[Alopecia and COVID-19: possible etiopathogenetic variants and therapeutic approach]. / Alopetsiya i COVID-19: vozmozhnye etiopatogeneticheskie varianty i printsipy lecheniya.

Sudden hair thinning, phantom trichalgia in the early and late rehabilitation period after novel coronavirus infection (COVID-19) are the most common complaints of patients, that can be considered by both dermatocosmetologist and medical rehabilitation specialist. A telogen hair loss was found in 19.8% of patients, whereby 27.3% of patients suffering from hair loss during disease and 72.7% - at 3rd-6th month after recovery. Most commonly, hair loss is non-structural and associated with an abnormal ovulatory cycle shift and diffuse asynchronous loss of hair follicles in telogen phase, as well as with an increase of total predisposed to loss hair follicles number. Nevertheless, the analysis of clinical observations of patients with post-COVID hair loss has shown that this disorder is registered not only in telogen phase. There is a rapid disease progression up to the final stages in the presence of verified androgenetic alopecia diagnosis. The cases of alopecia areata and cicatricial alopecia, associated with previous COVID-19, also were registered. Androgenetic alopecia is the first (30.7%) and diffuse alopecia is the second (19.8%) by degree of incidence. The relapses or much less frequently the onsets of alopecia areata and the unexplained pronounced pain at the hair roots in parietal region (7.8%) are in the third place. The article presents in detail the possible reasons and mechanisms of hair loss associated with COVID-19, determines necessary examinations with consideration to the scientific analysis of domestic and foreign literature sources.

[The role of gene-gene and gene-environmental interactions of polymorphic matrix metalloproteinases loci in the formation of the risk of stroke in men with hypertension]. / Rol' gen-gennykh i genno-sredovykh vzaimodeistvii polimorfnykh lokusov matriksnykh metalloproteinaz v formirovanii riska razvitiya ishemicheskogo insul'ta na fone arterial'noi gipertenzii u muzhchin.

OBJECTIVE: Analysis of the role of genetic polymorphisms of matrix metalloproteinases (MMPs), their gene-gene and gene-environment interactions in the formation of ischemic stroke in men with arterial hypertension (AI). MATERIAL AND METHODS: The study included 523 men with arterial hypertension: 201 patients with ischemic stroke and 322 patients without stroke. The association of MMPs loci with stroke with hypertension was determined by logistic regression analysis in dominant, recessive, additive genetic models in PLINK v.2.050. For five SNPs co-located on chromosome 11 (314.3 kb), haplotypic analysis was performed, the relationship of haplotypes with stroke development was determined by the EM algorithm. Gene-gene and gene-environment interactions of MMPs with smoking and alcohol consumption during stroke development were evaluated by GMDR (Generalized Multifactor Dimensionality Reduction) using GMDR v.0.9 software. RESULTS: Polymorphic locus rs3025058 is associated with stroke in men in dominant and additive genetic models (OR=0.63-0.74, pperm=0.03). Four haplotypes of MMPs have a protective effect on the development of stroke with hypertension (OR=0.48-0.50, pperm=0.02-0.03). Four models of gene-gene interactions of polymorphic MMPs loci (OR=2.19-2.55, pperm<0.001) and three four-factor models of gene-environment interactions of MMPs with alcohol abuse (OR=2.82-3.11, pperm<0.001) are associated with a high risk of ischemic stroke in men with hypertension. rs3025058, rs1320632, rs11225395 and rs1799750 demonstrate the greatest contribution to gene-gene and gene-environment interactions in the formation of AI. CONCLUSION: Thus, the results of the study indicate that the interactions of MMPs genes with each other and with modifiable environmental factors play a significant role in the development of stroke with hypertension in men.

[Study of the functional significance of polymorphic loci of the LOXL1 gene associated with glaucoma according to genome-wide studies (in silico analysis)]. / Izuchenie funktsional'nogo znacheniya polimorfnykh lokusov gena LOXL1, assotsiirovannykh s glaukomoi po dannym polnogenomnykh issledovanii (analiz in silico).

