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Chronic heart failure (CHF) is a global medical, social, and economic problem. It is a syndrome caused by imbalanced neurohumoral regulation of the cardiovascular system, which is accompanied by impaired systolic and/or diastolic function of the heart. Currently, the search and study of new biological markers that can help in the early diagnosis of CHF, serve as a laboratory tool for assessing treatment effectiveness, or be used as prognostic markers and risk stratification criteria are ongoing. Researchers focused on studying the role of Klotho protein, fibroblast growth factor 23 (FGF23), and sclerostin in patients with CHF. Klotho expression decreases as the body ages, and impaired production has been reported in various aging-related diseases. The FGF23 / Klotho axis plays a key regulatory role in cardiovascular pathology. Laboratory, clinical, and genetic studies have suggested that sclerostin is associated with heart disease, although available data are not entirely consistent. Clinical work conducted on the study of the Klotho protein, FGF-23, and sclerostin indicates the potentially important diagnostic and prognostic significance of their analysis in patients with CHF. Thus, more studies of the issues related to serial testing of these biological markers, including in the aspect of the multibiomarker model, are needed.

Despite significant advances in medicine, cardiovascular disease continues to be the leading cause of death worldwide. An important task in cardiology is the search and study of new cardiovascular biological markers. In recent years, salusins have attracted the interest of scientists. Salusins are endogenous biologically active peptides, which were first identified in 2003. Thus far, studies have demonstrated that salusin-α and salusin-β play important roles in vascular remodeling, inflammation, hypertension, and atherosclerotic processes. Salusin-α exhibits an antiatherogenic effect, whereas salusin-β plays a proatherogenic role. Despite the diverse biological, physiological, and pathophysiological aspects of salusins, the exact mechanism of their cardiovascular effects is not fully known. Further in-depth studies of the role of salusins in cardiovascular diseases are required. The regulation of the concentration and expression of salusin-α and salusin-β may prove to be a promising strategy for the treatment of patients with cardiac diseases.

Cardiovascular pathology is a leading cause of morbidity and mortality. An important task of modern cardiology is the search and study of new biological markers. Scientists’ interest is actively focused on the study of interleukin-38. Interleukin-38 is an anti-inflammatory cytokine and a member of the interleukin-1 family. This study aimed to analyze literature sources devoted to the study of interleukin-38 as a cardiovascular biological marker. Literature sources, including all relevant publications in PubMed (MEDLINE), RSCI, Google Scholar, and Science Direct, were analyzed. The search depth was 9 years. Interleukin-38 is found in the skin, heart, placenta, fetal liver, spleen, thymus, and activated B cells of the tonsils. Interleukin-38 protein is detected in human plasma, serum, and cell cultures by enzyme-linked immunosorbent assay. Interleukin-38 regulates immune and inflammatory responses by binding to its receptors and activating downstream signals. Its deficiency is associated with increased systemic inflammation in aging, cardiovascular diseases, and metabolic diseases. Currently, not much clinical and experimental data have been accumulated regarding the effect of interleukin-38 on the cardiovascular system; however, further studies are expected to demonstrate the possibility of its use as an additional laboratory tool for diagnosis and assessment of prognosis in patients with cardiac problems. Regulating the concentration and expression of interleukin-38 is a promising strategy for the treatment of cardiovascular diseases.

Introduction. The objects of the research are experimental specimens of glued laminated wood with a steel rod glued along the wood fibres in each of them. The subject of the research is the values of resistance of wood to pulling out or push-through of the rod glued along the fibres, as well as the compliance of the joint. The goal of the research is to calculate the resistance according to the test results and compare the obtained value with normative data. The relevance of the research is due to the widespread application in construction of glued wood structures and joints on glued rods. The obtained data can be used in calculation models and in the calculation of nodes.Materials and methods. Experiment and calculation methods are used in the research.Results. The results of five specimens were used to obtain the values of total deformations for each stage of loading. It occurred due to chipping of the wooden element along the fibres at the border of the adhesive joint and the wood. Wood resistance and compliance values for each specimen were calculated and tabulated. The normative value of wood resistance was obtained. It exceeded the value specified in the normative document data. A numerical normative value of compliance was also obtained.Conclusions. The excess of the resistance obtained from the experiment over the value in the normative document indicates its applicability with provided safety factor. In the calculation of unique structures according to special technical specifications, it is possible to use an increased resistance value obtained as the result of the experiment. The compliance of a rigid joint on rods glued along the fibres is small. In wooden structures it is not possible to avoid it completely.

