SARS-CoV-2, responsible for the ongoing global pandemic, must overcome a conundrum faced by all viruses. To achieve its own replication and spread, it simultaneously depends on and subverts cellular mechanisms. At the early stage of infection, SARS-CoV-2 expresses the viral nonstructural protein 1 (NSP1), which inhibits host translation by blocking the mRNA entry tunnel on the ribosome; this interferes with the binding of cellular mRNAs to the ribosome. Viral mRNAs, on the other hand, overcome this blockade. We show that NSP1 enhances expression of mRNAs containing the SARS-CoV-2 leader. The first stem-loop (SL1) in viral leader is both necessary and sufficient for this enhancement mechanism. Our analysis pinpoints specific residues within SL1 (three cytosine residues at the positions 15, 19 and 20) and another within NSP1 (R124) which are required for viral evasion, and thus might present promising drug targets. We target SL1 with the anti-sense oligo (ASO) to efficiently and specifically downregulate SARS-CoV-2 mRNA. Additionally, we carried out analysis of a functional interactome of NSP1 using BioID and identified components of anti-viral defense pathways. Our analysis therefore suggests a mechanism by which NSP1 inhibits the expression of host genes while enhancing that of viral RNA. This analysis helps reconcile conflicting reports in the literature regarding the mechanisms by which the virus avoids NSP1 silencing.
CVD is a leading public health problem. We first assessed the economic burden of CVD in Russia. Our results can be used for planning investments in prevention programs and measures for improving care for patients with CVD. Regular monitoring of the economic burden of CVD in the future at the federal, regional, and municipal levels will allow assessment of the dynamics of economic burden, as well as the effectiveness of investments in the economy in primary and secondary prevention. Because data are relatively unavailable, there are important limitations to this study, which highlight the need for more accurate CVD-specific information.
Uncertainties in instantaneous dam-break floods are difficult to assess with standard methods (e.g., Monte Carlo simulation) because of the lack of historical observations and high computational costs of the numerical models. In this study, polynomial chaos expansion (PCE) was applied to a dam-break flood model reflecting the population of large concrete dams in Switzerland. The flood model was approximated with a metamodel and uncertainty in the inputs was propagated to the flow quantities downstream of the dam. The study demonstrates that the application of metamodeling for uncertainty quantification in dam-break studies allows for reduced computational costs compared to standard methods. Finally, Sobol’ sensitivity indices indicate that reservoir volume, length of the valley, and surface roughness contributed most to the variability of the outputs. The proposed methodology, when applied to similar studies in flood risk assessment, allows for more generalized risk quantification than conventional approaches.
Aim. To analyze the social and economic burden of cardiovascular disease (CVD) in the Russian Federation for the period of 2006-2009. Material and methods. The analysis of the economic CVD burden included direct spending and economic loss related to CVD. Direct spending included hospitalization, ambulance service use, out-patient visits, high medical technologies, and out-patient pharmaceutical treatment. Economic loss included the loss in gross domestic product (GDP) due to death or disability in working-age people, as well as the disability benefits. Results. Total economic burden of CVD for 2008-2009 exceeded 1 trillion RUB, or 3 % of GDP for the respective period. Only one-fifth (21,3 %) of total economic burden of CVD in 2009 was represented by direct costs of the healthcare system. As much as 78,7 % of the total economic burden of CVD was represented by such indirect costs as economic loss, mostly due to premature mortality in working-age men. Conclusion. Substantial economic burden of CVD in theRussian Federation requires increased funding of preventive programs, aimed at CVD risk reduction, and healthcare optimization programs. This increased funding should facilitate mortality risk reduction in the working-age population.
Aims
To adapt and validate the Alcohol Use Disorders Identification Test (AUDIT) for use in the Russian Federation and countries with Russian-speaking populations by:
Methods
Systematic review of past use and validation of the Russian-language AUDIT. Interviews to be conducted with experts to identify problems encountered in the use of existing Russian-language AUDIT versions. A pilot study using a revised translation of the Russian-language AUDIT that incorporates country-specific drinking patterns in the Russian Federation.
Results and Conclusions
The systematic review identified over 60 different Russian-language AUDIT versions without systematic validation studies. The main difficulties encountered with the use of the AUDIT in the Russian Federation were related to the lack of:
A revised version of the Russian-language AUDIT was created based on the pilot studies, and was validated in primary healthcare facilities in all regions in 2019/2020.
Aim. Estimation of social, demographic and anamnestic characteristics of patients survived cerebral stroke as well as the medical treatment received by the patients before the reference stroke in the hospital and at discharge within the framework of the stroke register LIS-2 (study of mortality among patients survived stroke in Lyubertsy district). Material and methods. All the patients (637 persons) admitted to the Lyubertsy regional hospital №2 due to stroke from 01.01.2009 to 31.12.2010 were enrolled into the study. Results. 36% were men and 64% were women with mean age of 70.99±9.6 years old. 554 (87.0%) patients had history of arterial hypertension and 155 (24.3%)-of atrial fibrillation. 147 (23.1%) patients had previous stroke. In-hospital mortality made up 21.8% (mean age of 139 deceased patients was 72.7±9.6 years old). 374 (75%) patients were prescribed ACE inhibitors, 421 (85%)-antiplatelet agents, 4 (1%)-warfarin. Statins intake was recommended to 3 (1%) patients. Conclusion. We revealed low frequency of prescription of drugs with proven positive prognostic value in patients after stroke.
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