Glaucoma is one of the most common eye diseases leading to blindness, and whole-genome studies have shown that genetic factors are important in its formation.Purpose - to perform an in silico analysis of the functional significance of polymorphic loci of the LOXL1 gene associated with glaucoma, using data from wholegenome studies. MATERIAL AND METHODS: Using the catalog of genome-wide studies (GWAS) of the National Human Genome Research Institute (https://www.genome.gov/gwastudies/), three polymorphic loci of the LOXL1 gene (rs2165241, rs4886776, rs893818) associated with glaucoma (pseudoexfoliation glaucoma/syndrome) were chosen for the study. Using modern databases on functional genomics (SIFT, PolyPhen-2, HaploReg, GTExportal), the functional significance of these polymorphic loci was assessed (nonsynonymous substitutions, epigenetic effects, association with gene expression, associations with alternative splicing of gene transcripts). RESULTS: The work establishes the important functional significance of the rs2165241, rs4886776 and rs893818 polymorphic loci of the LOXL1 gene. They demonstrate significant epigenetic effects (affect the affinity to five transcription factors, are located in the region of promoters and enhancers, in the region of hypersensitivity to DNase-1), are associated with the expression and alternative splicing of three genes (LOXL1, LOXL1-AS1, RP11-24D15.1) in cell cultures, organs and tissues pathogenetically significant for development of glaucoma, are strongly linked to the rs1048661 polymorphism, which causes the replacement of the Arg141Leu amino acid in the LOXL1 polypeptide. CONCLUSION: Polymorphic loci of the LOXL1 gene (rs2165241, rs4886776, and rs893818) are of great functional importance (epigenetic, eQTL, and sQTL), which may be the biomedical basis of their associations with glaucoma.

[Analysis of the functional role of polymorphism in the CDKN2B-AS1 gene GWAS-significant for primary open-angle glaucoma (an in-silico study)]. / Analiz funktsional'nogo znacheniya GWAS-znachimogo dlya pervichnoi otkrytougol'noi glaukomy polimorfizma gena CDKN2B-AS1 (in silico issledovanie).

Primary open-angle glaucoma (POAG) is the most common form of glaucoma in which genetic factors play a significant role. According to genome-wide studies (GWAS), the CDKN2B-AS1 gene is associated with POAG. PURPOSE: To study in silico the functional significance of the CDKN2B-AS1 gene polymorphism GWAS-significant for primary open-angle glaucoma. MATERIAL AND METHODS: The in-silico analysis was based on data from the GWAS catalog, five polymorphic loci of the CDKN2B-AS1 gene (rs1063192, rs7865618, rs2157719, rs944800, rs4977756) associated with POAG were selected. The study evaluated the regulatory potential, the relationship with the expression and alternative splicing of genes of the CDKN2B-AS1 gene polymorphism using modern databases for functional genomics - HaploReg and GTExportal. RESULTS: An important functional significance of the polymorphic loci rs1063192, rs7865618, rs2157719, rs944800, rs4977756 of the CDKN2B-AS1 gene was revealed. These loci are located in the region of histones marking enhancers and in the region of hypersensitivity to DNAse-1, can be found in more than ten different organs and tissues, in the regions of regulatory DNA motifs to five transcription factors (AIRE, GATA, Tgif1, Pou2f2, and Zfp187), and are associated with expression of three genes (CDKN2B-AS1, CDKN2B, CDKN2A) and alternative splicing of transcripts of two genes (CDKN2B-AS1 and RP11-149I2.4) in cell cultures, organs and tissues with pathogenic significance for glaucoma development. CONCLUSION: Polymorphism of the CDKN2B-AS1 gene (rs1063192, rs7865618, rs2157719, rs944800, rs4977756) has significant regulatory potential and is associated with the expression and alternative splicing of genes, which possibly underlies its association with primary open-angle glaucoma.

[Polymorphic locus rs1061624 of the ТNFR2 gene is associated with the development of arterial hypertension in males].

Aim To study the involvement of cytokine polymorphous loci in development of arterial hypertension (AH) in men from the Central Black Earth region of Russia.Materials and methods 821 men were evaluated, including 564 patients with AH and 257 individuals of the control group. Analysis of 8 cytokine mononucleotide polymorphisms (MNP) was performed using the real-time polymerase chain reaction with TagMan probes. Statistical analysis was performed with the STATISTICA (v.10.0) and PLINK (v.1.06) software. The regulatory potential of MNP was analyzed with the HaploReg (v.4.1) service (http://archive.broadinstitute.org).Results The rs1061624 ТNFR2 polymorphous locus was associated with development of AH in men in recessive (odd ratio (OR), 0.33; 95 % confidence interval (CI): 0.18-0.61, рperm=0.0004) and additive (OR, 0.50, 95 % CI: 0.34-0.74, рperm=0.0006) genetic models and exerted a protective effect in development of AH. The rs1061624 MNP of the ТNFR2 gene has a regulatory significance; it is located in the DNA sites hypersensitive to the action of DNAase 1 and in binding sites for transcriptional factors and histones that mark enhancers and promoters in different organs and tissues.Conclusion The rs1061624 ТNFR2 gene polymorphism is involved in the development of AH in men of the Central Black Earth region of Russia.

