Perinatal Vaccination by Transamniotic Fetal mRNA Delivery: Immunization Against Human Cytomegalovirus in a Rodent Model.

Purpose: Gestational cytomegalovirus (CMV) infection is a prevalent disease with significant fetal and neonatal morbidity. MRNA vaccines have emerged as powerful options for postnatal immunization against infections. It has been shown that mRNA delivered into the amniotic fluid reaches the fetal circulation via the placenta.

Choroid Plexus Pathophysiology.

This review examines the crucial roles of the choroid plexus (ChP) in central nervous system (CNS) pathology, emphasizing its involvement in disease mechanisms and therapeutic potential. Structural changes in the human ChP have been reported across various diseases in case reports and descriptive work, but studies have yet to pin down the physiological relevance of these changes. We highlight primary pathologies of the ChP, as well as their significance in neurologic disorders, including stroke, hydrocephalus, infectious diseases, and neurodegeneration.

Exposure to aircraft noise exacerbates cardiovascular and oxidative damage in three mouse models of diabetes.

Background: Epidemiology links noise to increased risk of metabolic diseases like diabetes and obesity. Translational studies in humans and experimental animals showed that noise causes reactive oxygen species (ROS)-mediated cardiovascular damage. The interaction between noise and diabetes, specifically potential additive adverse effects, remains to be determined.

A cell type-aware framework for nominating non-coding variants in Mendelian regulatory disorders.

Unsolved Mendelian cases often lack obvious pathogenic coding variants, suggesting potential non-coding etiologies. Here, we present a single cell multi-omic framework integrating embryonic mouse chromatin accessibility, histone modification, and gene expression assays to discover cranial motor neuron (cMN) cis-regulatory elements and subsequently nominate candidate non-coding variants in the congenital cranial dysinnervation disorders (CCDDs), a set of Mendelian disorders altering cMN development. We generate single cell epigenomic profiles for ~86,000 cMNs and related cell types, identifying ~250,000 accessible regulatory elements with cognate gene predictions for ~145,000 putative enhancers.

Co-creation in healthcare and research to improve service delivery for young people with chronic pain.

Introduction: The process of co-creation can enable more effective, agile and integrated healthcare solutions achieving outcomes that effectively translate to healthcare delivery. Collaborative knowledge generation is particularly important in fields such as pediatric chronic pain where there is a complex interplay between biological, social, environmental, emotional, familial and school factors. The co-creation initiative described here was designed to amplify the voices of youth with chronic pain and their families and a variety of key stakeholders and generate novel approaches to the management of chronic pediatric pain in the setting of the South Australian Pediatric Chronic Pain Service.

Sacubitril/Valsartan in Pediatric Heart Failure (PANORAMA-HF): A Randomized, Multicenter, Double-Blind Trial.

Background: Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), is an established treatment for heart failure (HF) with reduced left ventricular ejection fraction. It has not been rigorously compared with angiotensin-converting enzyme inhibitors in children. PANORAMA-HF (Prospective Trial to Assess the Angiotensin Receptor Blocker Neprilysin Inhibitor LCZ696 Versus Angiotensin-Converting Enzyme Inhibitor for the Medical Treatment of Pediatric HF) is a randomized, double-blind trial that evaluated the pharmacokinetics and pharmacodynamics (PK/PD), safety, and efficacy of sacubitril/valsartan versus enalapril in children 1 month to <18 years of age with HF attributable to systemic left ventricular systolic dysfunction (LVSD).

Identification of pharmacological inducers of a reversible hypometabolic state for whole organ preservation.

Drugs that induce reversible slowing of metabolic and physiological processes would have great value for organ preservation, especially for organs with high susceptibility to hypoxia-reperfusion injury, such as the heart. Using whole-organism screening of metabolism, mobility, and development in , we identified an existing drug, SNC80, that rapidly and reversibly slows biochemical and metabolic activities while preserving cell and tissue viability. Although SNC80 was developed as a delta opioid receptor activator, we discovered that its ability to slow metabolism is independent of its opioid modulating activity as a novel SNC80 analog (WB3) with almost 1000 times less delta opioid receptor binding activity is equally active.

Detailed delineation of the fetal brain in diffusion MRI via multi-task learning.

Diffusion-weighted MRI is increasingly used to study the normal and abnormal development of fetal brain inutero. Recent studies have shown that dMRI can offer invaluable insights into the neurodevelopmental processes in the fetal stage. However, because of the low data quality and rapid brain development, reliable analysis of fetal dMRI data requires dedicated computational methods that are currently unavailable.

Intravenous fluorescein overdose in a child undergoing fluorescein angiography.

Fluorescein angiography is a fluorescent dye-based imaging procedure, most commonly indicated in the pediatric setting to evaluate peripheral retinal vascular lesions. Fluorescein dye is organic, water soluble, and largely excreted renally, with a reassuring safety profile at therapeutic doses. While toxicity with intrathecal overdose has been reported, the effect of intravenous exposure to supratherapeutic levels has not been previously documented in the literature.