Haemodynamic consequences of targeted single- and dual-site right ventricular pacing in adults with congenital heart disease undergoing surgical pulmonary valve replacement

Aims The purpose of this study was to create an epicardial electroanatomic map of the right ventricle (RV) and then apply post-operative-targeted single- and dual-site RV temporary pacing with measurement of haemodynamic parameters. Cardiac resynchronization therapy is an established treatment for symptomatic left ventricular (LV) dysfunction. In congenital heart disease, RV dysfunction is a common cause of morbidity—little is known regarding the potential benefits of CRT in this setting. Methods and results Sixteen adults (age = 32 ± 8 years; 6 M, 10 F) with right bundle branch block (RBBB) and repaired tetralogy of Fallot (n = 8) or corrected congenital pulmonary stenosis (n = 8) undergoing surgical pulmonary valve replacement (PVR) for pulmonary regurgitation underwent epicardial RV mapping and haemodynamic assessment of random pacing configurations including the site of latest RV activation. The pre-operative pulmonary regurgitant fraction was 49 ± 10%; mean LV end-diastolic volume (EDV) 85 ± 19 mL/min/m2 and RVEDV 183 ± 89 mL/min/m2 on cardiac magnetic resonance imaging. The mean pre-operative QRS duration is 136 ± 26 ms. The commonest site of latest activation was the RV free wall and DDD pacing here alone or combined with RV apical pacing resulted in significant increases in cardiac output (CO) vs. AAI pacing (P < 0.01 all measures). DDDRV alternative site pacing significantly improved CO by 16% vs. AAI (P = 0.018), and 8.5% vs. DDDRV apical pacing (P = 0.02). Conclusion Single-site RV pacing targeted to the region of latest activation in patients with RBBB undergoing PVR induces acute improvements in haemodynamics and supports the concept of ‘RV CRT’. Targeted pacing in such patients has therapeutic potential both post-operatively and in the long term

Knockdown of ZNF268, which Is Transcriptionally Downregulated by GATA-1, Promotes Proliferation of K562 Cells

The human ZNF268 gene encodes a typical KRAB-C2H2 zinc finger protein that may participate in hematopoiesis and leukemogenesis. A recent microarray study revealed that ZNF268 expression continuously decreases during erythropoiesis. However, the molecular mechanisms underlying regulation of ZNF268 during hematopoiesis are not well understood. Here we found that GATA-1, a master regulator of erythropoiesis, repressed the promoter activity and transcription of ZNF268. Electrophoretic mobility shift assays and chromatin immunoprecipitation assays showed that GATA-1 directly bound to a GATA binding site in the ZNF268 promoter in vitro and in vivo. Knockdown of ZNF268 in K562 erythroleukemia cells with specific siRNA accelerated cellular proliferation, suppressed apoptosis, and reduced expression of erythroid-specific developmental markers. It also promoted growth of subcutaneous K562-derived tumors in nude mice. These results suggest that ZNF268 is a crucial downstream target and effector of GATA-1. They also suggest the downregulation of ZNF268 by GATA-1 is important in promoting the growth and suppressing the differentiation of K562 erythroleukemia cells

Effects of perceptions of information overload, noise and environmental demands on wellbeing and academic attainment.

The present research considers components of information overload, which may have a negative impact on wellbeing and academic attainment. 179 university students completed a survey consisting of an information overload scale (IOS) and the wellbeing process questionnaire. Their academic attainment scores were also added to the database. The IOS scale also included questions relating to noise exposure. Both the noise scores and non-noise IOS scores were associated with greater negative wellbeing and lower positive wellbeing. There were no significant effects of noise or IOS scores on academic attainment. Wellbeing is predicted by a number of factors such as exposure to stressors, negative coping, social support and psychological capital. When these established factors were included in the analyses, the effects of noise and other aspects of IOS could be accounted for by exposure to other stressors and were no longer significant predictors of negative or positive wellbeing

Direct Binding of pRb/E2F-2 to GATA-1 Regulates Maturation and Terminal Cell Division during Erythropoiesis

Cell differentiation is often coupled with cell cycle arrest. Here, we show that direct binding of the erythroid transcription factor GATA-1 to the retinoblastoma protein and the pRb/E2F transcription factor complex is critical for red blood cell formation

Associations between job demands, perceptions of noise at work and the psychological contract

Despite the widespread interest in the effects of workload on behaviour, there has been little research on the effects of it on attitudes and values in the workplace and life generally. The aim of the present research was to examine associations between noise exposure (which increases workload) and components of the psychological contract (fairness; trust; organisational commitment; work satisfaction; motivation; organisational citizenship; and intention to stay/quit). 166 workers completed a survey measuring components of the psychological contract, perceptions of noise exposure and other job characteristics. Univariate analyses showed that higher noise exposure was associated with a more negative psychological contract. However, adjustment for other job characteristics, both negative (e.g. job demands) and positive (e.g. control and support), removed the significant effects of noise. These results confirm previous research suggesting that psychosocial stressors have greater behavioural effects than components of the physical working environment such as noise

On the Mental Workload Assessment of Uplift Mapping Representations in Linked Data

Self-reporting procedures have been largely employed in literature to measure the mental workload experienced by users when executing a specific task. This research proposes the adoption of these mental workload assessment techniques to the task of creating uplift mappings in Linked Data. A user study has been performed to compare the mental workload of “manually” creating such mappings, using a formal mapping language and a text editor, to the use of a visual representation, based on the block metaphor, that generate these mappings. Two subjective mental workload instruments, namely the NASA Task Load Index and the Workload Profile, were applied in this study. Preliminary results show the reliability of these instruments in measuring the perceived mental workload for the task of creating uplift mappings. Results also indicate that participants using the visual representation achieved smaller and more consistent scores of mental workload

Cyclic Nucleotide-Gated Channels Contribute to Thromboxane A2-Induced Contraction of Rat Small Mesenteric Arteries

Background: Thromboxane A 2 (TxA 2)-induced smooth muscle contraction has been implicated in cardiovascular, renal and respiratory diseases. This contraction can be partly attributed to TxA2-induced Ca 2+ influx, which resulted in vascular contraction via Ca 2+-calmodulin-MLCK pathway. This study aims to identify the channels that mediate TxA2-induced Ca 2+ influx in vascular smooth muscle cells. Methodology/Principal Findings: Application of U-46619, a thromboxane A2 mimic, resulted in a constriction in endothelium-denuded small mesenteric artery segments. The constriction relies on the presence of extracellular Ca 2+, because removal of extracellular Ca 2+ abolished the constriction. This constriction was partially inhibited by an L-type Ca 2+ channel inhibitor nifedipine (0.5–1 mM). The remaining component was inhibited by L-cis-diltiazem, a selective inhibitor for CNG channels, in a dose-dependent manner. Another CNG channel blocker LY83583 [6-(phenylamino)-5,8-quinolinedione] had similar effect. In the primary cultured smooth muscle cells derived from rat aorta, application of U46619 (100 nM) induced a rise in cytosolic Ca 2+ ([Ca 2+]i), which was inhibited by L-cis-diltiazem. Immunoblot experiments confirmed the presence of CNGA2 protein in vascular smooth muscle cells. Conclusions/Significance: These data suggest a functional role of CNG channels in U-46619-induced Ca 2+ influx and contraction of smooth muscle cells