Pathophysiological Mechanisms of Premature Ventricular Complexes

Premature ventricular complexes (PVCs) are the most common ventricular arrhythmia. Despite the high prevalence, the cause of PVCs remains elusive in most patients. A better understanding of the underlying pathophysiological mechanism may help to steer future research. This review aims to provide an overview of the potential pathophysiological mechanisms of PVCs and their differentiation

Effects of Key2Teach on students' externalising and social-emotional problem behaviours, mediated by the teacher-student relationship

Teaching students with externalising problem behaviours is difficult for teachers, as it challenges the relationship that teachers engage in with their students. In this study, effects of Key2Teach on externalising and social-emotional problem behaviours and the mediating role of conflict in the teacher-student relationship were studied using a randomised controlled trial (RCT)-design. In two cohorts, 103 teacher-student dyads and peer-students (n = 1643) were assessed two times during a school year. Fifty-three dyads received the intervention (experimental group), whereas 50 dyads received no intervention (control group). Data were collected on teacher-reported externalising and social-emotional problem behaviours in students, and on teacher-student conflict. For dyad-students, results showed a direct effect of Key2Teach on conduct problems and an indirect effect, via teacher-student conflict, for hyperactivity problems. No effects on social-emotional problems were established. For peer-students, results showed indirect effects on externalising problems and direct effects on social-emotional problems. Implications for practice and future research are discussed

The impact of teacher's self-efficacy and classroom externalising problem behaviors on emotional exhaustion:Between- and within-person associations

Teaching can be a challenging profession, which puts teachers at high risk for developing burnout symptoms, such as emotional exhaustion. In this study we aim to investigate the interplay between classroom externalising problem behaviours (as a job demand), teachers’ self-efficacy (as a job resource) and emotional exhaustion over a school year. Conducting three measurements during a school year among 103 Dutch primary education teachers, we examine the sensitivity for, and the individual development of, emotional exhaustion. Findings show that emotional exhaustion, classroom externalising problem behaviours, and teachers’ self-efficacy are stable constructs in teachers. Traditional (between-person) cross-lagged panel models indicate that teachers with low levels of self-efficacy are more likely to develop emotional exhaustion during the school year, compared to their colleagues. We found no evidence that teachers confronted with classroom externalising problem behaviours were more likely to develop emotional exhaustion. Random intercept (within-person) cross-lagged panel models indicate that teachers with high levels of classroom externalising problem behaviours do not show increased emotional exhaustion at a later time point. For self-efficacy and emotional exhaustion, we could not estimate the within-person model due to limited variance in the variables. Implications of these findings and suggestions for further research were discussed

Effect of Key2Teach on Dutch teachers' relationships with students with externalizing problem behavior:A randomized controlled trial

The teacher-student relationship plays an important role in the academic and behavioral development of primary school children with externalizing problem behavior. However, such problem behavior often threatens the quality of the teacher-student relationship. Teacher-focused coaching intervention Key2Teach aims to improve elements of the relationship between teachers and students with externalizing problem behavior and consists of two phases and four building blocks. This intervention provides primary school teachers with insight into their mental representation of the relationship and opportunities to practice functional interaction skills. In a randomized controlled trial (RCT), effects of Key2Teach on different aspects of the relationship between teachers and students with externalizing problem behavior were examined. In two cohorts, 103 dyads consisting of a teacher and a student with externalizing problem behavior in grades 3-6 were assessed three times during a school year. Fifty-three dyads received the intervention (intervention group), whereas 50 dyads received no intervention (control group). Data were collected on teacher-reported teacher-student closeness and conflict, and on teacher interaction skills in various domains. Results show a significant increase in closeness and a decrease in conflict as a result of Key2Teach, with substantial effect sizes. No effects on teacher interaction skills were found. This study indicates that Key2Teach may help teachers to improve elements of the relationship they have with students with externalizing problem behavior. Implications for practice and future research are discussed

Childrearing style of anxiety-disordered parents

FSW - Self-regulation models for health behavior and Psychopathology - Ou

Resequencing three candidate genes for major depressive disorder in a Dutch cohort

