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Background. Alagille syndrome (ALGS) is a rare autosomal dominant genetic disease caused by pathogenic variants in two genes: Jagged Canonical Notch Ligand 1 (JAG1) and Notch Receptor 2 (NOTCH2). It is characterized by phenotypic variability and incomplete penetrance with multiorgan clinical signs. Methods. Using Next Generation Sequencing (NGS), we analyzed a panel of liver-disease-related genes in a population of 230 patients with cholestasis and hepatopathies. For the rare variants, bioinformatics predictions and pathogenicity classification were performed. Results. We identified eleven rare NOTCH2 variants in 10 patients, two variants being present in the same patient. Ten variants had never been described before in the literature. It was possible to classify only two null variants as pathogenic, whereas the most of variants were missense (8 out of 11) and were classified as uncertain significance variants (USVs). Among patients with ALGS suspicion, two carried null variants, two carried variants predicted to be pathogenic by bioinformatics, one carried a synonymous variant and variants in glycosylation-related genes, and two carried variants predicted as benign in the PEST domain. Conclusions. Our results increased the knowledge about NOTCH2 variants and the related phenotype, allowing us to improve the genetic diagnosis of ALGS. [ABSTRACT FROM AUTHOR]

Background: Oral nutritional supplements (ONSs) are crucial for supporting the nutritional needs of pediatric populations, particularly those with medical conditions or dietary deficiencies. Bioactive compounds within ONSs play a pivotal role in enhancing health outcomes by exerting various physiological effects beyond basic nutrition. However, the comprehensive understanding of these bioactives in pediatric ONSs remains elusive. Objective: This systematic narrative review aims to critically evaluate the existing literature concerning bioactive compounds present in oral nutritional supplements from a pediatric standpoint, focusing on their types, sources, bioavailability, physiological effects, and clinical implications. Methods: A systematic search was conducted across the major academic databases, including PubMed, Scopus, and Web of Science, employing predefined search terms related to oral nutritional supplements, bioactives, and pediatrics. Studies published between 2013 and 2024 were considered eligible for inclusion. Data extraction and synthesis were performed according to the PRISMA guidelines. Results: The initial search yielded 558 of articles, of which 72 met the inclusion criteria. The included studies encompassed a diverse range of bioactive compounds present in pediatric ONS formulations, including, but not limited to, vitamins, minerals, amino acids, prebiotics, probiotics, and phytonutrients. These bioactives were sourced from various natural and synthetic origins and were found to exert beneficial effects on growth, development, immune function, gastrointestinal health, cognitive function, and overall well-being in pediatric populations. However, variations in bioavailability, dosing, and clinical efficacy were noted across different compounds and formulations. Conclusions: Bioactive compounds in oral nutritional supplements offer promising avenues for addressing the unique nutritional requirements and health challenges faced by pediatric populations. However, further research is warranted to elucidate the optimal composition, dosage, and clinical applications of these bioactives in pediatric ONS formulations. A deeper understanding of these bioactive compounds and their interplay with pediatric health may pave the way for personalized and effective nutritional interventions in pediatric clinical practice. [ABSTRACT FROM AUTHOR]

New evidence supports the benefits of bolus feeding for children receiving home enteral feeding (HEN). Current home methods of bolus feeding have certain limitations, particularly in mobile or restless patients. Therefore, innovative delivery methods have been introduced to provide more flexible methods of reducing feeding time and formula handling. This manuscript presents an expert review of the updates in HEN for children and the results of an online user experience questionnaire about an innovative new cap-based bolus feeding system. A literature bibliographic search was conducted on Medline via PubMed up to September 2023 to collect relevant studies. We presented recent evidence demonstrating a dramatic increase in HEN use among children requiring EN and its benefits on patients' nutritional status and quality of life. In addition, the article examined the clinical and social benefits of bolus feeding and current challenges in delivery methods. We described the benefits of the new system and its user experience. The uses and indications for bolus feeding in HEN are increasing among children. However, there are still some unmet needs regarding traditional delivery methods. Innovative techniques can improve flexibility, reduce feeding time, and improve user experience and quality of life. [ABSTRACT FROM AUTHOR]

The authors tested a combination of drugs, including ritonavir, in HIV-positive children whose intestines were losing the ability to absorb nutrition. The combination restored intestinal function very quickly and the children began gaining weight and increasing their CD4 count.

Variants in the ACTG2 gene, encoding a protein crucial for correct enteric muscle contraction, have been found in patients affected with chronic intestinal pseudo‐obstruction, either congenital or late‐onset visceral myopathy, and megacystis‐microcolon‐intestinal hypoperistalsis syndrome. Here we report about ten pediatric and one adult patients, from nine families, carrying ACTG2 variants: four show novel still unpublished missense variants, including one that is apparently transmitted according to a recessive mode of inheritance. Four of the remaining five probands carry variants affecting arginine residues, that have already been associated with a severe phenotype. A de novo occurrence of the variants could be confirmed in six of these families. Since a genotype–phenotype correlation is affected by extrinsic factors, such as, diagnosis delay, quality of clinical management, and intra‐familial variability, we have undertaken 3D molecular modeling to get further insights into the effects of the variants here described. The present findings and further ACTG2 testing of patients presenting with intestinal pseudo‐obstruction, will improve our understanding of visceral myopathies, including implications in the prognosis and genetic counseling of this set of severe disorders. [ABSTRACT FROM AUTHOR]