Abstract The genomic landscape of Stone Age Europe was shaped by multiple migratory waves and population replacements, but different regions do not all show similar patterns. To refine our understanding of the population dynamics before and after the dawn of the Neolithic, we generated and analyzed genomic sequence data from human remains of 56 individuals from the Mesolithic, Neolithic, and Eneolithic across Central and Eastern Europe. We found that Mesolithic European populations formed a geographically widespread isolation-by-distance zone ranging from Central Europe to Siberia, which was already established 10,000 years ago. We found contrasting patterns of population continuity during the Neolithic transition: people around the lower Dnipro Valley region, Ukraine, showed continuity over 4000 years, from the Mesolithic to the end of the Neolithic, in contrast to almost all other parts of Europe where population turnover drove this cultural change, including vast areas of Central Europe and around the Danube River.

Research into new biological markers may help early diagnosis and effective therapy for cardiology patients. The use of biomarkers to evaluate patients has made a major impact in oncology, but is still in its infancy in the cardiology field. Studies on secreted frizzled-related protein 5 (SFRP5) have revealed its potential use as a marker of cardiovascular pathology. Preclinical studies have highlighted the important role this protein plays in many biological processes. It reduces the proliferation and migration of cardiac fibroblasts and suppresses the Wnt5A/JNK signaling pathway thus reducing the severity of oxidative stress and inflammation. It normalizes nitric oxide production and has several other effects. However, recent clinical studies of SFRP5 have produced conflicting data. Nevertheless, this protein shows promise as a marker for several metabolic and cardiovascular diseases. Preliminary data also suggest SFRP5 may be a therapeutic target. Further study of SFRP5 and its role in cardiovascular pathology is necessary, and will create new diagnostic and prognostic possibilities for this biological marker.

It has been proven that in patients with heart failure (HF), there is an increased level of adrenomedullin (ADM) in plasma. Biomarker indices correlate with the severity of hemodynamic dysfunction, as well as with neurohumoral indices, which are activated depending on the severity of congestive circulatory failure. In addition, the expression of the ADM gene in the heart and kidneys is increased in experimental and clinical HF. A small number of studies have examined the effect of ADM infusion. These studies have generally shown that hormone infusion has beneficial hemodynamic effects and promotes the maintenance/improvement of renal function, but most of the studies have been short-lived. The available results suggest that increasing ADM levels reduce the negative effects of vasoconstriction and sodium retention. A better understanding of the role of a biological marker in congestive circulatory failure may lead to the development of drugs that target ADM receptors.

This study presents a rare clinical case of encapsulated necrotic pancreatitis, which was a complication of acute pancreatitis that arose against the background of alimentary disorders. The aspects of the semiotics of radiation diagnostic methods in the follow-up control of these pathologies were presented. This case is notable for the manifestation of diseases upon hospital admission, as in the classical edematous form of acute pancreatitis, with a further increase in negative dynamics. This demonstrated the possible stepwise disease development, accompanied by a series of follow-up computed tomography between the clinical and morphological phases of acute pancreatitis and before the formation of pancreatic necrosis, which was complicated by sequestration of the pancreatic body with peripancreatic abscess formation. Afterward, the therapeutic paradigm was changed, and the place of the conservative approach was taken by active surgical tactics, followed by repeated manipulations and follow-up computed tomography and magnetic resonance until the improvement of the patients condition.

The establishment of agrarian economy in Eneolithic East Europe is associated with the Pre-Cucuteni-Cucuteni-Trypillia complex (PCCTC). PCCTC farmers interacted with Eneolithic forager-pastoralist groups of the North Pontic steppe as PCCTC extended from the Carpathian foothills to the Dnipro Valley beginning in the late 5th millennium BCE. While the cultural interaction between the two groups is evident through the Cucuteni C pottery style that carries steppe influence, the extent of biological interactions between Trypillian farmers and the steppe remains unclear. Here we report the analysis of artefacts from the late 5th millennium Trypillian settlement at the Kolomiytsiv Yar Tract (KYT) archaeological complex in central Ukraine, focusing on a human bone fragment found in the Trypillian context at KYT. Diet stable isotope ratios obtained from the bone fragment suggest the diet of the KYT individual to be within the range of forager-pastoralists of the North Pontic area. Strontium isotope ratios of the KYT individual are consistent with having originated from contexts of the Serednii Stih (Sredny Stog) culture sites of the Middle Dnipro Valley. Genetic analysis of the KYT individual indicates ancestry derived from a proto-Yamna population such as Serednii Stih. Overall, the KYT archaeological site presents evidence of interactions between Trypillians and Eneolithic Pontic steppe inhabitants of the Serednii Stih horizon and suggests a potential for gene flow between the two groups as early as the beginning of the 4th millennium BCE.

