Article
Clinical Neurology
Sangeetha Yoganathan, Madhan Kumar, Suvasini Sharma, Smruti Patel, Sumita Danda, Maya Thomas
Summary: A 5-year-old girl presented with myoclonus and frequent falls for 2.5 years. A pathogenic heterozygous nonsense variant in exon 3 of the SGCE gene was identified.
Review
Hematology
Inderjeet Dokal, Hemanth Tummala, Tom Vulliamy
Summary: Inherited bone marrow failure syndromes are a group of diseases characterized by diverse manifestations and involvement of bone marrow failure. Significant progress has been made in the genetics of these diseases, revealing how genetic mutations disrupt normal hematopoiesis. Furthermore, these studies provide insights into human development and cancer. Genetic testing facilitates accurate diagnosis in clinical practice. Current treatment options have improved patient outcomes, but managing certain complications remains challenging.
Article
Clinical Neurology
Phillip L. Pearl, Itay Tokatly Latzer, Henry H. C. Lee, Alexander Rotenberg
Summary: Treatment options for inherited metabolic epilepsies are expanding rapidly due to advancements in molecular biology and the genomic revolution. Traditional therapies like dietary modification and protein/enzyme inhibitors or enhancers are continually being improved to enhance efficacy and reduce side effects. Promising new approaches include enzyme replacement, gene replacement, and gene editing for targeted treatment and potential cures. Biomarkers such as molecular analysis, imaging, and neurophysiologic measurements are emerging as crucial indicators of disease pathophysiology, severity, and response to therapy.
Review
Chemistry, Multidisciplinary
Luisa Chiapparini, Marco Moscatelli
Summary: MRI is commonly used in the study of cerebellar degenerative diseases to identify a range of abnormalities, providing valuable insight in the clinical and genetic diagnosis of these conditions. Various neurological disorders exhibit distinct patterns on MRI, helping to differentiate between different diseases and guide specific molecular screenings.
APPLIED SCIENCES-BASEL
(2021)
Review
Nutrition & Dietetics
Teresa Di Chio, Christiane Sokollik, Diego G. Peroni, Lara Hart, Giacomo Simonetti, Franziska Righini-Grunder, Osvaldo Borrelli
Summary: Nutritional management in pediatric gastrointestinal diseases is increasingly popular, with disease-specific diets as conventional treatments. Nutritional support is crucial for maintaining growth and improving outcomes, but dietary modifications may have negative consequences. Expert supervision is advised to prevent misconceptions and potential adverse effects from diet modification.
Article
Biochemistry & Molecular Biology
Estefania Martinez-Barrios, Sergi Cesar, Jose Cruzalegui, Clara Hernandez, Elena Arbelo, Victoria Fiol, Josep Brugada, Ramon Brugada, Oscar Campuzano, Georgia Sarquella-Brugada
Summary: Sudden death is rare in the pediatric population, and in cases where the cause is inconclusive, sudden arrhythmic death syndrome is suggested as the main potential cause. However, the current challenges in genetic diagnosis include establishing the correct genotype-phenotype association and classifying variants of uncertain significance.
Article
Cardiac & Cardiovascular Systems
Shun-Qing Su, Di-Sheng Xiong, Xiu-Mei Ding, Jin-An Kuang, Yue-Chun Lin
Summary: This study reports two siblings with sitosterolemia, characterized by systemic multiple xanthomas and hypercholesterolemia. Genetic testing revealed compound heterozygous mutations in the ABCG5 gene, leading to metabolic disorder of plant sterols. Dietary control and oral lipid-lowering therapy with Ezetimibe effectively controlled the disease, and surgical removal of xanthomas achieved primary wound healing.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Review
Microbiology
Zahra Dossaji, Adam Khattak, Kyaw Min Tun, Mark Hsu, Kavita Batra, Annie S. S. Hong
Summary: There is a high prevalence of gastrointestinal-related symptoms among children with autism spectrum disorder (ASD), and these symptoms are associated with the severity of behavioral symptoms. Fecal microbiota transplantation (FMT) is a potential therapeutic strategy for addressing gut microbiome dysregulation in pediatric patients with ASD. A systematic review found that FMT led to significant improvements in both behavioral and gastrointestinal symptoms in these patients. These findings suggest that FMT holds promise as an intervention for treating pediatric patients with autism.
