested, membranes modified with In-PB@SW nanofillers exhibited superior antifouling properties with flux recovery ratios (FRRs) of 78.9% for the humic acid (HA) solution and 85% for the municipal wastewater (MWW), suggesting a strong potential for long-term filtration use. These results highlight the promise of porphyrin-functionalized membranes as multifunctional tools in advanced water treatment technologies. Full article

Background: Thyroid eye disease (TED) is a rare autoimmune orbital disorder predominantly associated with Graves’ disease. It is characterized by orbital inflammation, tissue remodeling, and potential visual morbidity. Conventional therapies, particularly systemic glucocorticoids, offer only partial symptomatic relief, failing to reverse chronic structural changes such as proptosis and diplopia, and are associated with substantial adverse effects. This review aims to synthesize recent developments in understandings of TED pathogenesis and to critically evaluate emerging therapeutic strategies. Methods: A systematic literature review was conducted using MEDLINE, Embase, and international clinical trial registries focusing on pivotal clinical trials and investigational therapies targeting core molecular pathways involved in TED. Results: Current evidence suggests that TED pathogenesis is primarily driven by the autoimmune activation of orbital fibroblasts (OFs) through thyrotropin receptor (TSH-R) and insulin-like growth factor-1 receptor (IGF-1R) signaling. Teprotumumab, a monoclonal IGF-1R inhibitor and the first therapy approved by the U.S. Food and Drug Administration for TED, has demonstrated substantial clinical benefit, including improvements in proptosis, diplopia, and quality of life. However, concerns remain regarding relapse rates and treatment-associated adverse events, particularly hearing impairment. Investigational therapies, including next-generation IGF-1R inhibitors, small-molecule antagonists, TSH-R inhibitors, neonatal Fc receptor (FcRn) blockers, cytokine-targeting agents, and gene-based interventions, are under development. These novel approaches aim to address both inflammatory and fibrotic components of TED. Conclusions: Teprotumumab has changed TED management but sustained control and toxicity reduction remain challenges. Future therapies should focus on targeted, mechanism-based, personalized approaches to improve long-term outcomes and patient quality of life. Full article

Heavy metal contamination in freshwater ecosystems poses persistent threats to aquatic organisms and public health. This study evaluates the transgenerational toxicity of cadmium chloride and copper sulfate on Culex pipiens, focusing on development, reproduction, and midgut histopathology over two successive generations. Larval bioassays showed cadmium chloride to be more toxic than copper sulfate, with early instars exhibiting higher sensitivity (LC₅₀ = 8.66 μg/L for Cd; 175.63 μg/L for Cu). Both metals significantly delayed larval and pupal development, reduced fecundity, and decreased egg hatchability in a dose-dependent manner. Histopathological examination revealed midgut epithelial degeneration, vacuolation, and brush border loss, with copper sulfate inducing more severe cytotoxicity. These findings confirm that sublethal, chronic metal exposure can impair physiological and reproductive traits across generations. Moreover, this study highlights the utility of mosquitoes as sensitive bioindicators of aquatic pollution, and underscores the long-term ecological implications of heavy metal contamination on vector dynamics and disease transmission. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a significant comorbidity in individuals with type 1 diabetes (T1D), despite its historical association with type 2 diabetes. This review focuses on summarizing current findings regarding the role of insulin resistance in the development of MASLD in T1D, as well as examining the relationship between MASLD and diabetes-related complications. We will also briefly discuss the prevalence, diagnostic challenges, associated complications, and potential mechanisms underlying MASLD in T1D. Although insulin resistance is well established in MASLD among those with type 2 diabetes, its role in T1D requires further clarification. Emerging markers, such as the estimated glucose disposal rate, offer early insight into this relationship. MASLD in T1D is linked to both microvascular and macrovascular complications, including nephropathy, retinopathy, neuropathy, and cardiovascular disease. Variability in prevalence estimates reflects inconsistencies among imaging modalities, emphasizing the need for standardized, non-invasive diagnostic approaches. Recognizing and addressing MASLD and its links to insulin resistance and diabetes complications in T1D is vital for mitigating long-term complications and enhancing clinical outcomes. Full article

