In the last decade the search for and annotation of human genome polymorphisms associated with phenotype have become particularly important concerning the opportunity of their use in medical and population genetics, pharmacogenomics and evolutionary biology. The study was aimed to calculate the frequencies and analyze the prevalence of 13 germline polymorphisms of two genes, ТР53 encoding the genome-keeper p53 protein and WRAP53 involved in regulation of p53 production, in 28 Russian populations. We obtained data on 9 exonic ТР53 variants (rs587781663, rs17882252, rs150293825, rs112431538, rs149633775, rs144340710, rs1042522, rs1800371, rs201753350), one intronic polymorphism (rs17881850), and three variants of WRAP53 (rs17880282, rs2287499, rs34067256). In the majority of populations the sample size was over 50 people (except five populations with 30–49 surveyed people). The alternative alleles’ population frequencies for studies genetic variants in most Russian populations were close to appropriate allele frequencies in European and Asian populations of similar origin taken from global databases. The exceptions were six populations ("Central Caucasus", "Dagestan", "northern Russians", "southeastern Russians", "Tatars" and "Transcaucasia") with increased alternative alleles’ population frequencies. All listed populations except the population of “southeastern Russians” are characterized by polymorphisms with high allele frequencies not satisfying the Hardy–Weinberg principle.
The negative impact of the digital environment on the health of young people necessitates the search for new methods of hygienic education. This study aimed to test and assess the hygienic qualities of the practice designed to give students and schoolchildren the skills allowing safe use of electronic devices. The study involved 256 students, 200 senior schoolchildren, 400 teachers and 251 parent. The hygienic education practice relied on the healthy lifestyle materials published in scientific literature, as well as materials posted on the Internet resources of medical organizations professionally engaged in the area considered, as well as their groups in the social networks Odnoklassniki, VKontakte, Facebook, Instagram, etc. We observed physical development of the schoolchildren and students dynamically and polled schoolchildren, students, teachers, and parents. For statistical processing of the results, we used methods of descriptive statistics, Student's t-test, correlation, discriminant and cluster analysis, and calculated risks. As the most popular source of information about health maintenance, Internet scored as follows: among schoolchildren — 79.0%, students — 88.6%, parents — 64.9%, teachers — 50.4%. The tested hygienic education practice allowed for a reduction of the number of schoolchildren and students who did not have the skills to safely use electronic devices to 20 and 25%, respectively. The practice also taught the participants to reduce their daily smartphone use time, engage in physical activity more often, which ultimately increased the share of children whose physical development was normal (p ≤ 0.01), and helped to increase the duration of night sleep. The tested methods of education are not costly; they can be replicated in other regions and organizations.
Neuroimmune interactions represent a highly dynamic mechanism for the regulation of cognitive function in chronic cerebral ischemia (CCI). The aim of this study was to investigate changes in salivary proinflammatory cytokines IL1β and IL6 and anti-inflammatory IL10 in patients with CCI (mean age 65.4 ± 9.1 years) before and after cognitive tests. After cognitive tests, the levels of salivary IL1β and IL6 were significantly elevated by 101.6 ± 19.1 pg/ml (n = 74) and 32.8 ± 6.1 pg/ml (n = 74), respectively. Using one-way ANOVA ana non-parametric statistical methods, we were able to demonstrate associations between changes in salivary interleukins and cognitive performance. In the group of patients with a significant increase in IL1β, some cognitive parameters were lower than in the group with negative or zero dynamics of this cytokine: the patients made more mistakes in the subtraction test (F = 11.5; n = 63; p = 0.001) and performed worse in the Luria test (F = 6.8; n = 65; p = 0.01). For IL6, Spearman’s rank correlation coefficient for the number of mistakes in the subtraction test was positive and differed significantly from 0 (R = 0.26; n = 62; p = 0.042). The group with positive IL10 dynamics performed better in N-back test (F = 5.2; n = 67; p = 0.03) and made fewer mistakes in the subtraction test (F = 6.8; n = 63; p = 0.01) in comparison with patients who demonstrated negative IL10 dynamics. Good performance in other cognitive tests was not correlated with interleukin dynamics. The article also discusses possible mechanisms underlying interleukin effects on cognitive function in patients with CCI and applications of the obtained data.
The paper reports the results of survey carried out in order to assess patients’ opinion on the remote medical care provided by the telemedicine center of theDepartment of health of Moscow during the pandemic. Survey of 216 COVID-19 patients who received outpatient care made it possible to assess their healthcondition and determine the factors contributing to satisfaction with care provided. Patients’ health condition was evaluated based on the course of underlyingdisease and comorbidities, which were revealed in 24.3% of COVID-19 patients. The following three groups were formed: patients with favorable (37.5%),satisfactory (36.7%) and unfavorable (25.8%) health condition. The majority of patients (76.4%) were satisfied with telemedicine consultations; men (79.8%),individuals with favorable condition (83.1%) and patients under 50 (81.9%) demonstrated significantly higher level of satisfaction. The following arguments in favourof telemedicine consultations were specified by patients: appointment of the specialist’s consultation, promptness of treatment appointment, provision of medicalrecommendations, including recommendations on a healthy lifestyle, as well as promptness of house call and ambulance call. The main dissatisfaction reasons wereas follows: lack of appropriate equipment, difficulties when setting up the equipment, complexity of the instructions for connecting to telemedicine consultations,poor quality of video/audio conferencing; these indicated the patients’ inadequate technical resources. Telemedicine consultations may be considered an effectivemethod of outpatient care provision for COVID-19 patients, especially since 64.7% of patients plan to use telemedicine consultations in the future, and 72.3% ofpatients are ready to recommend them to others.
