Digital consults in heart failure care: a randomized controlled trial.

Guideline-directed medical therapy (GDMT) has clear benefits on morbidity and mortality in patients with heart failure; however, GDMT use remains low. In the multicenter, open-label, investigator-initiated ADMINISTER trial, patients (n = 150) diagnosed with heart failure and reduced ejection fraction (HFrEF) were randomized (1:1) to receive usual care or a strategy using digital consults (DCs). DCs contained (1) digital data sharing from patient to clinician (pharmacotherapy use, home-measured vital signs and Kansas City Cardiomyopathy Questionnaires); (2) patient education via a text-based e-learning; and (3) guideline recommendations to all treating clinicians.

Digital consults to optimize guideline-directed therapy: design of a pragmatic multicenter randomized controlled trial.

Aims: Many heart failure (HF) patients do not receive optimal guideline-directed medical therapy (GDMT) despite clear benefit on morbidity and mortality outcomes. Digital consults (DCs) have the potential to improve efficiency on GDMT optimization to serve the growing HF population. The investigator-initiated ADMINISTER trial was designed as a pragmatic multicenter randomized controlled open-label trial to evaluate efficacy and safety of DC in patients on HF treatment.

PTPA variants and impaired PP2A activity in early-onset parkinsonism with intellectual disability.

The protein phosphatase 2A complex (PP2A), the major Ser/Thr phosphatase in the brain, is involved in a number of signalling pathways and functions, including the regulation of crucial proteins for neurodegeneration, such as alpha-synuclein, tau and LRRK2. Here, we report the identification of variants in the PTPA/PPP2R4 gene, encoding a major PP2A activator, in two families with early-onset parkinsonism and intellectual disability. We carried out clinical studies and genetic analyses, including genome-wide linkage analysis, whole-exome sequencing, and Sanger sequencing of candidate variants.

Boundary Objects as Dialogical Learning Accelerators for Social Change in Design for Health: Systematic Review.

Background: Boundary objects can add value for innovative design and implementation research in health care through their organizational focus and the dynamic structure between ill-structured and tailored use. However, when innovation is approached as a boundary object, more attention will need to be paid to the preimplementation phase. Research and design thinking pay attention to the preimplementation stage but do not have a social or organizational focus per se.

WARS2 mutations cause dopa-responsive early-onset parkinsonism and progressive myoclonus ataxia.

Introduction: Sixteen subjects with biallelic WARS2 variants encoding the tryptophanyl mitochondrial aminoacyl-tRNA synthetase, presenting with a neonatal- or infantile-onset mitochondrial disease, have been reported to date. Here we present six novel cases with WARS2-related diseases and expand the spectrum to later onset phenotypes including dopa-responsive early-onset parkinsonism and progressive myoclonus-ataxia.

Methods: Six individuals from four families underwent whole-exome sequencing within research and diagnostic settings.

The Development of an Escape Room-Based Serious Game to Trigger Social Interaction and Communication Between High-Functioning Children With Autism and Their Peers: Iterative Design Approach.

Background: Children with autism spectrum disorder (ASD) have social deficits that affect social interactions, communication, and relationships with peers. Many existing interventions focus mainly on improving social skills in clinical settings. In addition to the direct instruction-based programs, activity-based programs could be of added value, especially to bridge the relational gap between children with ASD and their peers.

EIF2AK2 Missense Variants Associated with Early Onset Generalized Dystonia.

Objective: The study was undertaken to identify a monogenic cause of early onset, generalized dystonia.

Methods: Methods consisted of genome-wide linkage analysis, exome and Sanger sequencing, clinical neurological examination, brain magnetic resonance imaging, and protein expression studies in skin fibroblasts from patients.

Results: We identified a heterozygous variant, c.

Design of a Digital Comic Creator (It's Me) to Facilitate Social Skills Training for Children With Autism Spectrum Disorder: Design Research Approach.

Background: Children with autism spectrum disorder (ASD) often face difficulties in social situations and are often lagging in terms of social skills. Many interventions designed for children with ASD emphasize improving social skills. Although many interventions demonstrate that targeted social skills can be improved in clinical settings, developed social skills are not necessarily applied in children's daily lives at school, sometimes because classmates continue to show negative bias toward children with ASD.

Clinical and Pathological Phenotypes of LRP10 Variant Carriers with Dementia.

Background: Rare variants in the low-density lipoprotein receptor related protein 10 gene (LRP10) have recently been implicated in the etiology of Parkinson's disease (PD) and dementia with Lewy bodies (DLB).

Objective: We searched for LRP10 variants in a new series of brain donors with dementia and Lewy pathology (LP) at autopsy, or dementia and parkinsonism without LP but with various other neurodegenerative pathologies.

Methods: Sanger sequencing of LRP10 was performed in 233 donors collected by the Netherlands Brain Bank.

LRP10 variants in progressive supranuclear palsy.

