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Here, we present DNA aptamers capable of specific binding to glial tumor cells in vitro, ex vivo, and in vivo for visualization diagnostics of central nervous system tumors. We selected the aptamers binding specifically to the postoperative human glial primary tumors and not to the healthy brain cells and meningioma, using a modified process of systematic evolution of ligands by exponential enrichment to cells; sequenced and analyzed ssDNA pools using bioinformatic tools and identified the best aptamers by their binding abilities; determined three-dimensional structures of lead aptamers (Gli-55 and Gli-233) with small-angle X-ray scattering and molecular modeling; isolated and identified molecular target proteins of the aptamers by mass spectrometry; the potential binding sites of Gli-233 to the target protein and the role of post-translational modifications were verified by molecular dynamics simulations. The anti-glioma aptamers Gli-233 and Gli-55 were used to detect circulating tumor cells in liquid biopsies. These aptamers were used for in situ, ex vivo tissue staining, histopathological analyses, and fluorescence-guided tumor and PET/CT tumor visualization in mice with xenotransplanted human astrocytoma. The aptamers did not show in vivo toxicity in the preclinical animal study. This study demonstrates the potential applications of aptamers for precise diagnostics and fluorescence-guided surgery of brain tumors. peerReviewed

The article offers an economic justification of the location coefficient used to determine the amount of payment for the placement of non-stationary retail facilities in buildings, structures or on land plots. The methods used in different cities of Russia for calculating fees for the place-ment of non-stationary retail facilities often do not have an economic justification for the indica-tors and coefficients used. This casts doubt on the correctness of setting the initial price (fee) for the placement of non-stationary retail facilities, becomes the basis for challenging charges and leads to losses of local budget revenues. In the course of the study, the analysis of factors influ-encing the formation of fees for the placement of non-stationary retail facilities, in general, and the location coefficient, in particular, was carried out. The economic justification of the calculation of the location coefficient as a key element of the payment for the placement of non-stationary retail facilities in the conditions of incomplete information on the local real estate mar-ket has been carried out. The location coefficient is proposed to be determined based on the indicators of remoteness and socio-economic condition of the city area, as well as taking into account the territorial differentiation of residential real estate prices. The method of calculating the coefficient of location of the object of non-stationary trade on the data of the city of Norilsk was tested.

INTRODUCTION: Anaplastic thyroid carcinoma (ATC) is the most aggressive type of thyroid cancer accounting for 12% of all malignancies. Systemic therapy remains the main treatment strategy. Targeted therapy and immunotherapy are prescribed when certain molecular genetic aberrations are detected. THE AIM: To investigate the molecular genetic profile of samples of anaplastic thyroid carcinoma. MATERIALS AND METHODS: The study included 37 patients with ATC. Mutation V600E BRAF, mutations in the gene NRAS and KRAS were detected by allele-specific polymerase chain reaction (AS-PCR). Microsatellite instability (MSI) was determined by fragment analysis in according to ESMO recommendations. Mutations in the promoter region of the TERT gene were used by Sanger sequencing. NTRK1, EML4-ALK, PAX8/PPARy и RET/PTC translocations were determined in all patients with ATC by real-time polymerase chain reaction (PCR). RESULTS: According to the results of the study, the frequency of the V600E mutation in the BRAF gene was 32.4% (12/37). The frequency of aberrations in the NRAS, KRAS genes in anaplastic thyroid carcinoma was 13.5% (n=5). The prevalence of point mutations in the promoter gene TERT in food samples of ATC was 24.3% (n=9). MSI was found in 2.7% (1/37) of cases of anapalastic thyroid carcinoma. NTRK1, EML4-ALK, PAX8/PPARy and RET/PTC translocations were not detected in cases with anaplastic thyroid carcinoma. CONCLUSION: The further study of the main specific molecular targets in cancer cells will allow to personalize the tactics of patients with anaplastic thyroid carcinoma.

Aim: To summarize the state-of-the-art data on the molecular mechanisms of bile acid (BA) synthesis and absorption, their impaired absorption and receptor-dependent signaling, as well as on the effects of the gut microbiota on BA metabolism in inflammatory bowel diseases (IBD). Key messages: BA malabsorption is one of the relevant mechanisms in the development of diarrhea in IBD. It may occur due to various disorders of the ileum, such as terminal ileitis, ileocolitis or ileocecal resection in Crohn's disease and ileoanal reservoir in ulcerative colitis. Molecular mechanisms of BA malabsorption in IBD are related to a defect in the BA uptake by the apical sodium dependent bile acid transporter (ASBT), as well as to a decrease in the expression of pregnane X receptor (PXR) and farnesoid X receptor (FXR), whose activation by glucocorticoids results in an increase in the BA reabsorption in the ileum and a decrease in hologenic diarrhea. The metabolic profile of luminal BA in IBD is characterized by an increased content of conjugated and 3-OH-sulfated BA and reduced levels of secondary BA. The decrease in the relative abundance of the Lachnospiraceae and Oscillospiraceae spp. in IBD patients leads to a decrease in the efficiency of microbial biotransformation of BA. Changes in the BA metabolic profile in IBD affect the gut microbiota, and impaired interaction with the FXR, PXR, G protein-coupled bile acid receptor (GPBAR1), retinoid-related orphan receptors (RORs) and vitamin D receptor (VDR) results in a pro-inflammatory response and increased intestinal permeability, bacterial translocation, and IBD progression. BA metabolism in IBD-associated primary sclerosing cholangitis (PSC-IBD) is characterized by a significant decrease in the luminal BA pool, and the microbiota composition is remarkable for an increase in the relative abundance of Fusobacterium and Ruminococcus spp., and a decrease in Veillonella, Dorea, Blautia, Lachnospira and Roseburia. Conclusion: Disordered synergistic interplay of BA with intestinal microbiota results in disruption of the ligand-receptor interaction and BA metabolic transformation, which contributes to the activation of the immune system, formation of a vicious circle of chronic inflammation and IBD progression. Further studies into mutual influence of the gut microbiota, BA metabolism and receptor signaling may promote the development of new methods for the diagnosis and treatment of IBD.

