Initial viral cycle threshold values in patients with COVID-19 and their clinical significance.

BACKGROUND: The connection between initial viral cycle threshold (Ct) values of the SARS-CoV-2 with symptoms and hospital course is not clearly studied. METHODS: This is a retrospective study of hospitalized COVID-19 patients from Jun 1st 2020 to March 30th, 2021 examining the relationship between initial viral cycle threshold (Ct) values of SARS-CoV-2 as obtained from nasopharyngeal samples. The clinical presentations and outcomes were analyzed in relation to the initial Ct values. RESULTS: The study included 202 hospitalized COVID-19 patients with a mean age (± SD) of 54.75 (± 15.93) and 123 (60.9%) males and 79 (39.1%) females. Of all the patients, the most frequent comorbidity was diabetes mellitus (95; 47%) and the most frequent symptoms were fever (148; 73.3%) and cough (141; 69.8%). There was no significant difference in relation to underlying conditions, clinical presentation, radiographic and laboratory data among those with low, medium and high Ct values. The mean Ct values showed no statistical change over the 10-month study period. CONCLUSIONS: Initial SARS-CoV-2 Ct values did not show any association with clinical symptoms and did not predict the need for mechanical intubation or death.

Detection of CD34/CXCR4+ stem cells in peripheral blood of patients following acute myocardial infarction.

Bone marrow harbors a population of tissue-committed stem cells that are CD34+/CXCR4+. These potential cardiac progenitors which express cardiac and endothelial markers may contribute to cardiac regeneration. The ability of injured myocardium to recruit extracardiac stem cells after injury would be beneficial to aid in myocardial repair and regeneration. The aim of this study was to answer the question whether acute myocardial infarction (AMI) related stress may trigger the increase of CD34/CXCR4+ stem cells number in peripheral blood in response to myocardial ischemic injury which might be accompanied with increased release of this population of stem cells in peripheral blood as well as to correlate this phenomenon with other clinical and laboratory parameters such as diabetes, chest pain, smoking, streptokinase administration and elevated cardiac enzymes. The study was conducted on 25 newly diagnosed AMI patients who attended the emergency department of National Heart Institute. They were compared to a control group of 25 apparently healthy sex and age matched individuals. The percentage of CD34+ cells as well as percentage of cells coexpressing CD34/CXCR4+ and their expression intensity were assessed by Flowcytometery. These parameters were correlated to other laboratory and clinical data. The absolute CD34+ as well as the CD34/CXCR4+ cell counts were significantly higher in patients upon admission in comparison to control group (P < 0.01). While CD34 expression was significantly higher in patients compared to control group, CXCR4 expression on CD34+ cells was significantly lower in patients than control group (P < 0.05). Diabetes, duration of chest pain and streptokinase administration had no significant effect on CD34/CXCR4+ number or the expression intensity of both markers (p > 0.05). Otherwise, CXCR4 intensity was lower in non-smoker than smoker patients (P < 0.05). Patients admitted with normal cardiac enzymes, including Creatine Kinase (CK) and Creatine Kinase MB fraction (CK-MB) activity, showed no significant difference in CD34/CXCR4+ number or the expression intensity of CD34 marker in comparison to those admitted with high levels of enzymes (P > 0.05). However, the expression intensity of CXCR4 was significantly low in patients admitted with elevated cardiac enzymes (P < 0.05). In conclusion, there is a pool of CD34/CXCR4+ stem cells circulating in large number in peripheral blood of AMI patients post infarction together with low CXCR4 expression on these cells which are likely to contribute to myocardial repair following the acute ischemic injury.

Rap1 relocalization contributes to the chromatin-mediated gene expression profile and pace of cell senescence.

Cellular senescence is accompanied by dramatic changes in chromatin structure and gene expression. Using Saccharomyces cerevisiae mutants lacking telomerase (tlc1Δ) to model senescence, we found that with critical telomere shortening, the telomere-binding protein Rap1 (repressor activator protein 1) relocalizes to the upstream promoter regions of hundreds of new target genes. The set of new Rap1 targets at senescence (NRTS) is preferentially activated at senescence, and experimental manipulations of Rap1 levels indicate that it contributes directly to NRTS activation. A notable subset of NRTS includes the core histone-encoding genes; we found that Rap1 contributes to their repression and that histone protein levels decline at senescence. Rap1 and histones also display a target site-specific antagonism that leads to diminished nucleosome occupancy at the promoters of up-regulated NRTS. This antagonism apparently impacts the rate of senescence because underexpression of Rap1 or overexpression of the core histones delays senescence. Rap1 relocalization is not a simple consequence of lost telomere-binding sites, but rather depends on the Mec1 checkpoint kinase. Rap1 relocalization is thus a novel mechanism connecting DNA damage responses (DDRs) at telomeres to global changes in chromatin and gene expression while driving the pace of senescence.