The mitochondrial DNA T16189C polymorphism and HIV-associated cardiomyopathy: a genotype-phenotype association study

<p>Abstract</p> <p>Background</p> <p>The mitochondrial DNA (mtDNA) T16189C polymorphism, with a homopolymeric C-tract of 10–12 cytosines, is a putative genetic risk factor for idiopathic dilated cardiomyopathy in the African and British populations. We hypothesized that this variant may predispose to dilated cardiomyopathy in people who are infected with the human immunodeficiency virus (HIV).</p> <p>Methods</p> <p>A case-control study of 30 HIV-positive cases with dilated cardiomyopathy and 37 HIV-positive controls without dilated cardiomyopathy was conducted. The study was confined to persons of black African ancestry to minimize confounding of results by population admixture. HIV-positive patients with an echocardiographically confirmed diagnosis of dilated cardiomyopathy and HIV-positive controls with echocardiographically normal hearts were studied. Patients with secondary causes of cardiomyopathy (such as hypertension, diabetes, pregnancy, alcoholism, valvular heart disease, and opportunistic infection) were excluded from the study. DNA samples were sequenced for the mtDNA T16189C polymorphism with a homopolymeric C-tract in the forward and reverse directions on an ABI3100 sequencer.</p> <p>Results</p> <p>The cases and controls were well matched for age (median 35 years versus 34 years, P = 0.93), gender (males 60% vs 53%, P = 0.54), and stage of HIV disease (mean CD4 T cell count 260.7/μL vs. 176/μL, P = 0.21). The mtDNA T16189C variant with a homopolymeric C-tract was detected at a frequency of 26.7% (8/30) in the HIV-associated cardiomyopathy cases and 13.5% (5/37) in the HIV-positive controls. There was no significant difference between cases and controls (Odds Ratio 2.33, 95% Confidence Interval 0.67–8.06, p = 0.11).</p> <p>Conclusion</p> <p>The mtDNA T16189C variant with a homopolymeric C-tract is not associated with dilated cardiomyopathy in black African people infected with HIV.</p

The impact of formative testing on study behaviour and study performance of (bio)medical students: a smartphone application intervention study.

BACKGROUND: Formative testing can increase knowledge retention but students often underuse available opportunities. Applying modern technology to make the formative tests more attractive for students could enhance the implementation of formative testing as a learning tool. This study aimed to determine whether formative testing using an internet-based application ("app") can positively affect study behaviour as well as study performance of (bio)medical students. METHODS: A formative testing app "Physiomics, to the next level" was introduced during a 4-week course to a large cohort (n = 461) of Dutch first year (bio)medical students of the Radboud University. The app invited students to complete 7 formative tests throughout the course. Each module was available for 3-4 days to stimulate the students to distribute their study activities throughout the 4-week course. RESULTS: 72% of the students used the app during the course. Study time significantly increased in intensive users (p < 0.001), while no changes were observed in moderate (p = 0.07) and non-users (p = 0.25). App-users obtained significantly higher grades during the final exam of the course (p < 0.05). Non-users more frequently failed their final exam (34%, OR 3.6, 95% CI: 2.0-6.4) compared to moderate users (19%) and intensive users (12%). Students with an average grade <6.5 during previous courses benefitted most from the app, as intensive (5.8 ± 0.9 / 36%) and moderate users (5.8 ± 0.9 / 33%) obtained higher grades and failed their exam less frequently compared to non-users (5.2 ± 1.1 / 61%). The app was also well appreciated by students; students scored the app with a grade of 7.3 ± 1.0 out of 10 and 59% of the students indicated that they would like the app to be implemented in future courses. CONCLUSIONS: A smartphone-based application of formative testing is an effective and attractive intervention to stimulate study behaviour and improve study performance in (bio) medical students

Essential role of the Na+-Ca2+ exchanger (NCX) in glutamate-enhanced cell survival in cardiac cells exposed to hypoxia/reoxygenation

Abstract Myocardial ischemia culminates in ATP production impairment, ionic derangement and cell death. The provision of metabolic substrates during reperfusion significantly increases heart tolerance to ischemia by improving mitochondrial performance. Under normoxia, glutamate contributes to myocardial energy balance as substrate for anaplerotic reactions, and we demonstrated that the Na+/Ca2+ exchanger1 (NCX1) provides functional support for both glutamate uptake and use for ATP synthesis. Here we investigated the role of NCX1 in the potential of glutamate to improve energy metabolism and survival of cardiac cells subjected to hypoxia/reoxygenation (H/R). Specifically, in H9c2-NCX1 myoblasts, ATP levels, mitochondrial activities and cell survival were significantly compromised after H/R challenge. Glutamate supplementation at the onset of the reoxygenation phase significantly promoted viability, improved mitochondrial functions and normalized the H/R-induced increase of NCX1 reverse-mode activity. The benefits of glutamate were strikingly lost in H9c2-WT (lacking NCX1 expression), or in H9c2-NCX1 and rat cardiomyocytes treated with either NCX or Excitatory Amino Acid Transporters (EAATs) blockers, suggesting that a functional interplay between these transporters is critically required for glutamate-induced protection. Collectively, these results revealed for the first time the key role of NCX1 for the beneficial effects of glutamate against H/R-induced cell injury