The aim of this study was to explore whether variants in LRP10, recently associated with Parkinson's disease and dementia with Lewy bodies, are observed in 2 large cohorts (discovery and validation cohort) of patients with progressive supranuclear palsy (PSP). A total of 950 patients with PSP were enrolled: 246 patients with PSP (n = 85 possible (35%), n = 128 probable (52%), n = 33 definite (13%)) in the discovery cohort and 704 patients with definite PSP in the validation cohort. Sanger sequencing of all LRP10 exons and exon-intron boundaries was performed in the discovery cohort, and whole-exome sequencing was performed in the validation cohort.

Late-onset phenotype associated with a homozygous GJC2 missense mutation in a Turkish family.

Objective: Recessive mutations in the Gap Junction Protein Gamma 2 (GJC2) gene cause Pelizaeus-Merzbacher-like disease type 1, a severe infantile-onset hypomyelinating leukodystrophy. Milder, late-onset phenotypes including complicated spastic paraplegia in one family (SPG44), and mild tremor in one case, were reported associated to GJC2 homozygous missense mutations. Here, we report a new family with two siblings carrying a different homozygous GJC2 mutation, presenting with late-onset ataxic and pyramidal disturbances, and parkinsonism in one of them.

Maximizing Authentic Learning and Real-World Problem-solving in Health Curricula Through Psychological Fidelity in a Game-Like Intervention: Development, Feasibility, and Pilot Studies.

High fidelity is regarded as a hallmark of educational games and simulations for health education. Mainly physical and functional fidelity are associated with authenticity, resulting in the pursuit of a true-to-life simulation and suggesting the imposition of a generally accepted and often unintentional design rationale that assumes that the greater the fidelity of a game or simulation to the real world, the more authentic the intervention is perceived as. Psychological fidelity receives significantly less attention, although it correlates strongly to credibility, suspension of disbelief, and engagement.

PTRHD1 Loss-of-function mutation in an african family with juvenile-onset Parkinsonism and intellectual disability.

Background: The genetic bases of PD in sub-Saharan African (SSA) populations remain poorly characterized, and analysis of SSA families with PD might lead to the discovery of novel disease-related genes.

Objectives: To investigate the clinical features and identify the disease-causing gene in a black South African family with 3 members affected by juvenile-onset parkinsonism and intellectual disability.

Methods: Clinical evaluation, neuroimaging studies, whole-exome sequencing, homozygosity mapping, two-point linkage analysis, and Sanger sequencing of candidate variants.

LRP10 genetic variants in familial Parkinson's disease and dementia with Lewy bodies: a genome-wide linkage and sequencing study.

Background: Most patients with Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies do not carry mutations in known disease-causing genes. The aim of this study was to identify a novel gene implicated in the development of these disorders.

Methods: Our study was done in three stages.

The Role of Transfer in Designing Games and Simulations for Health: Systematic Review.

Background: The usefulness and importance of serious games and simulations in learning and behavior change for health and health-related issues are widely recognized. Studies have addressed games and simulations as interventions, mostly in comparison with their analog counterparts. Numerous complex design choices have to be made with serious games and simulations for health, including choices that directly contribute to the effects of the intervention.

The p.Thr11Met mutation in c19orf12 is frequent among adult Turkish patients with MPAN.

Introduction: Mutations in the C19orf12 gene cause mitochondrial membrane protein associated neurodegeneration (MPAN), an autosomal recessive form of neurodegeneration with brain iron accumulation (NBIA). A limited number of patients with C19orf12 mutations, particularly those with adult onset of symptoms, have been reported.

Methods: We sequenced the entire coding region of C19orf12 in 15 Turkish adult probands with idiopathic NBIA.

iLift: A health behavior change support system for lifting and transfer techniques to prevent lower-back injuries in healthcare.

Objective: Lower back problems are a common cause of sick leave of employees in Dutch care homes and hospitals. In the Netherlands over 40% of reported sick leave is due to back problems, mainly caused by carrying out heavy work. The goal of the iLift project was to develop a game for nursing personnel to train them in lifting and transfer techniques.

Mycobacterium genotypes in pulmonary tuberculosis infections and their detection by trained African giant pouched rats.

Tuberculosis (TB) diagnosis in low-income countries is mainly done by microscopy. Hence, little is known about the diversity of Mycobacterium spp. in TB infections.

Epithelial repair is a two-stage process driven first by dying cells and then by their neighbours.

Epithelial cells maintain an essential barrier despite continuously undergoing mitosis and apoptosis. Biological and biophysical mechanisms have evolved to remove dying cells while maintaining that barrier. Cell extrusion is thought to be driven by a multicellular filamentous actin ring formed by neighbouring cells, the contraction of which provides the mechanical force for extrusion, with little or no contribution from the dying cell.

Alkaline pH activates the transport activity of GLUT1 in L929 fibroblast cells.

The widely expressed mammalian glucose transporter, GLUT1, can be acutely activated in L929 fibroblast cells by a variety of conditions, including glucose deprivation, or treatment with various respiration inhibitors. Known thiol reactive compounds including phenylarsine oxide and nitroxyl are the fastest acting stimulators of glucose uptake, implicating cysteine biochemistry as critical to the acute activation of GLUT1. In this study, we report that in L929 cells glucose uptake increases 6-fold as the pH of the uptake solution is increased from 6 to 9 with the half-maximal activation at pH 7.