Cancer is the leading cause of death in the world. The development of oncopathology is closely related to various changes in the genetic material that occur in malignantly transformed cells. Medical decision-making requires a clear differentiation between normal and pathological indicators, which are, among other things, the results of application of quantitative methods in laboratory medicine. Studies of DNA isolated from a patient’s biological material, identification and measurement of the content of nucleotide sequences acting as oncopathology biomarkers allow to solve the problems of determining the genetic prerequisites for cancer, its early diagnosis, determining the treatment strategy, monitoring, and confirming the patient’s cure.The purpose of this research is to develop the main approaches to the design of DNA reference materials (RMs) for metrological support of molecular diagnostics of oncopathology through the example of the RM for the HER2 gene sequence content in the human genome, with the value of «the number of copies of the DNA sequence» which is metrologically traceable to the natural SI unit «one».In the course of the research, a technique for measuring the HER2 gene amplification (the number of copies of the gene sequence per genome) was developed based on the use of the digital PCR method (dPCR). Comparability of measurement results for the method developed by the authors, and the results obtained using a commercial kit by the MLPA method on samples of human biological material is shown.Five permanent cell lines obtained from the CUC «Vertebrate Cell Culture Collection» were characterized in relation to the copy number ratios of HER2 gene sequence and CEP17 and RPPH1 genes sequences. A cell line with the HER2 gene amplification was identified. The results obtained will be used to create the RM for the copy number ratio of the HER2 gene sequences and the RPPH1 and CEP17 gene sequences. Creation of matrix DNA RMs based on human cell cultures certified using dPCR will allow transferring the unit of copy numbers of the DNA sequence to calibrators included in medical devices, thereby ensuring the required reliability and comparability of measurement results in the laboratory diagnostics of oncopathology, as well as the possibility of calibrating routine methods of DNA diagnostics and intralaboratory quality control.

Helicobacter pylori (H. pylori) increases the risk of diseases associated with mucous membrane inflammation of gastrointestinal tract, in particular, gastritis, stomach ulcers, and duodenal ulcers. It may also induce a chronic immune response, causing damage to the mucous membrane and development of these diseases. In addition, the role of H. pylori in the initiation of a wide range of autoimmune diseases is discussed. The aim of this study was to assess the level of autoantibodies – markers of various autoimmune diseases in the blood of H. pylori-infected patients with chronic gastritis. We used samples of whole peripheral blood from 267 primary patients with chronic gastritis in the acute stage. The presence of H. pylori in gastric juice from patients was determined using real-time PCR. The level of autoantibodies to double-stranded and single-stranded DNA, autoantibodies to thyroglobulin, thyroid peroxidase, concentration of rheumatoid factor, IgG autoantibodies to the cyclic citrullinated peptide, IgM and IgG autoantibodies to beta(2)-glycoprotein were determined by the enzyme immunoassay. The average level of rheumatoid factor in blood serum was similar for H. pylori-infected and non-infected patients, and did not exceed the normal values. The level of antibodies to cyclic citrullinated peptide, one of the sensitive markers of rheumatoid arthritis, was increased in all patients, being, however, significantly lower in H. pylori-infected patients compared with non-infected persons. Autoantibodies to thyroglobulin, thyroid peroxidase are considered classic markers of autoimmune diseases of the thyroid gland. In blood of H. pylori-infected patients we have found an increased concentration of autoantibodies to thyroglobulin and thyroid peroxidase in comparison with non-infected ones, but the average level of these antibodies did not exceed the normal range. Any differences in the levels of systemic lupus erythematosus serological markers, i.e., autoantibodies to double-stranded and single-stranded DNA, were found between H. pylori-infected and non-infected patients. The levels of thrombosis risk marker in patients with systemic lupus erythematosus (IgG and IgM autoantibodies to beta(2)-glycoprotein) were also within the normal ranges. However, in H. pylori-infected patients, it even turned out to be statistically significantly lower than in non-infected ones. Thus, no data have been obtained on increased levels of the tested markers of autoimmune pathology in blood of H. pylori-infected patients with chronic gastritis at the acute stage. However, this does not allow us to make an unambiguous conclusion that the influence of H. pylori does not affect the development of immunological changes associated with autoimmune diseases.

Introduction. The article concentrates on improving the efficiency of double-circuit diaphragm pumps, which can be successfully used in heat and water supply systems of industrial and agricultural facilities where there is excess head. It is advisable to equip double-circuit diaphragm pumps with disc-shaped diaphragms interconnected by a rod, for example, from motor vehicles, and to drive them from the available head of the hydraulic network. In order to increase the efficiency of their work and further use, it is necessary to predict the hydraulic characteristics according to the geometric parameters of the membranes and the cycle of their operation in dynamics. Aim of the Article. The article aims at obtaining adequate calculated dependencies of pumped liquid flow rate on speed of double-circuit diaphragm pumps. Materials and Methods. There were used the idealization method from differential geometry, physical experiment, and mathematical statistics to solve the tasks for identifying the relationship between the rod motion and the liquid flow rate for a poppet diaphragm with different geometric surfaces in dynamics. There have been obtained the dependences of pumped liquid volume on the movement of the point of attachment by the poppet diaphragm and the volume flow rate on the movement speed of the point of attachment by the poppet diaphragm with specific geometric parameters for the parabolic and chain line. An experimental testing of the dependence of displaced pumped liquid flow rate on the movement of the attachment point to the stem for the diaphragm type 30 was carried out. Results. Based on the obtained dependences of the volume flow rate on the speed of movement of the point of attachment by a poppet diaphragm with specific geometric parameters for a parabolic and chain line, there were constructed the graphs of dependences of the volume flow rate on the frequency of the working cycle. For practical implementation, there are proposed the dependencies for constructing the hydraulic characteristics of a two-circuit membrane (the dependence of the volume flow rate on the frequency of the working cycle) obtained on the basis of a parabolic interpretation. Discussion and Conclusion. The hydraulic characteristics of a two-circuit membrane pump are close to the equation of a straight line and are consistent with experimental dependencies within 4%.

Objective. To evaluate the effectiveness of extremely high frequency (EHF) millimeter range electromagnetic radiation (EMR) of low intensity in patients with malignant neoplasms suffering from chronic pain syndrome (CPS).Materials and methods. The study included 60 patients with diagnosed malignant neoplasm (MN) who were treated in a palliative care unit. They were divided into 2 groups. The main group consisted of 30 patients who underwent additional EHF-exposure with a course of 10 sessions of 15 minutes simultaneously with the main therapeutic measures. The comparison group consisted of patients who did not undergo electromagnetic exposure 30 people. Questioning was conducted twice: on the 2nd and 14th days of treatment. Treatment efficiency was assessed using standardized questionnaires.Results. The analgesic effect of additional use of EHF therapy with a fixed frequency of 53.534 ± 0.015 GHz in patients with MN was significantly higher than the analgesic effect of standard treatment. In particular, there was an increase in mobility, as well as a decrease in depression and reactive anxiety.Conclusion. The additional use of EHF therapy in patients with MN provides the advantage of improving quality of life by reducing CPS, improving psychological well-being and improving the ability to move independently.

