Adult T-cell leukemia (ATL) is an often fatal malignancy caused by infection with the complex retrovirus, human T-cell Leukemia Virus, type 1 (HTLV-1). In ATL patient samples, the tumor suppressor, p53, is infrequently mutated; however, it has been shown to be inactivated by the viral protein, Tax. Here, we show that another HTLV-1 protein, HBZ, represses p53 activity. In HCT116 p53+/+ cells treated with the DNA-damaging agent, etoposide, HBZ reduced p53-mediated activation of p21/CDKN1A and GADD45A expression, which was associated with a delay in G2 phase-arrest. These effects were attributed to direct inhibition of the histone acetyltransferase (HAT) activity of p300/CBP by HBZ, causing a reduction in p53 acetylation, which has be linked to decreased p53 activity. In addition, HBZ bound to, and inhibited the HAT activity of HBO1. Although HBO1 did not acetylate p53, it acted as a coactivator for p53 at the p21/CDKN1A promoter. Therefore, through interactions with two separate HAT proteins, HBZ impairs the ability of p53 to activate transcription. This mechanism may explain how p53 activity is restricted in ATL cells that do not express Tax due to modifications of the HTLV-1 provirus, which accounts for a majority of patient samples.

Aims Electrical cardioversion is commonly used to restore sinus rhythm in patients with atrial fibrillation (AF), but procedural technique and clinical success vary. We sought to identify techniques associated with electrical cardioversion success for AF patients. Methods and results We searched MEDLINE, EMBASE, CENTRAL, and the grey literature from inception to October 2022. We abstracted data on initial and cumulative cardioversion success. We pooled data using random-effects models. From 15 207 citations, we identified 45 randomized trials and 16 observational studies. In randomized trials, biphasic when compared with monophasic waveforms resulted in higher rates of initial [16 trials, risk ratio (RR) 1.71, 95% CI 1.29–2.28] and cumulative success (18 trials, RR 1.10, 95% CI 1.04–1.16). Fixed, high-energy (≥200 J) shocks when compared with escalating energy resulted in a higher rate of initial success (four trials, RR 1.62, 95% CI 1.33–1.98). Manual pressure when compared with no pressure resulted in higher rates of initial (two trials, RR 2.19, 95% CI 1.21–3.95) and cumulative success (two trials, RR 1.19, 95% CI 1.06–1.34). Cardioversion success did not differ significantly for other interventions, including: antero-apical/lateral vs. antero-posterior positioned pads (initial: 11 trials, RR 1.16, 95% CI 0.97–1.39; cumulative: 14 trials, RR 1.01, 95% CI 0.96–1.06); rectilinear/pulsed biphasic vs. biphasic truncated exponential waveform (initial: four trials, RR 1.11, 95% CI 0.91–1.34; cumulative: four trials, RR 0.98, 95% CI 0.89–1.08) and cathodal vs. anodal configuration (cumulative: two trials, RR 0.99, 95% CI 0.92–1.07). Conclusions Biphasic waveforms, high-energy shocks, and manual pressure increase the success of electrical cardioversion for AF. Other interventions, especially pad positioning, require further study.

Background: Atrial fibrillation (AF) is frequently reported as a complication of noncardiac surgery. It is unknown whether new-onset perioperative AF is associated with an increased risk of stroke and death beyond the perioperative period. We performed a systematic review and meta-analysis to assess the long-term risks of stroke and mortality associated with new-onset perioperative AF after noncardiac surgery. Methods: MEDLINE and EMBASE were searched from inception to March 2020 for studies reporting on the association between R ESUM E Contexte : La fibrillation atriale (FA) est une arythmie fr equemment attribu ee à une complication d'une chirurgie non cardiaque. On ne sait toutefois pas si l'apparition d'une FA p eriop eratoire est associ ee à un risque accru d'accident vasculaire c er ebral et de d ecès au-delà de la p eriode p eriop eratoire. Nous avons donc proc ed e à un examen et à une m eta-analyse syst ematiques dans le but d' evaluer les risques à long terme d'accident vasculaire c er ebral et de d ecès associ es à l'apparition d'une FA p eriop eratoire à la suite d'une chirurgie non cardiaque.

Background: Electrical cardioversion (ECV) is a common management strategy for atrial fibrillation (AF). ECV contains multiple modifiable components, including pad size and placement, shock energy, and waveform phases. Guidance on optimal technique, however, is limited. A comprehensive review of interventions used to increase ECV success will guide ideal clinical practice and identify techniques that could be studied in future randomized controlled trials. Methods: This review will include RCTs randomized controlled trial and observational studies that compare acute cardioversion success between 2 or more non-pharmacological interventions in patients with AF undergoing ECV. We will search CENTRAL, MEDLINE and EMBASE from inception to present and will also include the grey literature as part of our search. We will assess the risk of bias for each study and summarize the extracted data in a narrative report with a table of findings included. Results: Based on a full search strategy developed for MEDLINE along with findings from the grey literature search, the non-pharmacological interventions are expected to include pad placement, shock energy, waveform phases, and manual pressure, among others. Conclusions: The objective of this scoping review is to identify and examine the evidence on non-pharmacological interventions to improve electrical cardioversion in patients with AF. Registered on Open Science Framework: https://osf.io/gdh27/