Search Results (10,911)

14-3-3 proteins are highly conserved regulatory molecules in plants. In grapevine (Vitis vinifera L.), 14-3-3 proteins are studied under abiotic stress. However, the role of 14-3-3 proteins in the interaction between grapevine and downy mildew is yet to be studied. In this study, we identified a highly conserved 14-3-3 protein in grapevine and performed a phylogenetic analysis, revealing a close relationship between one of its homologs, 14-3-3ω proteins from Arabidopsis thaliana and Nicotiana benthamiana. We designated this homolog as Vv14-3-3ω. Subcellular localization studies showed that Vv14-3-3ω resides in the plasma membrane and cytoplasm. Expression analysis revealed a strong induction of Vv14-3-3ω at early time points following Plasmopara viticola infection, correlating with enhanced pathogen sporulation in grapevine. Furthermore, transient overexpression of Vv14-3-3ω in N. benthamiana increased susceptibility to the Phytophthora capsici pathogen and suppressed Flg22-induced pattern-triggered immunity (PTI) responses. Overexpression of Vv14-3-3ω in Nb14-3-3-silenced N. benthamiana plants resulted in increased susceptibility to P. capsici, suggesting functional conservation of this isoform. These findings indicate that Vv14-3-3ω functions as a susceptibility factor, facilitating pathogen infection and disease progression in grapevine, and highlight its potential role for improving resistance against downy mildew. Full article

This retrospective review traces personal encounters along the complex path of plant yellowing diseases—graft-transmissible disorders historically attributed to elusive viruses, but later linked to phloem-invading, wall-less bacteria known as Mollicutes. These include two plant-infecting genera: the cultivable Spiroplasma and the non-cultivable ‘Candidatus Phytoplasma’. A third group—the walled, psyllid-transmitted Candidatus Liberibacter—was later implicated in closely similar syndromes. This shift in understanding marked a major turning point in plant pathology, offering new insights into yellowing diseases characterized by stunting, decline, and poor or deformed growth. The review focuses on key syndromes: citrus little leaf disease (LLD), or citrus stubborn disease (CSD), caused by Spiroplasma citri; and several Mollicute -related disorders, including safflower phyllody, Bermuda grass yellowing, and papaya dieback (PDD) (Nivun Haamir), the latter linked to ‘Candidatus Phytoplasma australiense’. Despite differing causes and vectors, citrus LLD-CSD and PPD share an erratic, unpredictable pattern of natural outbreaks—sometimes a decade apart—hindering grower engagement and sustained control efforts. While scientific understanding has deepened, practical management remains limited. The recent global spread of Huanglongbing (HLB), caused by Candidatus Liberibacter species, underscores the urgent need for improved strategies to manage this resilient group of phloem-limited bacterial pathogens. Full article

Background: Immunization coverage has increased substantially in the Western Pacific Region, saving millions of lives and supporting disease elimination efforts. However, gaps in coverage and inequitable vaccine access persist, leaving millions unvaccinated. Wealth-based inequalities remain a critical barrier to achieving equitable immunization coverage and maximizing the health benefits of vaccination programs. Methods: We analyzed full immunization coverage among 1-year-olds in 10 middle-income countries of the Western Pacific Region using data from the WHO Health Inequalities Data Repository. National and wealth quintile-specific coverage rates and within-country inequalities were assessed using absolute and relative measures (difference, ratio, slope index of inequality, and relative index of inequality). Trends over time were examined in countries with longitudinal data (n = 5), identifying pro-rich or pro-poor changes based on shifts in quintile-specific coverage. We also calculated the population attributable risk (PAR) and fraction (PAF) to estimate the potential increase in national coverage if wealth-based inequalities were eliminated. Findings: Substantial gaps in immunization coverage persist across all countries studied (n = 10), but with substantial between- and within-country disparities. Coverage was higher among the richest quintiles in half of the countries, with the rest showing no significant disparities. Trends in inequalities were mixed: Cambodia, Mongolia, and Viet Nam experienced pro-poor improvements over time; the Philippines saw widening pro-rich inequalities; and Lao PDR showed little change. Population attributable risks (PAR) showed that eliminating wealth-based inequalities could increase national coverage significantly in five countries (Fiji, Lao PDR, Papua New Guinea, Samoa, and Tonga), with relative gains that could increase national coverage by up to 50% while achieving equity gains. Conclusions: Addressing wealth-based inequalities in immunization could drive substantial gains in national coverage across the Western Pacific Region. Sustained, equity-oriented approaches are essential to achieving universal vaccine access and ensuring no population is left behind. Inequality patterns can guide equity-focused policies to reach underserved and disadvantaged populations. Full article

