Search Results (2,926)

With increasing life expectancy, the number of older people living with comorbid diabetes and frailty is increasing. The development of frailty accelerates diabetes-related adverse outcomes. Frailty is a multidimensional syndrome with physical, mental and social aspects which is associated with increased risk of hypoglycaemia, dementia and hospitalisation. Therefore, regular screening for all aspects of frailty should be an integrated part of the care plans of older people with diabetes. In addition, every effort should be made for prevention, which includes adequate nutrition combined with regular resistance exercise training. In already frail older people with diabetes, metabolic targets should be relaxed and hypoglycaemic agents should be of low hypoglycaemic risk potential. Furthermore, the metabolic phenotype of frailty should be considered when choosing hypoglycaemic agents and determining targets. With increasing severity of frailty, proactive chronological plans of de-escalation, palliation and end-of-life care should be considered. These plans should be undertaken in a shared decision-making manner which involves patients and their families. This ensures that patients’ views, wishes and preferences are in the heart of these plans. Full article

Background/Objectives: Antimicrobial resistance (AMR) contributes to millions of deaths globally each year, creating an urgent need for new therapeutic agents. Antimicrobial peptides (AMPs) have emerged as promising candidates due to their potential to combat AMR pathogens. This study aimed to evaluate the antimicrobial activity of an AMP from a soil-derived bacterial isolate against Gram-negative bacteria. Method: Soil bacteria were isolated and screened for antimicrobial activity. The bioactive peptide was purified and determined its structure and antimicrobial efficacy. Genomic analysis was conducted to predict the biosynthetic gene clusters (BGCs) responsible for AMP production. Results: Genomic analysis identified the isolate as Paenibacillus sp. Na14, which exhibited low genomic similarity (61.0%) to other known Paenibacillus species, suggesting it may represent a novel species. The AMP from the Na14 strain exhibited heat stability up to 90 °C for 3 h and retained its activity across a broad pH range from 3 to 11. Structural analysis revealed that the Na14 peptide consisted of 14 amino acid residues, adopting an α-helical structure. This peptide exhibited bactericidal activity at concentrations of 2–4 µg/mL within 6–12 h, and its killing rate was concentration-dependent. The peptide was found to disrupt the bacterial membranes. The Na14 peptide shared 64.29% sequence similarity with brevibacillin 2V, an AMP from Brevibacillus sp., which also belongs to the Paenibacillaceae family. Genomic annotation identified BGCs associated with secondary metabolism, with a particular focus on non-ribosomal peptide synthetase (NRPS) gene clusters. Structural modeling of the predicted NRPS enzymes showed high similarity to known NRPS modules in Brevibacillus species. These genomic findings provide evidence supporting the similarity between the Na14 peptide and brevibacillin 2V. Conclusions: This study highlights the discovery of a novel AMP with potent activity against Gram-negative pathogens and provides new insight into conserved AMP biosynthetic enzymes within the Paenibacillaceae family. Full article

Background/Objectives: Diabetic retinopathy is a leading cause of vision impairment worldwide, and the development of reliable automated classification systems is crucial for early diagnosis and clinical decision-making. This study presents a comprehensive comparative evaluation of two state-of-the-art deep learning families for the task of classifying diabetic retinopathy using retinal fundus images. Methods: The models were trained and tested in both binary and multi-class settings. The experimental design involved partitioning the data into training (70%), validation (20%), and testing (10%) sets. Model performance was assessed using standard metrics, including precision, sensitivity, specificity, F1-score, and the area under the receiver operating characteristic curve. Results: In binary classification, the ResNeXt101-64x4d model and RegNetY32GT model demonstrated outstanding performance, each achieving high sensitivity and precision. For multi-class classification, ResNeXt101-32x8d exhibited strong performance in early stages, while RegNetY16GT showed better balance across all stages, particularly in advanced diabetic retinopathy cases. To enhance transparency, SHapley Additive exPlanations were employed to visualize the pixel-level contributions for each model’s predictions. Conclusions: The findings suggest that while ResNeXt models are effective in detecting early signs, RegNet models offer more consistent performance in distinguishing between multiple stages of diabetic retinopathy severity. This dual approach combining quantitative evaluation and model interpretability supports the development of more robust and clinically trustworthy decision support systems for diabetic retinopathy screening. Full article