[Study of associations of polymorphism of matrix metalloproteinases genes with the development of arterial hypertension in men].

The aim of research. To study the association of polymorphic loci of matrix metalloproteinases with the development of essential hypertension (EH) in men of the Central Chernozem Region of Russia. Materials and methods. A study of 564 men with EH and 257 control men was performed. Analysis of the polymorphic loci of metalloproteinases rs11568818 MMР7, rs1320632 MMР8, rs11225395 MMР8, rs1799750 MMР1, rs3025058 MMР3 was performed using real-time PCR. The study of associations of SNPs and their haplotypes with the development of arterial hypertension was carried out using logistic regression analysis in the PLINK software (v. 2.050). The regulatory potential of polymorphic loci was analyzed in the HaploReg software (v. 4.1) (http://archive.broadinstitute.org). The effect of SNP on gene expression was studied using the data of the Genotype-Tissue Expression project (http://www.gtexportal.org/). Results. Haplotype including rs11568818 MMP7, rs1320632 MMP8, rs11225395 MMP8 and rs1799750 MMP1 associated with a high risk of disease in men (OR=2,58, pperm=0,04). These polymorphisms located in region of promoter and enhancer histone marks and in the region of hypersensitivity to DNAse-1. They located in sites of proteins bound (TBP, CJUN, CFOS and GATA2) and they associated with the level of gene expression ММР7, ММР27 and RP11-817J15.3 (in peripheral blood, skeletal muscles, nervous tissue and other). Сonclusion. Haplotype G-A-C-1G for polymorphisms rs11568818 MMP7, rs1320632 MMP8, rs11225395 MMP8, rs1799750 MMP1 are associated with the development of essential hypertension in men in the Central Chernozem Region of Russia.

[Extracorporeal Membrane Oxygenation in the Therapy of Cardiogenic Shock Due to Fulminant Myocarditis].

This article presents a clinical case of a 40-year-old woman with fulminant myocarditis which progressed rapidly to the development of cardiogenic shock resistant to standard intensive care, but with a positive response to extracorporeal membrane oxygenation.

[The role of stress factors and genetic predisposition in the development of stroke in patients with essential hypertension]. / Rol' stressovogo faktora v realizatsii geneticheskoi predraspolozhennosti k razvitiiu insul'ta na fone gipertonicheskoi bolezni.

To study the interaction of polymorphic markers of matrix metalloproteinases (MMP) and chronic stress in the development of stroke associated with hypertension. MATERIAL AND METHODS: A total of 830 patients, including 303 patients with ischemic stroke associated with essential hypertension (EH) and 527 patients with EH without stroke, were examined. The study of metalloproteinases SNP was carried out using real-time PCR. The functional significance and influence of polymorphic loci on gene expression was studied using of HaploReg (v4.1) (http://archive.broadinstitute.org) and GTEx-portal (http://www.gtexportal.org). RESULTS AND CONCLUSION: An association of the genotype GG (rs11568818) of MMP7 with a high risk of stroke in patients exposed to regular stress (OR=1.71) was observed. It was found that allele 5A and genotype 5A/5A (rs3025058) of MMP3 had a protective effect on the development of stroke in patients without regular stress in the anamnesis (OR=0.73 and OR=0.60, respectively). Those SNPs are localized in the region of histone proteins H3K4me1 and H3K4me3, in the region of hypersensitivity to DNase-1, in the region of binding of regulatory proteins and transcription factors. The polymorphic locus rs11568818 is associated with the expression level of MMP7.

Thrombosis risk factors and gene mutations in young age patients with acute coronary syndrome.