Usatove was an important southeast European culture, part of Gimbutas’ kurgan cultures, that connected the world of farmers of Old Europe with the rising influence of steppe nomads at the Eneolithic–Bronze Age transition. While the Usatove culture is currently placed within the late Eneolithic–Early Bronze Age chronological period, emerging evidence suggests the culture formed genetically and culturally in the early part of the 4th millennium BCE. We propose that the biological and cultural foundations of Usatove lie at the juncture of the Suvorove–Novodanylivka branch of the Seredny Stig complex of the North Pontic Steppe, the Trypillian farmers of southeast Europe, with influences from Varna–Karanovo VI–Gumelniţa and late Stone Age cultures of the North Caucasus.

This study reviewed the head and neck cancer diagnosis publications using dual-energy computed tomography (DECT). The qualitative and quantitative analysis of the data was DECT obtained using intravenous contrast enhancement for localized tumors, which shows the importance of constructing iodine maps for obtaining additional diagnostic information. Including the article is described aspects of improving visualization of the oropharyngeal region against the background of artifacts from dental implants. Several research articles highlight the current state of the issue and the role of post-processing of raw data DECT, obtaining a range of monochromatic images of a tumor and other pathological changes in the head and neck region in the article. Several learned treatises were also reflected. DECT with intravenous contrast enhancement and routine computed tomography to reduce radiation exposure to patients were compared particularly due to the possibility of obtaining virtual native diagnostic images from a contrasting series of DECT volumes during post-processing. In addition, this review also includes references to works that highlight the development of DECT as the method. Finally, the physical principles underlying DECT and the prospects for the development of the method are briefly represented.

Determination of the mutations' status in the KRAS and NRAS genes is a necessary requirement in the treatment of patients with colorectal cancer (CRC). Patients with certain mutations in the KRAS and NRAS genes are resistant to anti-EGFR drug therapy and have a lower median survival rate than those with WT (wild type) genotypes, that indicates a negative prognosis in the case when mutations are present. Currently, there are no registered targeted drugs for carriers of the KRAS and NRAS genes mutations, however, preparations based on small molecules are under way. The gold standard for detecting mutations in the KRAS and NRAS genes is the analysis of the biopsy material in paraffin blocks. However, this method has significant limitations that can be circumvented by the analysis of circulating tumor DNA a promising new method in the diagnosis of colorectal cancer.

Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease, with a prevalence of approximately 1 in 500 among the adult cohort. It is a common etiological factor of sudden cardiac death in the young and a common cause of morbidity and mortality in all age groups. HCM is characterized by a complex pathophysiology, which is manifested by a heterogeneous clinical picture. The mechanism of development of this variant of hypertrophy is not fully understood. Currently, only a part of the genetic mutations that correlate with the development of this pathology has been identified. In this regard, the issue of genetic diagnosis of HCM is very relevant, as it will allow us to conduct advanced screening. A very important task is to develop a personalized approach in the conservative and surgical treatment of people suffering from this variant of cardiopathy.

Background. The development of hereditary cancer syndromes is caused by genetic disorders in the DNA repair system, which consists of more than 100 genes. However, at present, in the majority of medical centers in Russia, the diagnosis of hereditary OC and BC is limited to the determination of the most frequent mutations (8 points) in BRCA1 and BRCA2 genes using PCR methods. However, the given mutations are frequent for Slavic population while in other populations of Russia they occur less often or do not occur at all. Aim. To reveal the landscape of hereditary pathogenic variants in the genes of the reparation system and develop methods for a fast analysis of the NGS data. Methods. A panel of 34 genes of the reparation system was analyzed by next generation sequencing (NGS) in 1644 samples of patients with inherited cancer syndromes. Results. The NGS analysis revealed 119 pathogenic mutations of BRCA1/BRCA2 genes in 374 patients, with a marked difference in mutation frequencies between different ethnic groups Slavs, Tatars, Bashkirs and Chuvash. A public database of the frequencies of mutations and polymorphisms of the genes of the DNA reparation system in different ethnoses was created at https://oncobrca.ru. Methods were created for automatic parallel processing of any number of samples from the raw data to the final report. Conclusions. The NGS method has created a possibility to identify rare mutations characteristic of different ethnic groups, which makes it possible to prescribe optimal chemotherapy and develop diagnostic methods of population screening for carrying gene mutations of the DNA repair system. The modern approaches to the analysis of genome sequencing data allowed reducing the time of obtaining the result to several hours after the analysis.