Introduction. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is common variant of small vessel disease. Determination of neuroimaging markers have already contributed at an early stage to the more timely diagnosis of the CADASIL.Objective. The aim of the study was to determine probable CADASIL magnetic resonance imaging (MRI) biomarkers for patients from the Russian population.Material and methods. The study included 16 patients. Diagnosis of CADASIL was suspected based on clinical data and an MRI and confi rmed by a molecular genetic study of the NOTCH3 gene. Brain MRI data from 16 patients and spinal cord MRI data from 5 patients were collected and analyzed. Cerebrospinal fl uid (CSF) analysis was performed for diff erential diagnosis in 2 subjects.Results. White matter hyperintensity was observed in 100% of cases. The involvement of the anterior temporal lobes and external capsules was revealed in 62 and 68% of subjects respectively. Multiple lacunar infarcts are characteristic for CADASIL. Microbleeds were detected in 27% of patients. Brain atrophy was observed in 56% of cases. Lesions in corpus callosum and cervical spinal cord were found in 2 patients.Conclusion. Detection of white matters hyperintensities in frontal and parietal lobes, multiple lacunar infarcts with suspected CADASIL makes it possible to select the group of patients for further molecular genetic testing in order to detect mutations in NOTCH3 gene.

Environmental issues in large, including industrial cities of Russia, are acute, since the execution of production processes and simultaneous control over the well-being of the environment is a complex multifactorial aspect that requires careful study and elaboration. In addition, there is a sharp shortage of public green spaces in many territories, which are regulated by legislation and are designed to increase the environmental comfort of citizens. In densely populated cities, the issue of providing residents with green spaces is accompanied by a lack of free space, «green roofs» are able to solve this problem without taking up additional space in the city, compactly placed on the roofs of existing buildings, while increasing the commercial attractiveness of objects and preserving the enclosing multilayer coating system. The article considers a brief historical background of the development of the technology of «green» roofs in the world and in Russia, provides examples of modern buildings and structures actively using this technology, explains the general structure of the modern «green» roof in the context of the current regulatory documentation. The collection and analysis of data on the example of the Tula region concerning demographic, social and environmental indicators for correlation calculation was carried out. Graphs and polynomial trend lines of various environmental factors are constructed, determination coefficients and functions of trend lines are determined. A correlation matrix is compiled, conclusions are drawn about the possible improvement of the ecology of the urban architectural environment. A regression analysis was performed with statistical results entered into a tabular form. Based on the function obtained as a result of regression analysis, simulation modeling of the population was carried out, taking into account the increase in the area of green spaces of general use

Severe poisoning with cardiotropic drugs in children, accompanied by pronounced rhythm disorders and low cardiac output syndrome, is quite rare, but sometimes they can end fatally.The objective was to demonstrate the successful use of electrocardiostimulation in acute propafenone poisoning in a child of three years old.Materials and Methods. A retrospective analysis of the features of the course of severe propafenone poisoning in a three-year-old child who required pacing was carried out. Special attention was paid to the analysis of rhythm disorders that led to cardiac arrest by the type of electrical activity without a pulse, high efficiency of timely electrocardiostimulation in order to relieve bradyarrhythmia. Against the background of the therapy, a stable recovery of the correct sinus rhythm was achieved six hours after the connection of a temporary electrocardiostimulator.Conclusion. The presence of persistent bradyarrhythmia-type rhythm disorders in acute poisoning with antiarrhythmic drugs in children is an indication for the emergency use of electrocardiostimulation.

Proliferation and hyperactivation of B-lymphocytes in the salivary glands is a feature of primary Sjцgren's syndrome (pSS). Detection in saliva of proteins synthesized by B-lymphocytes may be important in the diagnosis of this disease.Objective: to evaluate the diagnostic value of measuring the concentration of immunoglobulin free light chains (FLC) in saliva in patients with pSS.Material and methods. The cross-sectional study included 24 patients with pSS over the age of 18 years. PSS was diagnosed according to the 2016 ACR/EULAR classification criteria. The control group consisted of 11 healthy volunteers. Blood-salivary glands histohematic barrier permeability ratio for albumin, FLC was measured. Quantitative determination of FLC and in blood and saliva was performed by enzyme immunoassay. An immunohistochemical study of biopsies of minor salivary glands (MSG) was carried out with a quantitative assessment of CD3+, CD4+, CD8+, CD20+, CD21+, CD68+, CD138+ cells. The Mann–Whitney U-test was used to compare quantitative traits. Identification of diagnostic thresholds for the concentration of FLC in saliva for the diagnosis of pSS was carried out using the ROC analysis method. An operating characteristic curve was plotted, the area under the curve, indicators of diagnostic specificity, diagnostic sensitivity, and diagnostic accuracy were calculated.Results and discussion. The obtained values corresponded to the low permeability of the histohematic barrier of the salivary glands for albumin and FLC in patients with pSS and healthy individuals. The median concentrations of FLC ê and ë in the saliva of patients with pSS and healthy volunteers were 1.08 [0.58; 1.91], 1.038 [0.55; 2.03] mg/l and 0.36 [0.32; 0.54], 0.35 [0.21; 0.52] mg/l, respectively. The concentration of FLC in the saliva of patients with pSS was statistically significantly higher than in the control group (pê and ë in saliva correlated with the rate of unstimulated saliva flow: rs=-0.483 (p=0.02), rs=-0.491 (p=0.017), respectively.A relationship was found between the concentration of ê-chains in saliva and the specific number of CD138+ cells: rs=0.733 (p=0.025). Statistically significant correlations between the concentration of ë-chains and the number of mononuclear cells in the MSG have not been established.Based on the results of ROC analysis, diagnostic thresholds for FLC concentrations in the saliva of patients with pSS were determined. Concentrations of ê- and ë-type FLC in saliva of 0.56 and 0.68 mg/l correspond to area under the curve values of 0.84 (95% confidence interval, CI 0.69–0.98) and 0.83 (95% CI 0.71–0.97), sensitivity 79.2% (95% CI 59.5–90.8) and 75% (95% CI 55.1–88), specificity 81.8% (95% CI 52.3–96.8) and 90.9% (95% CI 62.3–99.5), respectively.Salivary FLC concentrations were compared in patients with pSS receiving and not receiving glucocorticoids (GC). The groups did not differ in a statistically significant way in terms of clinical and laboratory parameters. The median daily dose of GC was 10 [5; 10] mg in prednisolone equivalent. There were no significant differences between the concentrations of saliva FLC in patients of these groups.Conclusion. Salivary-fixed FLCs are most likely produced by cells localized in the stroma of the salivary glands. Determination of the concentration of FLC in saliva can be proposed as a diagnostic test for the pSS. The concentration of free ê-chains in saliva can be considered as a surrogate marker of benign B-cell proliferation in the MSG. Therapy with low and medium doses of GC in pSS does not affect the concentration of FLC in saliva.

The article is devoted to the construction and study of a finite-difference scheme for a one-dimensional diffusion–convection equation with a fractional derivative with respect to the characteristic of the convection operator. It develops the previous results of the authors from [5, 6] in the following ways: the differential equation contains a fractional derivative of variable order along the characteristics of the convection operator and a quasi-linear diffusion operator; a new accuracy estimate is proved, which singles out the dependence of the accuracy of mesh scheme on the curvature of the characteristics.

