A36 The TP53 mutations in the Russian patients with de novo DLBCL

BackgroundTP53 dysfunction is implicated in lymphomagenesis and disease progression. Information about the frequency and spectrum of TP53 mutations in the Russian pathients with diffuse large B-cell lymphoma (DLBCL) in the current version of the IARC TP53 Mutation Database R17 is not represented. The goal of this work was to study the frequency, spectrum and functional significance of TP53 mutations in Russian patients with DLBCL.Material and methodsAt the present time the pilot group of 14 patients were included in the study. Diagnosis was assessed according to the criteria of the WHO classification system. Genomic DNA was isolated from formalin-fixed, paraffin embedded tissue blocks. Direct sequence analysis of gene TP53 was performed according to the IARC protocol, 2010 update.ResultsIn two patients were identified single nucleotide substitutions that are not described in the current version of the PubMed database. All of mutations occurred in the DNA-binding domain of p53. The nonsense mutation Arg196Ter was detected in one patient. Previously it was shown that formation of this premature stop codon might activate the nonsense-mediated RNA decay pathway. The second patient had two missense mutations – Leu130Phe and Arg156Cys. The first of them leads to p53 inactivation according to the analysis of the functional importance of amino acid substitutions using service PolyPhen-2.ConclusionWe detected TP53 mutation in 14% cases. The mutational rate in our study is in good agreement with other studies where the frequency of the TP53 mutations in patients with DLBCL ranged mostly from 13% to 23%

About inefficiency of personnel policy in health care of russia

The shortage of medical personnel, primarily in the district service and rural health care, the insufficient effectiveness of measures taken by the state to solve the personnel problem («presidential» allowance for the district service, the program «Zemsky doctor», etc.) indicate the insolvency of personnel policy in the industry. The state spending huge budgetary funds for training specialists deprived itself of the right to use them where they are urgently needed. The desire to improve the quality of training of medical students on the basis of accession to the Bologna agreement did not give the desired result. The availability of medical care is also limited by the fact that in the general structure of medical specialties, the number of doctors of clinical specialties, i.e. those who directly work with patients is significantly lower than in the EU and their share continues to decline. All of the above suggests that the Ministry of Health has no clear idea about the issue of personnel, is not formed the system able to solve it, which must include: career counseling -training - public distribution trained on a budgetary basis - professional development - career growth. The state and the leadership of the regions should create favorable conditions for work and life, attracting specialists, as well as interesting them in long-term work at the place of distribution. On the basis of the Soviet experience in the organization of personnel work in health care, best practice of other countries, the authors propose measures in the medical personnel training improvement, in attracting and long-term interest in their work in «problem» positions (district service, rural health care, etc.)

Application of reproductive technologies to the improvement of dairy cattle genomic selection

Genomic selection is a direction of breeding in which the value of an animal is predicted from DNA markers evenly covering the entire genome. This review summarizes information on modern trends in the genomic selection of dairy cattle and on application of reproductive technologies to the improvement of breeding process. The main trends in the development of genomic selection include improvement of the accuracy of breeding value estimations by combination of reference populations; use genotyping of cows in breeding programs; imputation of genotypes for absent SNPs with low marker density microarrays, and prediction of animal genotypes from the genotypes of relatives. Genomic selection can be even more profitable in combination with up-to-date reproductive biotechnologies: semen sexing, multiple ovulation and embryo transfer, ovum pick-up followed by in vitro fertilization, embryo genotyping, cloning of best breeders, etc. In programs of dairy cattle genomic selection, biotechnological procedures with gametes and embryos allow improvement of a variety of parameters determining breeding efficacy: selection intensity, accurate breeding value assessment, and generation interval. Successful methods for embryo genotyping for numerous markers after biopsy at the morula or blastocyst stage are based on whole genome amplification of embryo DNA. Eventually, these achievements will provide grounds for new approaches to the reduction of generation interval, selection of elite cows, reduction of inbreeding rate, etc

