Despite recent advances in the management of urothelial cancer (UC), cisplatin-based combination chemotherapy regimens remain critical. However, their use can be complicated in patients with chronic kidney disease (CKD), which is not uncommon in UC patients. Based on the Galsky criteria for cisplatin ineligibility, most patients with CKD will be excluded from receiving cisplatin-based chemotherapy altogether.
View Article and Find Full Text PDFObjectives: We used quality improvement methods to implement a care bundle for children presenting to a pediatric emergency department (ED) with mental health concerns. A bundle novelty was that it included an option for assessment in a partnered clinic, not in the ED, to families of children assessed as having no medical or safety concerns. The primary aim of this study was to establish successful implementation of the bundle prior to studying its impact.
View Article and Find Full Text PDFBackground: Pathogenic variants in , the gene encoding the cardiac Na+ channel α-subunit Nav1.5, result in life-threatening arrhythmias, e.g.
View Article and Find Full Text PDFBackground: Pathways to mental health services for youth are generally complex and often involve numerous contact points and lengthy delays. When starting treatment, there are a host of barriers that contribute to low rates of therapeutic engagement. Automated text messages offer a convenient, low-cost option for information sharing and skill building, and they can potentially activate positive behaviors in youth and caregivers prior to beginning formal therapy.
View Article and Find Full Text PDFCirc Arrhythm Electrophysiol
March 2022
Background: CaM (calmodulin), encoded by 3 separate genes (, , and ), is a multifunctional Ca-binding protein involved in many signal transduction events including ion channel regulation. CaM variants may present with early-onset long QT syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia, or sudden cardiac death. Most reported variants occurred de novo.
View Article and Find Full Text PDFUnlabelled: Loss-of-function mutations in the cardiac Na channel α-subunit Na1.5, encoded by , cause Brugada syndrome (BrS), a hereditary disease characterized by sudden cardiac death due to ventricular fibrillation. We previously evidenced the dominant-negative effect of the BrS Na1.
View Article and Find Full Text PDFIntroduction: Children and youth with mental health and addiction crises are a vulnerable patient group that often are brought to the hospital for emergency department care. We propose to evaluate the effect of a novel, acute care bundle that standardises a patient-centred approach to care.
Methods And Analysis: Two paediatric emergency departments in Alberta, Canada are involved in this prospective, pragmatic, 29-month interventional quasi-experimental study.
Ion channel trafficking powerfully influences cardiac electrical activity as it regulates the number of available channels at the plasma membrane. Studies have largely focused on identifying the molecular determinants of the trafficking of the atria-specific K1.5 channel, the molecular basis of the ultra-rapid delayed rectifier current I.
View Article and Find Full Text PDFBackground: Membrane-associated guanylate kinase proteins function as adaptor proteins to mediate the recruitment and scaffolding of ion channels in the plasma membrane in various cell types. In the heart, the protein calcium/calmodulin-dependent serine protein kinase (CASK) negatively regulates the main cardiac sodium channel Na1.5, which carries the sodium current (I) by preventing its anterograde trafficking.
View Article and Find Full Text PDFJ Can Acad Child Adolesc Psychiatry
August 2018
Objective: To examine sleep-related issues in children and adolescents presenting at community clinics with diverse mental health concerns using a brief sleep questionnaire and to examine whether sleep issues would improve with mental health interventions.
Method: Study 1: A questionnaire-based study that used a modified version of the Pittsburgh Sleep Quality Index to measure sleep-related issues in youth aged 4-18 years presenting at community mental health clinics. Study 2: A pre/post-treatment study that used the same questionnaire to measure changes in sleep-related issues in youth aged 4-19 years participating in a group mental health intervention.
Rationale: Mechanisms underlying membrane protein localization are crucial in the proper function of cardiac myocytes. The main cardiac sodium channel, NaV1.5, carries the sodium current (INa) that provides a rapid depolarizing current during the upstroke of the action potential.
View Article and Find Full Text PDFMyotonic dystrophy type 1 (DM1) is the most common neuromuscular disorder and is associated with cardiac conduction defects. However, the mechanisms of cardiac arrhythmias in DM1 are unknown. We tested the hypothesis that abnormalities in the cardiac sodium current (INa) are involved, and used a transgenic mouse model reproducing the expression of triplet expansion observed in DM1 (DMSXL mouse).
View Article and Find Full Text PDFBackground: Mutations in the SCN5A gene, encoding the α subunit of the cardiac Na(+) channel, Nav1.5, can result in several life-threatening arrhythmias.
Objective: To characterize a distal truncating SCN5A mutation, R1860Gfs*12, identified in a family with different phenotypes including sick sinus syndrome, atrial fibrillation (AF), atrial flutter, and atrioventricular block.
Atrial myocytes are continuously exposed to mechanical forces including shear stress. However, in atrial myocytes, the effects of shear stress are poorly understood, particularly with respect to its effect on ion channel function. Here, we report that shear stress activated a large outward current from rat atrial myocytes, with a parallel decrease in action potential duration.
View Article and Find Full Text PDFCardiac myocytes are characterized by distinct structural and functional entities involved in the generation and transmission of the action potential and the excitation-contraction coupling process. Key to their function is the specific organization of ion channels and transporters to and within distinct membrane domains, which supports the anisotropic propagation of the depolarization wave. This review addresses the current knowledge on the molecular actors regulating the distinct trafficking and targeting mechanisms of ion channels in the highly polarized cardiac myocyte.
View Article and Find Full Text PDFAims: Brugada syndrome (BrS) is an autosomal-inherited cardiac arrhythmia characterized by an ST-segment elevation in the right precordial leads of the electrocardiogram and an increased risk of syncope and sudden death. SCN5A, encoding the cardiac sodium channel Na(v)1.5, is the main gene involved in BrS.
View Article and Find Full Text PDFBackground: Brugada syndrome (BrS) is caused mainly by mutations in the SCN5A gene, which encodes the α-subunit of the cardiac sodium channel Na(v)1.5. However, ≈ 20% of probands have SCN5A mutations, suggesting the implication of other genes.
View Article and Find Full Text PDFBackground: Survival data of malignant rhabdoid tumour of the kidney (MRTK) registered in SIOP trials, advocating preoperative chemotherapy, are not available.
Aim: To evaluate characteristics, response and survival of MRTK patients registered in recent SIOP protocols.
Methods: An evaluation of all MRTK patients treated from 1993 to 2005 (SIOP trials 93-01 and 2001) was performed.
Rationale: The cardiac sodium channel Na(v)1.5 plays a key role in excitability and conduction. The 3 last residues of Na(v)1.
View Article and Find Full Text PDFThe electrical properties of the atria and ventricles differ in several aspects reflecting the distinct role of the atria in cardiac physiology. The study of atrial electrophysiology had greatly contributed to the understanding of the mechanisms of atrial fibrillation (AF). Only the atrial L-type calcium current is regulated by serotonine or, under basal condition, by phosphodiesterases.
View Article and Find Full Text PDFCholesterol is an important determinant of cardiac electrical properties. However, underlying mechanisms are still poorly understood. Here, we examine the hypothesis that cholesterol modulates the turnover of voltage-gated potassium channels based on previous observations showing that depletion of membrane cholesterol increases the atrial repolarizing current I(Kur).
View Article and Find Full Text PDFMembrane-associated guanylate kinase (MAGUK) proteins are major determinants of the organization of ion channels in the plasma membrane in various cell types. Here, we investigated the interaction between the MAGUK protein SAP97 and cardiac Kv4.2/3 channels, which account for a large part of the outward potassium current, I(to), in heart.
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