The prevalence of the chronic heart failure is increasing due to the success of cardiology and the increase in life expectancy of the population. A greater number of patients live up to the clinically pronounced stages of the chronic heart failure. This issue leads to an increasing in the absolute number of the patients in whom there is a lack of efficacy of optimally prescribed drug therapy. These patients are considering initiating cardiac resynchronization therapy (CRT). CRT is recommended for the patients with chronic heart failure II-IV functional class with severe left ventricular systolic dysfunction and prolonged QRS complex. Despite careful selection of patients for CRT implantation, the device does not lead to the expected result in one third of cases. To increase the effectiveness of this intervention, the procedure should be performed in accordance with current guidelines only for compliant patients who have been at least 3 months on selected optimal drug therapy, should use the optimal strategies and modes of stimulation and the adequate drug support after the intervention. The number of patients with long-term use of CRT is constantly growing. More and more patients with installed devices come into the field of vision of general practitioners and cardiologists of ambulatory clinics and hospitals, for whom it is extremely important to understand the specifics of the methods and tactics of managing such patients. This publication is dedicated to this.

Genome instability—the increased tendency of acquiring mutations in the genome and ability of a cell to tolerate high mutation burden—is one of the drivers of cancer. Genome instability results from many causes including defects in DNA repair systems. Previously, it has been shown that germline pathogenic mutations in DNA Mismatch Repair (MMR) pathway cause cancer-predisposing Lynch Syndrome. We proposed that Lynch Syndrome-related germline mutations (LS-mutations) are associated with breast cancer (BC). In this study, we performed Targeted Next-Generation Sequencing of MMR pathway genes MLH1, MSH2, MSH6, EPCAM, and PMS2 in a cohort of 711 patients with hereditary BC, 60 patients with sporadic BC, and 492 healthy donors. Sixty-nine patients (9.7%) with hereditary BC harbored at least one germline mutation in the MMR pathway genes, of them 32 patients (4.5%) harbored mutations in MMR pathway genes which we define as pathogenic or likely pathogenic, and of them 26 patients (3.6%) did not have any pathogenic mutations in DDR pathway genes, compared to two mutations in MMR pathway genes (0.4%) detected in a group of 492 healthy donors [p = 0.00013, OR = 8.9 (CI 95% 2.2–78.4)]. Our study demonstrates that LS-mutations are present in patients with hereditary BC more frequently than in healthy donors, and that there is an association of hereditary BC and mutations c.1321G>A in MLH1, c.260C>G and c.2178G>C in MSH2, c.3217C>T in MSH6, c.1268C>G and c.86G>C in PMS2 genes. This finding provides a rationale for including pathogenic LS-mutations into genetic counseling tests for patients with hereditary BC.

The paper describes a case of successful treatment for chronic viral hepatitis C after surgery for hepatocellular carcinoma developing in the presence of evolved compensated hepatic cirrhosis. It also gives current approaches to choosing antiviral therapy and estimates its possibilities in patients with different surgical options for hepatocellular carcinoma.

Background. Cystic fibrosis is a hereditary disease that occurs as a result of mutations in the regulator gene of chloride ion transmembrane transport (CFTR). Finding mutations in the CFTR gene is necessary for identification of the clinical features of cystic fibrosis.Objective. Our aim was to identify genotype-phenotype correlations between mutations of the first class of pathogenicity and clinical manifestations of cystic fibrosis based on studying the prevalence and structure of CFTR gene mutations.Methods. The study included children under 18 years with cystic fibrosis admitted to hospital between 2013 and 2017. Biallelic mutations in the CFTR gene were the noninclusion criterion. The CFTR gene variants were analyzed by next-generation sequencing method.Results. In 125 patients with cystic fibrosis, 59 different variants of the CFTR gene were detected, 11 of them not previously described. The most common was the deletion c.1521_1523del found in 98 (39.2%) of the 250 analyzed CFTR gene alleles and the deletion c.1545_1546del found in 22/250 (8.8%) alleles. It has been shown that the mutation c.1545_1546del, p.Y515* was more often found in children of the Chechen nation — odds ratio (OR) 139 (95% confidence interval 15–1,257). It has been established that meconium ileus, pancreatic deficiency and cirrhosis are more common in patients with mutations of the first category of pathogenicity: OR 3.9 (95% CI 1.0–15.0), 4.4 (95% CI 1.8–11.1), and 351 (95% CI 17.5–7,046), respectively. The association of CFTR gene mutations with the development of bronchiectases and polypous pancinusitis has not been found.Conclusion. Correlations between the genotype and clinical manifestations of cystic fibrosis in Russian children with CFTR gene mutations of the first class of pathogenicity have been established.