Standing deadwood is an important structural component of forest ecosystems. Its occurrence and dynamics influence both carbon fluxes and the availability of habitats for many species. However, deadwood is greatly reduced in managed, and even in many currently unmanaged temperate forests in Europe. To date, few studies have examined how environmental factors, forest management and changing climate affect the availability of standing deadwood and its dynamics. Data from five periods of the Austrian National Forest Inventory (1981-2009) were used to (I) analyse standing deadwood volume in relation to living volume stock, elevation, eco-region, forest type, ownership and management intensity, (II) investigate the influence of forest ownership and management intensity on snag persistence and (III) define drivers of standing deadwood volume loss for seven tree genera (Abies, Alnus, Fagus, Larix, Picea, Pinus and Quercus) using tree-related, site-related and climate-related variables, and predict volume loss under two climate change scenarios. Standing deadwood volume was mainly determined by living volume stock and elevation, resulting in different distributions between eco-regions. While forest type and management intensity influenced standing deadwood volume only slightly, the latter exhibited a significant effect on persistence. Snag persistence was shorter in intensively managed forests than in extensively managed forests and shorter in private than in public forests. Standing deadwood volume loss was driven by a combination of diameter at breast height, elevation, as well as temperature, precipitation and relative humidity. Volume loss under climate change predictions revealed constant rates for moderate climate change (RCP2.6) by the end of the 21st century. Under severe climate change conditions (RCP8.5), volume loss increased for most tree genera, with Quercus, Alnus and Picea showing different predictions depending on the model used as the baseline scenario. We observed trends towards faster volume loss at higher temperatures and lower elevations and slower volume loss at high precipitation levels. The tree genera most susceptible to climate change were Pinus and Fagus, while Abies was least susceptible. Synthesis and applications. We recommend to protect standing dead trees from regular harvesting to ensure the full decomposition process. The consequences for decomposition-dependent species must be taken into account to evaluate the influences of management and climate change on standing deadwood dynamics., Journal of Applied Ecology, 60 (4), ISSN:0021-8901, ISSN:1365-2664

Purpose: Circulating tumor DNA (ctDNA) has emerged as a promising tumor-specific biomarker in pancreatic cancer, but current evidence of the clinical potential of ctDNA is limited. In this study, we used comprehensive detection methodology to explore the utility of longitudinal ctDNA measurements in patients with advanced pancreatic cancer. Experimental Design: A targeted eight-gene next-generation sequencing panel was used to detect point mutations and copy-number aberrations (CNA) in ctDNA from 324 pre-treatment and longitudinal plasma samples obtained from 56 patients with advanced pancreatic cancer. The benefit of ctDNA measurements to predict clinical outcome and track disease progression was assessed. Results: We detected ctDNA in 35/56 (63%) patients at baseline and found that it was an independent predictor of shorter progression-free survival (PFS) and overall survival (OS). After initiation of treatment, ctDNA levels decreased significantly before significantly increasing by the time of progression. In some patients, ctDNA persistence was observed after the first chemotherapy cycles, and it was associated with rapid disease progression and shorter OS. Longitudinal monitoring of ctDNA levels in 27 patients for whom multiple samples were available detected progression in 19 (70%) patients. The median lead time of ctDNA measurements on radiologically determined progression/time of death was 19 days (P = 0.002), compared with 6 days (P = 0.007) using carbohydrate antigen 19–9. Conclusions: ctDNA is an independent prognostic marker that can be used to detect treatment failure and disease progression in patients with advanced pancreatic cancer.

Introduction. Several viruses including hepatitis C virus (HCV) and human immunodeficiency virus (HIV) can induce vasculitis.Aim. We aimed to study the incidence, risk factors, and severity of skin vasculitis in patients with HCV and HCV/HIV coinfection.Patients and Methods. The study group included 331 patients (254 patients with HCV and 77 patients with HCV/HIV coinfection) referred to a specialized hepatology center for antiviral therapy of HCV infection.Results. Skin vasculitis was found in 21% (95% CI: 17–25%) of cases, n = 69/331. Skin vasculitis was observed in in 20% of patients infected with HCV (95% CI: 15–25%) and in 25% of HIV/HCV co-infected patients (95% CI; 16–35%), χ2 = 0,892, р = 0,345. Most patients with vasculitis infected with HCV had cryoglobulinemia (94%, n = 47/50), meanwhile, in HIV/HCV co-infected patients, cryoglobulinemia was found in 63% cases (n = 12/19), χ2 = 10.568, р = 0.001. Multiple regression analysis showed that skin vasculitis was related with cryoglobulinemia (OR = 6,928, 95% CI: 3.245–14.790, р < 0.001), liver cirrhosis (OR = 2.015, 95% CI: 1.062–3.824, р = 0.032), duration of overt HCV infection (OR = 1.057, 95% CI: 1.021–1.094, р = 0.002), patients age (OR = 1.029, 95% CI: 1.002–1.057, р = 0.033) and inversely related with plasma alanine transaminase (OR 0.433, 95% CI: 0.229–0.820, р = 0.010). The statistical model was normalized for gender, HIV-positivity and bilirubin levels, and regression equation constant was 4.398 (p < 0.001). The intensity of skin rashes was comparable in HCV infected and HCV/HIV co-infected patients (χ2 = 6.741, р = 0.081), and was highly correlated with cryoglobulin levels both in HCV infected (r = 0.788, p < 0.001), and HCV/HIV co-infected patients (r = 0.909, p = 0.001).Conclusion. Skin vasculitis was found in 20–25% of cases among patients with HCV infection and HCV/HIV co-infection. Cryoglobulinemia was the main factor associated with skin vasculitis, and severity of skin lesions was closely related with cryoglobulin levels.

The aim of this work was to study the effect of vacuum sintering conditions and cerium concentration on the optical, luminescent and thermal properties of yttrium-aluminum garnet based ceramics doped with Се3+ cations. Series of ceramic powders were synthesized and samples of luminescent ceramics having the composition Y3-хСехAl5O12 were synthesized where x was in the range 0.01 to 0.025 f.u. We show that the phase composition and grain size distribution of the ceramic powders do not depend on cerium concentration. Without sintering additives, an increase in vacuum sintering temperature from 1675 to 1800 °C leads to an increase in the optical transmittance of luminescent ceramic specimens from 5 to 55% at a 540 nm wavelength and an increase in the thermal conductivity of the samples from 8.4 to 9.5 W/(m ∙ K). It was found that an increase in cerium concentration leads to a shift of the luminescent band peak from 535 to 545 nm where as the width of the luminescent band decreases with an increase in vacuum sintering temperature from 1675 to 1725 °C.