Background: Communication difficulty restricts education, healthcare, and social participation, yet population-level data for Saudi Arabia have been scarce. This study analysed the 2017 Saudi National Disability Survey to estimate prevalence, describe severity and demographic patterns, and identify factors linked to these difficulties. Objectives: We aimed to estimate national and regional prevalence, assess severity, and gender differences, and identify socio-demographic and disability-related correlates. Methods: A cross-sectional, two-stage stratified cluster sample of 33,575 households (weighted N = 20,408,362 citizens) provided self-reported data on communication difficulty and socio-demographics. Weighted frequencies described prevalence and multivariable logistic regression identified independent correlates. Results: Among all Saudi citizens, 7.1% reported at least one functional difficulty, and of this group 15.7%—equivalent to 1.1% of the total population (n = 226,510)—had a communication difficulty; within that communication difficulty stratum, (n = 185,508) (0.9% of all citizens) experienced it alongside additional impairments, whereas (n = 41,002) (0.2% of all citizens) reported communication difficulty in isolation. The communication difficulties exhibit significant regional variation, ranging from 0.45% in Najran to 1.55% in Aseer. Most cases were classified as being associated with some difficulty (72%); females were over-represented in the extreme category despite a modest male excess overall (adjusted odds ratio [AOR] = 1.09). Higher education, married status, and bilateral first-cousin marriage (AOR = 1.22) were associated with greater risk. Chronic disease (44%) and perinatal causes (13%) predominated, and 84% of cases co-occurred with at least one other disability. Independent predictors included a long duration (AOR = 4.18), disease or delivery-related cause, and consanguinity. Conclusions: Findings highlight geographically clustered need, genetic risk factors, and substantial multimorbidity, indicating the importance of region-specific screening, premarital counselling, and integrated rehabilitation within chronic disease services. Full article

Ilex verticillata (winterberry) is a valuable ornamental shrub increasingly threatened by leaf blight, a disease that compromises its aesthetic and economic value. While fungal pathogens like Alternaria alternata are known to cause leaf blight in horticultural crops, their role in I. verticillata and the host’s defense mechanisms have not been fully characterized. Our study investigated the pathogen-host interaction by identifying the causal agent and examining the physiological and molecular defense mechanisms of I. verticillata. Through morphological and multi-locus molecular analyses (ITS, TEF1-α, G3PDH, RPB2), A. alternata was confirmed as the primary pathogen, fulfilling Koch’s postulates. Pathogenicity assays revealed distinct disease progression stages, from necrotic lesions to tissue degradation. Transcriptomic profiling uncovered dynamic host responses, with early upregulation of pattern recognition receptors (PRRs) and transcripts encoding antioxidant enzymes (SOD, CAT), followed by downregulation of metabolic pathway genes. Phytohormone analysis highlighted intricate crosstalk, with salicylic acid (SA) peaking during mid-infection and jasmonic acid (JA) rebounding later, reflecting a coordinated defense strategy. Additionally, the oxidative stress marker malondialdehyde (MDA), an indicator of membrane lipid peroxidation, surged early, indicating membrane damage, while sustained induction of antioxidant enzymes suggested adaptive responses. The key finding was distinct phytohormone crosstalk, characterized by a mid-infection SA peak followed by a late JA rebound, alongside an early oxidative burst marked by MDA accumulation and sustained antioxidant enzyme activity. These findings provide a framework for understanding I. verticillata’s defense mechanisms and offer insights for developing targeted disease management strategies, such as resistant cultivar breeding or hormone-mediated interventions. Full article