Neurodevelopmental disorders (NDDs) significantly impact children’s health and development. They pose a substantial burden to families and the healthcare system. Challenges in early identification, accurate and timely diagnosis, and effective treatment persist due to overlapping symptoms, lack of appropriate diagnostic biomarkers, significant stigma and discrimination, and systemic barriers. Generative Artificial Intelligence (GenAI) offers promising solutions to these challenges by enhancing screening, diagnosis, personalized treatment, and research. Although GenAI is already in use in some aspects of NDD management, effective and strategic leveraging of evolving AI tools and resources will enhance early identification and screening, reduce diagnostic processing by up to 90%, and improve clinical decision support. Proper use of GenAI will ensure individualized therapy regimens with demonstrated 36% improvement in at least one objective attention measure compared to baseline and 81–84% accuracy relative to clinician-generated plans, customize learning materials, and deliver better treatment monitoring. GenAI will also accelerate NDD-specific research and innovation with significant time savings, as well as provide tailored family support systems. Finally, it will significantly reduce the mortality and morbidity associated with NDDs. This article explores the potential of GenAI in transforming NDD management and calls for policy initiatives to integrate GenAI into NDD management systems. Full article

Telomeres are terminal regions of chromosomes that protect and stabilize chromosome structures. Telomeres are usually composed of specific DNA repeats (motifs) that are maintained by telomerase and a complex of specific proteins. Telomeric DNA sequences are generally highly conserved throughout the evolution of different groups of eukaryotes. The most common motif in insects is TTAGG, but it is not universal, including in the large order Hemiptera. In particular, several derived telomeric motifs were identified in this order by analyzing chromosome-level genome assemblies or by FISH screening the chromosomes of target species. Here, we analyzed chromosome-level genome assemblies of 16 species from three hemipteran suborders, including Sternorrhyncha (Coccoidea: Planococcus citri, Acanthococcus lagerstroemiae, and Trionymus diminutus; Aphidoidea: Tuberolachnus salignus, Metopolophium dirhodum, Rhopalosiphum padi, and Schizaphis graminum), Auhenorrhyncha (Cicadomorpha: Allygus modestus, Arthaldeus pascuellus, Aphrophora alni, Cicadella viridis, Empoasca decipiens, and Ribautiana ulmi), and Heteroptera (Gerromorpha: Gerris lacustris; Pentatomomorpha: Aradus depressus and A. truncatus). In addition, scaffold-level genome assemblies of three more species of Heteroptera (Gerromorpha: Gerris buenoi, Microvelia longipes, and Hermatobates lingyangjiaoensis) were examined. The presumably ancestral insect motif TTAGG was found at the ends of chromosomes of all species studied using chromosome-level genome assembly analysis, with four exceptions. In Aphrophora alni, we detected sequences of 4 bp repeats of TGAC, which were tentatively identified as a telomeric motif. In Gerris lacustris, from the basal true bug infraorder Gerromorpha, we found a 10 bp motif TTAGAGGTGG, previously unknown not only in Heteroptera or Hemiptera but also in Arthropoda in general. Blast screening of the scaffold-level assemblies showed that TTAGAGGTGG is also likely to be a telomeric motif in G. buenoi and Microvelia. longipes, while the results obtained for H. lingyangjiaoensis were inconclusive. In A. depressus and A. truncatus from the basal for Pentatomomorpha family Aradidae, we found a 10 bp motif TTAGGGATGG. While the available data allowed us to present two alternative hypotheses about the evolution of telomeric motifs in Heteroptera, further data are needed to verify them, especially for the yet unstudied basal infraorders Enicocephalomorpha, Dipsocoromorpha, and Leptopodomorpha. Full article