Review
Oncology
Piedad Alba-Pavon, Lide Alana, Itziar Astigarraga, Olatz Villate
Summary: Recent studies suggest that at least 10% of pediatric cancer patients carry a germline mutation in a cancer predisposition gene. Splicing mutations play a significant role in the development of pediatric solid tumors, and therapies to correct aberrant splicing in cancer have been developed.
Review
Biochemistry & Molecular Biology
Ana Marin-Quilez, Lorena Diaz-Ajenjo, Christian A. A. Di Buduo, Ana Zamora-Canovas, Maria Luisa Lozano, Rocio Benito, Jose Ramon Gonzalez-Porras, Alessandra Balduini, Jose Rivera, Jose Maria Bastida
Summary: Protein glycosylation, including sialylation, is important for various biological processes. Carbohydrate conjugation to molecules and receptors is critical for normal hematopoiesis and platelet regulation. More than 200 enzymes are involved in proper glycosylation and sialylation. Genetic alterations in GNE, SLC35A1, GALE, and B4GALT can lead to syndromic manifestations, severe inherited thrombocytopenia, and hemorrhagic complications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Jose Maria Bastida, Jose Ramon Gonzalez-Porras, Jose Rivera, Maria Luisa Lozano
Summary: Advancements in genetic testing have transformed the molecular diagnosis of inherited thrombocytopenias, yet the therapeutic management has not seen the same progress. The use of TPO-RA in ITs shows promise but requires further investigation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pediatrics
Kayla T. Hartjes, Tracey M. Dafonte, Austin F. Lee, Jenifer R. Lightdale
Summary: The study documented variation in anesthesiologist-administered sedation for pediatric endoscopy, with most patients not requiring endotracheal tube intubation and propofol being the most commonly used sedative. Adverse events occurred in over 3% of cases. Longer procedure time, younger age, and use of endotracheal tube intubation were associated with longer sedation time.
FRONTIERS IN PEDIATRICS
(2021)
Article
Pharmacology & Pharmacy
Benjamin Querin, Arnaud Schweitzer-Chaput, Salvatore Cisternino, Sylvain Auvity, Anne-Sophie Fauqueur, Abdel Negbane, Alice Hadchouel, Joel Schlatter, Camille Cotteret
Summary: This study developed an optimized pediatric pharmaceutical formulation of L-Methionine (Met) powder that can be reconstituted with water to obtain a stable oral suspension for children's treatment. The organoleptic characteristics and physicochemical stability of the powder and suspension were evaluated at different storage temperatures, showing no drug loss, pH changes, microbiological growth, or visual changes for an extended period of time. The developed formulation facilitates the preparation, administration, dose adjustment, and palatability of Met treatment in children.
