Pain Trajectories in Pediatric Inflammatory Bowel Disease: Disease Severity, Optimism, and Pain Self-efficacy.

Objectives: This study aimed to characterize pain intensity (average, worst) and disease severity in youth with inflammatory bowel disease in the 12-months post-diagnosis, and to examine the relation between pain and risk (disease severity) and resilience (optimism, pain self-efficacy) factors over time.

Methods: Data collection ran from February 2019 to March 2022. Newly diagnosed youth aged 8-17 with IBD completed numerical rating scales for average and worst pain intensity, Youth Life Orientation Test for optimism, and Pain Self-Efficacy Scale for pain self-efficacy via REDCap; weighted Pediatric Crohn's Disease Activity Index and the Pediatric Ulcerative Colitis Activity Index were used as indicators of disease severity.

An automated platform for simultaneous, longitudinal analysis of engineered neuromuscular tissues for applications in neurotoxin potency testing.

Animal models of the neuromuscular junction (NMJ) have been widely studied but exhibit critical differences from human biology limiting utility in drug and disease modelling. Challenges with scarcity, scalability, throughput, and ethical considerations further limit the suitability of animal models for preclinical screening. Engineered models have emerged as alternatives for studying NMJ functionality in response to genetic and/or pharmacological challenge.

Neutrophil-to-Lymphocyte Ratio at Diagnosis Predicts Colonoscopic Activity in Pediatric Inflammatory Bowel Diseases.

Introduction: Neutrophil-to-lymphocyte ratio (NLR) is a novel biomarker studied in several autoimmune diseases including inflammatory bowel disease (IBD) in adults but poorly characterized in pediatric IBD (pIBD). We aimed to primarily investigate the relationship between NLR and pIBD endoscopic disease severity. We also examined whether NLR predicted hospitalization, surgery, and therapy response by 52 weeks.

Sustained Release of HIF-2α Inhibitors Using Biodegradable Porous Silicon Carriers for Enhanced Immunogenic Cell Death of Malignant Merkel Cell Carcinoma.

Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine skin cancer with limited treatment options, often associated with Merkel cell polyomavirus (MCPyV) and marked by hypoxic tumor microenvironments that promote resistance to therapies. Belzutifan, an FDA-approved hypoxia-inducible factor-2α (HIF-2α) inhibitor, has shown promise in inhibiting tumor growth; however, its clinical efficacy is hindered by its low solubility, rapid clearance, and limited bioavailability. In this study, we present a strategy using porous silicon (pSi) microparticles and nanoparticles as carriers for the sustained delivery of benzoate to MCC cells.

Bolstering connectedness through peer support: Randomized-controlled trial of a web-based peer support program for adolescents with inflammatory bowel disease.

Background: Inflammatory bowel disease (IBD) is a chronic autoimmune disease often diagnosed during adolescence. IBD negatively impacts all aspects of health-related quality of life, resulting in physical, emotional, social, school, and work functioning challenges. Adolescents have identified the need for peer support in managing their disease and promoting positive health outcomes.

Uncovering the Embryonic Origins of Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is a severe degenerative muscle disease caused by mutations in the DMD gene, which encodes dystrophin. Despite its initial description in the late 19th century by French neurologist Guillaume Duchenne de Boulogne, and identification of causal DMD genetic mutations in the 1980s, therapeutics remain challenging. The current standard of care is corticosteroid treatment, which delays the progression of muscle dysfunction but is associated with significant adverse effects.

Gut Microbial Signatures in Pediatric Crohn's Disease Vary According to Disease Activity Measures and Are Influenced by Proxies of Gastrointestinal Transit Time: An ImageKids Study.

Introduction: We investigated relationships between disease activity measures and the gut microbiome in children with Crohn's disease (CD) and how these were confounded by gastrointestinal transit time.

Methods: Microbiome was profiled (16S rRNA sequencing) in feces from 196 children with CD. Sixty participants also provided samples after 18 months.

The intestinal microbiome, but not clinical aspects of inflammatory bowel disease, is impacted by lactose malabsorption compared to lactose digestion in children.

Background: Dietary exclusion of lactose from patients with inflammatory bowel disease (IBD) persists with speculation that deleterious effects are mediated through intestinal microbes.

Objectives: To compare IBD characteristics and changes in the intestinal microbiome (IM) at diagnosis in children with and without lactose malabsorption (LM).

Methods: A cross-sectional cohort of children (8-17 y of age) diagnosed with Crohn's disease [n = 149 (63%)] or ulcerative colitis (n = 86) that had undergone lactose breath hydrogen testing was evaluated.

Healthy First-Degree Relatives From Multiplex Families vs Simplex Families Have Higher Subclinical Intestinal Inflammation, a Distinct Fecal Microbial Signature, and Harbor a Higher Risk of Developing Crohn's Disease.

Background & Aims: Unaffected first-degree relatives (FDRs) from families with ≥2 affected FDRs with Crohn's disease (CD, multiplex families) have a high risk of developing CD, although the underlying mechanisms driving this risk are poorly understood. We aimed to identify differences in biomarkers between FDRs from multiplex vs simplex families and investigate the risk of future CD onset accounting for potential confounders.

Methods: We assessed the Crohn's and Colitis Canada Genetic Environmental Microbial cohort of healthy FDRs of patients with CD.

