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The article describes a clinical case of BRAHH syndrome in a patient with arterial hypertension and permanent atrial fibrillation (AF). The patient took perindopril 10 mg, indapamide 2.5 mg, amlodipine 10 mg, bisoprolol 2.5-5 mg daily. She was admitted to a hospital complaining of severe weakness, a heart rate decreases to 38 beats per minute against the background of high blood pressure. During the examination, she was diagnosed with complete atrioventricular block against the background of AF, stage 4 chronic kidney disease and severe hyperkalemia (potassium 8.7 mmol/l). The patient was prescribed treatment aimed at eliminating hyperkalemia, and temporary pacing was established. Against this background, her condition improved, and the complete atrioventricular blockade was resolved. This clinical example meets the criteria of BRAHH syndrome, since against the background of taking an atrioventricular node blocker in a small dose, a patient with chronic kidney disease and severe hyperkalemia developed complete atrioventricular block against the background of AF, accompanied by high blood pressure.

The influence of catastrophic forest fires in 2021 on the vegetation cover and soils of the middle taiga on the territory of distribution of light soil-forming rocks of Central Yakutia has been studied. Obtained results showed the cardinal dynamics of species diversity and productivity of the larch and pine forests surface vegetation in their natural state and in burnt areas. The stock of grass-shrub cover aboveground phytomass on the control larch and pine forests is higher for 5 and 10 times than that in the burnt areas, respectively. The work carried out revealed the effect of forest fires on the morphological structure (formation of pyrogenic layer, manifestation of pyro- and cryoturbations), the depth of thawing, the water regime of permafrost soils under larch and pine forests on control and burnt sites in the first year after strong fires. The soils in the study area are predominantly permafrost illuvial-ferruginous podzols. The study revealed an increase in the permafrost table depth of these soils, an increase in the level of ground water, and a decrease in acidity in the upper part of the profile. Intense ash formation was found due to the burning of litter. The characteristic of the current state of vegetation and soil cover is given.

Abstract ADP-ribosylation is a reversible post-translational modification involved in various cellular activities. Removal of ADP-ribosylation requires (ADP-ribosyl)hydrolases, with macrodomain enzymes being a major family in this category. The pathogen Legionella pneumophila mediates atypical ubiquitination of host targets using the SidE effector family in a process that involves ubiquitin ADP-ribosylation on arginine 42 as an obligatory step. Here, we show that the Legionella macrodomain effector MavL regulates this pathway by reversing the arginine ADP-ribosylation, likely to minimize potential detrimental effects caused by the modified ubiquitin. We determine the crystal structure of ADP-ribose-bound MavL, providing structural insights into recognition of the ADP-ribosyl group and catalytic mechanism of its removal. Further analyses reveal DUF4804 as a class of MavL-like macrodomain enzymes whose representative members show unique selectivity for mono-ADP-ribosylated arginine residue in synthetic substrates. We find such enzymes are also present in eukaryotes, as exemplified by two previously uncharacterized (ADP-ribosyl)hydrolases in Drosophila melanogaster. Crystal structures of several proteins in this class provide insights into arginine specificity and a shared mode of ADP-ribose interaction distinct from previously characterized macrodomains. Collectively, our study reveals a new regulatory layer of SidE-catalyzed ubiquitination and expands the current understanding of macrodomain enzymes.

Anthrax is a serious infectious disease with high mortality. The epidemiological security depends on the vaccination of susceptible animals and population at risk. But many of the existing anthrax vaccine strains possess low levels of protective antigen production and high reactogenicity. One of the most promising trends in production of new generation of vaccines is the cloning of particular determinants of immunogenicity of anthrax microbe for the creation of highly effective producers of Bacillus anthracis protective antigen. The aim of the article is to present the results of the study on the construction of recombinant Bacillus subtilis strain, producing B.anthracis protective antigen, promising for use in chemical anthrax vaccines technology. The pHT43PA plasmid containing the gene pag, providing the synthesis of protective antigen of the anthrax microbe and functioning stably in the cells of the recombinant strain Amy21(pHT43РА) of B. subtilis, was constructed on the basis of the shuttle vector pHT43. It is found out during the research, that the microbial cells of the recombinant strain Amy21(pHT43РА) of B. subtilis provide the production of immunologically active protective antigen in quantities, not inferior than anthrax vaccine strains. These data, as well as safety and simplicity of В. subtilis make it possible to continue the research of this recombinant strain as a producer of anthrax protective antigen, promising for use in vaccines production.