Background/Objective: Understanding how chronic conditions such as knee osteoarthritis (OA) and chronic obstructive pulmonary disease (COPD) influence long-term physical activity (PA) is essential for developing condition-specific rehabilitation strategies. This study aimed to examine whether baseline diagnoses of knee OA and COPD are independently associated with the trajectories of PA decline over five years in U.S. adults, informed by the disablement process model. Methods: We analyzed data from 855 adults aged ≥45 years enrolled in the Osteoarthritis Initiative (OAI). The participants were categorized into three baseline groups, control (n = 122), knee OA (n = 646), and COPD (n = 87), based on self-reports and prior clinical assessments. PA was measured annually for five years using the Physical Activity Scale for the Elderly (PASE). General linear mixed models assessed changes in PA over time, adjusting for demographic, behavioral, and clinical covariates. Results: Compared to the controls, participants with knee OA had a significant decline in PA over time (β = −6.62; 95% CI: −15.4 to −2.19; p = 0.014). Those with COPD experienced an even greater decline compared to the knee OA group (β = −11.2; 95% CI: −21.7 to −0.67; p = 0.037). These associations persisted after adjusting for age, sex, body mass index, comorbidities, and smoking. Conclusions: Baseline knee OA and COPD were independently associated with long-term reductions in PA. These findings underscore the importance of early, tailored rehabilitation strategies, particularly pulmonary rehabilitation, in preserving functional independence among older adults with chronic conditions. Full article

During the coronavirus 2019 pandemic, sports activities were restricted, raising concerns about their impact on the physical condition of adolescent athletes, which remained largely unquantified. This study was designed with two primary objectives: first, to precisely quantify and elucidate the differences in the physical condition of adolescent athletes before and after activity restrictions due to the pandemic; and second, to innovatively develop and validate a non-contact medical checkup application. Medical checks were conducted on 563 athletes designated for sports enhancement. Participants were junior high school students aged 13 to 15, and the sample consisted of 315 boys and 248 girls. Furthermore, we developed a smartphone application and compared self-checks using the application with in-person checks by orthopedic surgeons to determine the challenges associated with self-checks. Statistical tests were conducted to determine whether there were statistically significant differences in range of motion and flexibility parameters before and after the pandemic. Additionally, items with discrepancies between values self-entered by athletes using the smartphone application and values measured by specialists were detected, and application updates were performed. Student’s t-test was used for continuous variables, whereas the chi-square test was used for other variables. Following the coronavirus 2019 pandemic, athletes were stiffer than during the pre-pandemic period in terms of hip and shoulder joint rotation range of motion and heel–buttock distance. The dominant hip external rotation decreased from 53.8° to 46.8° (p = 0.0062); the non-dominant hip external rotation decreased from 53.5° to 48.0° (p = 0.0252); the dominant shoulder internal rotation decreased from 62.5° to 54.7° (p = 0.0042); external rotation decreased from 97.6° to 93.5° (p = 0.0282), and the heel–buttock distance increased from 4.0 cm to 10.4 cm (p < 0.0001). The heel–buttock distance and straight leg raising angle measurements differed between the self-check and face-to-face check. Although there are items that cannot be accurately evaluated by self-check, physical condition can be improved with less contact by first conducting a face-to-face evaluation under appropriate guidance and then conducting a self-check. These findings successfully address our primary objectives. Specifically, we demonstrated a significant decline in the physical condition of adolescent athletes following pandemic-related activity restrictions, thereby quantifying their impact. Furthermore, our developed non-contact medical checkup application proved to be a viable tool for monitoring physical condition with reduced contact, although careful consideration of measurable parameters is crucial. This study provides critical insights into the long-term effects of activity restrictions on young athletes and offers a practical solution for health monitoring during infectious disease outbreaks, highlighting the potential for hybrid checkup approaches. Full article

Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. Predicting its progression is crucial for preventing late-stage AMD, as it is an irreversible retinal disease. Both genetic factors and retinal images are instrumental in diagnosing and predicting AMD progression. Previous studies have explored automated diagnosis using single fundus images and genetic variants, but they often fail to utilize the valuable longitudinal data from multiple visits. Longitudinal retinal images offer a dynamic view of disease progression, yet standard Long Short-Term Memory (LSTM) models assume consistent time intervals between training and testing, limiting their effectiveness in real-world settings. To address this limitation, we propose time-varied Long Short-Term Memory (TV-LSTM), which accommodates irregular time intervals in longitudinal data. Our innovative approach enables the integration of both longitudinal fundus images and AMD-associated genetic variants for more precise progression prediction. Our TV-LSTM model achieved an AUC-ROC of 0.9479 and an AUC-PR of 0.8591 for predicting late AMD within two years, using data from four visits with varying time intervals. Full article

Background: Acute kidney injury (AKI) frequently occurs following major liver resection, adversely affecting both short- and long-term outcomes. This study aimed to determine the incidence of AKI post-hepatectomy and identify relevant pre- and intraoperative risk factors. Our secondary objectives were to develop a predictive score for postoperative AKI and assess the associations between AKI, chronic kidney disease (CKD), and 1-year mortality. Methods: This was a retrospective study in a cancer referral center in Marseille, France, from 2018 to 2022. Results: Among 169 patients, 55 (32.5%) experienced AKI. Multivariate analysis revealed several independent risk factors for postoperative AKI, including age, body mass index, the use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, time to liver resection, intraoperative shock, and bile duct reconstruction. Neoadjuvant chemotherapy was protective. The AKIMEBO score was developed, with a threshold of ≥15.6, demonstrating a sensitivity of 89.5%, specificity of 76.4%, positive predictive value of 61.8%, and negative predictive value of 94.4%. AKI was associated with increased postoperative morbidity and one-year mortality following major hepatectomy. Conclusion: AKI is a common complication post-hepatectomy. Factors such as time to liver resection and intraoperative shock management present potential clinical intervention points. The AKIMEBO score can provide a valuable tool for postoperative risk stratification. Full article

Background/Objectives: Celiac disease (CD) is an autoimmune disorder characterized by small intestinal enteropathy triggered by gluten ingestion, often associated with gut dysbiosis. The most effective treatment is strict adherence to a gluten-free diet (GFD), which alleviates symptoms. This study uniquely integrates taxonomic, functional, and resistance profiling to evaluate the gut microbiota of women with CD on a GFD. Methods: To evaluate the long-term impact of a GFD, this study analyzed the gut microbiota of 10 women with CD on a GFD for over a year compared to 10 healthy controls with unrestricted diets. Taxonomic diversity (16S rRNA gene sequencing and the analysis of α and β-diversity), metabolic functionality (Biolog EcoPlates^®), and antibiotic resistance profiles (Cenoantibiogram) were assessed. Results: Metagenomic analysis revealed no significant differences in taxonomic diversity but highlighted variations in the abundance of specific bacterial genera. Women with CD showed increased proportions of Bacteroides, Streptococcus, and Clostridium, associated with inflammation, but also elevated levels of beneficial genera such as Roseburia, Oxalobacter, and Paraprevotella. Despite no significant differences in metabolic diversity, higher minimum inhibitory concentrations (MICs) in women in the healthy control group suggest that dietary substrates in unrestricted diets may promote the proliferation of fast-growing bacteria capable of rapidly developing and disseminating antibiotic resistance mechanisms. Conclusions: These findings indicate that prolonged adherence to a GFD in CD supports remission of gut dysbiosis, enhances microbiota functionality, and may reduce the risk of antibiotic resistance, emphasizing the importance of dietary management in CD. Full article