Goal of research. Study the role of thrombosis risk factors and polymorphisms in genes in young age patients with acute coronary syndrome (ACS). MATERIALS AND METHODS: Te study included 299 patients of age 25 to 44 years old with ACS were treated from 2012 to 2017 at the department of myocardial infarction 1st KGBUZ Altay regional cardiological clinic. Te middle age of patients with ACS was 40.3 ± 0.2 years. Te control group included of 53 apparently healthy volunteers aged from 25 to 44 years old, the average age those patients was 39.94 ± 0.79 years. Also, those patients hadn't any comorbid conditions. Te control group hadn't any datas of ischemic heart disease by the results of exercise tolerance tests. All patients had standard clinical, anamnestic, biochemical tests, lipid profle, fasting plasma glucose, electrocardiogram, echocardiography and coronaroangiography, also they were determined growth and weight with body-weight index. 116 patients from the ACS group and 53 patients fromthe control group had screening of polymerase chain reaction for determine polymorphism of the FII genes G20210-A, FV G1691-A, and MTHFR C677-T. RESULTS: We identifed the most signifcant sets of risk factors associated with ACS in young age patients based on our multifactorial statistical analysis with binary logistic regression. Tis combination of risk factors was: increased levels of low-density lipoproteins, decreased levels of high-density lipoproteins, smoking, existence of MTHFR homozygous polymorphism, heredity in combination with smoking, FV homozygote, MTHFR homozygote, smoking with MTHFR-homozygote. CONCLUSION: Te ability predicting the risk of developing cardiovascular disease in young people based on traditional risk factors, partly modifable, as well as the researching of "new" risk factors, opens up new opportunities for developing a clinical approach of treating young patients with high risk of ACS.

[The clinical significance of copeptin and matrix metalloproteinases in men with acute coronary syndrome].

AIM: To evaluate clinical value copeptin and matrix metalloproteinases in men with acute coronary syndrome (ACS). MATERIALS AND METHODS: The study included 152 men with ACS. After evaluation of the traditional markers of myocardial damage, the patients were divided into 2 groups: the first group included patients with myocardial infarction (MI) - 84 people, the average age was 56.6±1.0 years, the second - with unstable angina (UA) - 68 at the age of 61,4±1.2 years. All patients at admission and after 6 hours and on day 6 of hospitalization were evaluated for the level of CPK MB, troponin I, copeptin, MMP-1, MMP-2, MMP-7, MMP-9 and TIMP-1. RESULTS: Concentration of copeptin at admission in patients with it is 3.5 times higher than in the group with UA and significantly higher than that of control group. To 6­th day of hospitalization, the concentration of copeptin reduced, but nonetheless remains significantly higher than in the control group (0,9±0,1 vs. 0.2±0,0, p=0.000) without significant differences with group UA. The level of MMP-1 and MMP-2 in patients with MI and UA at admission higher than in the control group, and in case of MI these levels are significantly higher than in case of UA. CONCLUSION: The obtained data indicates the possibility of using copeptin as a marker of myocardial damage. Additionally, it indicates myocardial damage an increase in the level of MMP-1, MMP-2 and MMP-7.

[Association of the -844G>A polymorphism in the catalase gene with the increased risk of essential hypertension in smokers]. / Assotsiatsiya polimorfizma -844G>A gena katalazy s povyshennym riskom razvitiya arterial'noi gipertonii u kuril'shchikov.

AIM: To investigate whether the functionally relevant -844G>A promotor polymorphism in the catalase (CAT) gene is associated with the development of essential hypertension (EH). SUBJECTS AND METHODS: The investigation enrolled 2,339 unrelated ethnic Russian people, including 1,269 EH patients and 770 apparently healthy individuals. Genotyping of CAT -844G>A (rs769214) polymorphism was performed using a TaqMan real-time polymerase chain reaction assay. RESULTS: The -844A allele (odds ratio (OR)=1.31; 95% confidence interval (CI), 1.04 to 1.64; р=0.02) and the -844AA genotype (OR=1.41; 95% CI, 1.02 to 1.94; р=0.03) were found to be related to a higher risk of EH in the smokers. No association was found between this polymorphism and EH risk in the non-smokers. CONCLUSION: Smoking is a predisposing factor for development of EH in CAT -844AA genotype carriers.

[Antegrade unilateral perfusion of the brain through the brachiocephalic trunk in operations on the aortic arch].

Presented herein is a technique of unilateral antegrade perfusion of the brain in operations on the aortic arch. The method makes it possible to perform both systemic artificial circulation and adequate physiological perfusion of the brain, promoting minimization of the number of neurological complications.