Late-spring frost events severely damage low-chill peach blossoms, causing significant yield losses. Although 5-aminolevulinic acid (ALA) enhances cold tolerance through the PpC3H37-PpWRKY18 module, the regulatory mechanism of ALA on PpC3H37 remains to be elucidated. Using yeast one-hybrid screening with the PpC3H37 promoter as bait, we identified PpDof9 as a key interacting transcription factor. A genome-wide analysis revealed 25 PpDof genes in peaches (Prunus persica). These genes exhibited variable physicochemical properties, with most proteins predicted as nuclear-localized. Subcellular localization experiments in tobacco revealed that PpDof9 was localized to the nucleus, consistent with predictions. A synteny analysis indicated nine segmental duplication pairs and tandem duplications on chromosomes 5 and 6, suggesting duplication events drove family expansion. A conserved motif analysis confirmed universal presence of the Dof domain (Motif 1). Promoter cis-element screening identified low-temperature responsive (LTR) elements in 12 PpDofs, including PpDof1, PpDof8, PpDof9, and PpDof25. The quantitative real-time PCR (qRT-PCR) results showed that PpDof1, PpDof8, PpDof9, PpDof15, PpDof16, and PpDof25 were significantly upregulated under low-temperature stress, and this upregulation was further enhanced by ALA pretreatment. Our findings demonstrate ALA-mediated modulation of specific PpDof TFs in cold response and provide candidates (PpDof1, PpDof9, PpDof8, PpDof25) for enhancing floral frost tolerance in peaches. Full article

Background/Objectives: Wilson’s disease (WD) is a rare autosomal recessive disorder of copper metabolism that results in hepatic, neurological, and psychiatric manifestations. Despite being described globally, data from the Middle East remains limited. This study presents the first comprehensive national cohort analysis of WD in Oman, examining clinical features, diagnostic challenges, treatment patterns, and long-term outcomes. Methods: A retrospective cohort study was conducted on 36 Omani patients diagnosed with WD between 2013 and 2020 at Sultan Qaboos University Hospital using AASLD diagnostic criteria. Clinical presentation, biochemical parameters, treatment regimens, and progression-free survival were analyzed. Results: The median age at diagnosis was 14.5 years, with a slight female predominance (55.6%). Clinical presentation varied: 25% had hepatic symptoms, 22.2% had mixed hepatic-neurological features, and 16.7% presented with neurological symptoms alone. Asymptomatic cases identified via family screening accounted for 33.3%. Diagnostic delays were most pronounced among patients presenting with neurological symptoms. A positive family history was reported in 88.9% of cases, suggesting strong familial clustering despite a low rate of consanguinity (5.6%). Regional distribution was concentrated in Ash Sharqiyah North and Muscat. Chelation therapy with trientine or penicillamine, often combined with zinc, was the mainstay of treatment. Treatment adherence was significantly associated with improved progression-free survival (p = 0.012). Conclusions: WD in Oman is marked by heterogeneous presentations, frequent diagnostic delays, and strong familial clustering. Early detection through cascade screening and sustained treatment adherence are critical for favorable outcomes. These findings support the need for national screening policies and structured long-term care models for WD in the region. Full article

Background and Clinical Significance: Multiple Endocrine Neoplasia type 1 (MEN1) is a rare autosomal dominant disorder caused by mutations in the MEN1 gene. Although primarily characterized by endocrine tumors, renal manifestations remain underreported. Case Presentation: We report a three-generation family carrying a pathogenic MEN1 mutation (c.1351-3_1359del) with a co-occurring Claudin 16 (CLDN16) variant (c.324+13C>G). Genetic testing included MLPA and whole-exome sequencing (WES), with bioinformatics analysis validating variant pathogenicity. All three patients exhibited primary hyperparathyroidism, hypercalcemia, hypercalciuria, early nephrocalcinosis, and renal hypomagnesemia. The CLDN16 variant, previously considered benign, co-segregated with hypomagnesemia and renal involvement, suggesting a potential modifying role. Conclusions: These findings support the need for comprehensive genetic screening in MEN1 patients with atypical renal presentations. Concomitant genetic variations can alter the principal phenotype. Full article