Introduction. Over the past 5 years, signifi cant progress has been achieved in the treatment of patients with Ph-negative acute lymphoblastic leukemia (ALL). Treatment results were compared between two protocols of the Russian multicenter studies «ALL-2009» and «ALL-2016», in which multicomponent high-dose consolidation was not used. The principle of continuity of treatment was observed with modifi cation of doses of cytostatic drugs depending on the depth of cytopenia.Aim – to compare the 5-year results of two studies and to determine the factors of unfavorable prognosis in the treatment of patients with ALL.Materials and methods. The studies were performed from April 2009 to April 2016 (ALL-2009) and from April 2016 to September 2021 (ALL-2016), and 596 patients were included: 330 in ALL-2009 and 266 in ALL-2016. The analysis was performed in March 2022. The median age of patients in ALL-2009 was 28 years (15–55), in ALL-2016 – 32.5 years (18–55). Cytogenetic studies were performed in 242 patients in ALL-2009 (73.3 %) and 236 patients in ALL-2016 (88.7 %). Patients in the ALL-2016 protocol underwent a centralized assessment of minimal residual disease (MRD) by fl ow cytometry on protocol +70 day (after completion of two induction phases), +133 and +190 days. Transplantation of allogeneic stem hematopoietic cells was performed in 7 % of patients in ALL-2009 and in 9 % in ALL-2016.Results. Overall, relapse-free survival (OS, RFS) and the probability of relapse for a period of 3 years from the moment of inclusion of patients in a particular study were 59 %, 63 % and 23 % for ALL-2009, and for ALL-2016 – 64 %, 59 % and 22 %, respectively. For patients with B-cell precursor ALL, two cytogenetic risk groups were formed, in which long-term survival rates differed signifi cantly: the standard group (hyperploid set of chromosomes and normal karyotype) – OS 63 %, RFS 70 %, and high cytogenetic risk (any abnormal karyotype, except for hyperploidy) – OS 49 %, RFS 52 % (р = 0.001, р = 0.0014). In T-ALL, cytogenetic markers had no prognostic value, but the immunophenotype of early T-cell precursor turned out to be an important predictor of poor prognosis (the probability of relapse was 52 % compared with 15 % for all other immunophenotypic variants). According to the results of centralized monitoring of MRD, it was determined that for B-cell precursor ALL, the signifi cant negative factors are the high cytogenetic risk group and positive MRD status at +70 day, and for T-cells, the early immunophenotype and positive MRD status at +133 day.

The issues of improving the efficiency of state management of high-tech projects with the direct participation of large Russian corporations are analyzed. The subject of the study is the process of implementing a sovereign technology policy. The purpose of the article is to reveal the mechanisms of public administration aimed at achieving the strategic goals of the technological policy of the state, to systematize recommendations to public administration bodies and business participants for the implementation of strategic plans of the state. Materials and methods. The methodological basis of the article is a systematic approach to consider the role of the state in the development of high-tech projects, as well as a statistical method for analyzing the implementation of the technological policy of the state. Results. The analysis of the implementation of the technological policy of Russia, the possibilities of stimulating mechanisms of the state for the development of a sovereign technological base is presented. Conclusions. Recommendations for the successful implementation of the technological policy of the state are presented. Application. The results obtained can be used to analyze the state management of high-tech sectors of the Russian economy.

Any material that we encounter in the world around us does not have such a widespread use as bacterial cellulose. This kind of unique material gained its popularity in the 20th century and became an excellent source for research. Its acquisition and practical application in various areas of our life activity is currently quite important. In addition, thanks to a wide range of studies aimed at the basics of its production, many promising areas of using by-products of the food industry as a source of energy for growth have been identified, which makes this material more environmentally friendly than its plant counterpart. Despite its rich history of studying and obtaining bacterial cellulose, it is still considered to be not fully studied material. This makes it possible for researchers to identify new sources of energy for the growth of bacterial cellulose, to improve the quality and increase its quantity, both in the laboratory and on an industrial scale, as well as to look for more and more new areas of its application, where it would seem it has no place. In the modern scientific world, bacterial cellulose is one of the promising sources of scientific research and further technological applications., Любой материал, который мы встречаем в окружающем нас мире, не имеет такого распространенного применения, как бактериальная целлюлоза. Этот своего рода уникальный материал получил свою популярность в XX веке и стал отличным источником для исследований. Его получение и практическое применение в различных областях нашей жизнедеятельности в настоящее время имеет достаточно большое значение. Помимо этого, благодаря широкому спектру исследований, направленных на основы его получения, было выявлено множество перспективных направлений использования побочных продуктов пищевой промышленности как источника энергии для роста, что делает данный материал более экологичным, чем его растительный аналог. Несмотря на богатую историю изучения и получения бактериальной целлюлозы, она по настоящее время считается не до конца изученным материалом. Это дает возможность исследователям выявлять новые источники энергии для роста бактериальной целлюлозы, улучшать качества и увеличивать ее количество как в лабораторных, так и промышленных масштабах, а также искать все более новые области ее применения, там где, казалось бы, ей не место. В современном научном мире бактериальная целлюлоза является одним из перспективных источников научных исследований и дальнейших технологических применений.

The aim of the work was to analyze the available therapeutic options for the conventional therapy of hereditary myopathies.Materials and methods. When searching for the material for writing a review article, such abstract databases as PubMed and Google Scholar were used. The search was carried out on the publications during the period from 1980 to September 2022. The following words and their combinations were selected as parameters for the literature selection: “myopathy”, “Duchenne”, “myodystrophy”, “metabolic”, “mitochondrial”, “congenital”, “symptoms”, “replacement”, “recombinant”, “corticosteroids”, “vitamins”, “tirasemtiv”, “therapy”, “treatment”, “evidence”, “clinical trials”, “patients”, “dichloracetate”.Results. Congenital myopathies are a heterogeneous group of pathologies that are caused by atrophy and degeneration of muscle fibers due to mutations in genes. Based on a number of clinical and pathogenetic features, hereditary myopathies are divided into: 1) congenital myopathies; 2) muscular dystrophy; 3) mitochondrial and 4) metabolic myopathies. At the same time, treatment approaches vary significantly depending on the type of myopathy and can be based on 1) substitution of the mutant protein; 2) an increase in its expression; 3) stimulation of the internal compensatory pathways expression; 4) restoration of the compounds balance associated with the mutant protein function (for enzymes); 5) impact on the mitochondrial function (with metabolic and mitochondrial myopathies); 6) reduction of inflammation and fibrosis (with muscular dystrophies); as well as 7) an increase in muscle mass and strength. The current review presents current data on each of the listed approaches, as well as specific pharmacological agents with a description of their action mechanisms.Conclusion. Currently, the following pharmacological groups are used or undergoing clinical trials for the treatment of various myopathies types: inotropic, anti-inflammatory and antifibrotic drugs, antimyostatin therapy and the drugs that promote translation through stop codons (applicable for nonsense mutations). In addition, metabolic drugs, metabolic enzyme cofactors, mitochondrial biogenesis stimulators, and antioxidants can be used to treat myopathies. Finally, the recombinant drugs alglucosidase and avalglucosidase have been clinically approved for the replacement therapy of metabolic myopathies (Pompe’s disease).

