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CRISPR-Based COVID-19 Smartphone Test in Development

JAMA - Mar, 09/02/2021 - 02:00
A simplified point-of-care assay that turns a smartphone into a fluorescence microscope could expand coronavirus disease 2019 (COVID-19) testing capability, researchers reported in a study in Cell.

Model Predicts Emergency Department Patients’ COVID-19 Outcomes

JAMA - Mar, 09/02/2021 - 02:00
A new artificial intelligence algorithm uses chest x-ray severity scores and clinical variables collected during emergency department (ED) visits to predict whether patients with coronavirus disease 2019 (COVID-19) will be intubated or will die. If further validated in larger studies with additional patient populations, the proof-of-concept model, described in Radiology: Artificial Intelligence, could be used to appropriately triage ED patients before they become seriously ill with COVID-19.

Death by Massive Hemorrhage in Robert Frost’s “Out, Out–”

JAMA - Mar, 09/02/2021 - 02:00
This Arts and Medicine feature uses poet Robert Frost’s poem “Out, Out–”, about the tragic death of a boy in the premodern era from a work injury and hemorrhagic shock, to discuss the stakes of developing a more effective public health response to traumatic injury.

Helping People Who Are Homeless Stay Healthy During the Pandemic

JAMA - Mar, 09/02/2021 - 02:00
This Medical News story profiles Harvard dermatologist Jennifer Tan, MD, who helps care for people experiencing homelessness.

Dorsal Foot Lesions In a Nigerian Woman With a Transfusion History

JAMA - Mar, 09/02/2021 - 02:00
A 32-year-old Nigerian woman with a childhood transfusion history developed scaly plaques with cobblestone surfaces on the dorsum of the forefoot and midfoot bilaterally; serologic testing was negative for HIV and positive for hepatitis C virus. What is the diagnosis and what would you do next?

Genetic Variants of SARS-CoV-2—What Do They Mean?

JAMA - Mar, 09/02/2021 - 02:00
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.

Problems With Paying People to Be Vaccinated Against COVID-19

JAMA - Mar, 09/02/2021 - 02:00
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.

Mandating COVID-19 Vaccines—Ethical and Legal Considerations

JAMA - Mar, 09/02/2021 - 02:00
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.

Epigenetic Dysregulation of the Dynamin-Related Protein 1 Binding Partners MiD49 and MiD51 Increases Mitotic Mitochondrial Fission and Promotes Pulmonary Arterial Hypertension [Original Research Article]

Circulation - Lun, 16/07/2018 - 19:44
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.

Deciphering the Role of Lipid Droplets in Cardiovascular Disease [White Paper]

Circulation - Lun, 16/07/2018 - 19:44
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.
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