Pilomatricomas are benign tumors originating from hair follicle matrix cells and represent the most common skin tumors in pediatric patients. Pilomatricomas may be associated with genetic syndromes such as myotonic dystrophy, familial adenomatous polyposis (FAP), Turner syndrome, Rubinstein–Taybi syndrome, Kabuki syndrome, and Sotos syndrome. This study reviews the literature on pilomatricomas occurring in syndromic contexts and presents a novel case linked to Apert syndrome. A systematic review was conducted using PubMed and Cochrane databases, focusing on case reports, case series, and reviews describing pilomatricomas associated with syndromes. A total of 1272 articles were initially screened; after removing duplicates and excluding articles without syndromic diagnoses or lacking sufficient data, 81 full-text articles were reviewed. Overall, 96 cases of pilomatricomas associated with genetic syndromes were identified. Reports of patients with Apert syndrome who do not develop pilomatricomas are absent in the literature. Pilomatricomas predominantly affect pediatric patients, with a slight female predominance, and are often the first manifestation of underlying genetic syndromes. Our study highlights previously unreported associations of pilomatricoma with Apert syndrome, providing molecular insights. This study contributes to understanding the clinical and molecular features of pilomatricomas in syndromic contexts and underscores the importance of genetic analysis for accurate diagnosis and management. Full article

Person-centered navigation (PCN) in healthcare refers to a proactive collaboration among professionals, researchers, patients, and their families to guide individuals toward timely access to screening, treatment, follow-up, and psychosocial support. PCN—which includes professional, peer, and virtual guidance, is particularly crucial for rare cancers, where affected individuals face uncertainty, limited support, financial strain, and difficulties accessing relevant information, testing, and other services. The Canadian Cholangiocarcinoma Collaborative (C3) prioritizes PCN implementation to address these challenges in the context of Biliary Tract Cancers (BTCs). C3 uses a virtual PCN model and staffs a “C3 Research Navigator” who provides clinical and research navigation such as personalized guidance and support, facilitating access to molecular testing, clinical trials, and case reviews through national multidisciplinary rounds. C3 also supports a national network of BTC experts, a patient research registry, and advocacy activities. C3’s implementation strategies include co-design, timely delivery of support, and optimal outcomes across its many initiatives. Future priorities include expanding the C3 network, enhancing user engagement, and further integrating its innovative approach into routine care. Full article

Microbe–microbe interactions have been explored at the molecular level to a lesser degree than plant–pathogen interactions, primarily due to the economic impact of crop losses caused by pathogenic microorganisms. Effector proteins are well known for their role in disease development in many plant–pathogen pleinteractions, but there is increasing evidence showing their involvement in other types of interaction, including microbe–microbe interactions. Through the use of LC-MS/MS sequencing, effector candidates were identified in the in vitro interaction between a banana pathogen, Pseudocercospora fijiensis and a biological control agent, Trichoderma harzianum. The diverse interaction secretome revealed various glycoside hydrolase families, proteases and oxidoreductases. T. harzianum secreted more proteins in the microbial interaction compared to P. fijiensis, but its presence induced the secretion of more P. fijiensis proteins that were exclusive to the interaction secretome. The interaction secretome, containing 256 proteins, was screened for effector candidates using the algorithms EffHunter and WideEffHunter. Candidates with common fungal effector motifs and domains such as LysM, Cerato-platanin, NPP1 and CFEM, among others, were identified. Homologs of true effectors and virulence factors were found in the interaction secretome of T. harzianum and P. fijiensis. Further characterization revealed a potential novel effector of T. harzianum. Full article

Chiroptera includes over 1400 bat species, with at least 35 of these present in Italy. Due to their role as Lyssavirus reservoirs, bats found dead, with and without signs suggestive of this infection, are routinely submitted to the laboratory network of the Istituti Zooprofilattici Sperimentali in the framework of the rabies national passive and active surveillance program. Carcasses and biological samples collected from January to December 2021 in Latium and Tuscany, regions of our jurisdiction, were further screened for the presence of Coronaviruses (CoVs) and Herpesviruses using pan-family virus PCR tests, and relative PCR products were Sanger sequenced. Genetic characterization through sequencing detected AlphaCoVs in Miniopterus schreibersii and Beta- and Gammaherpesviruses in Tadarida teniotis. Samples were also submitted to bat genetic species identification. Full article