Pachydermoperiostosis (PHO) or primary hypertrophic osteoarthropathy is a rare genetic disease that typically begins during childhood or adolescence. It is characterized by digital clubbing, pachydermia and periosteal reaction and progresses gradually over the years prior to disease stabilization. Two genes are reported to be associated with PHO HPGD and SLCO2A1. These genes are involved in prostaglandin E2 metabolism. We present a description of a 19-year-old patient with PHO. We found two mutations in the SLCO2A1 gene: p.Gly183Ar (chr3:133673888, NM_005630.2:c.547GA) and p.Cys444Gly (chr3:133664070, NM_005630.2:c.1330TG) through molecular genetic analysis. The mutation (p.Cys444Gly) has never been recorded in previous studies. This work expands our knowledge of the mutation spectrum of PHO, which will facilitate faster genetic diagnosis and interpretation of genetic information in prenatal diagnosis and genetic counseling.

To detect the reason of left ventricular hypertrophy (LVH) may be difficult in some cases especially in elite athletes. Object. To evaluate the efficiency of next generation sequencing (NGS) genetic test in differential diagnostics of pathological LVH in elite athletes. Material and methods. Analysis of echocardiographic data from 791 elite athletes revealed 15 individuals with LVH 12 mm (1,9%). Based on the criteria of abnormality (asymmetric, severe and changes on electrocardiogram) 5 (0,6%) athletes were selected for genetic test. TruSight Cardio panel (“Illumina”) was used to identify variants of 174 genes with known associations to inherited cardiac conditions. Results. In 3 out of 5 athletes the pathogenic variants in MBPC3 and LMNA genes previously associated with HCM and other CMs were found. One athlete with negative genetic test result had severe untreated arterial hypertension as a possible cause for LVH. The second athlete didn’t have LVH in magnetic resonance imaging. Conclusions. In elite athletes, the asymmetric LVH should be considered as pathological finding which requires comprehensive clinical evaluation and NGS genetic test.

Backgraund. MiсroRNA are small regulatory factors that regulate gene expression by post-transcriptional regulation of mRNA, playing an important role in numerous cellular processes including organogenesis, apoptosis, cell proliferation and differentiation. Acromegaly causes bone fragility, but the pathogenetic mechanism is generally unknown. Aim. To evaluate levels of microRNA related to bone remodeling regulation in plasma samples from patients with acromegaly Materials and methods. Fasting plasma samples were taken and stored in aliquot at ≤ -80°C from consecutive subjects with clinically evident and biochemically confirmed active acromegaly and healthy volunteers matched by age, sex and body mass index (BMI). miRNeasy Serum/Plasma Kit, TaqMan Advanced miRNA cDNA Synthesis Kit, TaqMan Advanced miRNA Assays were used to assay plasma miRNA expression. Insulin-like growth factor 1 (IGF1) was measured by immunochemiluminescence assay (Liaison). Results. We enrolled 40 subjects 22 patients suffered from acromegaly and 18 matched healthy controls) matched by sex, age and BMI. The median age of patients with acromegaly was 42 years (Q25;Q75 – 37;43) with no difference among the groups, p=0.205; BMI – 28 (24;32) kg/m2, p=0.253. The median IGF1 in subjects with acromegaly – 622 (514;1000) ng/ml was significantly higher as compared to the control group (p

Guidelines are given on terminology, nomenclature and determination of the clinical significance of various variants of the genome nucleotide sequence. Information on the use of specialised databases and literary sources when describing and interpreting molecular genetic research data is provided.

In the 21st century is an acute problem to find effective and inexpensive methods for the early detection of lung cancer. Patients suspected of having a malignant disease of the lungs, generally undergo clinical studies such as CT scans of the chest and bronchoscopy. The latter is mainly used to confirm the diagnosis. However, even when the signs, symptoms and radiological findings indicate that clinical diagnosis of malignant lung disease is evident, additional invasive procedures for obtaining the biological material suitable for the final confirmation of the presence of malignant cells. Currently, there is a clear understanding of the need to find biomarkers able to detect pre-clinical stage of cancer cells using minimally invasive procedures. In this paper, for the DNA of patients with different types of lung cancer samples, with a view to a better understanding of the causes of lung cancer pathology gene methylation analysis was conducted for SHOX2, TGFBR1 and MIR-375.