The purpose of this work was to study the features of the development of hemorrhagic complications in patients with bilateral viral pneumonia associated with COVID-19 of severe course, delivered to the hospital for emergency indications. The study included 561 patients with bilateral viral pneumonia. Various variants of bleeding were noted in 45 cases, all of them occurred in patients with severe new coronavirus infection (39 patients or 6.95% of all patients with severe NCI and 4.11% among all examined patients). Cases of combined hemorrhagic events were noted in 4 patients. In addition to age, gender, obesity and comorbidity, the use of antiplatelet therapy played a key role in the development of bleeding, which indicates the need to reduce the daily doses of such drugs at the later stages of treatment.

It is established that the dihedral homologies of involutive A ∞ A_{\infty } -algebras are homotopically invariant with respect to the homotopy equivalences of involutive A ∞ A_{\infty } -algebras. As a consequence, it is shown that over any field, the dihedral homologies of a topological space are isomorphic to the dihedral homologies of the involutive A ∞ A_{\infty } -algebra of homologies for the simplicial group of Kan loops of the original topological space.

This study considers the issue of assessing the time changes in forest plantations and constructing an algorithmic and software system for monitoring these changes. Modern systems that study vegetation changes do not have the necessary functionality and do not cover the range of observations discussed in this paper. Existing research methods are intended only to record changes that occur in forest ecosystems and take into consideration the peculiarities of a certain natural zone, which limits their use. At the same time, it should be understood that the requirements for modern systems should include additional components that could make the system universal and mobile. A comparative analysis of satellite images acquired from remote sensing by the Landsat 8 satellite system has been carried out to determine the areas affected by forest fires. During the classification, spectral analysis was used, and an index of fires was determined to indicate the burned areas. To analyze the changes that occur in forests due to fires, correlation-regression analysis is used. It has been proven that the area of sanitary felling after fires and the area of forest land traversed by fires demonstrated the greatest interconnection. The extrapolation and forecasting were carried out using a regression data model, the effectiveness of which is confirmed by a coefficient of determination of 0.87. The dependences built make it possible to conclude that by 2030 the number of forest fires will increase while the area of burned forests will not decrease. The developed mobile application could be popular among a significant group of users to monitor fire events. The practical result is the introduction of the built system, which makes it possible to quickly monitor forest plantations after fires and assess the areas that were affected.

Introduction. Primary mediastinal lymphoma (PML) is an aggressive lymphoid tumor treatment success of which is determined by induction therapy. To date, none of the standard chemotherapy regimens (CT) have demonstrated an advantage in efficacy. Intensive therapy programs are associated with high toxicity.Aim — to evaluate the efficacy and toxicity of two pilot prospective treatment protocols PML-16 and PML-19 as well as the possibility of using the analysis of freely circulating tumor DNA (ctDNA) to assess MRD in patients with PML.Materials and methods. From January 2016 to January 2022, 34 previously untreated PML patients were included in the study; average age — 32; stage > I — in 60 %; extramediastinal lesions — in 14.7 %; bulky disease — in 73.5 % of patients. Positron emission tomography combined with computed tomography (PET-CT) was performed; ctDNA was determined to assess the completeness of remission.Results. Eighteen patients received treatment according to the PML-16 protocol (6 courses of chemotherapy; 2 blocks of RmNHL-BFM-90 + 4 courses of R-EPOCH). After the end of therapy, all 18 patients achieved PET-negative remission. The next 16 patients received treatment according to the PML-19 protocol (4 courses of chemotherapy; 2 blocks of R-mNHL-BFM-90 + 2 courses of R-EPOCH) in combination with lenalidomide. After the end of therapy, 9 (56 %) patients achieved PET-negative remission; 7 (44 %) retained pathological activity (D4–5 points). After 3 and 6 months 15 (94 %) patients achieved normalization of metabolic activity. Considering the high frequency of false-positive results in patients with PML, a ctDNA study was performed to determine the depth of remission in 15 patients. After the end of therapy, all 15 patients had complete elimination of ctDNA. Of these, 5 (33 %) remained PET-positive at the end of treatment. During further observation, after 3–6 months, in 4 patients the level of metabolic activity decreased to physiological without the use of consolidating therapy. After the end of therapy, one patient suffered the new coronavirus infection, COVID-19. A month later, residual formation of SUVmax 14.2 remained in the mediastinum. The patient is currently under observation. With a median follow-up of 36 months (9 to 76 months) all 34 patients are in remission.Conclusion. The effectiveness of PML-16 made it possible to abandon the consolidation therapy and refuted the idea of the need for 6 courses of CT. The combination of programs based on the application of the principle of high-dose shortpulse induction of remission (R-mNHL-BFM-90) in combination with the prolonged administration of medium doses (R-EPOCH) was crucial in achieving a successful result. The inclusion of lenalidomide in the “PML-19” program made it possible to achieve complete remission in 100 % of cases after 4 courses. The possibility of using DNA analysis to assess MRD in patients with PML was shown.

The article analyzes the process of state management of high-tech projects in various sectors of the economy, provided for by strategic and program documents of the state, with the direct participation of large Russian corporations. The subject of the study is the sovereign technological policy of the Russian Federation. The purpose of the article is to reveal the strategic goals of the technological policy of the state. Materials and methods. To study the role of the state in the development of high-tech projects in various sectors of the economy, system analysis, methods of analysis and synthesis were used. Results. The directions and main participants of the technological policy of Russia are systematized. Conclusions. The results of the analysis of Russia's technological policy demonstrated the ability of the state and business to achieve the goal for the development of high-tech industries on a sovereign technological base in the prevailing military-geopolitical and economic conditions. Application. The results obtained can be used to analyze the public management of high-tech sectors of the Russian economy.

Introduction. COVID-associated coagulopathy is an important pathogenetic factor in the development of new coronavirus infection (NCI) complications. Therefore the use of anticoagulants is considered as one of the fundamental components of the therapy of NCI. The aim of the study was to find the optimal anticoagulant therapy regimen in patients with severe NCI. Materials and methods. The study is retrospective and included an analysis of 947 cases of confirmed NCI. A survival analysis was performed with the construction of Kaplan-Meyer curves in order to assess the effect of a particular anticoagulant therapy regimen on the occurrence of thrombosis, bleeding, and death. In order to exclude the influence of cofounders due to the retrospective nature of the study, the pseudorandomization method («propensity score matching») was used, followed by the re-construction of Kaplan-Meyer curves. Results. Among 947 patients with severe COVID-19, 27 thrombotic events were verified in 24 patients and 44 hemorrhagic incidents in 38 patients. The day of the event, regardless of the choice of the starting point (the onset of the disease or the 1st day of hospitalization) and its nature (thrombosis or bleeding), had no statistical differences (p=0.33 and p=0.12, respectively). The use of a particular anticoagulant therapy regimen did not significantly affect the development of thrombosis, bleeding or death, including the use of the propensity score matching method. Conclusion. Thus, using therapeutic doses of anticoagulants in COVID-19 patients does not give advantages over the use of preventive doses concerning the risk of thrombosis, bleeding and death.

