Impact of optimal therapy for noncommunicable diseases on the course and outcome of COVID-19 inpatients

Aim. To carry out a comparative analysis of the impact of optimal and suboptimal therapy for noncommunicable diseases (NCDs) at the prehospital stage on the severity and outcomes of coronavirus disease 2019 (COVID-19).Material and methods. The study included 158 patients hospitalized with a diagnosis of COVID-19 and having one or more concomitant NCDs. Patients were divided into two groups depending on the quality of initial therapy for NCDs: group 1 — patients receiving treatment that does not meet modern clinical guidelines, taking drugs not regularly or not taking them at all (n=100; 63%), and group 2 — patients receiving treatment in accordance with current clinical guidelines, taking regularly prescribed therapy (n=58; 37%). The primary endpoint was inhospital death, while secondary endpoints — duration of fever, length of intensive care unit (ICU) stay, length of hospital stay.Results. Inhospital mortality was significantly higher in the 1st group of patients compared with the 2nd group (18,0% vs 1,7%, p=0,002). Analysis of secondary endpoints revealed that patients of the 1st group (nonoptimal therapy), in comparison with the 2nd group (optimal therapy), had significantly longer period of fever (10 [7; 12] vs 9 [7; 10] days, p=0,03), longer ICU (0 [0; 3] vs 0 [0; 0] days, p<0,001) and hospital stay (10 [8; 14] vs 8 [7; 11] days, p=0,001).Conclusion. Patients who received standard NCD therapy before admission to the infectious disease hospital, in accordance with current clinical guidelines and who regularly take drugs, have a more favorable course of COVID-19 at the hospital stage and a lower inhospital mortality rate than patients with suboptimal therapy who are not adherent to treatment or not receiving drugs, but having indications for taking them

Common conformational changes induced in type 2 picornavirus IRESs by cognate trans-acting factors

Type 2 internal ribosomal entry sites (IRESs) of encephalomyocarditis virus (EMCV), foot-and-mouth disease virus (FMDV) and other picornaviruses comprise five major domains H-L. Initiation of translation on these IRESs begins with specific binding of the central domain of initiation factor, eIF4G to the J-K domains, which is stimulated by eIF4A. eIF4G/eIF4A then restructure the region of ribosomal attachment on the IRES and promote recruitment of ribosomal 43S pre-initiation complexes. In addition to canonical translation factors, type 2 IRESs also require IRES trans-acting factors (ITAFs) that are hypothesized to stabilize the optimal IRES conformation that supports efficient ribosomal recruitment: the EMCV IRES is stimulated by pyrimidine tract binding protein (PTB), whereas the FMDV IRES requires PTB and ITAF45. To test this hypothesis, we assessed the effect of ITAFs on the conformations of EMCV and FMDV IRESs by comparing their influence on hydroxyl radical cleavage of these IRESs from the central domain of eIF4G. The observed changes in cleavage patterns suggest that cognate ITAFs promote similar conformational changes that are consistent with adoption by the IRESs of comparable, more compact structures, in which domain J undergoes local conformational changes and is brought into closer proximity to the base of domain I

Physiology and pathology of extracellular vesicules

This year marks the 50th anniversary of the first publication about blood plasma microparticles. Initially considered as cell fragments or “platelet dust”, extracellular vesicles currently attracted the attention of biochemists, biophysicists, physicians, pharmacists around the world. They are heterogeneous in structure and derived from many cell types, express different antigen and contain variety of biomolecules that determines wide range of biological activity, including procoagulant, regenerative, immunomodulating, and others. They play an important role in the pathophysiology of different diseases and conditions – from infarction, injuries and pregnancies to the “graft versus host” disease. The vesicles as medicaments and their carriers, as well as the drugs that affect them, are a rapidly developing field of research

Procoagulant Platelets Form an -Granule Protein-covered "Cap" on Their Surface That Promotes Their Attachment to Aggregates

International audienc

Laboratory Techniques Used to Diagnose Constitutional Platelet Dysfunction

International audiencePlatelets play a major role in primary hemostasis, where activated platelets form plugs to stop hemorrhaging in response to vessel injuries. Defects in any step of the platelet activation process can cause a variety of platelet dysfunction conditions associated with bleeding. To make an accurate diagnosis, constitutional platelet dysfunction (CPDF) should be considered once von Willebrand disease and drug intake are ruled out. CPDF may be associated with thrombocytopenia or a genetic syndrome. CPDF diagnosis is complex, as no single test enables the analysis of all aspects of platelet function. Furthermore, the available tests lack standardization, and repeat tests must be performed in specialized laboratories especially for mild and moderate forms of the disease. In this review, we provide an overview of the laboratory tests used to diagnose CPDF, with a focus on light transmission platelet aggregation (LTA), flow cytometry (FC), and granules assessment. Global tests, mainly represented by LTA, are often initially performed to investigate the consequences of platelet activation on platelet aggregation in a single step. Global test results should be confirmed by additional analytical tests. FC represents an accurate, simple, and reliable test to analyze abnormalities in platelet receptors, and granule content and release. This technique may also be used to investigate platelet function by comparing resting- and activated-state platelet populations. Assessment of granule content and release also requires additional specialized analytical tests. High-throughput sequencing has become increasingly useful to diagnose CPDF. Advanced tests or external research laboratory techniques may also be beneficial in some cases