A Short-Term Murine Toxicity Study of 4'-Phosphopantetheine, a Rational Therapeutic for the Dietary Management of Inborn Errors of Coenzyme A Metabolism.

Vitamin B, or pantothenate, forms the molecular "backbone" of coenzyme A (CoA), which is essential for more than a hundred biochemical reactions in humans. Genetic defects that disrupt the CoA pathway cause severe degenerative disorders that may be amenable to treatment with compounds that can bypass the metabolic block. The pantothenate metabolite, 4'-phosphopantetheine (4'PPT), can serve as an alternative substrate for cellular CoA synthesis and may therefore be an essential nutrient in managing disorders where pantothenate cannot meet all metabolic requirements.

[TUMOR-LIKE EFFECT AS INITIAL PRESENTATION OF PEDIATRIC MULTIPLE SCLEROSIS].

In both children and adults, magnetic resonance imaging of the brain in cases of multiple sclerosis (MS) has typical indications, where one of the key points for differentiating between demyelinating processes and place-taking processes is the fact that most of the lesions that appear in multiple sclerosis do not cause a mass effect or much edema around them. There are several uncommon subtypes of multiple sclerosis that can appear specifically in adolescents, presenting with a stormy clinical course and accompanied by brain lesions that resemble space-occupying lesions. These include Marburg disease, Balò's concentric sclerosis, and tumefactive MS.

Femur Fractures in 5 Individuals With Pantothenate Kinase-associated Neurodegeneration: The Role of Dystonia and Suggested Management.

Background: Pantothenate kinase-associated neurodegeneration (PKAN) is a rare, neurodegenerative disorder that manifests with progressive loss of ambulation and refractory dystonia, especially in the early-onset classic form. This leads to osteopenia and stress on long bones, which pose an increased risk of atraumatic femur fractures. The purpose of this study is to describe the unique challenges in managing femur fractures in PKAN and the effect of disease manifestations on surgical outcomes.

The phenotypic presentation of adult individuals with -related neurodevelopmental disorders.

Introduction: is one of the most common monogenic causes of epilepsy and is a well-established cause of neurodevelopmental disorders. -neurodevelopmental disorders have a consistent phenotype of mild to severe intellectual disability (ID), epilepsy, language delay and behavioral disorders. This phenotypic description is mainly based on knowledge from the pediatric population.

SLC6A1 variant pathogenicity, molecular function and phenotype: a genetic and clinical analysis.

Genetic variants in the SLC6A1 gene can cause a broad phenotypic disease spectrum by altering the protein function. Thus, systematically curated clinically relevant genotype-phenotype associations are needed to understand the disease mechanism and improve therapeutic decision-making. We aggregated genetic and clinical data from 172 individuals with likely pathogenic/pathogenic (lp/p) SLC6A1 variants and functional data for 184 variants (14.

Patterns of developmental regression and associated clinical characteristics in SLC6A1-related disorder.

Introduction: SLC6A1-related disorder is a genetic neurodevelopmental disorder that is caused by loss of function variants in the gene. Solute Carrier Family 6 Member 1 () gene encodes for gamma-aminobutyric acid (GABA) transporter type 1 (GAT1), which is responsible for reuptake of GABA from the synaptic cleft. Tight regulation of GABA levels plays an important role in brain development by balancing inhibitory and excitatory neuronal signaling.

A draft conceptual model of SLC6A1 neurodevelopmental disorder.

Introduction: Neurodevelopmental Disorder (SLC6A1-NDD), first described in 2015, is a rare syndrome caused by a mutation in the gene which encodes for the GABA Transporter 1 (GAT-1) protein. Epilepsy is one of the most common symptoms in patients and is often the primary treatment target, though the severity of epilepsy is variable. The impact of seizures and other symptoms of SLC6A1-NDD on patients and caregivers is wide-ranging and has not been described in a formal disease concept study.

ORCA, a values-based decision aid for selecting additional findings from genomic sequencing in adults: Efficacy results from a randomized trial.

Purpose: Individuals having genomic sequencing can choose to be notified about pathogenic variants in genes unrelated to the testing indication. A decision aid can facilitate weighing one's values before making a choice about these additional results.

Methods: We conducted a randomized trial (N = 231) comparing informed values-choice congruence among adults at risk for a hereditary cancer syndrome who viewed either the Optional Results Choice Aid (ORCA) or web-based additional findings information alone.

ClinGen's Pediatric Actionability Working Group: Clinical actionability of secondary findings from genome-scale sequencing in children and adolescents.

Purpose: Synthesis and curation of evidence regarding the clinical actionability of secondary findings (SFs) from genome-scale sequencing are needed to support decision-making on reporting of these findings. To assess actionability of SFs in children and adolescents, the Clinical Genome Resource established the Pediatric Actionability Working Group (AWG).

Methods: The Pediatric AWG modified the framework of the existing Adult AWG, which included production of summary reports of actionability for genes and associated conditions and consensus actionability scores for specific outcome-intervention pairs.

CHRNB1-associated congenital myasthenia syndrome: Expanding the clinical spectrum.

