This Viewpoint discusses emerging genetic variants of SARS-CoV-2, including new “UK” and “mink” variants and the significance of the new variants to coronavirus transmissibility, spread, virulence, and efforts to vaccinate the population against COVID-19.

This Viewpoint describes features of 2 proposals to pay US residents to be vaccinated against COVID-19 and proposes ethical and practical complications of the plans, arguing that they are morally suspect, likely unnecessary, and may be counterproductive.

This Viewpoint discusses whether US states, businesses, health care facilities, and schools and universities can mandate vaccination against coronavirus as a condition of employment or service.

Background:Mitotic fission is increased in pulmonary arterial hypertension (PAH), a hyperproliferative, apoptosis-resistant disease. The fission mediator dynamin-related protein 1 (Drp1) must complex with adaptor proteins to cause fission. Drp1-induced fission has been therapeutically targeted in experimental PAH. Here, we examine the role of 2 recently discovered, poorly understood Drp1 adapter proteins, mitochondrial dynamics protein of 49 and 51 kDa (MiD49 and MiD51), in normal vascular cells and explore their dysregulation in PAH.Methods:Immunoblots of pulmonary artery smooth muscle cells (control, n=6; PAH, n=8) and immunohistochemistry of lung sections (control, n=6; PAH, n=6) were used to assess the expression of MiD49 and MiD51. The effects of manipulating MiDs on cell proliferation, cell cycle, and apoptosis were assessed in human and rodent PAH pulmonary artery smooth muscle cells with flow cytometry. Mitochondrial fission was studied by confocal imaging. A microRNA (miR) involved in the regulation of MiD expression was identified using microarray techniques and in silico analyses. The expression of circulatory miR was assessed with quantitative reverse transcription–polymerase chain reaction in healthy volunteers (HVs) versus patients with PAH from Sheffield, UK (plasma: HV, n=29, PAH, n=27; whole blood: HV, n=11, PAH, n=14) and then confirmed in a cohort from Beijing, China (plasma: HV, n=19, PAH, n=36; whole blood: HV, n=20, PAH, n=39). This work was replicated in monocrotaline and Sugen 5416-hypoxia, preclinical PAH models. Small interfering RNAs targeting MiDs or an miR mimic were nebulized to rats with monocrotaline-induced PAH (n=4–10).Results:MiD expression is increased in PAH pulmonary artery smooth muscle cells, which accelerates Drp1-mediated mitotic fission, increases cell proliferation, and decreases apoptosis. Silencing MiDs (but not other Drp1 binding partners, fission 1 or mitochondrial fission factor) promotes mitochondrial fusion and causes G1-phase cell cycle arrest through extracellular signal-regulated kinases 1/2– and cyclin-dependent kinase 4–dependent mechanisms. Augmenting MiDs in normal cells causes fission and recapitulates the PAH phenotype. MiD upregulation results from decreased miR-34a-3p expression. Circulatory miR-34a-3p expression is decreased in both patients with PAH and preclinical models of PAH. Silencing MiDs or augmenting miR-34a-3p regresses experimental PAH.Conclusions:In health, MiDs regulate Drp1-mediated fission, whereas in disease, epigenetic upregulation of MiDs increases mitotic fission, which drives pathological proliferation and apoptosis resistance. The miR-34a-3p-MiD pathway offers new therapeutic targets for PAH.

Lipid droplets (LDs) are distinct and dynamic organelles that affect the health of cells and organs. Much progress has been made in understanding how these structures are formed, how they interact with other cellular organelles, how they are used for storage of triacylglycerol in adipose tissue, and how they regulate lipolysis. Our understanding of the biology of LDs in the heart and vascular tissue is relatively primitive in comparison with LDs in adipose tissue and liver. The National Heart, Lung, and Blood Institute convened a working group to discuss how LDs affect cardiovascular diseases. The goal of the working group was to examine the current state of knowledge on the cell biology of LDs, including current methods to study them in cells and organs and reflect on how LDs influence the development and progression of cardiovascular diseases. This review summarizes the working group discussion and recommendations on research areas ripe for future investigation that will likely improve our understanding of atherosclerosis and heart function.

Background:Randomized, clinical trials in selected acute ischemic stroke patients reported that for every hour delay of endovascular treatment (EVT), chances of functional independence diminish by up to 3.4%. These findings may not be fully generalizable to clinical practice because of strict in- and exclusion criteria in these trials. Therefore, we aim to assess the association of time to EVT with functional outcome in current, everyday clinical practice.Methods:The MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands) is an ongoing, prospective, observational study in all centers that perform EVT in The Netherlands. Data were analyzed from patients treated between March 2014 and June 2016. In the primary analysis we assessed the association of time from stroke onset to start of EVT and time from stroke onset to successful reperfusion with functional outcome (measured with the modified Rankin Scale), by means of ordinal logistic regression.Results:We analyzed 1488 patients with acute ischemic stroke who underwent EVT. An increased time to start of EVT was associated with worse functional outcome (adjusted common odds ratio, 0.83 per hour; 95% confidence interval, 0.77–0.89) and a 2.2% increase in mortality. Every hour increase from stroke onset to EVT start resulted in a 5.3% decreased probability of functional independence (modified Rankin Scale, 0–2). In the 742 patients with successful reperfusion, every hour increase from stroke onset to reperfusion was associated with a 7.7% decreased probability of functional independence.Conclusions:Time to EVT for acute ischemic stroke in current clinical practice is strongly associated with functional outcome. Our data suggest that this association might be even stronger than previously suggested in reports on more selected patient populations from randomized, controlled trials. These findings emphasize that functional outcome of EVT patients can be greatly improved by shortening onset to treatment times.