Left Ventricular Dyssynchrony Acutely After Myocardial Infarction Predicts Left Ventricular Remodeling

ObjectivesWe sought to identify predictors of left ventricular (LV) remodeling after acute myocardial infarction.BackgroundLeft ventricular remodeling after myocardial infarction is associated with an adverse long-term prognosis. Early identification of patients prone to LV remodeling is needed to optimize therapeutic management.MethodsA total of 178 consecutive patients presenting with acute myocardial infarction who underwent primary percutaneous coronary intervention were included. Within 48 h of intervention, 2-dimensional echocardiography was performed to assess LV volumes, LV ejection fraction (LVEF), wall motion score index, left atrial dimension, E/E′ ratio, and severity of mitral regurgitation. Left ventricular dyssynchrony was determined using speckle-tracking radial strain analysis. At 6-month follow-up, LV volumes, LVEF, and severity of mitral regurgitation were reassessed.ResultsPatients showing LV remodeling at 6-month follow-up (20%) had comparable baseline characteristics to patients without LV remodeling (80%), except for higher peak troponin T levels (p < 0.001), peak creatine phosphokinase levels (p < 0.001), wall motion score index (p < 0.05), E/E′ ratio (p < 0.05), and a larger extent of LV dyssynchrony (p < 0.001). Multivariable analysis demonstrated that LV dyssynchrony was superior in predicting LV remodeling. Receiver-operating characteristic curve analysis demonstrated that a cutoff value of 130 ms for LV dyssynchrony yields a sensitivity of 82% and a specificity of 95% to predict LV remodeling at 6-month follow-up.ConclusionsLeft ventricular dyssynchrony immediately after acute myocardial infarction predicts LV remodeling at 6-month follow-up

Factors potentially contributing to the decline of the mpox outbreak in the Netherlands, 2022 and 2023

Background: In 2022 and 2023, a global outbreak of mpox affected mostly gay, bisexual and other men having sex with men (GBMSM). Outbreak control in the Netherlands included isolation, quarantine, post-exposure prophylaxis vaccination and primary preventive vaccination (PPV). Aim: We describe the course of the outbreak, the vaccination programme, vaccine effectiveness (VE) of full vaccination against symptomatic disease, and trends in behaviour to generate hypotheses about factors that influenced the outbreak’s decline. Methods: In this observational study, we collected data from public health services on notified cases, number of PPV invitations and PPV doses administered. We calculated PPV uptake and coverage. Trends in behavioural data of GBMSM visiting sexual health centres were analysed for all consultations in 2022. We estimated VE using the screening method. Results: Until 31 December 2023, 1,294 mpox cases were reported. The outbreak peaked in early July 2022 and then declined sharply. PPV started on 25 July 2022; in total 29,851 doses were administered, 45.8% received at least one dose, 35.4% were fully vaccinated. The estimated VE was 68.2% (95% CI 4.3–89.5%). We did not observe an evident decrease in high-risk behaviour. Discussion: It is unlikely that PPV was a driver of the outbreak’s decline, as incidence started to decline well before the start of the PPV programme. The possible impact of behavioural change could not be demonstrated with the available indicators, however, the data had limitations, hampering interpretation. We hypothesise that infection-induced immunity in high-risk groups was an important factor explaining the decline

A simple model to quantitatively account for periodic outbreaks of the measles in the Dutch Bible Belt

In the Netherlands there has been nationwide vaccination against the measles since 1976. However, in small clustered communities of orthodox Protestants there is widespread refusal of the vaccine. After 1976, three large outbreaks with about 3000 reported cases of the measles have occurred among these orthodox Protestants. The outbreaks appear to occur about every twelve years. We show how a simple Kermack-McKendrick-like model can quantitatively account for the periodic outbreaks. Approximate analytic formulae to connect the period, size, and outbreak duration are derived. With an enhanced model we take the latency period in account. We also expand the model to follow how different age groups are affected. Like other researchers using other methods, we conclude that large scale underreporting of the disease must occur

Nuclear Receptor Rev-erb Alpha (Nr1d1) Functions in Concert with Nr2e3 to Regulate Transcriptional Networks in the Retina

The majority of diseases in the retina are caused by genetic mutations affecting the development and function of photoreceptor cells. The transcriptional networks directing these processes are regulated by genes such as nuclear hormone receptors. The nuclear hormone receptor gene Rev-erb alpha/Nr1d1 has been widely studied for its role in the circadian cycle and cell metabolism, however its role in the retina is unknown. In order to understand the role of Rev-erb alpha/Nr1d1 in the retina, we evaluated the effects of loss of Nr1d1 to the developing retina and its co-regulation with the photoreceptor-specific nuclear receptor gene Nr2e3 in the developing and mature retina. Knock-down of Nr1d1 expression in the developing retina results in pan-retinal spotting and reduced retinal function by electroretinogram. Our studies show that NR1D1 protein is co-expressed with NR2E3 in the outer neuroblastic layer of the developing mouse retina. In the adult retina, NR1D1 is expressed in the ganglion cell layer and is co-expressed with NR2E3 in the outer nuclear layer, within rods and cones. Several genes co-targeted by NR2E3 and NR1D1 were identified that include: Nr2c1, Recoverin, Rgr, Rarres2, Pde8a, and Nupr1. We examined the cyclic expression of Nr1d1 and Nr2e3 over a twenty-four hour period and observed that both nuclear receptors cycle in a similar manner. Taken together, these studies reveal a novel role for Nr1d1, in conjunction with its cofactor Nr2e3, in regulating transcriptional networks critical for photoreceptor development and function