Article
Nutrition & Dietetics
Caterina Strisciuglio, Sabrina Cenni, Maria Rosaria Serra, Pasquale Dolce, Sanja Kolacek, Sara Sila, Ivana Trivic, Michal Rozenfeld Bar Lev, Raanan Shamir, Aco Kostovski, Alexandra Papadopoulou, Eleftheria Roma, Christina Katsagoni, Danijela Jojkic-Pavkov, Angelo Campanozzi, Elena Scarpato, Erasmo Miele, Annamaria Staiano
Summary: 《Mediterranean diet has a protective effect on functional gastrointestinal disorders》
Article
Multidisciplinary Sciences
Matilde Cirnigliaro, Timothy S. Chang, Stephanie A. Arteaga, Laura Perez-Cano, Elizabeth K. Ruzzo, Aaron Gordon, Lucy K. Bicks, Jae-Yoon Jung, Jennifer K. Lowe, Dennis P. Wall, Daniel H. Geschwind
Summary: This study conducted whole-genome sequencing on the largest cohort of multiplex families with autism spectrum disorder (ASD) to date and identified seven previously unrecognized ASD risk genes. The results showed that autistic children from multiplex families have an increased burden of rare inherited protein-truncating variants and that common polygenic risk is overtransmitted from nonautistic parents to autistic children who also have rare inherited variants. Additionally, language delay is associated with the genetic risk of ASD.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Surgery
Arnaud G. L'Huillier, Anne I. Dipchand, Vicky L. Ng, Diane Hebert, Yaron Avitzur, Melinda Solomon, Bo-Yee Ngan, Derek Stephens, Angela S. Punnett, Michelle Barton, Upton D. Allen
AMERICAN JOURNAL OF TRANSPLANTATION
(2019)
Article
Pediatrics
Sneha Suresh, Julia Upton, Michael Green, Anne Pham-Huy, Klara M. Posfay-Barbe, Marian G. Michaels, Karina A. Top, Yaron Avitzur, Catherine Burton, Pearlie P. Chong, Lara Danziger-Isakov, Anne I. Dipchand, Diane Hebert, Deepali Kumar, Shaun K. Morris, Nadya Nalli, Vicky Lee Ng, Sarah Kogan Nicholas, Joan L. Robinson, Melinda Solomon, Bruce Tapiero, Anita Verma, Jolan E. Walter, Upton D. Allen
PEDIATRIC TRANSPLANTATION
(2019)
Article
Cell Biology
Phi Luong, Qian Li, Pin-Fang Chen, Paul J. Wrighton, Denis Chang, Sean Dwyer, Marie-Theres Bayer, Scott B. Snapper, Steen H. Hansen, Jay R. Thiagarajah, Wolfram Goessling, Wayne I. Lencer
MOLECULAR BIOLOGY OF THE CELL
(2020)
Article
Pediatrics
Mohit Kehar, Eyal Grunebaum, Carolina Jimenez-Rivera, Yael Mozer-Glassberg, Alisha Jamal, Vicky Lee Ng, Yaron Avitzur
PEDIATRIC TRANSPLANTATION
(2020)
Review
Pediatrics
Taryn J. Rohringer, Jessica H. Hannick, Armando Lorenzo, Yaron Avitzur, Michael Temple, Dimitri A. Parra
PEDIATRIC TRANSPLANTATION
(2020)
Article
Multidisciplinary Sciences
Abir Maarouf Kabbani, Krishnan Raghunathan, Wayne Lencer, Anne K. Kenworthy, Christopher Kelly
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Pediatrics
Iyad Faden, Yaron Avitzur, Oussama Abla, Dimitri A. Parra
Summary: This case report discusses a four-year-old boy diagnosed with LCH involving the liver, requiring a liver transplant. Six months post-transplant, recurrence of the primary disease led to biliary dilatation. Imaging showed strictures mimicking primary sclerosing cholangitis, ultimately resulting in biliary-enteric anastomosis stenosis and the need for re-transplantation.
PEDIATRIC TRANSPLANTATION
(2021)
Article
Multidisciplinary Sciences
Denis Chang, Aaron T. Whiteley, Katlynn Bugda Gwilt, Wayne Lencer, John J. Mekalanos, Jay R. Thiagarajah
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Nutrition & Dietetics
Melanie Lissa Schmidt, Danielle Wendel, Simon Peter Horslen, Erin Richardson Lane, Leonardo Rodrigues Brandao, Emily Gottschalk, Christina Belza, Glenda Courtney-Martin, Paul William Wales, Yaron Avitzur
Summary: Long-term secondary anticoagulation prophylaxis with LMWH can reduce the incidence of secondary thrombosis in children with CRT requiring prolonged PN. Compliance with the protocol was high, with good efficacy and safety outcomes observed in the study.