Definition of epigenetic disorders is important for early diagnosis of colorectal cancer. To obtain a model of diagnostic test system with high sensitivity and specificity, we determined the frequency of methylation in SEPT9 and VIM genes. Epigenetic events also were compared with mutations in the RAS family genes. It was confirmed the presence of aberrant methylation in SEPT9 and VIM genes in tumor cells. DNA of tumor samples was significantly more methylated than samples with DNA from adjacent tissue (P = 8,67E-19 for SEPT9 gene and P=8,68E-19 for VIM gene). In the group of patients carried mutations in KRAS or NRAS genes tumor DNA significantly more methylated in gene SEPT9 (P = 0.0018), in contrast to the tumor DNA from patients not carried mutations. We have demonstrated that the combined use of methylation markers can improve the sensitivity of the test systems used in the diagnostics of colon cancer.

Aim. To investigate the association of variation in lipid-lowering response and endothelial function (EF) parameters after atorvastatin therapy in patients with type 2 diabetes mellitus (T2DM) with genetic markers of atherosclerosis.Methods. We included 97 patients with T2DM who were prescribed atorvastatin. Fasting lipid profiles and EF parameters were assessed before and after 12 months of statin therapy. For EF evaluation, we performed pulse-wave analysis during reactive hyperaemia. The genotypes for polymorphic markers were identified by real-time polymerase chain reaction with TaqMan probes. The statistical analysis included Wilcoxon, Mann–Whitney and Kruskal–Wallis tests. P-values

The Russian population consists of more than 100 ethnic groups, presenting a unique opportunity for the identification of hereditary pathogenic mutations. To gain insight into the landscape of heredity pathogenic variants, we employed targeted next-generation sequencing to analyze the germline mutation load in the DNA damage response and repair genes of hereditary breast and ovary cancer syndrome (HBOCS) patients of Tatar ethnicity, which represents ~4% of the total Russian population. Several pathogenic mutations were identified in DNA double-strand break repair genes, and the spectrum of these markers in Tatar patients varied from that previously reported for patients of Slavic ancestry. The CDK12 gene encodes cyclin-dependent kinase 12, the key transcriptional regulator of the genes involved in DNA damage response and repair. CDK12 analysis in a cohort of HBOCS patients of Tatar decent identified a c.1047-2A>G nucleotide variant in the CDK12 gene in 8 of the 106 cases (7.6%). The c.1047-2A>G nucleotide variant was identified in 1 of the 93 (1.1%) HBOCS patients with mixed or unknown ethnicity and in 1 of the 238 (0.42%) healthy control patients of mixed ethnicity (Tatars and non-Tatars) (p = 0.0066, OR = 11.18, CI 95% = 1.53–492.95, Tatar and non-Tatar patients vs. healthy controls). In a group of mixed ethnicity patients from Tatarstan, with sporadic breast and/or ovarian cancer, this nucleotide variant was detected in 2 out of 93 (2.2%) cases. In a cohort of participants of Slavic descent from Moscow, comprising of 95 HBOCS patients, 80 patients with sporadic breast and/or ovarian cancer, and 372 healthy controls, this nucleotide variant was absent. Our study demonstrates a strong predisposition for the CDK12 c.1047-2A>G nucleotide variant in HBOCS in patients of Tatar ethnicity and identifies CDK12 as a novel gene involved in HBOCS susceptibility.

Objective: Our aim was to study the prevalence and clinical features of autoinflammatory syndromes among patients with systemic juvenile idiopathic arthritis. Methods: A prospective nonrandomized study was conducted. All its members have been studied for mutations in TNFRSF1A and NLRP3 genes by the sequencing method. Results: 90 children (27 boys, 63 girls) aged from 1 to 17 (average age 8.2) years, with a guide diagnosis: «Systemic juvenile idiopathic arthritis», were examined. As a result, 10 (14%) patients showed mutations in TNFRSF1A gene, leading to the development of TRAPS-syndrome (8 had the most common mutation of R92Q; 3 — not previously described mutations in NLRP3 gene). 2 patients had the diagnosis of CINCA/NOMID Syndrome, 1 — Muckle–Wells Syndrome. In three cases, mutations leading to the development of TRAPS-syndromethe were identified in the first line of descent. Classical examples of autoinflammatory syndromes such as cryopyrin-associated periodic syndrome (CAPS), and tumor necrosis factor receptor associated periodic syndrome (TRAPS). The data about their pathogenesis, clinical features, diagnosis and treatment is presented. Conclusion: It is shown that early detection and adequate treatment of patients with autoinflammatory syndromes, characterized by severe disease and serious prognosis, is difficult due to lack of awareness of pediatricians and unavailability of genetic diagnosis of these syndromes. The necessity of the development of a universal model of the diagnostic algorithm for identification of autoinflammatory syndromes using next-generation sequencing technologies is grounded.

