.Real-world drug repurposing-the immediate "off-label" prescribing of drugs to address urgent clinical needs-is a widely overlooked opportunity. Off-label prescribing (ie, for a nonapproved indication) is legal in most countries and tends to shift the burden of liability and cost to physicians and patients, respectively. Nevertheless, health crises may mean that real-world repurposing is the only realistic source for solutions. Optimal real-world repurposing requires a track record of safety, affordability, and access for drug candidates. Although thousands of such drugs are already available, there is no central repository of off-label uses to facilitate immediate identification and selection of potentially useful interventions during public health crises. Using the current coronavirus disease (COVID-19) pandemic as an example, we provide a glimpse of the extensive literature that supports the rationale behind six generic drugs, in four classes, all of which are affordable, supported by decades of safety data, and targeted toward the underlying pathophysiology that makes COVID-19 so deadly. This paper briefly summarizes why cimetidine or famotidine, dipyridamole, fenofibrate or bezafibrate, and sildenafil citrate are worth considering for patients with COVID-19. Clinical trials to assess efficacy are already underway for famotidine, dipyridamole, and sildenafil, and further trials of all these agents will be important in due course. These examples also reveal the unlimited opportunity to future-proof our health care systems by proactively mining, synthesizing, cataloging, and evaluating the off-label treatment opportunities of thousands of safe, well-established, and affordable generic drugs. ©Moshe Rogosnitzky, Esther Berkowitz, Alejandro R Jadad. Originally published in JMIR Public Health and Surveillance (http//publichealth.jmir.org), 13.05.2020.The Triatominae are a vector species for Trypanosoma cruzi, the aetiological agent of the neglected tropical Chagas disease. Their distribution stretches across Latin America, with some species occurring outside of the Americas. In particular, the cosmopolitan vector, Triatoma rubrofasciata, has already been detected in many Asian and African countries. We applied an ensemble forecasting niche modelling approach to project the climatic suitability of 11 triatomine species under current climate conditions on a global scale. Our results revealed potential hotspots of triatomine species diversity in tropical and subtropical regions between 21°N and 24°S latitude. We also determined the climatic suitability of two temperate species (T. infestans, T. sordida) in Europe, western Australia and New Zealand. Triatoma rubrofasciata has been projected to find climatically suitable conditions in large parts of coastal areas throughout Latin America, Africa and Southeast Asia, emphasising the importance of an international vector surveillance program in these regions. © 2020, Eberhard et al.The transport of substances across the placenta is essential for the development of the fetus. Here, we were interested in the role of channels of the calcium homeostasis modulator (CALHM) family in the human placenta. By transcript analysis, we found the paralogs CALHM2, 4, and 6 to be highly expressed in this organ and upregulated during trophoblast differentiation. Based on electrophysiology, we found that activation of these paralogs differs from the voltage- and calcium-gated channel CALHM1. Cryo-EM structures of CALHM4 display decameric and undecameric assemblies with large cylindrical pore, while in CALHM6 a conformational change has converted the pore shape into a conus that narrows at the intracellular side, thus describing distinct functional states of the channel. The pore geometry alters the distribution of lipids, which occupy the cylindrical pore of CALHM4 in a bilayer-like arrangement whereas they have redistributed in the conical pore of CALHM6 with potential functional consequences. © 2020, Drożdżyk et al.The histone modification writer Prdm9 has been shown to deposit H3K4me3 and H3K36me3 at future double-strand break (DSB) sites during the very early stages of meiosis, but the reader of these marks remains unclear. Here, we demonstrate that Zcwpw1 is an H3K4me3 reader that is required for DSB repair and synapsis in mouse testes. We generated H3K4me3 reader-dead Zcwpw1 mutant mice and found that their spermatocytes were arrested at the pachytene-like stage, which phenocopies the Zcwpw1 knock-out mice. Based on various ChIP-seq and immunofluorescence analyses using several mutants, we found that Zcwpw1's occupancy on chromatin is strongly promoted by the histone-modification activity of PRDM9. Zcwpw1 localizes to DMC1-labelled hotspots in a largely Prdm9-dependent manner, where it facilitates completion of synapsis by mediating the DSB repair process. In sum, our study demonstrates the function of ZCWPW1 that acts as part of the selection system for epigenetics-based recombination hotspots in mammals. © 2020, Huang et al.An accurate functional assessment of coronary artery stenosis is pivotal in the management and clinical outcomes of patients. The hemodynamic relevance of coronary artery stenoses can be assessed using coronary flow surrogates, namely fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR). This review provides an overview of these indexes, their clinical relevance, as well as a review of the literature supporting their use.  https://www.selleckchem.com/products/ITF2357(Givinostat).html  It also reviews novel image-based FFR (e.g. FFRangio), the evidence showing the accuracy of this technique when compared to conventional wire-based techniques, as well as the clinical implications of non-invasive coronary artery stenosis functional assessments.OBJECTIVES To assess the impact of different types of anemia and of concomitant non-cardiovascular chronic illnesses on outcomes of patients with ST-segment elevation myocardial infarction (STEMI) and baseline anemia admitted to the Intensive Cardiac Care Unit. METHODS Based on the mean corpuscular volume, anemia was stratified into microcytic ( less then 80 fL), normocytic (≥80, less then 96 fL), and macrocytic (≥96 fL). Data on concomitant chronic non-cardiovascular illnesses including malignancies were carefully collected. Endpoints included in-hospital bleeding as well as all-cause mortality at long-term follow-up. RESULTS Of 1,390 patients with STEMI, 294 patients had baseline anemia (21.2%), in whom normocytic, microcytic, and macrocytic anemia was present in 77.2%, 17.0%, and 5.8% patients, respectively. In-hospital bleeding occurred in 25 (8.5%) of the study population without significant differences between the three groups. At a mean follow-up of 5.5±3.5 years, 104 patients (35.4%) had died. Mortality was the highest in patients with macrocytic anemia, followed by patients with normocytic anemia and microcytic anemia (58.