High mobility group box 1 (HMGB1) is a potential disease biomarker in cell and mouse models of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disorder affecting 1:3500 male births and is associated with myofiber degeneration, regeneration, and inflammation. Glucocorticoid treatments have been the standard of care due to immunomodulatory/immunosuppressive properties but novel genetic approaches, including exon skipping and gene replacement therapy, are currently being developed. The identification of additional biomarkers to assess DMD-related inflammatory responses and the potential efficacy of these therapeutic approaches are thus of critical importance.

Dystrophin deficiency impairs cell junction formation during embryonic myogenesis from pluripotent stem cells.

Mutations in the gene lead to Duchenne muscular dystrophy (DMD), a severe neuromuscular disorder affecting young boys as they acquire motor functions. DMD is typically diagnosed at 2-4 years of age, but the absence of dystrophin has negative impacts on skeletal muscles before overt symptoms appear in patients, which poses a serious challenge in current standards of care. Here, we investigated the consequences of dystrophin deficiency during skeletal muscle development.

Engineered Heart Tissues for Standard 96-Well Tissue Culture Plates.

Engineered heart tissues (EHTs) have been shown to be a valuable platform for disease investigation and therapeutic testing by increasing human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) maturity and better recreating the native cardiac environment. The protocol detailed in this chapter describes the generation of miniaturized EHTs (mEHTs) incorporating hiPSC-CMs and human stromal cells in a fibrin hydrogel. This platform utilizes an array of silicone posts designed to fit in a standard 96-well tissue culture plate.

YAP dysregulation triggers hypertrophy by CCN2 secretion and TGFβ uptake in human pluripotent stem cell-derived cardiomyocytes.

Hypertrophy Cardiomyopathy (HCM) is the most prevalent hereditary cardiovascular disease - affecting >1:500 individuals. Advanced forms of HCM clinically present with hypercontractility, hypertrophy and fibrosis. Several single-point mutations in b-myosin heavy chain (MYH7) have been associated with HCM and increased contractility at the organ level.

Mental Health Experiences of Adolescents and Young Adults with Inflammatory Bowel Disease During Transition to Adult Care: A Qualitative Descriptive Study.

Objective: To explore the mental health experiences of adolescents and young adults (AYA) with inflammatory bowel disease (IBD) enrolled in a randomized controlled trial evaluating the impact of a multimodal transition intervention.

Study Design: Virtual semistructured interviews were held with 21 AYA aged 16 through 18 years with IBD. Guided by qualitative description, interviews were digitally recorded, transcribed verbatim, and analyzed using an inductive approach to reflexive thematic analysis.

Landscape of TPMT and NUDT15 Pharmacogenetic Variation in a Cohort of Canadian Pediatric Inflammatory Bowel Disease Patients.

Background: Patients with inflammatory bowel disease (IBD) exhibit considerable interindividual variability in medication response, highlighting the need for precision medicine approaches to optimize and tailor treatment. Pharmacogenetics (PGx) offers the ability to individualize dosing by examining genetic factors underlying the metabolism of medications such as thiopurines. Pharmacogenetic testing can identify individuals who may be at risk for thiopurine dose-dependent adverse reactions including myelosuppression.

Far-red and sensitive sensor for monitoring real time HO dynamics with subcellular resolution and in multi-parametric imaging applications.

HO is a key oxidant in mammalian biology and a pleiotropic signaling molecule at the physiological level, and its excessive accumulation in conjunction with decreased cellular reduction capacity is often found to be a common pathological marker. Here, we present a red fluorescent Genetically Encoded HO Indicator (GEHI) allowing versatile optogenetic dissection of redox biology. Our new GEHI, oROS-HT, is a chemigenetic sensor utilizing a HaloTag and Janelia Fluor (JF) rhodamine dye as fluorescent reporters.

Incomplete-penetrant hypertrophic cardiomyopathy G256E mutation causes hypercontractility and elevated mitochondrial respiration.

Determining the pathogenicity of hypertrophic cardiomyopathy-associated mutations in the β-myosin heavy chain () can be challenging due to its variable penetrance and clinical severity. This study investigates the early pathogenic effects of the incomplete-penetrant G256E mutation on myosin function that may trigger pathogenic adaptations and hypertrophy. We hypothesized that the G256E mutation would alter myosin biomechanical function, leading to changes in cellular functions.

Pre-Diagnosis Diet Predicts Response to Exclusive Enteral Nutrition and Correlates with Microbiome in Pediatric Crohn Disease.

Exclusive enteral nutrition (EEN) is effective in inducing remission in pediatric Crohn disease (CD). EEN alters the intestinal microbiome, but precise mechanisms are unknown. We hypothesized that pre-diagnosis diet establishes a baseline gut microbiome, which then mediates response to EEN.

Ultra-fast genetically encoded sensor for precise real-time monitoring of physiological and pathophysiological peroxide dynamics.

Hydrogen Peroxide (HO) is a central oxidant in redox biology due to its pleiotropic role in physiology and pathology. However, real-time monitoring of HO in living cells and tissues remains a challenge. We address this gap with the development of an optogenetic hydRogen perOxide Sensor (oROS), leveraging the bacterial peroxide binding domain OxyR.