PGE2 alters chromatin through H2A.Z-variant enhancer nucleosome modification to promote hematopoietic stem cell fate

Prostaglandin E2 (PGE2) and 16,16-dimethyl-PGE2 (dmPGE2) are important regulators of hematopoietic stem and progenitor cell (HSPC) fate and offer potential to enhance stem cell therapies [C. Cutler et al. Blood 122, 3074–3081(2013); W. Goessling et al. Cell Stem Cell 8, 445–458 (2011); W. Goessling et al. Cell 136, 1136–1147 (2009)]. Here, we report that PGE2-induced changes in chromatin at enhancer regions through histone-variant H2A.Z permit acute inflammatory gene induction to promote HSPC fate. We found that dmPGE2-inducible enhancers retain MNase-accessible, H2A.Z-variant nucleosomes permissive of CREB transcription factor (TF) binding. CREB binding to enhancer nucleosomes following dmPGE2 stimulation is concomitant with deposition of histone acetyltransferases p300 and Tip60 on chromatin. Subsequent H2A.Z acetylation improves chromatin accessibility at stimuli-responsive enhancers. Our findings support a model where histone-variant nucleosomes retained within inducible enhancers facilitate TF binding. Histone-variant acetylation by TF-associated nucleosome remodelers creates the accessible nucleosome landscape required for immediate enhancer activation and gene induction. Our work provides a mechanism through which inflammatory mediators, such as dmPGE2, lead to acute transcriptional changes and modify HSPC behavior to improve stem cell transplantation

Building consensus in defining and conceptualizing acceptability of healthcare: A Delphi study

Background The concept of healthcare acceptability is important for nursing staff spending most of their time with patients. Nevertheless, acceptability remains confusing without a collective definition in existing literature. Objective This study aimed to create a consensus among experts on definition and conceptual framework of healthcare acceptability. Methods We conducted two rounds of Delphi surveys to collect opinions from experts on definition and conceptual framework of healthcare acceptability proposed following thematic content analysis. We calculated the consensus among experts using the modified Appraisal of Guidelines for Research & Evaluation II (AGREE II) instrument and followed the guidance on conducting and reporting Delphi studies (CREDES) best practices. Results A total of 34 experts completed two rounds of Delphi survey. The definition was validated through consensus as: “a multi-construct concept describing the nonlinear cumulative combination in parts or in whole of experienced or anticipated specific healthcare from the relevant patients/participants, communities, providers/researchers or healthcare systems' managers and policy makers' perspectives in a given context.” The overall quality rating was 92.6% and 95.1% for the proposed definition and conceptual framework respectively. Conclusion Opinions collected from experts provided significant insights to build a consensus on healthcare acceptability advancing public health nursing

Evaluation of ENACTS‐Rwanda: A new multi‐decade, high‐resolution rainfall and temperature data set—Climatology

There were a large number of active meteorological stations in Rwanda prior to the mid‐1990s and since around 2010. However, from around the time of the Rwandan genocide in 1994 throughout the late 2000s, the number of active stations was greatly reduced. To address temporal and spatial gaps in meteorological observation in several African nations (including Rwanda), the ENACTS (Enhancing National Climate Services) initiative reconstructs rainfall and temperature data by combining station data with satellite rainfall estimates, and with reanalysis products for temperature. Bias correction factors are applied to the satellite and reanalysis data and the merged final product is spatiotemporally complete from the early 1980s to the present at a high spatial resolution (4–5 km). This paper offers the first analysis of Rwanda's climatology using this new ENACTS data set for 1981–2016. The temperature and rainfall climatology of Rwanda are analysed at both annual and seasonal timescales as are the climatological influences of topography and regional winds. Climatology maps of mean rainfall intensity, rainy day, 5‐day dry spell and extreme rain day (20+mm) frequency are shown, and spatial pattern correlations are analysed. The rainfall climatology of Rwanda exhibits a clear seasonal bimodality typical of the East Africa region. Topography has a significant effect with the more mountainous, higher‐elevation western part of the country being consistently cooler and wetter than the lower, flatter eastern region. Southeasterly winds tend to prevail over Rwanda, but in some seasons, the climatological winds weaken and shift direction. While spatial patterns of rainy day and dry spell frequency are consistent with the spatial patterns of the seasonal rainfall total, climatologically drier regions have a higher mean rainfall intensity on rainy days. This analysis demonstrates the value of the ENACTS product and illustrates climatological patterns in Rwanda over the last 30 years