Effect of Characteristic Inflammatory and Structural Pelvic Magnetic Resonance Imaging Lesions on Expert Assessment of Axial Juvenile Spondyloarthritis.

Objective: To evaluate the influence of pelvic magnetic resonance imaging (MRI) findings on axial disease assessment in juvenile spondyloarthritis (JSpA).

Methods: This was a cross-sectional study of patients with JSpA with suspected axial disease. Three experts reviewed each case and rated their confidence (-3 to +3) in the presence of axial disease, first with clinical data and second with clinical and MRI data.

Child Neurology: Severe -Related Congenital Muscular Dystrophy With Rapidly Progressive Encephalopathy Leading to Infantile Death.

Pathogenic variants in cause congenital muscular dystrophy through hypoglycosylation of alpha-dystroglycan (OMIM #615350). The established phenotypic spectrum of GMPPB-related disorders includes recurrent rhabdomyolysis, limb-girdle muscular dystrophy, neuromuscular transmission abnormalities, and congenital muscular dystrophy with variable brain and eye anomalies. We report a 9-month-old male infant with congenital muscular dystrophy, infantile spasms, and compound heterozygous pathogenic variants (c.

regulates melanocortin 4 receptor transcription and energy homeostasis.

Disruption of hypothalamic melanocortin 4 receptors (MC4Rs) causes obesity in mice and humans. Here, we investigated the transcriptional regulation of in the hypothalamus. In mice, we show that the homeodomain transcription factor Orthopedia (OTP) is enriched in MC4R neurons in the paraventricular nucleus (PVN) of the hypothalamus and directly regulates transcription.

Mutations disrupting the kinase domain of IKKα lead to immunodeficiency and immune dysregulation in humans.

IKKα, encoded by CHUK, is crucial in the non-canonical NF-κB pathway and part of the IKK complex activating the canonical pathway alongside IKKβ. The absence of IKKα causes fetal encasement syndrome in humans, fatal in utero, while an impaired IKKα-NIK interaction was reported in a single patient and causes combined immunodeficiency. Here, we describe compound heterozygous variants in the kinase domain of IKKα in a female patient with hypogammaglobulinemia, recurrent lung infections, and Hay-Wells syndrome-like features.

Prevalence of pathogenic variants of inborn errors of immunity in critically ill children admitted to the pediatric intensive care unit for sepsis: A Moroccan cohort study.

Introduction: Pediatric sepsis remains a leading cause of morbidity and mortality in Africa. Nearly half of pediatric sepsis deaths occur in previously healthy children. The role of inborn errors of immunity (IEI) in susceptibility to sepsis is yet to be identified and their prevalence amongst previously healthy children admitted to the pediatric intensive care unit (PICU) is unclear.

Utilities Associated with the Treatment of Growth Hormone Deficiency (GHD): A Time Trade-off (TTO) Study in the UK and Canada.

Purpose: Growth hormone deficiency (GHD) causes decreased growth rate in children, resulting in short stature in childhood and adulthood. Daily subcutaneous injections with growth hormone (GH) have been standard treatment. Newer weekly GH formulations now exist.

Visual Acuity, Full-field Stimulus Thresholds, and Electroretinography for 4 Years in The Rate of Progression of USH2A-related Retinal Degeneration (RUSH2A) Study.

Purpose: To describe progression of best-corrected visual acuity (BCVA), full-field stimulus thresholds (FST), and electroretinography (ERG) over 4 years in the -related Retinal Degeneration study and to assess their suitability as clinical trial endpoints.

Design: Prospective natural history study.

Participants: Participants (n = 105) with biallelic disease-causing sequence variants in USH2A and BCVA letter scores of ≥54 were included.

Neonatal Encephalopathy: Novel Phenotypes and Genotypes Identified by Genome Sequencing.

Background And Objectives: Neonatal encephalopathy (NE) is characterized by an abnormal level of consciousness with or without seizures in the neonatal period. It affects 1-6/1,000 live term newborns. We applied genome sequencing (GS) in term newborns with NE to investigate the underlying genetic causes.

Achieving Language Justice in Pediatric Hematology-Oncology: A Multinational Perspective for Language-Concordant Equitable Patient- and Family-Centered Care and Research Inclusion.