Alpha-synuclein (αsyn) misfolding and aggregation underlie several neurodegenerative disorders, including Parkinson’s disease. Early oligomeric intermediates are particularly toxic yet remain challenging to detect and characterize within cellular systems. Here, we employed the luminescent conjugated oligothiophene h-FTAA to investigate early aggregation events of human wildtype (huWT) and A53T-mutated αsyn (huA53T) both in vitro and in HEK293 cells stably expressing native human-αsyn. Comparative fibrillation assays revealed that h-FTAA detected αsyn aggregation with higher sensitivity and earlier onset than Thioflavin T, with the A53T variant displaying accelerated fibrillation. HEK293 cells stably expressing huWT- or huA53T-αsyn were exposed to respective pre-formed fibrils (PFFs), assessed via immunocytochemistry, h-FTAA staining, spectral emission profiling, and fluorescence lifetime imaging microscopy (FLIM). Notably, huA53T PFFs promoted earlier aggregation patterns and yielded narrower fluorescence lifetime distributions compared with huWT PFFs. Spectral imaging showed h-FTAA emission maxima (~550–580 nm) red-shifted and broadened in cells along with variable lifetimes (0.68–0.87 ns), indicating heterogeneous aggregate conformations influenced by cellular milieu. These findings demonstrate that h-FTAA is useful for distinguishing early αsyn conformers in living systems and, together with stable αsyn-expressing HEK293 cells, offers a platform for probing early αsyn morphotypes. Taken together, this opens for further discovery of biomarkers and drugs that can interfere with αsyn aggregation. Full article

Background and objectives: Clinical laboratory analyses are essential for diagnosing and treating allergic diseases mediated by immunoglobulin E (IgE). Identifying the sources of sensitivity, subject to regional variations, enables the implementation of effective management strategies, such as prevention and immunotherapy. Through a cross-sectional study, this study aimed to determine the sensitivity profile to aeroallergens (latent class) and their correlation with age, sex, and season in the population sampled. Methods: The purpose was to map the concentrations of specific IgE serum levels linked to the most prevalent allergens, considering variations related to age, specific IgE levels, and seasons of the year through a cross-sectional study. Results: The 995 reports of specific IgE tests analyzed were clustered into six aeroallergen categories and were predominantly composed of female individuals (57.1%). The most prevalent age group was younger than 18 (56.5%), and most exams were performed in the spring (27.7%). The aeroallergen category ‘grass’ significantly correlated with sex and age, indicating that men have a 65% greater probability of having high levels of specific IgE as a response to this allergen, and age is related to higher IgE levels. Latent class analysis identified an optimal three-class solution for specific IgE sensitization patterns: Class 1: Moderate Sensitization; Class 2: Low Sensitization; and Class 3: High Sensitization. Conclusion: The present study highlights the importance of knowing the local aeroallergen profile for early diagnosis and prevention of allergic diseases, emphasizing the relevance of the allergen category related to the age and sex of the individuals. Full article

Human cytomegalovirus (HCMV) establishes lifelong latency following primary infection, residing within myeloid progenitor cells and monocytes. To achieve this, the virus employs multiple immune evasion strategies. It suppresses innate immune signaling by inhibiting Toll-like receptor and cGAS-STING pathways. In addition, the virus suppresses major histocompatibility complex (MHC)-dependent antigen presentation to evade T cell recognition. As the downregulation of MHC molecules may trigger NK cell activation, the virus compensates for this by expressing proteins such as UL40 and IL-10, which engage inhibitory NK cell receptors and block activating signals, thereby suppressing NK cell immune surveillance. Viral proteins like UL36 and UL37 block host cell apoptosis and necroptosis, allowing HCMV to persist undetected and avoid clearance. In settings of profound immunosuppression, such as after allogeneic hematopoietic stem cell transplantation (allo-HSCT) or solid organ transplantation, slow immune reconstitution creates a window for viral reactivation. Likewise, immunosenescence and chronic low-grade inflammation during aging increases the risk of reactivation. Once reactivated, HCMV triggers programmed cell death, releasing viral PAMPs (pathogen-associated molecular patterns) and host-derived DAMPs (damage-associated molecular patterns). This release fuels a potent inflammatory response, promoting further viral reactivation and exacerbating tissue damage, creating a vicious cycle. This cycle of inflammation and reactivation contributes to both transplant-related complications and the decline of antiviral immunity in the elderly. Therefore, understanding the immune regulatory mechanisms that govern the switch from latency to reactivation is critical, especially within the unique immune landscapes of transplantation and aging. Elucidating these pathways is essential for developing strategies to prevent and treat HCMV-related disease in these high-risk populations. Full article