Botulism is dangerous toxic infection caused by a toxin produced by the bacterium Clostridium botulinum. The mortality rate from botulism can reach 70% of all cases of illness in case of untimely initiation of treatment. The pathogenesis of botulism involves the damage to the central nervous system by a toxin produced by C. botulinum. Currently there are seven recognized antigenic types of this toxin. Botulinum toxin is included into the group of biological agents and it is one of the most likely agents to be used in a biological attack. Since botulinum neurotoxin is a complex nucleoprotein complex and the traces of DNA can be detected even in purified toxin preparations, we have elaborated a technique for detecting and identifying DNA of toxigenic strains of Clostridium botulinum types A, B, E, that cause human botulism in most cases. This technique is based on the the detection of residual amounts of this DNA in botulinum toxin using multiplex real-time polymerase chain reaction (PCR) assay with fluorescent hybridization detection. The main obstacle to development of a technique for the detection and identification of DNA of toxigenic strains is the high variability of the genes responsible for the synthesis of botulinum toxin. We have established a region of the gene with the lowest homology in all strains. This requirement is met by a fragment of the bont gene that encodes a light chain of a neurotoxin and is highly conserved in the strains of C. botulinum producing one type of toxin. The paper represents the results of the definition of analytical sensitivity and specific activity of the developed method. The specificity of the determination is 100%, the analytical sensitivity – 1×102 mc./ml. The method can be used to analyze food, samples of clinical materials and environmental samples suspected of being contaminated with toxigenic strains of C. botulinum.

Hydraulic fracturing (HF) is an effective way to intensify oil production, which is currently widely used in various conditions, including complex carbonate reservoirs. In the conditions of the field under consideration, the hydraulic fracturing leads to a significant differentiation of technological efficiency indicators, which makes it expedient to study the patterns of crack formation in detail. Studies were carried out for all wells, which were considered as the objects of impact, to assess the spatial orientation of the cracks formed. The developed indirect method was used for this purpose, the reliability of which was confirmed by geophysical methods. During the analysis, it was found that in all cases, the crack is oriented in the direction of the section of the development system element characterized by the maximum reservoir pressure. At the same time, the reservoir pressure values for all wells were determined at one point in time (at the beginning of HF) using machine learning methods. The reliability of the machine learning methods used is confirmed by the high convergence with the actual (historical) reservoir pressures obtained during hydrodynamic studies of wells. The obtained conclusion about the influence of the reservoir pressure on the patterns of fracture formation should be taken into account when planning hydraulic fracturing under the conditions studied.

The objective: to justify the optimal duration of chemotherapy with Lzd and Bdq by evaluating the long-term treatment outcomes in patients with multiple/pre-extensive drug resistant (MDR/preXDR) tuberculosis who interrupted treatment at different time points.Subjects and Methods. 800 patients with MDR/preXDR tuberculosis were enrolled in the study, they were from all regions of the Russian Federation and they started a course of chemotherapy with regimens containing Lzd and Bdq in 2017-2018. All patients who interrupted their chemotherapy (124) were divided at 4 groups. Group 1-43 patients who received less than 90 doses, Group 2-37 patients who received from 91 to 180 doses, Group 3-39 patients who received from 181 to 270 doses, and Group 4-5 patients who received from 271 to 360 doses of anti-tuberculosis drugs.Results. In Group 3, the effectiveness of reaching a favorable outcome during observation for 3-4 years made 53.8% in 21/39, which was comparable to the effectiveness of treatment with a 24-month course of chemotherapy (2017 – 58.0 and 2018 – 52.1%). The treatment duration of patients from Group 3 was additionally analyzed, the arithmetic mean of the number of administered doses makes 262 ± 15, which allowed recommending 9-month courses of chemotherapy.

Hydraulic fracturing is an effective way to stimulate oil production, which is currently widely used in various conditions, including complex carbonate reservoirs. In the conditions of the considered field, hydraulic fracturing leads to a significant differentiation of technological efficiency indicators, which makes it expedient to study in detail the crack formation patterns. For all affected wells, the assessment of the resulting fractures spatial orientation was performed using the developed indirect technique, the reliability of which was confirmed by geophysical methods. In the course of the analysis, it was found that in all cases the fracture is oriented in the direction of the development system element area, which is characterized by the maximum reservoir pressure. At the same time, reservoir pressure values for all wells were determined at one point in time (at the beginning of hydraulic fracturing) using machine learning methods. The reliability of the used machine learning methods is confirmed by high convergence with the actual (historical) reservoir pressures obtained during hydrodynamic studies of wells. The obtained conclusion about the influence of the formation pressure on the patterns of fracturing should be taken into account when planning hydraulic fracturing in the considered conditions.

