Genotype-phenotype correlation in CLCN4-related developmental and epileptic encephalopathy.

CLCN4-related disorder is a rare X-linked neurodevelopmental condition with a pathogenic mechanism yet to be elucidated. CLCN4 encodes the vesicular 2Cl/H exchanger ClC-4, and CLCN4 pathogenic variants frequently result in altered ClC-4 transport activity. The precise cellular and molecular function of ClC-4 remains unknown; however, together with ClC-3, ClC-4 is thought to have a role in the ion homeostasis of endosomes and intracellular trafficking.

Investigating the research capacity and productivity of Canadian sports chiropractors.

Objectives: To investigate the research capacity and productivity of Canadian sports chiropractors.

Methods: A cross-sectional survey (phase one) and scoping review (phase two) investigated the research capacity and productivity (from 2015-2020) of the Canadian sports chiropractic field.

Results: Most respondents (72%) reported obtaining research training from fellowship and master's programs, with only 2 (1%) PhD qualifications identified.

Longitudinal Characterization of the Clinical Course of Intermediate-Severe Salla Disease.

Background: Biallelic pathogenic variants in SLC17A5 cause three forms of free sialic acid storage disease categorized based on severity from least to most severe: Salla disease, intermediate-severe Salla disease, and infantile free sialic acid storage disease. Intermediate-severe Salla disease is the most recently described form. Here, we report a longitudinal characterization of intermediate-severe Salla disease progression in two sisters carrying the following biallelic variants in SLC17A5: c.

The Experience of Parents of Children With Genetically Determined Leukoencephalopathies With the Health Care System: A Qualitative Study.

Parents of children with genetically determined leukoencephalopathies play a major role in their children's health care. We sought to gain a better understanding of their experience with the public health care system in Quebec, Canada, to obtain suggestions for improving their services, and to identify modifiable factors to improve their quality of life. We conducted interviews with 13 parents.

Hidden in the photograph: The myth of complete metabolic coverage possible in metabolomics investigations.

Since the late 1970s, many 'omics-style investigations have advanced our understanding of systems at all levels, from community level, through organismal, to individual cellular processes. Beginning with genomics and progressing through transcriptomics, proteomics and finally to metabolomics, the scope of interest shifts significantly from what is genetically possible to what is currently expressed, produced and measurable in a system. While the ideal goal of any 'omics investigation is to fully describe a system, loss of information occurs at each decision-making juncture.

MyLynch: A Patient-Facing Clinical Decision Support Tool for Genetically-Guided Personalized Medicine in Lynch Syndrome.

Lynch syndrome (LS) is a hereditary cancer susceptibility condition associated with varying cancer risks depending on which of the five causative genes harbors a pathogenic variant; however, lifestyle and medical interventions provide options to lower those risks. We developed MyLynch, a patient-facing clinical decision support (CDS) web application that applies genetically-guided personalized medicine (GPM) for individuals with LS. The tool was developed in R Shiny through a patient-focused iterative design process.

Randomized placebo-controlled crossover trial of memantine in children with epileptic encephalopathy.

Memantine is an N-methyl-D-aspartate receptor antagonist, approved for dementia treatment. There is limited evidence of memantine showing benefit for paediatric neurodevelopmental phenotypes, but no randomized placebo-controlled trials in children with developmental and epileptic encephalopathy. In this randomized double-blind placebo-controlled crossover trial (Trial registration: https://clinicaltrials.

Spontaneous Resolution of Drug-Resistant Epilepsy in Patients with Sturge-Weber Syndrome.

Sturge-Weber syndrome (SWS) is often associated with drug resistant epilepsy. The literature is unclear as to how often these patients can be weaned off of antiepileptic drugs (AEDs) to become seizure-free. We describe two patients with SWS.

Experience of Parents of Children with Genetically Determined Leukoencephalopathies Regarding the Adapted Health Care Services During the COVID-19 Pandemic.

Parents of children with genetically determined leukoencephalopathies play a major role in their children's health care. Because of the COVID-19 pandemic, many health care services were suspended, delayed or delivered remotely with telemedicine. We sought to explore the experience of parents of children with genetically determined leukoencephalopathies during the pandemic given the adapted health care services.

Hirayama Disease in a Patient with a History of Late-Onset Symptomatic Vein of Galen Aneurysmal Malformation.

Introduction: The purpose of this report is to present a rare case of Hirayama disease (HD) in a patient with a history of late-onset symptomatic vein of Galen aneurysmal malformation (VGAM). This report may provide new insights into the pathophysiology of HD, a rare disorder consisting of insidious onset of unilateral weakness and atrophy of the forearm and intrinsic hand muscles. These symptoms are believed to result from cervical myelopathy affecting the anterior horn cells due to abnormal compressive forces on the spinal cord from adjacent anatomical structures (i.

A Novel Variant in Causes Spinal Muscular Atrophy Lower Extremity Predominant in Identical Twins: A Case Report.