Ethnicity-specific distribution of <em>TRPM8</em> gene variants in Eurasian populations: signs of selection

The TRPM8 gene encodes the ion channel, which is a cold receptor in afferent neurons of the mammalian somatosensory system. We studied the frequency of haplotype distribution from six SNPs in the TRPM8 gene in Eurasian human populations, including Russians, Kazakhs and Chukchi. Four of the six SNPs are located in exon 7 (rs13004520, rs28901637, rs11562975, rs17868387), rs7593557 is in exon 11. These exons encode parts of the N-terminus, which is necessary for channel functioning in the plasma membrane of neurons. The rs11563071 is in exon 23 encoding part of the C-terminus. The primary difference in population distribution of haplotypes determines the SNP from exon 11 which leads to Ser419Asn substitution in protein. The most pronounced dif­ferences in the patterns of diversity and frequencies of haplotypes were observed between Chukchi and Russians. The frequency of major H1 haplotype encompassing the 419Ser gene variant differs in examined populations; 0.738 (Russians), 0.507 (Kazakhs) and 0.337 (Chukchi), p &lt; 0.001. The TRPM8 gene variants encoding 419Asn and carrying the minor alleles of rs28901637 (P249P) and rs11562975 (L250L) in exon 7 are characteristic of Asian populations. The frequency of all 419Asn variants in Chukchi is comparable to that in Africans, however, the minor allele frequencies of rs28901637, rs11562975 in Africans is low. Apparently in the process of human colonization of Eurasia, minor alleles of these SNPs diverged depending on rs7593557 structure in exon 11. We analyzed sequences of five TRPM8 mRNA isoforms extracted by researchers from different tissues. Sequence analysis demonstrates that they are transcribed from major H1 variant of the TRPM8 gene but contain different translation start codons, which are generated by alternative splicing from pro-mRNA

Rural healthcare of Russia. Status, problems, prospects

The transformations of domestic healthcare carried out in the last three decades have not led to the planned results, and in some areas the consequences have turned out to be negative. Rural healthcare suffered the most significantly. The aim of the study was based on the analysis of the situation in the rural health care of the country to propose measures to improve it. Material and methods. The statistical data of the Ministry of Health of Russia, Rosstat, Central Research Institute of Organization and Informatization of Healthcare, as well as data on the Siberian Federal District for the period from 1990 to 2020 were used. Scientific publications on the problem under consideration have been studied. Results and their discussion. The course taken in the early 90s of the last century towards the commercialization of medicine remains. So for the period from 2005 to 2018 in the structure of the country’s medical personnel, the number of people employed in the public sector decreased from 93.6 to 86.8 % (by 237 000), whereas in private medical organizations it increased by 2.3 times. In 2020, 38.4 % of medical organizations were already private. The most significant changes have occurred in rural healthcare. The number of paramedic and obstetric stations decreased by 21.1 %, the provision of beds in hospitals is 2 times lower than the national average, and doctors are 3 times fewer than in cities. In the age structure, the share of doctors over the age of 60 increased from 13.5 % (2017) to 18.1 % (2020). The implementation of the programs “Zemsky Doctor” and “Zemsky paramedic” did not lead to an increase in the provision of medical workers in rural areas. Today, medical care is geographically available only to 49 % of villagers, for 40 % it is difficult to access, and 9 % is practically inaccessible (2 % of respondents could not answer the question). This has led to the fact that the average life expectancy of the villagers is 1.5 years lower than that of the townspeople, and the total mortality is 1.2 % higher than the national average. Conclusion. The problem of accessibility of medical care to the rural population has worsened in the last three decades. The implemented programs aimed at improving its accessibility and quality, including for rural residents, have not led to a significant positive result

Results of targeted sequencing of the <i>PRL, PRLR, PRLHR</i> genes in young women with non-tumor hyperprolactinemia

