A mixed method study investigating the key translational competencies acquired during a challenge-based course.

Background: The translational domain is a complex subfield of the biomedical life sciences focused on bridging the gap between scientific research and clinical application, with the ultimate goal of improving patient care through healthcare innovations. Professionals in this field, ranging from researchers to clinicians and industry experts, require specific core competencies. These include communication, collaboration, boundary crossing, innovation, and the ability to integrate diverse scientific domains.

One size does not fit all: an exploratory interview study on how translational researchers navigate the current academic reward system.

Introduction: Translational research is a subfield of the biomedical life sciences that focuses on clinically driven healthcare innovations. The workforce of this subfield, i.e.

Plakophilin-2 Haploinsufficiency Causes Calcium Handling Deficits and Modulates the Cardiac Response Towards Stress.

Human variants in plakophilin-2 (PKP2) associate with most cases of familial arrhythmogenic cardiomyopathy (ACM). Recent studies show that PKP2 not only maintains intercellular coupling, but also regulates transcription of genes involved in Ca cycling and cardiac rhythm. ACM penetrance is low and it remains uncertain, which genetic and environmental modifiers are crucial for developing the cardiomyopathy.

Students generate items for an online formative assessment: Is it motivating?

Background: A reported problem with e-learning is sustaining students' motivation. We propose a framework explaining to what extent an e-learning task is motivating. This framework includes students' perceived Value of the task, Competence in executing the task, Autonomy over how to carry out the task, and Relatedness.

At the cross-point of connexins, calcium, and ATP: blocking hemichannels inhibits vasoconstriction of rat small mesenteric arteries.

Aims: Connexins form gap-junctions (GJs) that directly connect cells, thereby coordinating vascular cell function and controlling vessel diameter and blood flow. GJs are composed of two hemichannels contributed by each of the connecting cells. Hemichannels also exist as non-junctional channels that, when open, lead to the entry/loss of ions and the escape of ATP.

Peer-instructed seminar attendance is associated with improved preparation, deeper learning and higher exam scores: a survey study.

Background: Active engagement in education improves learning outcomes. To enhance active participation in seminars, a student-centered course design was implemented and evaluated in terms of self-reported preparation, student motivation and exam scores. We hypothesized that small group learning with intensive peer interaction, using buzz-groups followed by plenary discussion, would motivate students to prepare seminar assignments at home and to actively engage in the seminars.

Calmodulin/CaMKII inhibition improves intercellular communication and impulse propagation in the heart and is antiarrhythmic under conditions when fibrosis is absent.

Aim: In healthy hearts, ventricular gap junctions are mainly composed by connexin43 (Cx43) and localize in the intercalated disc, enabling appropriate electrical coupling. In diseased hearts, Cx43 is heterogeneously down-regulated, whereas activity of calmodulin/calcium-calmodulin protein kinase II (CaM/CaMKII) signalling increases. It is unclear if CaM/CaMKII affects Cx43 expression/localization or impulse propagation.

Spatial Heterogeneity of Cx43 is an Arrhythmogenic Substrate of Polymorphic Ventricular Tachycardias during Compensated Cardiac Hypertrophy in Rats.

Background: Ventricular remodeling increases the propensity of ventricular tachyarrhythmias and sudden death in patients. We studied the mechanism underlying these fatal arrhythmias, electrical and structural cardiac remodeling, as well as arrhythmogeneity during early, compensated hypertrophy in a rat model of chronic pressure overload.

Methods: Twenty-six Wistar rats were subjected to transverse aortic constriction (TAC) (n = 13) or sham operation (n = 13).

CTGF knockout does not affect cardiac hypertrophy and fibrosis formation upon chronic pressure overload.

Background: One of the main contributors to maladaptive cardiac remodeling is fibrosis. Connective tissue growth factor (CTGF), a matricellular protein that is secreted into the cardiac extracellular matrix by both cardiomyocytes and fibroblasts, is often associated with development of fibrosis. However, recent studies have questioned the role of CTGF as a pro-fibrotic factor.

Arrhythmogenic Remodeling in Murine Models of Deoxycorticosterone Acetate-Salt-Induced and 5/6-Subtotal Nephrectomy-Salt-Induced Cardiorenal Disease.

Background: Renal failure is associated with adverse cardiac remodeling and sudden cardiac death. The mechanism leading to enhanced arrhythmogenicity in the cardiorenal syndrome is unclear. The aim of this study was to characterize electrophysiological and tissue alterations correlated with enhanced arrhythmogenicity in two distinct mouse models of renal failure.

Passive ventricular remodeling in cardiac disease: focus on heterogeneity.

Passive ventricular remodeling is defined by the process of molecular ventricular adaptation to different forms of cardiac pathophysiology. It includes changes in tissue architecture, such as hypertrophy, fiber disarray, alterations in cell size and fibrosis. Besides that, it also includes molecular remodeling of gap junctions, especially those composed by Connexin43 proteins (Cx43) in the ventricles that affect cell-to-cell propagation of the electrical impulse, and changes in the sodium channels that modify excitability.

Ex vivo and in vivo administration of fluorescent CNA35 specifically marks cardiac fibrosis.

Cardiac fibrosis is a major hallmark of cardiac diseases. For evaluation of cardiac fibrosis, the development of highly specific and preferably noninvasive methods is desired. Our aim was to evaluate CNA35, a protein known to specifically bind to collagen, as a specific marker of cardiac fibrosis.

