Testing a Home Solution for Preparing Young Children for an Awake MRI: A Promising Smartphone Application.

Thanks to its non-invasive nature and high-resolution imaging capabilities, magnetic resonance imaging (MRI) is a valuable diagnostic tool for pediatric patients. However, the fear and anxiety experienced by young children during MRI scans often result in suboptimal image quality and the need for sedation/anesthesia. This study aimed to evaluate the effect of a smartphone application called COSMO@home to prepare children for MRI scans to reduce the need for sedation or general anesthesia.

Extracellular vesicle-derived miRNAs improve stem cell-based therapeutic approaches in muscle wasting conditions.

Skeletal muscle holds an intrinsic capability of growth and regeneration both in physiological conditions and in case of injury. Chronic muscle illnesses, generally caused by genetic and acquired factors, lead to deconditioning of the skeletal muscle structure and function, and are associated with a significant loss in muscle mass. At the same time, progressive muscle wasting is a hallmark of aging.

Human iPSC model reveals a central role for NOX4 and oxidative stress in Duchenne cardiomyopathy.

Duchenne muscular dystrophy (DMD) is a progressive muscle disorder caused by mutations in the Dystrophin gene. Cardiomyopathy is a major cause of early death. We used DMD-patient-specific human induced pluripotent stem cells (hiPSCs) to model cardiomyopathic features and unravel novel pathologic insights.

Unravelling the disease mechanism for TSPYL1 deficiency.

We describe a lethal combined nervous and reproductive systems disease in three affected siblings of a consanguineous family. The phenotype was characterized by visceroautonomic dysfunction (neonatal bradycardia/apnea, feeding problems, hyperactive startle reflex), severe postnatal progressive neurological abnormalities (including abnormal neonatal cry, hypotonia, epilepsy, polyneuropathy, cerebral gray matter atrophy), visual impairment, testicular dysgenesis in males and sudden death at infant age by brainstem-mediated cardiorespiratory arrest. Whole-exome sequencing revealed a novel homozygous frameshift variant p.

Defining the phenotype of FHF1 developmental and epileptic encephalopathy.

Fibroblast growth-factor homologous factor (FHF1) gene variants have recently been associated with developmental and epileptic encephalopathy (DEE). FHF1 encodes a cytosolic protein that modulates neuronal sodium channel gating. We aim to refine the electroclinical phenotypic spectrum of patients with pathogenic FHF1 variants.

Seasonal drivers of understorey temperature buffering in temperate deciduous forests across Europe.

Aim: Forest understorey microclimates are often buffered against extreme heat or cold, with important implications for the organisms living in these environments. We quantified seasonal effects of understorey microclimate predictors describing canopy structure, canopy composition and topography (i.e.

Long-term data with idebenone on respiratory function outcomes in patients with Duchenne muscular dystrophy.

Decline in respiratory function in patients with DMD starts during early teenage years and leads to early morbidity and mortality. Published evidence of efficacy for idebenone on respiratory function outcomes is currently limited to 12 months of follow-up time. Here we report data collected as retrospective cohort study (SYROS) from 18 DMD patients not using glucocorticoids who were treated with idebenone (900 mg/day) under Expanded Access Programs (EAPs).

Dystrophin deficiency leads to dysfunctional glutamate clearance in iPSC derived astrocytes.

Duchenne muscular dystrophy (DMD) results, beside muscle degeneration in cognitive defects. As neuronal function is supported by astrocytes, which express dystrophin, we hypothesized that loss of dystrophin from DMD astrocytes might contribute to these cognitive defects. We generated cortical neuronal and astrocytic progeny from induced pluripotent stem cells (PSC) from six DMD subjects carrying different mutations and several unaffected PSC lines.

Home-Based Monitoring of Pulmonary Function in Patients with Duchenne Muscular Dystroph.

Background: Loss of pulmonary function is a main cause of early morbidity and mortality in patients with Duchenne muscular dystrophy (DMD). Standard of care guidelines recommend regular assessment of pulmonary function by hospital-based spirometry to detect onset and monitor progression of pulmonary function decline.