Language-discordant healthcare encounters-when the patient/caregiver and clinician are not able to communicate directly in the patient's/caregiver's preferred language-are associated with worse quality of care, increased adverse events, and research exclusion. Here, we describe the current state of language justice in clinical practice and research in the United States, Canada, and Spain, discuss the role of social determinants of health and language, in patient safety and health outcomes and review an example of culturally and linguistically concordant interventions to increase research participation. We close with practical and global strategies to increase multilingual research participation and to provide equitable patient- and family-centered care in pediatric hematology-oncology.

High cellular plasticity state of medulloblastoma local recurrence and distant dissemination.

Medulloblastoma (MB), a heterogeneous pediatric brain tumor, poses challenges in the treatment of tumor recurrence and dissemination. To characterize cellular diversity and genetic features, we comprehensively analyzed single-cell/nucleus RNA sequencing (sc/snRNA-seq), single-nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq), and spatial transcriptomics profiles and identified distinct cellular populations in SHH (sonic hedgehog) and Group_3 subgroups, with varying proportions in local recurrence or dissemination. Local recurrence showed higher cycling tumor cell enrichment, whereas disseminated lesions had a relatively notable presence of differentiated subsets.

Precision Medicine for High-Risk Gene Fusions in Paediatric AML: a focus on KMT2A, NUP98, and GLIS2 Rearrangements.

Robust genetic characterization of paediatric AML has demonstrated that fusion oncogenes are highly prevalent drivers of AML leukemogenesis in young children. Identification of fusion oncogenes associated with adverse outcomes has facilitated risk stratification of patients, although successful development of precision medicine approaches for most fusion-driven AML subtypes have been historically challenging. This knowledge gap has been in part due to difficulties in targeting structural alterations involving transcription factors and in identification of a therapeutic window for selective inhibition of the oncofusion without deleterious effects upon essential wild-type proteins.

Outcomes following resective and disconnective strategies in the treatment of epileptic spasms: a systematic review of the literature and individual patient data meta-analysis.

Epileptic spasms (ES) are a unique seizure type typically presenting in the form of infantile epileptic spasms syndrome (IESS) with characteristic hypsarrhythmia on scalp EEG and a preponderance with developmental delay or regression. While pharmacotherapy is the mainstay of treatment, surgical options, including disconnective or resective procedures, are increasingly recognized as viable therapeutic options for recurrent or persistent ES. However, limited data on safety, effectiveness, and prognostic factors hinder informed decision-making regarding surgery indications, timing, and intervention type.

Negative Staining Electron Microscopy of a Highly Flexible Sec1/Munc18 Protein Complex Stabilized by Glutaraldehyde Crosslinking.

Negative staining electron microscopy is one of the easiest ways to determine the shape and dimensions of multimeric protein complexes over 100 kDa molecular weight. This method requires small volumes (< 10 μL) of dilute protein (0.01-0.

Glycogen synthase GYS1 overactivation contributes to glycogen insolubility and malto-oligoglucan-associated neurodegenerative disease.

Polyglucosans are glycogen molecules with overlong chains, which are hyperphosphorylated in the neurodegenerative Lafora disease (LD). Brain polyglucosan bodies (PBs) cause fatal neurodegenerative diseases including Lafora disease and adult polyglucosan body disease (ABPD), for which treatments, biomarkers, and good understanding of their pathogenesis are currently missing. Mutations in the genes for the phosphatase laforin or the E3 ubiquitin ligase malin can cause LD.

The birth of the virtual clinic: welcome to the Mediverse.

The COVID-19 pandemic triggered a global pivot to virtual care (VC) technologies. While there has been considerable academic work exploring the "how" of VC, few studies have explored the impact of this pivot, its unintended consequences, and its governing rationales. This study addresses this gap in relation to care, professional identity and the evolving requirements for health professions education.

Pre-T cell receptor-α immunodeficiency detected exclusively using whole genome sequencing.

Maturation of αβ lineage T cells in the thymus relies on the formation and cell surface expression of a pre-T cell receptor (TCR) complex, composed of TCRβ chain and pre-TCRα (pTCRα) chain heterodimers, giving rise to a diverse T cell repertoire. Genetic aberrations in key molecules involved in T cell development lead to profound T cell immunodeficiency. Definitive genetic diagnosis guides treatment choices and counseling.

Validity of the Diabetic Wound Assessment Learning Tool.