This paper presents an analysis of human and animal remains from Verteba cave, near Bilche Zolote, western Ukraine. This study was prompted by a paucity of direct dates on this material and the need to contextualise these remains in relation both to the transition from hunting and gathering to farming in Ukraine, and their specific place within the Cucuteni-Trypillia culture sequence. The new absolute dating places the remains studied here in Trypillia stages BII/CI at c. 3900–3500 cal BC, with one individual now redated to the Early Scythian period. As such, these finds are even more exceptional than previously assumed, being some of the earliest discovered for this culture. The isotope analyses indicate that these individuals are local to the region, with the dietary stable isotopes indicating a C3 terrestrial diet for the Trypillia-period humans analysed. The Scythian period individual has δ13C ratios indicative of either c. 50% marine, or alternatively C4 plant inputs into the diet, despite δ18O and 87Sr/86Sr ratios that are comparable to the other individuals studied.

Background The association of type 2 diabetes mellitus (T2DM) with the KCNJ11, CDKAL1, SLC30A8, CDKN2B, and FTO genes in the Russian population has not been well studied. In this study, we analysed the population frequencies of polymorphic markers of these genes. Methods The study included 862 patients with T2DM and 443 control subjects of Russian origin. All subjects were genotyped for 10 single nucleotide polymorphisms (SNPs) of the genes using real-time PCR (TaqMan assays). HOMA-IR and HOMA-β were used to measure insulin resistance and β-cell secretory function, respectively. Results The analysis of the frequency distribution of polymorphic markers for genes KCNJ11, CDKAL1, SLC30A8 and CDKN2B showed statistically significant associations with T2DM in the Russian population. The association between the FTO gene and T2DM was not statistically significant. The polymorphic markers rs5219 of the KCNJ11 gene, rs13266634 of the SLC30A8 gene, rs10811661 of the CDKN2B gene and rs9465871, rs7756992 and rs10946398 of the CDKAL1 gene showed a significant association with impaired glucose metabolism or impaired β-cell function. Conclusion In the Russian population, genes, which affect insulin synthesis and secretion in the β-cells of the pancreas, play a central role in the development of T2DM.

The article describes the monitoring of severe cryopyrin-associated syndrome (syndrome CINCA/NOMID). The following clinical case indicates successful application of homogeneous antibodies to interleukin 1 — canakinumab — in patient with chronic neurologic dermatic articular syndrome. Fever, rush and pain syndrome completely jugulated, contractures of articulation joints decreased in a week since the beginning of the treatment. In 8 weeks of therapy movements of affected joints almost completely restored, the boy could stay, spell simple words; decreased and normalized laboratory test values of disease activity (erythrocyte sedimentation rate, C-reactive protein). In 12 weeks the child could move with assistance, say simple phrases. The following clinical case shows high efficiency of application of canakinumab in chronic neurologic dermatic articular syndrome treatment and indicates the perspectives of therapeutic use of interleukin 1 blocking agent in patients with early stage of disease before the progress of nonreversible osteohondrous destruction and serious injury of cerebrospinal nervous system. No adverse event were registered on treatment with application of canakinumab.Key words: children, autophologistic syndromes, cryopyrin-associated syndrome, CINCA/NOMID, canakinumab.

Objective: on the basis of philosophical, sociological, political science and jurisprudence to implement a comprehensive general theoretical and legal analysis of existing classifications and types of extremist behavior Methods: universal dialectical method of cognition that allows to study the phenomena and processes of reality in their historical development, interrelationship and interdependence, and general scientific, special and private-legal research methods based on it. Results: basing on the analysis of a significant number of domestic and foreign research on countering extremist activity, it is revealed that the existing classifications of extremism are extremely numerous, contradictory, many of them do not follow the classification rules (no substantiation of classifications, explanations and clarifications of the terms introduced into the scientific circulation) Scientific novelty: classification of extremist activity is developed and introduced into scientific circulation, depending on extremism correlation with the current laws and regulations; author’s definitions are formulated of extremist activities in the framework of the rules and extremist activity in the framework of the law, illegal extremist activity; it is proposed to avoid a regulatory interpretation of legal acts of "extremism" as a necessarily negative notion. Practical value: the theoretical propositions formulated in the research can be used in scientific, legislative and law enforcement activity, educational process of higher education institutions for law, in professional development of practitioners and scientific-pedagogical personnel in the field of jurisprudence.