Objective: To assess the feasibility of home-based monitoring of pulmonary function by a hand-held device (HHD) in adolescent and adult patients with DMD over a period of 12 months.

Efficacy of Idebenone to Preserve Respiratory Function above Clinically Meaningful Thresholds for Forced Vital Capacity (FVC) in Patients with Duchenne Muscular Dystrophy.

Background: Patients with DMD experience progressive restrictive respiratory disease and eventual respiratory failure. Standard of care guidelines command changes in disease management when forced vital capacity percent of predicted (FVC% p) falls below clinically relevant thresholds. The Phase 3 DELOS trial in patients with DMD demonstrated that idebenone reduces the loss of peak expiratory flow and FVC compared to placebo (Buyse GM, et al.

Validation of the Child HCAHPS survey to measure pediatric inpatient experience of care in Flanders.

Unlabelled: The recently developed Child HCAHPS provides a standard to measure US hospitals' performance on pediatric inpatient experiences of care. We field-tested Child HCAHPS in Belgium to instigate international comparison. In the development stage, forward/backward translation was conducted and patients assessed content validity index as excellent.

Characterization of pulmonary function in 10-18 year old patients with Duchenne muscular dystrophy.

Pulmonary function loss in patients with Duchenne muscular dystrophy (DMD) is progressive and leads to pulmonary insufficiency. The purpose of this study in 10-18 year old patients with DMD is the assessment of the inter-correlation between pulmonary function tests (PFTs), their reliability and the association with the general disease stage measured by the Brooke score. Dynamic PFTs (peak expiratory flow [PEF], forced vital capacity [FVC], forced expiratory volume in one second [FEV1]) and maximum static airway pressures (MIP, MEP) were prospectively collected from 64 DMD patients enrolled in the DELOS trial (ClinicalTrials.

Activin A Modulates CRIPTO-1/HNF4 Cells to Guide Cardiac Differentiation from Human Embryonic Stem Cells.

The use of human pluripotent stem cells in basic and translational cardiac research requires efficient differentiation protocols towards cardiomyocytes. In vitro differentiation yields heterogeneous populations of ventricular-, atrial-, and nodal-like cells hindering their potential applications in regenerative therapies. We described the effect of the growth factor Activin A during early human embryonic stem cell fate determination in cardiac differentiation.

Long-Term Efficacy, Safety, and Pharmacokinetics of Drisapersen in Duchenne Muscular Dystrophy: Results from an Open-Label Extension Study.

Background: Drisapersen induces exon 51 skipping during dystrophin pre-mRNA splicing and allows synthesis of partially functional dystrophin in Duchenne muscular dystrophy (DMD) patients with amenable mutations.

Methods: This 188-week open-label extension of the dose-escalation study assessed the long-term efficacy, safety, and pharmacokinetics of drisapersen (PRO051/GSK2402968), 6 mg/kg subcutaneously, in 12 DMD subjects. Dosing was once weekly for 72 weeks.

Treatment effect of idebenone on inspiratory function in patients with Duchenne muscular dystrophy.

Assessment of dynamic inspiratory function may provide valuable information about the degree and progression of pulmonary involvement in patients with Duchenne muscular dystrophy (DMD). The aims of this study were to characterize inspiratory function and to assess the efficacy of idebenone on this pulmonary function outcome in a large and well-characterized cohort of 10-18 year-old DMD patients not taking glucocorticoid steroids (GCs) enrolled in the phase 3 randomized controlled DELOS trial. We evaluated the effect of idebenone on the highest flow generated during an inspiratory FVC maneuver (maximum inspiratory flow; V'I,max(FVC)) and the ratio between the largest inspiratory flow during tidal breathing (tidal inspiratory flow; V'I,max(t)) and the V'I,max(FVC).

Idebenone reduces respiratory complications in patients with Duchenne muscular dystrophy.