Purpose: The development of the Diabetic Wound Assessment Learning Tool (DiWALT) has previously been described. However, an examination of its application to a larger, more heterogeneous group of participants is lacking. In order to allow for a more robust assessment of the psychometric properties of the DiWALT, we applied it to a broader group of participants.

Six-Month Outcomes in the Long-Term Outcomes After the Multisystem Inflammatory Syndrome in Children Study.

Importance: Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening complication of COVID-19 infection. Data on midterm outcomes are limited.

Objective: To characterize the frequency and time course of cardiac dysfunction (left ventricular ejection fraction [LVEF] <55%), coronary artery aneurysms (z score ≥2.

Effects of Food Processing on Allergenicity.

Purpose Of Review: There is an increasing awareness among clinicians that industrial and household food processing methods can increase or decrease the allergenicity of foods. Modification to allergen properties through processing can enable dietary liberations. Reduced allergenicity may also allow for lower risk immunotherapy approaches.

Cardiac growth patterns and metabolism before and after birth in swine: Role of miR in proliferation, hypertrophy and metabolism.

The adult mammalian heart is unable to undergo cardiac repair, limiting potential treatment options after cardiac damage. However, the fetal heart is capable of cardiac repair. In preparation for birth, cardiomyocytes (CMs) undergo major maturational changes that include exit from the cell cycle, hypertrophic growth, and mitochondrial maturation.

Structural variation in nebulin and its implications on phenotype and inheritance: establishing a dominant distal phenotype caused by large deletions.

Introduction: Structural variants (SVs) of the nebulin gene (), including intragenic duplications, deletions, and copy number variation of the triplicate region, are an established cause of recessively inherited nemaline myopathies and related neuromuscular disorders. Large deletions have been shown to cause dominantly inherited distal myopathies. Here we provide an overview of 35 families with muscle disorders caused by such SVs in .

Impact of obesity on outcome in children diagnosed with cancer in Canada: A report from Cancer in Young People in Canada.

Background: Childhood obesity can result in adverse health outcomes. The objectives of this study were to describe the prevalence of obesity and determine the association between obesity at cancer diagnosis and event-free survival (EFS) and overall survival (OS) in children diagnosed with cancer in Canada.

Methods: The authors conducted a retrospective cohort study using the Cancer in Young People in Canada database, including all children with newly diagnosed cancer aged 2-18 years across Canada from 2001 to 2020.

Staged Approach: The Role of Delayed Repair Following Complete Unifocalization of Major Aortopulmonary Collateral Arteries with Ventricular Septal Defect and Pulmonary Atresia.

The presentation of pulmonary vasculature in pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries (PA/VSD/MAPCA) is highly variable-as is the number, size and position of the MAPCAs and their relationship with the native pulmonary artery system. The priority in the management of this disease should be attaining timely and complete unifocalization, as opposed to single-stage full repair in every case. The merit of early unifocalization is that it secures the pulmonary vascular bed by (a) avoiding loss of lung segments from progressive stenosis/atresia of MAPCA origins, (b) preventing lung injury from high pressure/flow in areas fed by large, unobstructed MAPCAs, and (c) restoring central continuity of the pulmonary vasculature.

Does using the Lung Clearance Index (LCI) inform clinical decisions in children with cystic fibrosis?

Introduction: The Lung Clearance Index (LCI) is an established research test, but its role in clinical decision-making is not well defined. This study estimated the proportion of treatment decisions that are changed or supported by the added information provided by LCI.

Methods: A mixed methods prospective observational study was conducted in North America.

Right ventricular remodeling in complex congenital heart disease.

In congenital heart diseases (CHD) of moderate to great complexity involving the right ventricle (RV), the morphologic RV can be exposed to significant stressors across the lifespan either in a biventricular circulation in a sub-pulmonary or sub-aortic position, or as part of a univentricular circulation. These include pressure and/or volume overload, hypoxia, ischemia, and periprocedural surgical stress leading to remodeling, maladaptation, dilation hypertrophy and dysfunction. This review examines the macroscopic remodeling of the RV in various forms of CHD and explores remodeling trajectories, along with the effects of surgeries and residual lesion repair, in tetralogy of Fallot, Ebstein anomaly, congenitally corrected transposition of the great arteries, transposition of the great arteries with atrial switch surgery, and single ventricle palliated by Fontan.