Osteoarthritis (OA) remains a major contributor to pain and disability; however, the current management is largely reactive, focusing on symptoms rather than preventing irreversible cartilage loss. This review first examines the mechanistic foundations for pharmacological chondroprotection—illustrating how conventional agents, such as glucosamine sulfate and chondroitin sulfate, can potentially restore extracellular matrix (ECM) components, may attenuate catabolic enzyme activity, and might enhance joint lubrication—and explores the delivery challenges posed by avascular cartilage and synovial diffusion barriers. Subsequently, a practical “What–How–When” framework is introduced to guide community pharmacists in risk screening, DMOAD selection, chronotherapeutic dosing, safety monitoring, and lifestyle integration, as exemplified by the CHONDROMOVING infographic brochure designed for diverse health literacy levels. Building on these strategies, the P4–4P Chondroprotection Framework is proposed, integrating predictive risk profiling (physicians), preventive pharmacokinetic and chronotherapy optimization (pharmacists), personalized biomechanical interventions (physiotherapists), and participatory self-management (patients) into a unified, feedback-driven OA care model. To translate this framework into routine practice, I recommend the development of DMOAD-specific clinical guidelines, incorporation of chondroprotective chronotherapy and interprofessional collaboration into health-professional curricula, and establishment of multidisciplinary OA management pathways—supported by appropriate reimbursement structures, to support preventive, team-based management, and prioritization of large-scale randomized trials and real-world evidence studies to validate the long-term structural, functional, and quality of life benefits of synchronized DMOAD and exercise-timed interventions. This comprehensive, precision-driven paradigm aims to shift OA care from reactive palliation to true disease modification, preserving cartilage integrity and improving the quality of life for millions worldwide. Full article

Background: Patients diagnosed with melanoma are at increased risk of developing multiple primary melanomas (MPMs). Identifying clinical and genetic factors associated with MPM is critical for implementing personalized surveillance strategies. This study aims to describe the clinical, histopathological, and genetic characteristics of patients with MPM managed in a tertiary hospital and to contextualize findings within the current literature. Methods: We conducted a retrospective review of patients diagnosed with two or more primary melanomas between 2010 and 2023 at a tertiary dermatology unit. Demographic data, personal and family cancer history, phototype, melanoma characteristics, genetic testing, staging, treatments, and outcomes were collected. These data were compared with findings from the recent literature. Results: Thirteen patients (ten males, three females; median age: 59 years) were found to have a total of 33 melanomas. Most patients had Fitzpatrick phototype II and no immunosuppression. The number of melanomas per patient ranged from two to five. Synchronous lesions were observed in two patients. Common locations included the trunk and extremities. Histologically, 57% were in situ melanomas, and subsequent melanomas were generally thinner than the index lesion. Two patients showed progression to advanced disease. One patient was positive for MC1R mutation; the rest were negative or inconclusive. Additional phenotypic and environmental risk factors were extracted from patient records and are summarized as follows: Ten patients (76.9%) had Fitzpatrick skin phototype II, and three (23.1%) had phototype III. Chronic occupational sun exposure was reported in four patients (30.8%), while five (38.5%) recalled having suffered multiple sunburns during childhood or adolescence. Eight patients (61.5%) presented with a total nevus count exceeding 50, and five (38.5%) exhibited clinically atypical nevi. None of the patients reported use of tanning beds. Conclusions: Our findings are consistent with the existing literature indicating that patients with MPM often present with thinner subsequent melanomas and require long-term dermatologic follow-up. The inclusion of genetic testing and phenotypic risk factors enables stratified surveillance and supports the application of personalized medicine in melanoma management. Full article

Background: The education process for newly diagnosed Type 1 diabetes mellitus (T1D) patients and their families, primarily led by diabetes specialist nurses, is essential for gaining knowledge about the disease and its management. However, few assessment tools have been employed to evaluate long-term knowledge retention among T1D patients years after diagnosis. Methods: We developed a 20-question test to assess the knowledge of patients and their families at the conclusion of the initial education process and again 6–12 months later. Demographic and clinical data were also collected. Statistical analyses included comparisons between the first and second test results, as well as evaluation of potential contributing factors. The internal consistency and construct validity of the questionnaire were evaluated. Results: Forty-four patients completed both assessments, with a median interval of 11.5 months between them. The average score on the first test was 88.6, which declined to 82.7 on the second assessment (p < 0.001). In univariate analysis, factors positively associated with higher scores included Jewish ethnicity, lower HbA1c levels, and shorter hospitalization duration. Multivariate analysis revealed that parents had lower odds of experiencing a significant score decline compared to patients. Cronbach’s alpha was 0.69, and Principal Component Analysis (PCA) identified eight components accounting for 67.1% of the total variance. Conclusions: Healthcare providers should consider offering re-education to patients and their families approximately one year after diagnosis, with particular attention to high-risk populations during the initial education phase. Further studies are needed to examine this tool’s performance in larger cohorts. Full article