Mutations in have been shown to cause spinal muscular atrophy lower extremity predominant type 1 (SMALED1), an autosomal dominant genetic neuromuscular disorder characterized by degeneration of spinal cord motor neurons resulting in muscle weakness. Here, we describe monozygotic twins, one with a more severe upper motor neuron phenotype as a result of a suspected perinatal hypoxic-ischemic event and the other presenting a typical lower motor neuron phenotype. Using exome sequencing, we identified the novel variant c.

Preliminary evidence for timing abnormalities in the CNTNAP2 knockout rat.

The CNTNAP2 gene has been implicated in several neuropsychological disorders, including autism spectrum disorder (ASD) and schizophrenia. The CNTNAP2 knockout (KO) rat model, rats without the CNTNAP2 gene, exhibits deficits in social interaction and increases in both repetitive and anxiety-like behaviors. However, deficits in time perception that may underlie several of the neuropsychological disorders implicated have not been investigated.

A retrospective analysis of memantine use in a pediatric neurology clinic.

Background: Memantine is an N-methyl-D-aspartate receptor (NMDA-R) antagonist, approved for dementia, but also studied in pediatric autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD).

Methods: We reviewed children treated with memantine in a single-centre pediatric neurology clinic. Clinical data extracted included age, sex, weight, clinical history, reason for memantine prescription, period of treatment trial and dosage, treatment response, side effects, and concomitant medications.

Integration of In Situ Simulation Into an Emergency Department Code Orange Exercise in a Tertiary Care Trauma Referral Center.

Objectives: Disaster-preparedness and response are a commonly overlooked aspect of hospital policy and can frequently be outdated and undertested. Simulation-based education has become a core education modality within Canadian medical training programs. We hypothesized that integrating in situ simulation (ISS) into a hospital-wide, mass-casualty response exercise would enhance realism and our ability to identify latent safety threats (LSTs).

Handgrip Strength in People With Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

Objective: The purpose of this study was to systematically review the association between handgrip strength (HGS) and mortality, morbidity, and health-related quality of life (HRQL) in individuals with chronic obstructive pulmonary disease (COPD).

Methods: The following databases were used: CENTRAL, CINAHL, EMBASE, MEDLINE Ovid, SPORTDiscus, and PsycINFO. Studies published between 2000 and 2020 in English, Portuguese, or French that examined the association of HGS with mortality, morbidity, and HRQL in individuals with stable COPD were selected.

'We're Not Doing It To Be Nasty': Caregivers' Ethical Dilemmas in Negotiating Driving Safety with Older Adults.

The purpose of this research was to investigate how informal caregivers of older adults cope with and negotiate driving safety when their loved one is no longer safe to drive. Fifteen informal caregivers of an older adult living at home took part in the present study. Participants cared for individuals with a range of health conditions that significantly impaired driving safety, including dementia, Parkinson's disease, macular degeneration, and stroke.

What Environmental Factors Influence the Concentration of Fecal Indicator Bacteria in Groundwater? Insights from Explanatory Modeling in Uganda and Bangladesh.

Information about microbial water quality is critical for managing water safety and protecting public health. In low-income countries, monitoring all drinking water supplies is impractical because financial resources and capacity are insufficient. Data sets derived from satellite imagery, census, and hydrological models provide an opportunity to examine relationships between a suite of environmental risk factors and microbial water quality over large geographical scales.

The Canadian Neuromuscular Disease Registry 2010-2019: A Decade of Facilitating Clinical Research Througha Nationwide, Pan-NeuromuscularDisease Registry.

We report the recruitment activities and outcomes of a multi-disease neuromuscular patient registry in Canada. The Canadian Neuromuscular Disease Registry (CNDR) registers individuals across Canada with a confirmed diagnosis of a neuromuscular disease. Diagnosis and contact information are collected across all diseases and detailed prospective data is collected for 5 specific diseases: Amyotrophic Lateral Sclerosis (ALS), Duchenne Muscular Dystrophy (DMD), Myotonic Dystrophy (DM), Limb Girdle Muscular Dystrophy (LGMD), and Spinal Muscular Atrophy (SMA).

Stress Testing the Resuscitation Room: Latent Threats to Patient Safety Identified During Interprofessional In Situ Simulation in a Canadian Academic Emergency Department.

Objectives: Emergency department (ED) resuscitation is a complex, high-stakes procedure where positive outcomes depend on effective interactions between the health care team, the patient, and the environment. Resuscitation teams work in dynamic environments and strive to ensure the timely delivery of necessary treatments, equipment, and skill sets when required. However, systemic failures in this environment cannot always be adequately anticipated, which exposes patients to opportunities for harm.

A National Spinal Muscular Atrophy Registry for Real-World Evidence.

Background: Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype.

Selective Dorsal Root Rhizotomy for Spastic Cerebral Palsy: A Longitudinal Case-Control Analysis of Functional Outcome.

Background: The benefit of selective dorsal rhizotomies (SDR) on motor function relative to the cerebral palsy (CP) natural history remains unknown.

Objective: To determine the functional benefit of SDR over the longitudinal CP natural history.

Methods: Retrospective, single-center, case-control study of patients post-SDR after 1990.