The agricultural revolution in Eastern Europe began in the Eneolithic with the Cucuteni-Trypillia culture complex. In Ukraine, the Trypillian culture (TC) existed for over two millennia (ca. 5,400-2,700 BCE) and left a wealth of artifacts. Yet, their burial rituals remain a mystery and to date almost nothing is known about the genetic composition of the TC population. One of the very few TC sites where human remains can be found is a cave called Verteba in western Ukraine. This report presents four partial and four complete mitochondrial genomes from nine TC individuals uncovered in the cave. The results of this analysis, combined with the data from previous reports, indicate that the Trypillian population at Verteba carried, for the most part, a typical Neolithic farmer package of mitochondrial DNA (mtDNA) lineages traced to Anatolian farmers and Neolithic farming groups of central Europe. At the same time, the find of two specimens belonging to haplogroup U8b1 at Verteba can be viewed as a connection of TC with the Upper Paleolithic European populations. At the level of mtDNA haplogroup frequencies, the TC population from Verteba demonstrates a close genetic relationship with population groups of the Funnel Beaker/ Trichterbecker cultural complex from central and northern Europe (ca. 3,950-2,500 BCE).

Raman spectroscopy method have been used to study structure of the amorphous hydrogenated carbon films with silver nanoclusters a-C:H(Ag). These films were obtained by ion-plasma magnetron sputtering of the combined graphite-silver target in argon-hydrogen plasma. Raman scattering spectrums of the films with different silver concentration and various deposition temperature, were studied. It was established, that the film’s structure consist of two phases: amorphous and nanocrystalline. Increasing of silver concentration and growing deposition temperature modifies the structure of a-C:H films to the graphite like.

In 2012, in Federal research and clinical centre of FMBA of Russia the laboratory of genetics was established, which conducts scientific research in the field of genetic predisposition to socially significant diseases, early diagnosis of oncopathology, as well as methods for processing genomic data. Significant experience in molecular genetic testing have allowed to help to implement a routine practice of a multiprofile hospital modern methods of genetic analysis that were previously available only to large specialized centers.

Moldova has a rich historical and cultural heritage, which may be reflected in the current genetic makeup of its population. To date, no comprehensive studies exist about the population genetic structure of modern Moldavians. To bridge this gap with respect to paternal lineages, we analyzed 37 binary and 17 multiallelic (STRs) polymorphisms on the non-recombining portion of the Y chromosome in 125 Moldavian males. In addition, 53 Ukrainians from eastern Moldova and 54 Romanians from the neighboring eastern Romania were typed using the same set of markers. In Moldavians, 19 Y chromosome haplogroups were identified, the most common being I-M423 (20.8%), R-M17* (17.6%), R-M458 (12.8%), E-v13 (8.8%), R-M269* and R-M412* (both 7.2%). In Romanians, 14 haplogroups were found including I-M423 (40.7%), R-M17* (16.7%), R-M405 (7.4%), E-v13 and R-M412* (both 5.6%). In Ukrainians, 13 haplogroups were identified including R-M17 (34.0%), I-M423 (20.8%), R-M269* (9.4%), N-M178, R-M458 and R-M73 (each 5.7%). Our results show that a significant majority of the Moldavian paternal gene pool belongs to eastern/central European and Balkan/eastern Mediterranean Y lineages. Phylogenetic and AMOVA analyses based on Y-STR loci also revealed that Moldavians are close to both eastern/central European and Balkan-Carpathian populations. The data correlate well with historical accounts and geographical location of the region and thus allow to hypothesize that extant Moldavian paternal genetic lineages arose from extensive recent admixture between genetically autochthonous populations of the Balkan-Carpathian zone and neighboring Slavic groups.

Two Maxwell-Chern-Simons (MCS) models in the (1 + 3)-dimensional space-space are discussed and families of their exact solutions are found. In contrast to the Carroll-Field-Jackiw (CFE) model [2] these systems are relativistically invariant and include the CFJ model as a particular sector.Using the InNonNu-Wigner contraction a Galilei-invariant non-relativistic limit of the systems is found, which makes possible to find a Galilean formulation of the CFJ model.