JOURNAL OF PARENTERAL AND ENTERAL NUTRITION
(2021)
Article
Cell Biology
Denis Chang, Phi Luong, Qian Li, Jamie LeBarron, Michael Anderson, Lee Barrett, Wayne Lencer
Summary: The inflammatory bowel disease risk gene INAVA has dual functions in epithelial cells, affecting mucosal barrier function at lateral membranes and enhancing IL-1β signal transduction and protein ubiquitination in the cytosol, forming puncta. The biomolecular condensates of IL-1β-induced INAVA rapidly assemble and contain ubiquitin and the E3 ligase beta TrCP2, playing a role in regulation of cellular proteostasis. Small-molecule agonists and inhibitors of various pathways influence the formation and resolution of INAVA condensates in different cellular contexts.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Senthil Arumugam, Stefanie Schmieder, Weria Pezeshkian, Ulrike Becken, Christian Wunder, Dan Chinnapen, John Hjort Ipsen, Anne K. Kenworthy, Wayne Lencer, Satyajit Mayor, Ludger Johannes
Summary: The study reveals that the acyl chain structure of GM1 determines the establishment of nanodomains when actively clustered by actin.
NATURE COMMUNICATIONS
(2021)
Article
Biology
Jenny K. Gustafsson, Jazmyne E. Davis, Tracy Rappai, Keely G. McDonald, Devesha H. Kulkarni, Kathryn A. Knoop, Simon P. Hogan, James A. J. Fitzpatrick, Wayne Lencer, Rodney D. Newberry
Summary: Intestinal goblet cells maintain the protective epithelial barrier through mucus secretion and form goblet cell associated antigen passages (GAPs) for immune processing. Acetylcholine triggers both mucus release and GAP formation in goblet cells, with these processes being functionally independent and regulated by different receptors and signaling pathways.
Article
Surgery
Amin J. Roberts, Paul W. Wales, Sue Beath, Helen M. Evans, Jonathan Hind, David Mercer, Theodoric Wong, Jason Yap, Christina Belza, Yaron Avitzur
Summary: This study validates the Toronto criteria for selecting pediatric patients for intestinal transplantation, which include >= 2 ICU admissions, persistent CB >= 75 mu mol/L, and loss of >= 3 CVC sites.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Article
Immunology
Kumar Subramanian, Saikat Paul, Andrew Libby, Jordan Patterson, Adam Arterbery, James Knight, Christopher Castaldi, Guilin Wang, Yaron Avitzur, Mercedes Martinez, Steve Lobritto, Yanhong Deng, Gan Geliang, Alexander Kroemer, Thomas Fishbein, Andrew Mason, Margarita Dominguez-Villar, Malaiyalam Mariappan, Udeme D. Ekong
Summary: It has been observed that patients with de novo autoimmune hepatitis and autoimmune hepatitis have an increased expression of human endogenous retrovirus 1 (HERV1-env) proteins in regulatory T cells (Tregs). This leads to endoplasmic reticulum (ER) stress, which activates the unfolded protein response (UPR) through the IRE1, ATF6, and PERK branches. Coimmunoprecipitation studies show an interaction between HERV1-env proteins and the ATF6 branch. Activated ATF6a activates the expression of RORC and STAT3 by binding to promoter sequences and induces IL-17A production. Silencing HERV1-env restores Treg suppressive function. These findings highlight the importance of ER stress and UPR activation in driving Treg plasticity.
JOURNAL OF IMMUNOLOGY
(2023)
Article
Medicine, Research & Experimental
Michael J. Grey, Heidi De Luca, Doyle V. Ward, Irini A. M. Kreulen, Katlynn Bugda Gwilt, Sage E. Foley, Jay R. Thiagarajah, Beth A. McCormick, Jerrold R. Turner, Wayne I. Lencer
Summary: Epithelial cells lining mucosal surfaces of the gastrointestinal and respiratory tracts express ERN2/IRE1 beta, which prevents ER stress in goblet cells by splicing Xbp1 mRNA and regulates the assembly of the colon mucus layer and gut microbiota composition.
JOURNAL OF CLINICAL INVESTIGATION
(2022)