[Bioinformatic investigation of the involvement of candidate genes of cytokines in the formation of large myomatous nodes in women with uterine cancer in older age groups].

The aim was to study bioinformatics involvement of candidate genes of cytokines in the formation of large fibroids in women with uterine cancer in older age groups. Genotyping of 15 molecular genetic markers cytokines was performed in 120 patients with uterine myoma with large myoma nodes and 107 patients with myoma nodes of small size. The study found that genetic risk factors for fibroids with large uterine fibroids are two combinations of genetic variants: G SDF-1, CC IL-1ß, A RANTES (OR=5,56) and A RANTES with genotype CC IL-1ß (OR=4,60). 12 of 15 polymorphic loci studied in various combinations (8 revealed significant combinations) have protective value in the formation of large fibroids with uterine cancer (OR=0,09-0,31).

[Clinical features of patients of older age groups with uterine myoma].

The study analyzed 301 patients with uterine cancer at the age of 45 years and older and 304 patients with uterine myoma 45 years. It was found that patients with uterine myoma of the older age group (45 and older) have the following clinical features: overweight and thus increased BMI these women, a lower percentage of a family history of uterine cancer, a smaller percentage of infertility, a greater number of pregnancies, births, medical abortions, the high prevalence of diseases of the cardiovascular system and pathology of the cervix, large size fibroids and as a consequence more common compartment syndrome adjacent organs by myoma nodes (disuric disorders).

[Toxicological-hygienic assessment of the low-alcohol tonic (energizing) carbonated drinks].

The impact of the low-alcohol tonic (energizing) carbonated drinks on biochemical and hematological indices, on the functional state of the central nervous system and cardiovascular system was studied within the experiment over the outbred white male rats. The gained results were compared to indices of animals receiving the same concentrated solution of ethanol used for drinks preparation as well as to figures of intact group animals. The results gained from all compared animals groups had no significant differences.

[Hygienic characteristics of children's educational establishments].

The improved procedure for an integrated assessment of the state-of-the-art of preschool educational establishments was appraised. This procedure provides the qualitative and quantitative characteristics of each factor, the degree of its incompliance to the hygienic standards, reveals risk factors, and allows one to take operative decisions to manage a risk, which are aimed at promoting the health status in infants, and expands a sociohygienic monitoring methodology, by increasing the number of accountable objects of the vital activity medium.

[Hygienic aspects of health hazards at school age].

The researchers have developed a method of qualitative and quantitative evaluation of risk factors in various types of educational institution. The use of this method in the system of social-and-hygienic monitoring makes it possible to take into account a greater number of objects of vital activity environment, objectively characterize factors of vital activity environment that are hazardous to schoolchildren, and determine the order and extent of necessary preventive measures. Use of computer techniques in hygienic investigations promotes early prenosological diagnostics of school-age conditions that develop under the influence of factors of vital activity environment, and allows their timely correction.

[Computer technologies in the hygienic studies of children and adolescents]. / Komp'iuternye tekhnologii v gigienicheskikh issledovaniiakh detei i podrostkov.

Computer technologies were used to develop new hygienic technologies of the activities of civil service in providing sanitary and epidemiological well-being to the population, to devise methods for evaluating and predicting the influence of environmental factors on human health. The specific developmental features of the psychophysiological status in schoolchildren were revealed in relation to their age, sex, the hygienic schooling and living conditions, which may substantiate a package of goal-oriented measures for health promotion and preservation in children.

[The effect of histochrome on the lipid peroxidation indices during the surgical treatment of patients with ischemic heart disease of different functional classes]. / Vliianie gistokhroma na pokazateli perekisnogo okisleniia lipidov pri khirurgicheskom lechenii patsientov s ishemicheskoi bolezn'iu serdtsa raznykh funktsional'nykh klassov.

The cardioprotector effect of the antioxidant histochrom was studied during surgical creation of an aortocoronary shunt in patients suffering from ischemic heart disease with angina pectoris of different functional classes (FC). The initial content of lipid peroxidation (LPO) products in the blood of patients with angina pectoris of functional class II was much lower than that in patients with angina pectoris of FC IV. This difference disappeared practically after intravenous infusion of histochrom in the pre- and postoperative period. Besides with the use of histochrom the incidence of early postoperative complications reduced significantly.