Aim. To study the spectrum of variants in the PRL, PRLR, PRLHR genes in women of reproductive age with non-tumor hyperprolactinemia. Material and methods. In women with non-tumor hyperprolactinemia (n = 15), targeted high-throughput sequencing of the PRL, PRLR, and PRLHR genes was performed. The target panel of genes included coding regions and adjacent splicing sites. Results. When analyzing the PRL, PRLR, PRLHR genes, a number of rare and common variants were identified. The common variant rs1205955 was found in the PRL gene (MAF А = 0.279). For the PRLR gene, a rare variant rs185353023 was identified in the 3’UTR (MAF А/С = 0.003) and 12 common variants. For the PRLHR gene, 10 common variants have been identified. The maximum number of variants was localized in the 3’UTR region and introns. Conclusions. For the first time in Russia, targeted high-throughput sequencing of the PRL, PRLR, PRLHR genes was performed, the results of which did not reveal obvious pathological variants in the studied genes in women with high prolactin content of non-tumor origin. The discovered polymorphism in these genes makes it possible to further study its association with impaired function of the prolactin link of hormonal regulation

The Risk of Type 2 Diabetes Mellitus in a Russian Population Cohort According to Data from the HAPIEE Project

The aim of this study is to investigate the 14-year risk of type 2 diabetes mellitus (T2DM) and develop a risk score for T2DM in the Siberian cohort. A random population sample (males/females, 45–69 years old) was examined at baseline in 2003–2005 (Health, Alcohol, and Psychosocial Factors in Eastern Europe (HAPIEE) project, n = 9360, Novosibirsk) and re-examined in 2006–2008 and 2015–2017. After excluding those with baseline T2DM, the final analysis included 7739 participants. The risk of incident T2DM during a 14-year follow-up was analysed using Cox regression. In age-adjusted models, male and female hazard ratios (HR) of incident T2DM were 5.02 (95% CI 3.62; 6.96) and 5.13 (95% CI 3.56; 7.37) for BMI ≥ 25 kg/m2; 4.38 (3.37; 5.69) and 4.70 (0.27; 6.75) for abdominal obesity (AO); 3.31 (2.65; 4.14) and 3.61 (3.06; 4.27) for fasting hyperglycaemia (FHG); 2.34 (1.58; 3.49) and 3.27 (2.50; 4.26) for high triglyceride (TG); 2.25 (1.74; 2.91) and 2.82 (2.27; 3.49) for hypertension (HT); and 1.57 (1.14; 2.16) and 1.69 (1.38; 2.07) for family history of diabetes mellitus (DM). In addition, secondary education, low physical activity (PA), and history of cardiovascular disease (CVD) were also significantly associated with T2DM in females. A simple T2DM risk calculator was generated based on non-laboratory parameters. A scale with the best quality included waist circumference >95 cm, HT history, and family history of T2DM (area under the curve (AUC) = 0.71). The proposed 10-year risk score of T2DM represents a simple, non-invasive, and reliable tool for identifying individuals at a high risk of future T2DM

Polymorphism of the LCT gene regulatory region in Turkicspeaking populations of the Altay-Sayan region (southern Siberia)

Retention of lactase activity in adulthood (lactase persistence) is one of the most important adaptive traits for human populations that consume fresh milk from domestic animals. At a molecular-genetic level, lactase persistence is determined by the presence of specific alleles of polymorphic sites in cis-regulatory elements of the LCT gene located on chromosome 2q21. Ascertainment of the molecular-genetic causes of lactase persistence has made this trait one of the most convenient for studying mechanisms of human population adaptation to environmental conditions. But the populations of many regions remain insufficiently investigated in relation to the genetic variability of the LCT loci. This paper presents the results of polymorphism analysis of loci, including the enhancer element for the LCT gene and its flanking regions, in two Turkic-speaking populations from southern Siberia, Altaian Kazakhs and Khakasses. It was found that the “European” allele LCT-13910T is the most characteristic of the Turkic-speaking populations from Altai-Sayan regions among all the polymorphic variants associated with lactase persistence. The expansion of the “European” allele LCT-13910T to the gene pool of the populations in southern Siberia could be related to migration waves of ancient herders form western Eurasia during the Bronze Age (in III – II millennium BC). A decrease of the LCT-13910T allele frequency and the total frequency of its carriers in the Turkic-speaking populations of southern Siberia in comparison with the majority of European populations and the Kazakhs from southern Central Asia can be attributed to: (1) a significant influence on the Altai- Sayan population’s gene pool by Eastern Eurasian populations, for which the LCT-13910T allele is rare; (2) a lesser adaptive significance of lactase persistence for south Siberian populations, compared to the populations of Europe. Rare and unique SNPs in the locus under consideration that were found in the Altaian Kazakhs (LCT-13895G &gt; C and LCT-13927C &gt; G) and Khakasses (LCT-14011C &gt; T) potentially play a role in regulation of LCT gene expression, because they are located within the enhancer, regulating activity of its promoter

