Sweat chloride reflects CFTR function and correlates with clinical outcomes following CFTR modulator treatment.

Background: Highly effective CFTR modulators improve CFTR function and lead to dramatic improvements in health outcomes in many people with cystic fibrosis (pwCF). The relationship between measures of CFTR function, such as sweat chloride concentration, and clinical outcomes in pwCF treated with CFTR modulators is poorly defined. We conducted analyses to better understand the relationships between sweat chloride and CFTR function in vitro, and between sweat chloride and clinical outcomes following CFTR modulator treatment.

3-year Outcomes of Botulinum Toxin versus Strabismus Surgery for the Treatment of Acute Acquired Comitant Esotropia in Children.

Introduction: Botulinum toxin is an alternative to conventional strabismus surgery for treatment for acute, acquired, comitant esotropia (AACE). Previous studies suggest that the two treatment approaches may be equally effective for 6 months. The purpose of our study was to determine whether botulinum toxin remains as effective as strabismus surgery for 36 months after treatment.

Rhinoconjunctivitis Symptoms in Children and Adolescents with Asthma: A Longitudinal Clustering Analysis.

Background: Rhinoconjunctivitis phenotypes are conventionally described based on symptom severity, duration and seasonality and aeroallergen sensitization. It is not known whether these phenotypes fully reflect the patterns of symptoms seen at a population level.

Objective: To identify phenotypes of rhinoconjunctivitis based on symptom intensity and seasonality using an unbiased approach and to compare their characteristics.

A Guide to Pediatric Antibiotic Allergy Testing: A Report from the United States Drug Allergy Registry.

Pediatric antibiotic labels are common, and unnecessary antibiotic avoidance is associated with negative personal and public health outcomes; as a result, there is an increasing emphasis on the importance of pediatric antibiotic allergy evaluations. Different testing strategies have been advised, including skin testing and challenge testing with varied doses and duration. Established consensus testing protocols are lacking.

Development and refinement of the Cardiovascular Health Equity through Food (CHEF) intervention for childhood cancer survivors.

Purpose: The aim of this study was to develop and refine Cardiovascular Health Equity through Food (CHEF), an intervention to address food insecurity (FI) in early childhood cancer survivors (CCS).

Methods: Single-center mixed-methods pilot study of a novel "food is medicine" intervention evaluating acceptability, satisfaction, and opportunities for refinement. CHEF participants were provided: (1) meal-kit delivery for 3 household meals/week for 3 months and (2) application assistance for federal nutrition benefits.

Impact of high maternal body mass index on fetal cerebral cortical and cerebellar volumes.

Objectives: Maternal obesity increases a child's risk of neurodevelopmental impairment. However, little is known about the impact of maternal obesity on fetal brain development.

Methods: We prospectively recruited 20 healthy pregnant women across the range of pre-pregnancy or first-trimester body mass index (BMI) and performed fetal brain magnetic resonance imaging (MRI) of their healthy singleton fetuses.

A Splice Site Variant in SENP7 Results in a Severe Form of Arthrogryposis.

Arthrogryposis multiplex congenita (AMC) is a heterogeneous disorder associated with 1/3000 to 1/5000 live births. We report a consanguineous family with multiple affected members with AMC and identified a recessive mutation in the highly conserved splice donor site, resulting in the mis-splicing of the affected exons. SENP7 is a deSUMOylase that is critical for sarcomere assembly and skeletal muscle contraction by regulating the transcriptional program in the skeletal muscle.

ZIC1 is a context-dependent medulloblastoma driver in the rhombic lip.

Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma).

CIROZ is dispensable in ancestral vertebrates but essential for left-right patterning in humans.

Four genes-DAND5, PKD1L1, MMP21, and CIROP-form a genetic module that has specifically evolved in vertebrate species that harbor motile cilia in their left-right organizer (LRO). We find here that CIROZ (previously known as C1orf127) is also specifically expressed in the LRO of mice, frogs, and fish, where it encodes a protein with a signal peptide followed by 3 zona pellucida N domains, consistent with extracellular localization. We report 16 individuals from 10 families with bi-allelic CIROZ inactivation variants, which cause heterotaxy with congenital heart defects.

Improved Patient-Reported Outcomes With Post-Transplant Cyclophosphamide: A Quality-of-Life Evaluation and 2-Year Outcomes of BMT CTN 1703.

