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Mechanisms involving PD-L1 Regulation in Cancerous and also Virus-Infected Cells.
The mechanisms and phenotype of ischemic stroke associated with coronavirus disease 2019 (COVID-19) remain uncertain. A retrospective study was conducted in patients with COVID-19 presenting with ischemic stroke from March 1 to May 25, 2020, and cases with large-vessel occlusion were identified. To provide baseline institutional stroke data within and outside the COVID-19 pandemic, all consecutive ischemic stroke and TIA admissions (COVID and non-COVID) to the hospital during a 10-week period from March 1 to May 10, 2020, were collected and compared with data from the same time period in 2019. Among 20 patients with COVID-19 and acute ischemic stroke, 15 (75%) had large-vessel occlusion. These patients were young (mean age, 46.5 years), male (93%), without major burden of traditional cardiovascular risk factors, and had a severe stroke presentation. Large-vessel occlusions were observed in multiple vessels (40%), uncommonly affected vessels, and atypical locations with a large thrombus burden. learn more Systemic thrombosis separate from large-vessel occlusion was not uncommon (26%). At short-term follow-up, stroke etiology remained undetermined in 46% of patients and functional outcome was poor. The above findings raise the possibility of stroke related to mechanisms induced by the COVID-19 infection itself, including a hypercoagulable state and/or endothelial damage. In addition, they document the severe presentation and poor outcomes of large-vessel occlusion in COVID-19 ischemic stroke.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of COVID-19, resulting in cases of mild to severe respiratory distress and significant mortality. The global outbreak of this novel coronavirus has now infected >20 million people worldwide, with >5 million cases in the United States (11 August 2020). The development of diagnostic and research tools to determine infection and vaccine efficacy is critically needed. We have developed multiple serologic assays using newly designed SARS-CoV-2 reagents for detecting the presence of receptor-binding antibodies in sera. The first assay is surface plasmon resonance (SPR) based and can quantitate both antibody binding to the SARS-CoV-2 spike protein and blocking to the Angiotensin-converting enzyme 2 (ACE2) receptor in a single experiment. The second assay is enzyme-linked immunosorbent assay (ELISA) based and can measure competition and blocking of the ACE2 receptor to the SARS-CoV-2 spike protein with antispike antibodies. The assay is highly versatile, and we demonstrate the broad utility of the assay by measuring antibody functionality of sera from small animals and nonhuman primates immunized with an experimental SARS-CoV-2 vaccine. In addition, we employ the assay to measure receptor blocking of sera from SARS-CoV-2-infected patients. The assay is shown to correlate with pseudovirus neutralization titers. This type of rapid, surrogate neutralization diagnostic can be employed widely to help study SARS-CoV-2 infection and assess the efficacy of vaccines.Cancer lineage/tissue-of-origin assignment in cancers of unknown primary remains a challenge even when aided by massively parallel sequencing. The stakes are high for patients as many contemporary therapeutic strategies are disease-specific, and the biological differences can influence the patients' responses. Herein, we provide an example of how Bayesian analysis can be used to merge data from clinical history, histology, immunohistochemistry (IHC) and cancer DNA sequencing to assist in tissue-of-origin assignment. Iterative Bayesian analysis is performed through a set of simple calculations to calculate the OR between the differential diagnoses. We illustrate a clinical case, where the distinction between a primary lung versus metastatic bladder cancer was aided meaningfully by iterative Bayesian analyses, incorporating IHC and sequencing data.Patients with COVID-19 commonly have elevated liver enzyme levels, which is associated with adverse outcomes during hospitalization including increased risk of ICU admission, intubation, and mortality. When assessing these patients, it is important to consider causes of liver injury unrelated to COVID-19. Therapies for COVID-19 may increase liver enzyme levels but are not contraindicated in patients with baseline abnormal liver tests. Liver enzymes should be regularly monitored in all hospitalized patients with COVID-19. Patients with preexisting liver disease such as cirrhosis and those who have received a liver transplant may be an increased risk of severe COVID-19 outcomes.Evidence shows that COVID-19 can exacerbate symptoms of inflammatory bowel disease (IBD) and pancreaticobiliary disorders, and it is important to distinguish between an IBD exacerbation and symptoms caused by COVID-19. Although IBD does not appear to increase the risk for COVID-19 or worsen outcomes, corticosteroids can increase the risk and should be avoided when treating these patients. Pancreatic and biliary disease have been described in patients with COVID-19, but it is not clear whether COVID-19 induces these diseases. For facilities resuming endoscopic procedures, there are consensus guidelines for minimizing the COVID-19 transmission risks with these procedures.Testosterone (T) affects β-cell function in men and women. T is a prohormone that undergoes intracrine conversion in target tissues to the potent androgen dihydrotestosterone (DHT) via the enzyme 5α-reductase (5α-R) or to the active estrogen 17β-estradiol (E2) via the aromatase enzyme. Using male and female human pancreas sections, we show that the 5α-R type 1 isoform (SRD5A1) and aromatase are expressed in male and female β-cells. We show that cultured male and female human islets exposed to T produce DHT and downstream metabolites. In these islets, exposure to the 5α-R inhibitors finasteride and dutasteride inhibited T conversion into DHT. We did not detect T conversion into E2 from female islets. However, we detected T conversion into E2 in islets from two out of four male donors. In these donors, exposure to the aromatase inhibitor anastrozole inhibited E2 production. Notably, in cultured male and female islets, T enhanced glucose-stimulated insulin secretion (GSIS). In these islets, exposure to 5α-R inhibitors or the aromatase inhibitor both inhibited T enhancement of GSIS.
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