Major depressive disorder (MDD) is a psychiatric disorder, characterized by periods of low mood of more than two weeks, loss of interest in normally enjoyable activities and behavioral changes. MDD is a complex disorder and does not have a single genetic cause. In 2009 a genome wide association study (GWAS) was performed on the Dutch GAIN-MDD cohort. Many of the top signals of this GWAS mapped to a region spanning the gene PCLO, and the non-synonymous coding single nucleotide polymorphism (SNP) rs2522833 in the PCLO gene became genome wide significant after post-hoc analysis. We performed resequencing of PCLO, GRM7, and SLC6A4 in 50 control samples from the GAIN-MDD cohort, to detect new genomic variants. Subsequently, we genotyped these variants in the entire GAIN-MDD cohort and performed association analysis to investigate if rs2522833 is the causal variant or simply in linkage disequilibrium with a more associated variant. GRM7 and SLC6A4 are both candidate genes for MDD from literature. We aimed to gather more evidence that rs2522833 is indeed the causal variant in the GAIN-MDD cohort or to find a previously undetected common variant in either PCLO, GRM7, or SLC6A4 with a higher association in this cohort. After next generation sequencing and association analysis we excluded the possibility of an undetected common variant to be more associated. For neither PCLO nor GRM7 we found a more associated variant. For SLC6A4, we found a new SNP that showed a lower P-value (P = 0.07) than in the GAIN-MDD GWAS (P = 0.09). However, no evidence for genome-wide significance was found. Although we did not take into account rare variants, we conclude that our results provide further support for the hypothesis that the non-synonymous coding SNP rs2522833 in the PCLO gene is indeed likely to be the causal variant in the GAIN-MDD cohort

The importance of engaging in physical activity in older adulthood for transitions between cognitive status categories and death: A coordinated analysis of 14 longitudinal studies

Background: Given increasing incidence of cognitive impairment and dementia, further understanding of modifiable factors contributing to increased healthspan is crucial. Extensive literature provides evidence that physical activity (PA) delays the onset of cognitive impairment; however, it is unclear whether engaging in PA in older adulthood is sufficient to influence progression through cognitive status categories. Method: Applying a coordinated analysis approach, this project independently analyzed 14 longitudinal studies (NTotal = 52 039; mean baseline age across studies = 69.9-81.73) from North America and Europe using multistate survival models to estimate the impact of engaging in PA on cognitive status transitions (nonimpaired, mildly impaired, severely impaired) and death. Multinomial regression models were fit to estimate life expectancy (LE) based on American PA recommendations. Meta-analyses provided the pooled effect sizes for the role of PA on each transition and estimated LEs. Results: Controlling for baseline age, sex, education, and chronic conditions, analyses revealed that more PA is significantly associated with decreased risk of transitioning from nonimpaired to mildly impaired cognitive functioning and death, as well as substantially longer LE. Results also provided evidence for a protective effect of PA after onset of cognitive impairment (eg, decreased risk of transitioning from mild-to-severe cognitive impairment; increased likelihood of transitioning backward from severe-to-mild cognitive impairment), though between-study heterogeneity suggests a less robust association. Conclusions: These results yield evidence for the importance of engaging in PA in older adulthood for cognitive health, and a rationale for motivating older adults to engage consistently in PA

Variant mapping using mass spectrometry–based proteotyping as a diagnostic tool in von Willebrand disease

Background: von Willebrand disease (VWD) is the most common inherited bleeding disorder, characterized by either partial or complete von Willebrand factor (VWF) deficiency or by the occurrence of VWF proteoforms of altered functionality. The gene encoding VWF is highly polymorphic, giving rise to a variety of proteoforms with varying plasma concentrations and clinical significance. Objectives: To address this complexity, we translated genomic variation in VWF to corresponding VWF proteoforms circulating in blood. Methods: VWF was characterized in VWD patients (n = 64) participating in the Willebrand in the Netherlands study by conventional laboratory testing, DNA sequencing and complementary discovery, and targeted mass spectrometry–based plasma proteomic strategies. Results: Unbiased plasma profiling combined with immune enrichment of VWF verified VWF and its binding partner factor VIII as key determinants of VWD and revealed a remarkable heterogeneity in VWF amino acid sequence coverage among patients. Subsequent VWF proteotyping enabled identification of both polymorphisms (eg, p.Thr789Ala, p.Gln852Arg, and p.Thr1381Ala), as well as pathogenic variants (n = 16) along with their corresponding canonical sequences. Targeted proteomics using stable isotope–labeled peptides confirmed unbiased proteotyping for 5 selected variants and suggested differential proteoform quantities in plasma. The variant-to-wild-type peptide ratio was determined in 6 type 2B patients heterozygous for p.Arg1306Trp, confirming the relatively low proteoform concentration of the pathogenic variant. The elevated VWF propeptide/VWF ratio indicated increased clearance of specific VWF proteoforms. Conclusion: This study highlights how VWF proteotyping from plasma could be the first step to bridge the gap between genotyping and functional testing in VWD.</p