University of Siena

About: University of Siena is a education organization based out in Siena, Italy. It is known for research contribution in the topics: Population & Cancer. The organization has 12179 authors who have published 33334 publications receiving 1008287 citations. The organization is also known as: Università degli studi di Siena & Universita degli studi di Siena.

COVID-19, Arrhythmic Risk and Inflammation: Mind the Gap!

Abstract: July 7, 2020 7 Pietro Enea Lazzerini , MD Mohamed Boutjdir, PhD* Pier Leopoldo Capecchi, MD* Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).1 Besides direct tissue invasion, SARS-CoV-2 can also elicit an exaggerated host immune response, frequently leading to a cytokine storm, which significantly contributes to multiorgan dysfunction.1 Indeed, high levels of circulating cytokines, particularly interleukin (IL)-6, are commonly found in patients with COVID-19, also associating with in-hospital death.1 Accumulating data point to an increased cardiovascular disease morbidity and mortality in these patients.1 In particular, growing evidence suggest that COVID-19 is burdened by a higher risk of arrhythmic events, with important implications for survival.1 Heart palpitations were reported as one of the most common initial symptom of the disease (7.3%).1 In 138 hospitalized patients with COVID-19, arrhythmias represented the leading complication (19.6%) after acute distress respiratory syndrome, particularly in those admitted to intensive care unit where the prevalence rose to 44.4%.1 Specifically, malignant ventricular arrhythmias (ie, ventricular tachycardia/fibrillation) were found in 5.9% of cases.1 It is currently believed that myocardial damage might represent a main driver of enhanced arrhythmic risk in these patients.1 Cardiac myocyte injury, reflected by increased troponin levels, was demonstrated in many individuals, particularly in those with severe disease. Accordingly, higher incidence of ventricular tachycardia/fibrillation was reported in patients with elevated troponin-T levels.1 Although the mechanisms of myocardial involvement are still under investigation, they probably include direct viral infection, hypoxia-induced apoptosis, and cytokine storm–related cell damage (Figure).1 However, the evidence presented that in intensive care unit patients, despite the high frequency of arrhythmias (≈50% of cases), only half showed acute cardiac injury (with median troponin-I levels falling in the normal range), which suggests that factors other than myocardial damage are also involved in enhancing the arrhythmic risk in COVID-19. In this regard, the potential role of pharmacological treatments in enhancing the susceptibility to QT-related life-threatening ventricular arrhythmias, particularly Torsades de Pointes (TdP), is increasingly recognized.1 In fact, some off-label drugs used to counteract the virus invasion and replication may promote corrected QTinterval (QTc) prolongation. This is the case of chloroquine/hydroxychloroquine, antimalarial agents blocking infection by increasing the endosomal pH required for virus/cell fusion, and lopinavir/ritonavir, protease inhibitors interfering with the virus RNA replication. Notably, in both cases, the impact on ventricular repolarization is direct, via inhibition of the hERG-K+ channel, and also indirect by increasing circulating levels of other concomitant QT-prolonging drugs.1 In fact, chloroquine and hydroxychloroquine inhibit CYP2D6 (cytochrome P450 2D6), which metabolizes several antipsychotics, antidepressants, and antihistamines, © 2020 American Heart Association, Inc. ON MY MIND

Crystallization of soluble proteins in vapor diffusion for x-ray crystallography

Abstract: The preparation of protein single crystals represents one of the major obstacles in obtaining the detailed 3D structure of a biological macromolecule. The complete automation of the crystallization procedures requires large investments in terms of money and labor, which are available only to large dedicated infrastructures and is mostly suited for genomic-scale projects. On the other hand, many research projects from departmental laboratories are devoted to the study of few specific proteins. Here, we try to provide a series of protocols for the crystallization of soluble proteins, especially the difficult ones, tailored for small-scale research groups. An estimate of the time needed to complete each of the steps described can be found at the end of each section.

CA19-9 serum levels in obstructive jaundice: clinical value in benign and malignant conditions

Abstract: Background Obstructive jaundice is frequently associated with false CA19-9 elevation in benign conditions. The diagnostic accuracy of this tumor marker was evaluated in the present longitudinal study. Methods In 128 patients admitted for obstructive jaundice (87 with pancreato-biliary malignancy and 41 benign disease) serum CA19-9 was measured. Statistical analysis of marker levels obtained before and after endoscopic biliary drainage was performed in 60 patients. Results Elevated CA19-9 levels (>37 U/mL) were found in 61% of benign cases and 86% of malignancies. After biliary drainage, decrease of serum CA19-9 was observed in 19 of 38 malignant cases and in almost all benign cases (Wilcoxon matched pairs test: P = .207 and P Conclusions In the presence of successfully drained obstructive jaundice, CA19-9 serum levels that remain unchanged or measure more than 90 U/mL are strongly indicative of a malignant cause of obstruction. However, the real clinical utility of this marker remains controversial.