On the state of public health and healthcare Siberian Federal District during the pandemic (some results of 2020)

Introduction. The COVID-19 pandemic has become a huge challenge for the entire healthcare system, medical institutions and doctors. The results of the industry’s activities turned out to be insufficiently effective, and therefore it is necessary to analyze not only what is directly related to the coronavirus infection, but also the consequences that the pandemic has led to. Goal. To analyze the results and consequences of health care activities and the health status of the population of the Siberian Federal District during the COVID-19 pandemic. Material and methods. The statistical data of the Ministry of Health of the Russian Federation, Rosstat, the Central Research Institute for the Organization and Informatization of Healthcare (TSNIIOIS), the Federal Service for Supervision of Consumer Rights Protection and Human Well-Being, as well as data for the Siberian Federal District were used. Scientific publications on the problem under consideration have been studied. Results and discussion. In connection with the beginning of the COVID-19 pandemic in Russia, as in all countries of the world, serious anti-epidemic measures were carried out, the procedure for providing medical care to the population changed, the consequences of which did not have the best effect on their health, including in the Siberian Federal District. The number of visits per resident of the district as a whole decreased by 16.2 %, in the polyclinic by 19.5 %, at home increased by 44.4 %. The number of visits for preventive purposes decreased by 6 %, and the coverage of dispensary observation by 11.2 %. The proportion of patients with oncological diseases in stages 3-4 increased to 40.6 %. Hospitalization of the SFO declined by 17.2 %, the number of operated patients 17.8 %, and postoperative complications have increased by 43.7 % from 1.07 to 1.54 %. Total mortality amounted to in 2020 for 14.5 per 1,000 population, i.e. increased by 18 % compared to 2019 year, while only 1/3 was due to COVID-19. In 2020, the number of Russians decreased by 510 thousand people. Conclusions. The results of health care activities, a significant deterioration in the health of the population and the complication of the demographic situation in the country during the pandemic, indicate serious shortcomings in the organization of medical care to the population, primarily in extreme situations, and requires a deep analysis and adequate measures to improve the structure and functioning of the industry in any conditions

Development of Education Districts in the Strategy of Strengthening the Axiological Foundations of the Russian Education Space

The article presents an analysis of the specific features of the socio-cultural modernization of education in contemporary Russia and the methodology of the development of the ethno-regional education systems against the background of strengthening the unified education space of Russia. Special attention is paid to the consideration of the strategy of the development of education districts of contemporary Russia as the foundation for building the government vertical of state management in the field of education.As part of the development of organizational and pedagogical resources of risk management of the gap between the scientific and education space of the country, the authors have worked out the idea of setting up scientific and education complexes and developing education districts in the country. This approach meets the objective of improving the quality of higher education in the regions of the country by establishing clear links with regional universities in the most “advanced” areas, organizing scientific and educational activities.Creating education districts serves as the foundation of building up a multicultural education space of the Russian Federation, the resource of lining up control at the federal and regional levels, the formation of a new vector of education policy focused on the preservation and development of a unified, internally differentiated scientific and education space of the country