Introduction. The COVID-19 impact on hemostasis of stroke survivors with community-acquired pneumonia is an urgent problem. The aim of the study is to analyze the features of clinical and laboratory parameters in cerebral stroke combined with community-acquired pneumonia caused by the SARS-Co-V-2 virus. Materials and methods. The instrumental and laboratory examination results of 88 patients aged 73.0 (12.3) years in the acute period of stroke with community-acquired viral pneumonia symptoms were analyzed. The present study included 39.8 % (n=53) male and 60.2 % female (n=35) with duration of diagnosed infectious disease less than 7 days. The symptoms of cerebral stroke were compared with the results of laboratory testing of the hemostasis system, lipid metabolism, and the activity of the systemic inflammatory response. The severity of lung tissue damage and the outcomes of the diagnosed changes were assessed. Results. All patients had mild or moderate COVID-19. In 87.5 % (n=77) cases unspecified (40.2 %, n=31), cardioembolic (36.4 %, n=28), lacunar (3.9 %, n=3) and atherothrombotic (19.5 %, n=15) ischemic stroke subtype was diagnosed. Focal ischemia lesion in the left middle cerebral artery (LMCA) territory was detected in 45.6 % (n=35), in the right middle cerebral artery (RMCA) territory in 41.6 % (n=32). Manifestations of hemorrhagic stroke were noted in 12.5 % (n=11) with signs of parenchymal hemorrhage in 54.5 % (n=6), ventricular hemorrhage in 27.3 % (n=3), subarachnoid hemorrhages were noted in 18.2 % (n=2). The indicators of the coagulation system in terms of the number of platelets corresponded to 251.3 (90.7); the APTT value was in the range of 29.2 (26.7 33.0) (s); the INR parameter was 1.16 (1.05 1.25); the value of prothrombin ( %) corresponded to the value of 85.9(23.4). Conclusion. We do not observe the great disorders of haemostasis in the most acute period of the stroke. When combined with COVID-19 the most common stroke is ischemic stroke. The stroke survivors with the community-acquired pneumonia caused by SARS-CoV-2 laboratory tests show that increase of inflammatory markers are above the reference range.

Anti-MuSK myasthenia is a chronic autoimmune disease caused by violation of the function of the agrin-MuSK-Lrp4 complex, accompanied by the development of pathological muscle fatigue and often muscle atrophy. The disease can be a primary, as well as a complication of immunosuppressive therapy and hematopoietic stem cell transplantation. We present a case of anti-MUSK myasthenia gravis that developed after allogeneic HSCT due to acute myeloid leukemia in a 44-year-old patient (born in 1975). A distinctive feature of the case was a generalized injury, including not only extraocular, but also paravertebral muscles, dropped head syndrome in the evening. In addition, laboratory, electroneuromyographic and neuroimaging (MRI of muscles, MR-spectroscopy) data indicating the neurogenic reversible nature of changes in the involved musculature are presented.Results. This study presents MRI and EMG signs of neurogenic damage of axial musculature in a patient with weakness and swelling of the paravertebral muscles (edematous changes according to STIR, corresponding to MR signs of early functional denervation) for a period of 2–4 months, due to anti-MUSK myasthenia gravis. Clinical manifestations, as well as edematous neurogenic changes in the paravertebral muscles, regressed after pathogenetic therapy. Conclusion. The article presents up-to-date data on the clinical and instrumental characteristics of myasthenia gravis. The considered clinical example confirms the presence of neurogenic changes at an early stage of anti-MUSK myasthenia gravis and indicates the need for immediate initiation of pathogenetic therapy to avoid the development of atrophy and fatty infiltration of muscles.

The article examines the relationship between the phenomenon of "trust in power" and the level of socio-political consolidation of society. The starting point of the study was the publications of French economists J.Algan and P.Kayu, as well as American scientists M.Norton and R.Buell, in which the authors pointed out the relationship between the level of trust in society and the degree of effectiveness of political and socio-economic activities of the authorities. Based on the analysis of these data, the article formulates the directions according to which it is advisable to build work to increase the level of public confidence in the authorities: the manifestation of responsiveness of the authorities to people's requests; improvement of operational transparency of the authorities; current activities focused on improving people's well-being. As a point of assembly of the interests of the government and society, it is proposed to use an appropriate image of the future, which can be integrated into the system of public administration, giving it a quantitative and qualitative assessment. In this case, the proper image of the future will be a goal setting not only for the authorities, but also for citizens in the search for an optimal balance of civil-state identity. The conceptual issues of measuring the level of public confidence in the government are also considered, mechanisms for ensuring socio-political consolidation of society within the framework of a social dialogue between government, business and civil society on the basis of a regional social contract are proposed.

Background. Proximal spinal muscular atrophy 5q (5q‑SMA) is one of the most common neuromuscular diseases, which is caused by mutations of the SMN1 gene. Despite the fact that most studies consider SMN1 “deletion” as the most common cause of 5q‑SMA, gene loss is in fact associated with both classical deletions and conversions of SMN1 and SMN2, as well as with formation of chimeric structures. Up to now, far too little attention has been paid to the prevalence of types of SMN1 loss. However, different types of mutations can have different influence on the clinical findings and the effectiveness of therapy. A deeper study of the structure of these genes will allow us to determine the predictors of response to treatment and bring us closer to understanding the reasons for the instability of the SMN region.Aim. To study genetic changes in the SMN1 gene, as well as the number of copies of the SMN1 and SMN2 genes in 5q‑SMA.Materials and methods. The study involved 703 patients, for whom the analysis of the number of copies of SMN1 and SMN2 was performed in the center of molecular medicine of I.P. Pavlov First Saint Petersburg State Medical University for 2018–2021. Gene copy number analysis was performed by multiplex ligation‑dependent probe amplification (MLPA) using the SALSA MLPA P021 SMA kit (MRC Holland).Results. Among 703 participants, a homozygous SMN1 deletion was found in 167 (24 %), 76 (11 %) were carriers of the deletion and no aberrations were found in the remaining 460 (65 %). Among patients with a homozygous deletion, 41 (24 %) cases of a true deletion were identified. Also, 11 (7 %) cases of partial deletion with a homozygous loss of the 7th exon and heterozygous of the 8th exon of SMN1 were identified. The most common type of aberration was the conversion of SMN1 to SMN2 – 94 (56 %) cases, which is characterized by a homozygous loss of SMN1 and a reciprocal increase in SMN2 copies. In addition, 21 (13 %) cases of the formation of hybrid genes were found.Conclusion. Types of genetic aberrations in 5q‑SMA have not been studied enough yet. A search of the literature revealed very few studies which results are comparable with ours. However, further research of genetic changes in SMN1 and SMN2 might bring more clarity on the causes and mechanisms of this disease, and get us closer to finding the most effective method of treatment.

