E670G PCSK9 polymorphism in HeFH & CAD with diabetes: is the bridge to personalized therapy within reach?

ObjectiveTo assess the distribution of PCSK9 E670G genetic polymorphism and PCSK9 levels in patients with Coronary Artery Disease (CAD) and Heterozygous Familial Hypercholesterolemia (HeFH), based on the presence of type 2 Diabetes Mellitus (T2DM).MethodsThe study included 201 patients with chronic CAD, including those with HeFH (n=57, group I) and without it (n=144, group II). DLCN was used to diagnose HeFH. The PCSK9 E670G (rs505151) polymorphism was genetically typed using the PCR-RFLP procedure. In both the patient and control groups, the genotype frequency matched the Hardy-Weinberg equilibrium distribution (P>0.05).ResultsThere were twice more G alleles in group I (13, 11.4%) than in group II (17, 6.0%), and thrice more (1, 3.0%) than in the healthy control group; nevertheless, these differences weren’t statistically significant. Simultaneously, PCSK9 levels were higher in HeFH patients (P<0.05) compared to non-HeFH patients not taking statins (n=63). T2DM was equally represented in groups I and II (31.6% vs. 33.3%). But carriers of AG+GG genotypes in group I had a higher chance of having a history of T2DM (RR 4.18; 95%CI 2.19-8.0; P<0.001), myocardial infarction (RR 1.79; 95%CI 1.18-2.73; P<0.05), and revascularization (RR 12.6; 95%CI 4.06-38.8; P<0.01), than AA carriers. T2DM was also more common among G allele carriers (RR 1.85; 95% CI 1.11-3.06; P<0.05) in patients with non-HeFH.ConclusionT2DM in patients with CAD, both with HeFH and non-HeFH, in the Uzbek population was significantly more often associated with the presence of the “gain-of-function” G allele of the PCSK9 E670G genetic polymorphism

COVID-19 Response in Uzbekistan: From RT-PCR Test System to the Clinical Trial of Subunit Vaccine

The coronavirus pandemic showed the need for urgently improvement of different sectors in Uzbekistan, especially, the healthcare system and the biopharma industries. Uzbekistan government and private sectors have taken comprehensive measures to control the spread of infection in the country and tried to mitigate the impact of the pandemic. In this chapter, we discussed the primary measures taken to combat the coronavirus pandemic and the details of developing a local reverse transcription real-time PCR (RT-qPCR) detection kit as well as the experience of conducting the phase III clinical trials of the recombinant Uzbek-Chinese vaccine-ZF-UZ-Vac2001 against coronavirus infection. Finally, information is given on the mass vaccination campaign in the country, the difficulties encountered and the achievements made. The developed RT-qPCR detection kit was successfully implemented into production and have widely used for pathogen diagnosis. A total of 6965 volunteers over 18 years old participated in the clinical trials of ZF2001 and the vaccine had an efficacy level of 84.8%. More than 67.6 million doses were administered using seven types of anti-COVID vaccines in the country. The pandemics urged the country to establish a scientific and technical base that aimed at quickly responding to potential future challenges and emergencies

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three genomic nomenclature systems to all sequence data from the World Health Organization European Region available until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation, compare the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Covid-19 pandemic in central Asia: policy and environmental implications and responses for SMES support in Uzbekistan

Today the economy of Uzbekistan, as well as the majority of other countries of the world, is developing in conditions of uncertainty. On the one hand, it is associated with the consequences of new coronavirus pandemic, and on the other - with the introduction of forced restrictions, which hinder business development. This article deals with the necessity to provide financial support to business during the coronavirus pandemic in developing countries. It shows the impact of measures to support small and medium enterprises on economic development. Finally, it outlines recommendations for additional interventions and further research

Scenarios for the development of the economy of Uzbekistan in the conditions of instability of the world economy

The article presents a systematic analysis of the natural and economic potential of the national economy of the Republic of Uzbekistan. The research methodology is based on the use of dialectical logic and a system-structural approach. General scientific methods and techniques were used in the work: scientific abstraction, grouping, qualitative expert assessments, quantitative assessments, comparative analysis and synthesis. Based on the study of trends in the development of the world economy and technologies of the future, the author proves that when choosing priority areas in economic sectors, the emphasis should be placed on those areas and technologies that will give the maximum effect for resource conservation, the growth of competitiveness of domestic products, sustainable employment, reduction of transaction costs, growth of human capital. During the discussion of the results of the study, the method of scenarios was used, which allows combining factors and conditions of development within a limited number of alternative models of economic growth, and using modern model analytical tools to assess the most likely consequences of their implementation. In conclusion, it is concluded that the considered scenarios represent extreme hypothetical directions of the long-term development of the national economy and determine the framework within which optimal solutions should be sought

ECONOMIC METHODS OF REGULATING THE INVESTMENT PROCESS BY STATE

This article analyzes the theoretical basis of investment and capital flows. The opinions of economist scientists were analyzed and concluded.In addition, the article analyzes the share of investments in long-term investments in shares, bonds and other securities issued by public and private companies, as well as in objects of acceleration, bank bonds. Unlike financial investments, Real investments are reflected as investments in the growth of fixed capital and material production reserves. The need to create this free environment in the economy, as well as the methods of state regulation of investment by subjecting it to market rules are analyze

ECONOMIC METHODS OF REGULATING THE INVESTMENT PROCESS BY STATE

This article analyzes the theoretical basis of investment and capital flows. The opinions of economist scientists were analyzed and concluded.In addition, the article analyzes the share of investments in long-term investments in shares, bonds and other securities issued by public and private companies, as well as in objects of acceleration, bank bonds. Unlike financial investments, Real investments are reflected as investments in the growth of fixed capital and material production reserves. The need to create this free environment in the economy, as well as the methods of state regulation of investment by subjecting it to market rules are analyzed