In Duchenne muscular dystrophy (DMD), progressive loss of respiratory function leads to restrictive pulmonary disease and places patients at significant risk for severe respiratory complications. Of particular concern are ineffective cough, secretion retention and recurrent respiratory tract infections. In a Phase 3 randomized controlled study (DMD Long-term Idebenone Study, DELOS) in DMD patients 10-18 years of age and not taking concomitant glucocorticoid steroids, idebenone (900 mg/day) reduced significantly the loss of respiratory function over a 1-year study period.

Differences in Contraction-Induced Hemodynamics and Surface EMG in Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is the most common and devastating type of muscular dystrophy worldwide. In this study we have investigated the potential of the combined use of non-invasive near-infrared spectroscopy (NIRS) and surface electromyography (sEMG) to assess contraction-induced changes in oxygenation and myoelectrical activity, respectively in the biceps brachii of eight DMD patients aged 9-12 years and 11 age-matched healthy controls. Muscle tissue oxygenation index (TOI), oxyhemoglobin (HbO2), and sEMG signals were continuously measured during a sustained submaximal contraction of 60% maximal voluntary isometric contraction, and post-exercise recovery period.

Efficacy of idebenone on respiratory function in patients with Duchenne muscular dystrophy not using glucocorticoids (DELOS): a double-blind randomised placebo-controlled phase 3 trial.

Background: Cardiorespiratory failure is the leading cause of death in Duchenne muscular dystrophy. Based on preclinical and phase 2 evidence, we assessed the efficacy and safety of idebenone in young patients with Duchenne muscular dystrophy who were not taking concomitant glucocorticoids.

Methods: In a multicentre phase 3 trial in Belgium, Germany, the Netherlands, Switzerland, France, Sweden, Austria, Italy, Spain, and the USA, patients (age 10-18 years old) with Duchenne muscular dystrophy were randomly assigned in a one-to-one ratio with a central interactive web response system with a permuted block design with four patients per block to receive idebenone (300 mg three times a day) or matching placebo orally for 52 weeks.

Investigating the genetic basis of fever-associated syndromic epilepsies using copy number variation analysis.

Fever-associated syndromic epilepsies ranging from febrile seizures plus (FS+) to Dravet syndrome have a significant genetic component. However, apart from SCN1A mutations in >80% of patients with Dravet syndrome, the genetic underpinnings of these epilepsies remain largely unknown. Therefore, we performed a genome-wide screening for copy number variations (CNVs) in 36 patients with SCN1A-negative fever-associated syndromic epilepsies.

Current treatment and management of dystrophinopathies.

• Duchenne muscular dystrophy (DMD), the most common and severe type of dystrophinopathy, is a progressive disease affecting primordially skeletal and cardiac muscle. A coordinated multidisciplinary approach is required to address its multisystemic manifestations and secondary problems.• Treatment with glucocorticosteroids (GCS) is accepted as standard of care in ambulant DMD.

The contribution of platelet studies to the understanding of disease mechanisms in complex and monogenetic neurological disorders.

Platelets, known for their role in primary haemostasis, prevent excessive bleeding after injury. The study of platelets has, therefore, traditionally focused on bleeding disorders. It has recently become evident, however, that platelet research can contribute to unravelling the disease mechanisms that underlie neuropathological disorders that have a subtle subclinical platelet phenotype.

Long-term outcome of intravesical oxybutynin in children with detrusor-sphincter dyssynergia: with special reference to age-dependent parameters.

Aims: Intravesical instillation of oxybutynin is an accepted and effective treatment in children with neuropathic bladder-sphincter dysfunction, when oral oxybutynin results in inadequate suppression of detrusor overactivity or intolerable side effects. However, as yet no data are available on long-term use and outcome.

Methods: A patient cohort with detrusor-sphincter dyssynergia that started oral oxybutynin between 1995 and 1997 was re-evaluated 15 ± 1 years after the switch from oral to intravesical (n = 10), with urodynamic investigations, renal ultrasounds, DMSA-scintigraphy, (51)Cr-EDTA-clearance, and validated questionnaires on incontinence and quality of life.