Standard asthma therapy includes prescription of β2-agonists. Changes in the functional activity of β2-adrenergic receptor are associated with ADRB2 gene polymorphism and related to the low therapeutic response to β2-agonists. Identification of carriers of the clinically significant gene variants will help to avoid ineffective treatment and prescribe an alternative therapy. This study aimed to assess clinical significance of the ADRB2 gene polymorphisms (Arg16Gly and Gln27Glu) associated with the therapeutic response to β2-agonists in the group of asthma patients. We subjected a small group of adult nonsmoking patients (n = 21) with moderate asthma (III–IV stage of GINA) to clinical and genetic examination. The group included patients with the new theratype, those that poorly respond to β2-adrenergic drugs but significantly to M-cholinergic agonists. The first group included patients responding well to both salbutamol and ipratropium bromide. The second group was comprised of the patients for whom salbutamol was not effective but who tested positive for response to ipratropium bromide. The analysis of distribution of polymorphic variants of Arg16Gly and Gln27Glu revealed no significant relationship between alleles and genotypes and the efficacy of β2-agonists (0.52 for the rs1042713 variant, p = 1.0; 1.0 for the rs1042714 variant, p = 0.74, respectively). The genotype of patients that did not respond to salbutamol was either Arg16Gly or Gly16Gly. Further studies are needed that would involve a larger number of patients and an expanded list of the tested polymorphic variants. 
HaCaT cell line is a widely used model for studying normal human keratinocytes. However, mutations of TP53 gene are typical for this cell line, which have a substantial impact on functions of the encoded protein. The features of this regulatory circuit should be considered when using HaСaT cells for assessment of human skin physiology and pathology in vitro. The study was aimed to assess the features of differentiation realization in HaCaT cells with modulated activity of p53 protein. The expression of р53 was reduced by knockdown of ТР53 gene by shRNA (by 2.2 times, p < 0.05), and the elevated concentration of the р53 active forms was achieved via exposure of cells to Nutlin-3a, the MDM2 inhibitor and the major negative regulator of р53. It has been found that regulation of at least three differentiation markers, СASP14, IVL (expression increase by 3.9 and 3.7 times respectively in the p53-knockdown cells, p < 0.05) and TGM1 (twofold expression decrease in the p53-knockdown cells, and 1.7-fold expression increase under exposure to Nutlin-3a, p < 0.05) in HaCaT cells is p53-mediated. The positive correlation has been revealed for expression of TGM1 and p53 that might be realized indirectly via ΔNp63 expression alteration. At the same time, modulation of p53 does not result in significant alterations in expression of cytokeratins.
The angio- and neurovisualization methods vigorously developing in recent decades determine the relevance of improvement of etiopathogenetic ischemic stroke classification used for the treatment tactics selection and for secondary prevention of the disorder. The study was aimed to clarify the capabilities of clinical diagnosis for pathogenetic variants of ischemic stroke. For that, in 125 postmortem cases, the macro and microscopic examination of brain and cardiovascular system was carried out in order to verify the stroke pathogenesis established as a result of the previous patients’ examination. The study demonstrates the great potential of the major pathogenetic stroke subtypes (large-artery atherosclerosis, cardioembolism, small-artery occlusion) diagnosis using the complex of contemporary clinical and instrumental methods and the main morphological criteria of these subtypes in accordance with the TOAST classification. Moreover, the clinical and pathomorphological assessment allowed us to differentiate stroke resulting from various alterations of single cerebral artery, the atherothrombotic occlusion (44% of cases for the subtype), arterio-arterial embolism (13%) and critical stenosis (10%), as well as stroke resulting from cerebrovascular insufficiency (33%), within the “large-artery atherosclerosis” subtype. Thus, the high informativity of the existing examination methods allows for a more differentiated understanding of the cause of ischemic stroke, which is fully in line with modern personalized medicine.
The lack of information about the frequency of pharmacogenetic markers in Russia impedes the adoption of personalized treatment algorithms originally developed for West European populations. The aim of this paper was to study the distribution of some clinically significant pharmacogenetic markers across Russia. A total of 45 pharmacogenetic markers were selected from a few population genetic datasets, including ADME, drug target and hemostasis-controlling genes. The total number of donors genotyped for these markers was 2,197. The frequencies of these markers were determined for 50 different populations, comprised of 137 ethnic and subethnic groups. A comprehensive pharmacogenetic atlas was created, i.e. a systematic collection of gene geographic maps of frequency variation for 45 pharmacogenetic DNA markers in Russia and its neighbor states. The maps revealed 3 patterns of geographic variation. Clinal variation (a gradient change in frequency along the East-West axis) is observed in the pharmacogenetic markers that follow the main pattern of variation for North Eurasia (13% of the maps). Uniform distribution singles out a group of markers that occur at average frequency in most Russian regions (27% of the maps). Focal variation is observed in the markers that are specific to a certain group of populations and are absent in other regions (60% of the maps). The atlas reveals that the average frequency of the marker and its frequency in individual populations do not indicate the type of its distribution in Russia: a gene geographic map is needed to uncover the pattern of its variation.