Dietary patterns greatly affect periodontitis, a chronic inflammatory disease that compromises both dental and systemic health. According to the emerging evidence, periodontal risk is more strongly associated with the overall dietary quality, especially fiber density intake, than any one micronutrient. While the average intake in industrialized countries is only half of the recommended 30 g day⁻¹, high-fiber diets such as the Mediterranean diet, the Dietary Approaches to Stop Hypertension (DASH), and whole-food plant-based diets are consistently associated with a 20–40% lower periodontitis prevalence. Dietary fiber plays a central role in regulating immune responses, strengthening tissue barriers, improving metabolic homeostasis, and shaping a healthy microbiome through its microbial fermentation products: short-chain fatty acids (SCFAs). This makes it a biologically rational and clinical evidence-supported strategy for the prevention and management of periodontitis. Integrating high-fiber diet recommendations into routine periodontal care and public health policies could be a crucial step towards more comprehensive oral and systemic health management. This narrative review elaborates on the mechanistic, observational, and intervention data highlighting the role of dietary fiber, especially SCFAs, in periodontal health. Full article

African swine fever (ASF) is a highly contagious viral disease with significant impacts on domestic pigs and wild boar populations. This study applies GIS-based spatial analysis to monitor ASF outbreaks in northwestern Italy (Piedmont and Liguria) and identify areas at increased risk. Key factors considered include pig density, wildlife proximity, and environmental conditions. The spatial analysis revealed that central–western municipalities exhibited higher risk due to favorable environmental conditions and dense wild boar populations, while peripheral areas showed a temporal delay in outbreak emergence. Mapping the spreading rate and habitat interfaces allowed the development of a spatial risk model, which was further analyzed using geostatistical techniques to understand disease dynamics. The results demonstrate the effectiveness of geospatial modeling in identifying high-risk zones, characterizing spatio-temporal patterns, and supporting targeted prevention and surveillance strategies. These findings provide actionable insights for ASF management and resource allocation. Future studies may refine these models by integrating additional datasets and environmental variables, enhancing predictive capacity and applicability across different regions. Full article

Background: Investigating human exposure to toxic contaminants through dietary consumption is critical to identify disease risk factors and health guidelines. Methods: In this study, we developed a cross-sectional online survey to collect information about dietary patterns and related food consumption habits among adults (age ≥ 18) and adolescents (ages 13–17) in Southern California, focusing on popular staple foods and/or those targeted most commonly under California’s Proposition 65 law for lead and acrylamide exposure. Results: Results identified root vegetables, rice, leafy greens, pasta/noodles, tea, juice, and seafood to be among the most heavily consumed foods by mass, while the daily intake of many foods such as stuffed grape leaves, tamarind/chili candy and herbs/spices varied by age and race/ethnicity, suggesting that many of Proposition 65’s pollution allowances may be exacerbating issues of health inequity and environmental injustice. Moreover, findings from this study indicate that the methods of exposure assessment often applied under Prop 65, especially relating to herbs/spices, are likely to underestimate single-day exposures, thus allowing unsafe products on the market without warning labels. Conclusions: Study outcomes are broadly relevant to environmental health and nutrition science, with particular relevance to public health practitioners and California’s Prop 65 regulators and other stakeholders. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), have become the leading causes of chronic liver disease worldwide, with increasing rates of cirrhosis, hepatocellular carcinoma, and cardiovascular complications. Pathogenesis involves a complex interplay of dietary excess, sedentary lifestyle, insulin resistance, adipose tissue dysfunction, and alterations in the gut microbiome, which collectively lead to hepatocellular stress, inflammation, and fibrogenesis. Despite ongoing advances in pharmacotherapy, lifestyle intervention remains the cornerstone of management. Evidence shows that sustained weight loss of ≥5% reduces hepatic steatosis, ≥7% improves necroinflammation, and ≥10% stabilizes or reverses fibrosis. Dietary strategies, including Mediterranean-style patterns, high-protein approaches, and intermittent fasting, have been shown to be effective in improving insulin sensitivity and reducing intrahepatic triglycerides. Exercise interventions, focusing on both aerobic fitness and resistance training, enhance metabolic flexibility and combat sarcopenia, thereby improving hepatic and systemic outcomes. Equally important are behavioral support, digital health tools, and multidisciplinary approaches that enhance adherence and address barriers such as socioeconomic disparities, limited access, and patient engagement issues. Personalized nutrition plans, integrating physical activity, and ongoing support for behavioral change are essential for long-term disease management. This review synthesizes current evidence on the roles of macronutrients, micronutrients, dietary quality, physical activity, and adjunctive behavioral strategies in managing MASLD. By translating mechanistic insights into practical, evidence-based recommendations, we aim to provide clinicians, dietitians, and exercise professionals with effective frameworks to slow disease progression and improve outcomes across diverse patient populations. Full article