BACKGROUND: The significance of copper (Cu) in the human body and its toxicological effects in elevated concentrations have now been fully established, although the presence of Cu in the environment and in the body of different populations across different regions warrants further research. AIM: To identify the level of Cu accumulation in the fine and solid phases of snow and hair of the population of Gorno-Altaysk. MATERIAL AND METHODS: The concentration of Cu in snow water, the solid phase of snow, and hair in the population of Gorno-Altaysk was determined by atomic absorption spectrometry. Snow samples were collected from the areas of 10 coal-fired boiler houses, and hair samples were collected from 122 people aged 450 years. RESULTS: The Cu content in melted water from all snow intakes in the areas of coal-fired boilers (0.0190.049 mg/L) did not exceed the maximum permissible concentration (MPC 0.1 mg/L). In 3 (56.4067.20 mg/kg) of the 10 samples in the solid phase of snow (19.3767.42 mg/kg), an excess of MPC (55.0 mg/kg) was detected. The Cu content in the hair of the subjects did not depend on gender (U=1741; p=0.580); in a population aged 421 years, the concentration of Cu decreased with age (U=29; p=0.05). The concentration of Cu in the hair of the residents of Gorno-Altaysk, when compared with other regions of the world, corresponded to low values (10.0 mg/kg), low concentrations (7.5 mg/kg, 31.9%) were more common among the population than high concentrations (25.0 mg/kg, 5.7%). No correlation was noted between the concentration of Cu in the hair of the population and that in snow water and the solid phase of snow. CONCLUSION: The Cu content in the fine-dispersed phases of snow collected from across areas of coal-fired boilers did not pose any danger to the people, whereas, in the solid phases, increased concentrations were recorded. The hair of the population more often contained a low content of Cu (31.9%) than a high content (5.7%).

To create a systematic database on the presence of metals in the environment and the human body, it is necessary to conduct local studies in different regions of the Russian Federation. A comprehensive analysis of the content of cadmium and lead in different coenotic links, including the human body, has not been carried out in the Altai Republic. The aim of the study was to reveal the level of lead and cadmium accumulation in the solid and finely dispersed phases of snow and hair of the population of Gorno-Altaisk. Material and methods. The content of lead and cadmium in the snow and hair of the population of Gorno-Altaisk was estimated by the atomic absorption method. Snow samples were taken in the areas of 10 central coal boilers, hair samples were taken from 122 volunteers permanently residing in the city. Results. The concentration of metals in snow water exceeded the maximum allowable concentrations: for cadmium (0.004–0.008 mg/kg) by 3.8–8.2 times; for lead (0.008–0.469 mg/kg) by 2–15.6 times. In the solid phases of snow, the content of metals exceeded the permissible level by about 3 times. The average value of the concentration of cadmium in the hair of the population was 0.16 mg/kg, which did not exceed the all-Russian reference value (0.25 mg/kg), the proportion of excess among the population was 6.5 %. The lead content (3.18 mg/kg) approximately corresponded to the all-Russian values (3.0 mg/kg), the excess was found among 43 % of the population. Conclusion. As a result of the widespread use of solid fuels, the presence of cadmium and lead in the environment increases, which is confirmed by the accumulation of these metals in the snow cover and the accumulation of the analyzed microelements in the hair of the population of Gorno-Altaisk.

Introduction. Fine needle aspiration biopsy followed by cytological examination is the gold standard in the diagnosis of thyroid nodules. However, up to one third of cases represent an indeterminate result (Bethesda Thyroid Classification, 2017) III—V). Among such cases, category IV is the most common and most difficult to interpret (Bethesda, 2017). The study objective is to determination of the diagnostic and prognostic significance of the molecular genetic study of the fine needle aspiration biopsy material in patients with thyroid nodules with the cytological category Bethesda, IV.Materials and methods. The study included surgical thyroid samples obtained from patients whose cytological examination revealed pathology of cytological category IV according to the Bethesda classification (2017). group 1 included surgical samples from 143 patients with thyroid lesions, and group 2 - cytological material from 45 patients. Determination of the BRAF V600E mutation, mutations in the RAS genes (KRAS, HRAS, NRAS) was carried out using allele-specific polymerase chain reaction, and the RET / PTC1, RET / PTC3 and PAX8 / PPARG translocations were determined using reverse transcription polymerase chain reaction. Sanger sequencing was used to detect mutations in the promoter region of the TERT gene.Results. In group 1, an overall prevalence of the studied mutations in thyroid cancer was 35.1 %: 8.8 % of cases were mutation BRAF V600E, 24.6 % - mutations in the RAS genes, 1.8 % - mutation C228T in the TERT gene. The C228T mutation in the TERT gene was found in 1 case of widely invasive Hurtle cell carcinoma. The prevalence of mutations in benign formations was 4.7 %. mutations in RAS genes were also found in them in group 1, mutation BRAF V600E was associated with the presence of extrathyroid invasion (p = 0.024), vascular invasion (p = 0.018), and lymph node metastases (p = 0.018). In group 2, using the genetic panel sensitivity and specificity were equal: 36.4 and 93.9 %, respectively. positive and negative predictive values were 66.7 and 81.6 %, respectively. No RET / PTC and PAX8 / PPARG translocations were found in groups 1 and 2.Conclusion. The investigated molecular genetic panel, having a high specificity for carcinomas, will make it possible to supplement the cytological diagnostics of material in the category Bethesda, IV. BRAF V600E was associated with an aggressive morphological pattern.

A homogeneous Dirichlet initial-boundary value problem for a quasilinear parabolic equation with a time-fractional derivative and coefficients at the elliptic part that depend on the gradient of the solution is considered. Conditions on the coefficients ensure the monotonicity and Lipschitz property of the elliptic operator on the set of functions whose gradients in space variables are uniformly bounded. For this problem, a linear regularized mesh scheme is constructed and investigated. A sufficient condition is derived for the regularization parameter that ensures the so-called local correctness of the mesh scheme. On the basis of correctness and approximation estimates for model problems with time-fractional Caputo or Caputo–Fabrizio derivatives, accuracy estimates are given in terms of mesh and regularization parameters under the assumption of the existence of a smooth solution to the differential problem. The presented results of the numerical experiments confirm the obtained asymptotic accuracy estimates.