The BMT CTN 1703 phase III trial confirmed that graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (PTCy), tacrolimus (Tac), and mycophenolate mofetil (MMF) results in superior GVHD-free, relapse-free survival (GRFS) compared with Tac/methotrexate (MTX) prophylaxis. This companion study assesses the effect of these regimens on patient-reported outcomes (PROs). Using the Lee Chronic GVHD Symptom Score and PROMIS subscales (physical function, GI symptoms, social role satisfaction) as primary end points and hemorrhagic cystitis symptoms and Lee subscales as secondary end points, responses from English and Spanish speakers were analyzed at baseline and days 100, 180, and 365 after transplant.

The American Clinical Neurophysiology Society Guideline on Indications for Continuous Electroencephalography Monitoring in Neonates.

Purpose: Continuous EEG (cEEG) monitoring is increasingly used in the management of neonates with seizures. There remains debate on what clinically relevant information can be gained from cEEG in neonates with suspected seizures, at high risk for seizures, or with definite seizures, as well as the use of cEEG for prognosis in a variety of conditions. In this guideline, we address these questions using American Clinical Neurophysiology Society structured methodology for clinical guideline development.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD), an age-associated neurodegenerative disorder, is characterized by progressive neuronal loss and the accumulation of misfolded proteins such as amyloid-β and tau. While neuroinflammation, mediated by microglia and brain-resident macrophages, plays a pivotal role in AD pathogenesis, the intricate interactions among age, genes, and other risk factors remain elusive. Somatic mutations, known to accumulate with age, instigate clonal expansion across diverse cell types, impacting both cancer and non-cancerous conditions.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the deposition of amyloid-beta and hyperphosphorylated tau (P-tau) proteins in the brain. P-tau accumulates in neurons and is strongly associated with AD severity and affected brain regions. However, only a subset of neurons in AD exhibit tau pathology.

Basic Science and Pathogenesis.

Background: Previously, we found that germline C3 deletion protected cognition and hippocampal synapses in aged APP/PS1dE9 mice, despite increasing Aß plaques. Here, we crossed our C3 inducible conditional mouse model to APP knockin mice to determine whether global C3 lowering in an adult amyloid mouse model would be protective.

Methods: C3;Rosa26-Cre-ERT2 (C3iKO) mice were crossed to C3;APP mice to generate APP;C3iKO mice, which received 75 mg/kg tamoxifen (TAM; n = 16) or corn oil (CO; n = 15) for 5 days at 3.

Basic Science and Pathogenesis.

Background: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive head impact (RHI) although little is known about its molecular pathogenesis. Previous studies of single neurons showed that private somatic mutations increase both during normal aging and in neurodegenerative disorders, and show diverse mutational patterns.

Method: We applied two orthogonal single-nucleus whole-genome sequencing (snWGS) methods to neurons isolated from the prefrontal cortex of 15 individuals with CTE, and 4 individuals with RHI but no CTE diagnosis, and compared mutational rates and spectra with neurons from neurotypical controls and Alzheimer's disease (AD).

Development of a reference standard to assign bacterial versus viral infection etiology using an all-inclusive methodology for comparison of novel diagnostic tool performance.

Background: Diagnostic test evaluation requires a reference standard. We describe an approach for creating a reference standard for acute infection using unrestricted adjudication and apply it to compare biomarker tools.

Methods: Adults and children with suspected acute infection enrolled in three prospective studies at emergency departments and urgent cares were included.

The substance-exposed birthing person-infant/child dyad and health information exchange in the United States.

Objective: Timely access to data is needed to improve care for substance-exposed birthing persons and their infants, a significant public health problem in the United States. We examined the current state of birthing person and infant/child (dyad) data-sharing capabilities supported by health information exchange (HIE) standards and HIE network capabilities for data exchange to inform point-of-care needs assessment for the substance-exposed dyad.

Material And Methods: A cross-map analysis was performed using a set of dyadic data elements focused on pediatric development and longitudinal supportive care for substance-exposed dyads (70 birthing person and 110 infant/child elements).

Topical Netarsudil in Childhood Glaucoma: A Systematic Review.

Purpose: To evaluate the effectiveness and safety of topical netarsudil 0.02% in managing childhood glaucoma.

Methods: A literature search in the electronic databases of PubMed CENTRAL, Google Scholar, EMBASE, the Register of Controlled Trials, and Ovid MEDLINE from January 2017 to August 2023 using one or a combination of the following terms: "netarsudil," "rhopressa," "Rho-kinase," "pediatric glaucoma," "childhood glaucoma," "intraocular pressure" was conducted.