Central nervous system (CNS) disorders present significant therapeutic challenges due to the limited regenerative capacity of neural tissues, resulting in long-term disability for many patients. Consequently, the development of novel therapeutic strategies is urgently warranted. Stem cell therapies show considerable potential for mitigating brain damage and restoring neural connectivity, owing to their multifaceted properties, including anti-apoptotic, anti-inflammatory, neurogenic, and vasculogenic effects. Recent research has also identified exosomes—small vesicles enclosed by a lipid bilayer, secreted by stem cells—as a key mechanism underlying the therapeutic effects of stem cell therapies, and given their enhanced stability and superior blood–brain barrier permeability compared to the stem cells themselves, exosomes have emerged as a promising alternative treatment for CNS disorders. A key challenge in the application of both stem cell and exosome-based therapies for CNS diseases is the method of delivery. Currently, several routes are being investigated, including intracerebral, intrathecal, intravenous, intranasal, and intra-arterial administration. Intracerebral injection can deliver a substantial quantity of stem cells directly to the brain, but it carries the potential risk of inducing additional brain injury. Conversely, intravenous transplantation is minimally invasive but results in limited delivery of cells and exosomes to the brain, which may compromise the therapeutic efficacy. With advancements in catheter technology, intra-arterial administration of stem cells and exosomes has garnered increasing attention as a promising delivery strategy. This approach offers the advantage of delivering a significant number of stem cells and exosomes to the brain while minimizing the risk of additional brain damage. However, the investigation into the therapeutic potential of intra-arterial transplantation for CNS injury is still in its early stages. In this comprehensive review, we aim to summarize both basic and clinical research exploring the intra-arterial administration of stem cells and exosomes for the treatment of CNS diseases. Additionally, we will elucidate the underlying therapeutic mechanisms and provide insights into the future potential of this approach. Full article

Background/Objectives: Neurodegenerative proteinopathies, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and dementia with Lewy bodies (DLB), are increasingly prevalent worldwide mainly due to population aging. These conditions are marked by complex etiologies, overlapping pathologies, and progressive clinical decline, with significant consequences for patients, caregivers, and healthcare systems. This review aims to synthesize evidence on the healthcare complexities of major neurodegenerative proteinopathies to highlight current knowledge gaps, and to inform future care models, policies, and research directions. Methods: We conducted a comprehensive literature search in PubMed/MEDLINE using combinations of MeSH terms and keywords related to neurodegenerative diseases, proteinopathies, diagnosis, sex, management, treatment, caregiver burden, and healthcare delivery. Studies were included if they addressed the clinical, pathophysiological, economic, or care-related complexities of aging-related neurodegenerative proteinopathies. Results: Key themes identified include the following: (1) multifactorial and unclear etiologies with frequent co-pathologies; (2) long prodromal phases with emerging biomarkers; (3) lack of effective disease-modifying therapies; (4) progressive nature requiring ongoing and individualized care; (5) high caregiver burden; (6) escalating healthcare and societal costs; and (7) the critical role of multidisciplinary and multi-domain care models involving specialists, primary care, and allied health professionals. Conclusions: The complexity and cost of neurodegenerative proteinopathies highlight the urgent need for prevention-focused strategies, innovative care models, early interventions, and integrated policies that support patients and caregivers. Prevention through the early identification of risk factors and prodromal signs is critical. Investing in research to develop effective disease-modifying therapies and improve early detection will be essential to reducing the long-term burden of these disorders. Full article