Background: Maternal and newborn health disparities remain a challenge in Puerto Rico, especially in underserved communities. Comienzo Saludable Puerto Rico, sponsored by the U.S. Department of Health and Human Services’ Healthy Start Initiative (HRSA), addresses these gaps through an integrated Networks of Care model known as Cuidado Compartido. Comienzo Saludable Puerto Rico is a maternal, paternal, and child health program aimed at improving the health and well-being of pregnant women, mothers, fathers, newborns, and children in Puerto Rico, particularly those from disadvantaged communities. Methods: This paper presents the Comienzo Saludable Puerto Rico program’s Cuidado Compartido model to integrate a network of healthcare providers and services across hospitals, community organizations, and families. This model aims to improve maternal and newborn/child health outcomes by focusing on the importance of integrated, hospital-community-based care networks. Results: Participants experienced significant improvements in key birth outcomes: low birth weight prevalence declined by 27.2% compared to the community baseline, premature birth rates decreased by 30.9%, and infant mortality dropped by 75%, reaching 0% by 2021 and remaining there through 2023. These results were complemented by increases in maternal mental health screening, paternal involvement, and breastfeeding practices. Conclusions: The Cuidado Compartido model demonstrates a scalable, culturally responsive strategy to improve maternal, newborn, and child health outcomes. It offers critical insights for implementation in other high-need contexts. Full article

Background: Cardiac involvement is common in Fabry disease (FD) and typically manifests with left ventricular hypertrophy (LVH). Patients with FD are frequently misdiagnosed, and this is mainly related to the lack of disease awareness among clinicians. The aim of this study was to determine whether providing a targeted educational intervention on FD may enhance FD diagnosis. Methods. This research was designed as a single-arm before-and-after intervention study and evaluated the impact of providing a specific training on FD to cardiologists from different Italian centers, without experience in rare diseases. In the 12-month period after the educational intervention, the rate of FD screening and diagnosis was assessed and compared with those conducted in the two years preceding the study initiation. Results: Fifteen cardiologists participated to this study, receiving a theoretical and practical training on FD. In the two previous two years, they conducted 12 FD screening (6/year), and they did not detect any cases of FD. After the training, they performed 45 FD screenings, with an eight-fold rise in the annual screening rate. The screened population (age: 61 ± 11 years, men: 82%) was mainly composed of patients with unexplained LVH (n = 43). There were four new FD diagnoses and, among of them, three had a late-onset GLA variant. After the cascade genetic screening, 11 affected relatives and 8 heterozygous carriers were also detected. Conclusions: A targeted educational intervention for cardiologists allowed the identification of four new families with FD. Enhancing FD awareness is helpful to reduce the diagnostic and therapeutic delay. Full article

Background/Objectives: Despite the importance of parent mental health for child health, there are no global prevalence data on parental mental health symptoms when children are hospitalized. We aimed to describe depression and anxiety symptom prevalence and associated factors among parents of hospitalized children. Methods: We conducted this 14-country prospective cohort survey with parents/primary caregivers staying at a nearby Ronald McDonald House^® during their child’s hospital treatment. We used the Hospital Anxiety and Depression Scale to measure depression and anxiety symptoms and validated scales and theory-based questions to measure parent, family, and child covariates. We calculated the prevalence of clinically significant or concerning symptoms of depression and anxiety, and used multivariable regression analyses to examine associations between covariates and outcomes. Results: Among 3350 participants, 1789 (49.7%) reported depression symptoms and 2286 (69.0%) reported anxiety symptoms. Worry about housing and poorer ratings of their child’s health were associated with increased risk of depression symptoms. Poorer rating of the child’s health, living with a partner, and discrimination in daily life were associated with increased risk of anxiety symptoms. Higher levels of self-care, hospital family-centered care, and social support were associated with reduced risk of depression symptoms. Higher levels of self-care and social support were associated with reduced risk of anxiety symptoms. Conclusions: Clinically significant or concerning depression and anxiety symptoms are common among parents of hospitalized children globally. Hospitals should consider offering routine mental health symptom screening and preventative mental health and support services to all parents. Full article