Changes in Cx43 and NaV1.5 expression precede the occurrence of substantial fibrosis in calcineurin-induced murine cardiac hypertrophy.

In mice, the calcium-dependent phosphatase calcineurin A (CnA) induces a transcriptional pathway leading to pathological cardiac hypertrophy. Interestingly, induction of CnA has been frequently noticed in human hypertrophic and failing hearts. Independently, the arrhythmia vulnerability of such hearts has been regularly associated with remodeling of parameters determining electrical conduction (expression level of connexin43 (Cx43) and NaV1.

Students' motives for using online formative assessments when preparing for summative assessments.

Background: Formative assessments intend to provide feedback on student performance in order to improve and accelerate learning. Several studies have indicated that students using online formative assessments (OFAs), have better results on their exams.

Aims: The present study aims to provide insight in student reasons for using or not using available OFAs.

Online formative tests linked to microlectures improving academic achievement.

Background: Online formative tests (OFTs) are powerful tools to direct student learning behavior, especially when enriched with specific feedback.

Aim: In the present study, we have investigated the effect of OFTs enriched with hyperlinks to microlectures on examination scores.

Methods: OFTs, available one week preceding each midterm and the final exams, could be used voluntarily.

Reduced plakoglobin immunoreactivity in arrhythmogenic cardiomyopathy: methodological considerations.

Background: Arrhythmogenic cardiomyopathy (AC) primarily is considered to be a desmosomal disease with a predominant right ventricular phenotype. Reduced signal intensity for junctional plakoglobin (JUP) at the intercalated disks has been proposed as a marker that contributes to diagnosis of the disease. In this technical study, we investigated how methodology-related differences caused by tissue preservation and antibody dilutions affect an appropriate diagnosis.

Remodeling of the cardiac sodium channel, connexin43, and plakoglobin at the intercalated disk in patients with arrhythmogenic cardiomyopathy.

Background: Arrhythmogenic cardiomyopathy (AC) is closely associated with desmosomal mutations in a majority of patients. Arrhythmogenesis in patients with AC is likely related to remodeling of cardiac gap junctions and increased levels of fibrosis. Recently, using experimental models, we also identified sodium channel dysfunction secondary to desmosomal dysfunction.

Reduced connexin40 protein expression in the right atrial appendage of patients bearing the minor connexin40 allele (-44 G --> A).

Aims: The occurrence of connexin40 (Cx40) minor polymorphism (-44 G → A) was increased in patients with idiopathic atrial fibrillation (AF), although its effect on atrial Cx40 protein expression is unknown. We aimed to evaluate whether alterations in Cx40 are directly linked to the development of AF, we studied the effect of this polymorphism on Cx40 expression and distribution in patients without any history of AF and in patients who developed post-operative AF.

Methods And Results: Hundred and eight patients (mean age 67 ± 9 years), without a history of AF or conditions that predispose to AF, were included.

Reduced Cx43 expression triggers increased fibrosis due to enhanced fibroblast activity.

Background: Arrhythmogenic ventricular remodeling is hallmarked by both reduced gap junction expression and increased collagen deposition. We hypothesized that reduced connexin43 (Cx43) expression is responsible for enhanced fibrosis in the remodeled heart, resulting in an arrhythmogenic substrate. Therefore, we investigated the effect of normal or reduced Cx43 expression on the formation of fibrosis in a physiological (aging) and pathophysiological (transverse aortic constriction [TAC]) mouse model.

Functional consequences of abnormal Cx43 expression in the heart.

The major gap junction protein expressed in the heart, connexin43 (Cx43), is highly remodeled in the diseased heart. Usually, Cx43 is down-regulated and heterogeneously redistributed to the lateral sides of cardiomyocytes. Reverse remodeling of the impaired Cx43 expression could restore normal cardiac function and normalize electrical stability.

A 50% reduction of excitability but not of intercellular coupling affects conduction velocity restitution and activation delay in the mouse heart.

Introduction: Computer simulations suggest that intercellular coupling is more robust than membrane excitability with regard to changes in and safety of conduction. Clinical studies indicate that SCN5A (excitability) and/or Connexin43 (Cx43, intercellular coupling) expression in heart disease is reduced by approximately 50%. In this retrospective study we assessed the effect of reduced membrane excitability or intercellular coupling on conduction in mouse models of reduced excitability or intercellular coupling.

Drug-induced torsade de pointes arrhythmias in the chronic AV block dog are perpetuated by focal activity.

Background: The electrically remodeled canine heart after chronic AV block (CAVB) has a high susceptibility for drug-induced torsade de pointes (TdP) arrhythmias. Although focal mechanisms have been considered for initiation, there is still controversy about whether reentry is the dominant mechanism for perpetuation of TdP. In this animal model with known nonuniform prolongation of repolarization, the mechanism of perpetuation of TdP arrhythmia was explored.

Biomarkers of myocardial fibrosis.

Increased cardiac collagen deposition is observed in almost every cardiac disease and plays an important role in the deteriorating function of the diseased heart. Propeptides of procollagen types I and III, the 2 major collagen types in the heart, can be detected in circulation. Although these propeptides reflect collagen synthesis, also breakdown products of collagen and the matrix metalloproteinases, responsible for the breakdown of the extracellular matrix, can be detected in blood and are used for investigating the turnover of collagen.