CHRNB1 encodes the β subunit of the acetylcholine receptor (AChR) at the neuromuscular junction. Inherited defects in the neuromuscular junction can lead to congenital myasthenia syndrome (CMS), a clinically and genetically heterogeneous group of disorders which includes fetal akinesia deformation sequence (FADS) on the severe end of the spectrum. Here, we report two unrelated families with biallelic CHRNB1 variants, and in each family, one child presented with lethal FADS.

FE vibration analyses of novel conforming meta-structures and standard lattices for simple bricks and a topology-optimized aerodynamic bracket.

Additive manufacturing (AM) enables production of components that are not possible to make using traditional methods. In particular, lattice-type structures are of recent interest due to their potential for high strength-to-weight ratios and other desirable properties. However, standard periodic lattice structures have problems conforming to complex curved and multi-connected shapes (e.

Current knowledge of SLC6A1-related neurodevelopmental disorders.

Advances in gene discovery have identified genetic variants in the solute carrier family 6 member 1 gene as a monogenic cause of neurodevelopmental disorders, including epilepsy with myoclonic atonic seizures, autism spectrum disorder and intellectual disability. The solute carrier family 6 member 1 gene encodes for the GABA transporter protein type 1, which is responsible for the reuptake of the neurotransmitter GABA, the primary inhibitory neurotransmitter in the central nervous system, from the extracellular space. GABAergic inhibition is essential to counterbalance neuronal excitation, and when significantly disrupted, it negatively impacts brain development leading to developmental differences and seizures.

A decision aid for additional findings in genomic sequencing: Development and pilot testing.

Objective: To describe the development of a web-based, patient-facing decision aid to support patients and research participants to make an informed, values-based decision about whether to receive additional results from genomic sequencing.

Methods: We developed the decision aid following the multi-step process described in the International Patient Decision Aids Standards. This utilized literature review, focus groups, and alpha testing with research participants undergoing clinical genomic sequencing.

A versatile biaxial testing platform for soft tissues.

Uniaxial testing remains the most common modality of mechanical analysis for biological and other soft materials; however, biaxial testing enables a more comprehensive understanding of these materials' mechanical behavior. In recent years, a number of commercially available biaxial testing systems designed for biological materials have been produced; however, there are common limitations that are often associated with using these systems. For example, the range of allowable sample geometries are relatively constrained, the clamping systems are relatively limited with respect to allowable configurations, the load and displacement ranges are relatively small, and the software and control elements offer relatively limited options.

Inpatient Culture and Satisfaction With Care: A Novel Perspective.

Background: Hospital professionals must attend to patients' satisfaction with care. Along with technical quality of care, patients' personal characteristics may affect that satisfaction, but standard demographics research often overlooks cultural links.

Methods: We, therefore, asked 58 San Antonio, Texas, inpatients their satisfaction with care and examined responses for attitudes related to ethnic-Mexican-American (MA), Euro-American (EA), or African-American (AA)-and gender cultures.

The Impact of Rapid Exome Sequencing on Medical Management of Critically Ill Children.

Objectives: To evaluate the clinical usefulness of rapid exome sequencing (rES) in critically ill children with likely genetic disease using a standardized process at a single institution. To provide evidence that rES with should become standard of care for this patient population.

Study Design: We implemented a process to provide clinical-grade rES to eligible children at a single institution.

Characterizing the non-linear mechanical behavior of native and biomimetic engineered tissues in 1D with physically meaningful parameters.

It is common practice to evaluate the mechanical performance of a scaffold for tissue engineering using concepts from linear elasticity theory (i.e. Young's modulus), or variations thereof, and uniaxial testing data.

Cannabis Use in Children With Pantothenate Kinase-Associated Neurodegeneration.

Background: Pantothenate kinase-associated neurodegeneration is characterized by severe, progressive dystonia. This study aims to describe the reported usage of cannabis products among children with pantothenate kinase-associated neurodegeneration.

Methods: A cross-sectional, 37-item survey was distributed in April 2019 to the families of 44 children who participate in a clinical registry of individuals with pantothenate kinase-associated neurodegeneration.

4'-Phosphopantetheine corrects CoA, iron, and dopamine metabolic defects in mammalian models of PKAN.

Pantothenate kinase-associated neurodegeneration (PKAN) is an inborn error of CoA metabolism causing dystonia, parkinsonism, and brain iron accumulation. Lack of a good mammalian model has impeded studies of pathogenesis and development of rational therapeutics. We took a new approach to investigating an existing mouse mutant of Pank2 and found that isolating the disease-vulnerable brain revealed regional perturbations in CoA metabolism, iron homeostasis, and dopamine metabolism and functional defects in complex I and pyruvate dehydrogenase.

Self-reported clinical competencies and expertise within the Massachusetts Department of Veterans' Services.

This exploratory study collected data via the Massachusetts Department of Veterans' Services (DVS) network from mental health providers and site administrators to examine current views on existing resources, challenges, opportunities, and attitudes towards treatment guidelines. Unlicensed providers, predominantly peer support specialists, were the largest professional group that responded to the state-wide survey. Results demonstrated significant differences between providers with and without military experience as it pertains to knowledge of military topics, ambivalence towards clients, ability to work with military families, and the use of standardized screening tools.