Smartphone overdependence among South Korean adolescents, affecting nearly 40%, poses a growing public health concern, with usage patterns varying by regional context. Leveraging conceptually informed AI/ML models, this study (1) develops a high-performing low-risk screening tool to monitor disease burden, (2) leverages AI/ML to explore psychologically meaningful constructs, and (3) provides place-based policy implication profiles to inform public health policy. This study uses data from 1873 adolescents in the 2023 Smartphone Overdependence Survey by the National Information Society Agency (NISA) in South Korea. Across the sample, the adolescents were about 14 years old (SD = 2.4) and equally distributed by sex (48.1% male). We then conceptually selected 131 features across two domains and 10 identified constructs. A nested modeling approach identified a low-risk screening tool using 59 features that achieved strong predictive accuracy (AUC = 81.5%), with Smartphone Use Case features contributing approximately 20% to performance. Construct-specific models confirmed the importance of Smartphone Use Cases, Perceived Digital Competence and Risk, and Consequences and Dependence (AUC range: 80.6–89.1%) and uncovered cognitive patterns warranting further study. Place-stratified analysis revealed substantial regional variation in model performance (AUC range: 71.4–91.1%) and distinct local feature importance. Overall, this study demonstrated the value of integrating conceptual frameworks with AI/ML to detect adolescent smartphone overdependence, offering novel approaches to monitoring disease burden, advancing construct-level insights, and providing targeted place-based public health policy recommendations within the South Korean context. Full article

Background/Objectives: Juvenile Idiopathic Arthritis (JIA) is the most common autoimmune rheumatic disease in children and can vary in presentation based on the properties of the JIA subtypes. Timely diagnosis and intervention are essential for maximizing quality of life, healthy growth and development, and prevention of long-term disability. This review aims to provide a clinically practical framework for the core elements important in recognition, monitoring, and management of JIA. Methods: We performed a narrative review of the current literature, complemented by real-world clinical experience from academic rheumatology practice. The review synthesizes evidence-based knowledge with practical insights to develop an approach that can be applied in daily clinical decision-making. Results: We propose a structured, stepwise method for evaluating suspected JIA, emphasizing the integration of pattern recognition with differential diagnosis. Our framework emphasizes two principal parameters: (1) the distribution of joint involvement (peripheral vs. axial) and (2) the presence of extra-articular manifestations, including uveitis, cutaneous findings, and gastrointestinal symptoms. This format aids in distinguishing major JIA subtypes and highlights their distinctive features. In addition, we review overarching principles for monitoring, assessing risk for uveitis, and treatment, and the importance of multidisciplinary care. Conclusions: This structured approach is intended to support clinicians in the accurate recognition of JIA and its subtypes, facilitate early diagnosis, and provide insights on management strategies that improve patient outcomes. Full article

Background/Objectives: Wilson’s disease (WD) is an autosomal recessive disorder characterized by pathological copper accumulation, primarily in the liver and brain. Severe hepatic involvement can be effectively treated with liver transplantation (LT). Geographic variation in ATP7B mutations suggests the presence of regional patterns that may impact disease presentation and management. This study aims to investigate the genetic basis of WD in patients from a major LT center in Iran. Methods: A retrospective analysis was conducted on clinical, biochemical, and pathological data from patients suspected of WD who underwent evaluation for LT between May 2020 and June 2025 at Shiraz University of Medical Sciences. Genetic testing was carried out on 20 patients at the Shiraz Transplant Research Center (STRC). Direct mutation analysis of ATP7B was performed for all patients, and the results correlated with clinical and demographic information. Results: In total, 20 WD patients who underwent liver transplantation (15 males, 5 females) carried 25 pathogenic or likely pathogenic ATP7B variants, 21 of which were previously unreported. Fifteen patients were homozygous, and five were compound-heterozygous; all heterozygous combinations occurred in the offspring of second-degree consanguineous unions. Recurrent changes included p.L549V, p.V872E, and p.P992S/L, while two nonsense variants (p.E1293X, p.R1319X) predicted truncated proteins. Variants were distributed across copper-binding, transmembrane, phosphorylation, and ATP-binding domains, and in silico AlphaMissense scores indicate damaging effects for most novel substitutions. Post-LT follow-up showed biochemical normalization in the majority of recipients, with five deaths recorded during the study period. Conclusions: This single-center Iranian study reveals a highly heterogeneous ATP7B mutational landscape with a large proportion of novel population-specific variants and underscores the benefit of comprehensive gene sequencing for timely WD diagnosis and family counseling, particularly in regions with prevalent consanguinity. Full article