This article presents, for the first time, a comparative analysis of the emission characteristics of large-area field-effect cathodes (LAFE) based on carbon nanotubes (CNTs) of various morphologies according to key parameters using a unique computerized technique. The work presents a description of a technology for creating various CNT arrays and their comprehensive structure characterization. All CNT arrays synthesized by the catalytic PECVD method on a silicon substrate showed a high degree of chemical purity under the presented technological conditions. In some cases, nanoisland films of Fe were used as a catalyst; in others, thin films of NiO were used, which were deposited on a silicon wafer by chemical vapor deposition (CVD) and atomic layer deposition (ALD), respectively. As a result of these studies, it turned out that an array with a thick CNT coating has good resistance to the action of strong electric fields, fairly good uniformity of distribution of emission centers, a fairly high selection current (2.88 mA/cm2 at 4.53 V/μm), and compliance with the normal current mode according to the “orthodox” test, which makes the morphology of such structures the most promising for further technological optimization of CNT-based cathodes for various practical applications.

The mechanical characteristics and sliding friction behaviors of AA7075 samples were studied in regard to structural states formed in them by ECAP and depending on the ECAP pass number. In addition, the effect of a counterbody’s material on the tribological characteristics of the samples was investigated by the examples of AISI 52100 steel, alumina Al2O3 and silicon nitride Si3N4. Vibration acceleration and acoustic emission signals with parameters such as acoustic emission energy and median frequency were used for characterizing the sliding regimes. The structural state and mechanical properties of the ECAPed AA7075 samples significantly affected their wear behaviors in dry sliding. The counterbody material had a significant influence on the formation of a transfer layer and the subsurface deformation of samples. The dynamic behavior of the tribosystem was studied and the relationship between the sliding parameters, vibrometry and acoustic emission signals was established.

Background: Despite advanced in interventional and medical treatment, mortality after myocardial infarction (MI) remains high, which necessitates the search for predictors of poor outcome. An association between the gene CYP2C19 alleles with lower functional activity and the rates of cardiovascular events has been found. In a number of studies, negative impact of the *2 and *3 alleles of this polymorphic gene on the post-infarction course was shown. However, in most of these studies the patients were followed up from 3 months to 1 year. Aim: To evaluate the effect of CYP2C19 gene polymorphism (*2, *3) on the long-term prognosis in patients with a history of ST-segment elevation myocardial infarction (STEMI). Materials and methods: This open-label prospective two-center study included 145 patients aged 45 to 75 years with a history of STEMI. For 1 year from STEMI on, all the patients were taking medications recommended for outcome improvement, such as statins, clopidogrel as a component of dual antiplatelet therapy, beta-blockers, angiotensin converting enzyme inhibitors. The outcomes were assessed at 12 months by the endpoints of cardiovascular death and recurrent non-fatal MI, and at 5 years by the endpoints of overall mortality and recurrent non-fatal MI. Results: During one year of the follow up, 7 of 145 patients (4.8%) died from cardiovascular causes. Recurrent MI occurred in 8.3% (n = 12) of the patients. The carriers of *1*2 and *1*3 genotypes of the polymorphic CYP2C19 gene were 3.27-fold more likely to experience recurrent MI within 1 year, compared to the carriers of other genotypes (relative risk = 3.27 [95% confidence interval 1.03; 10.36], p = 0.03). After 5 years of the follow up, this association has disappeared. No influence of the assessed polymorphisms on overall and cardiovascular mortality was found (p 0.05). One hundred and seven (107) patients were followed up for 5 years; 14 (13.0%) of them died, other 15 patients (14.0%) had recurrent MIs. Conclusion: *2 and *3 alleles of the polymorphic CYP2C19 gene responsible for the metabolism of clopidogrel, are risk factors of an unfavorable 12-month outcome after STEMI. Subsequently, the influence of the CYP2C19 gene polymorphism on the outcomes evades and is not associated with a 5-year prognosis. To improve post-STEMI outcomes at 1 year, it is necessary to implement the earliest personalized approached to antiplatelet treatment based on the results of the CYP2C19 gene polymorphism analysis.

Abstract Adjuvants play a determinant role in cancer vaccination by optimally activating APCs and shaping the T cell response. Bacterial-derived lipid A is one of the most potent immune-stimulators known, and is recognized via Toll-like receptor 4 (TLR4). In this study, we explore the use of the synthetic, non-toxic, lipid A analog CRX-527 as an adjuvant for peptide cancer vaccines. This well-defined adjuvant was covalently conjugated to antigenic peptides as a strategy to improve vaccine efficacy. We show that coupling of this TLR4 agonist to peptide antigens improves vaccine uptake by dendritic cells (DCs), maturation of DCs and T cell activation in vitro, and stimulates DC migration and functional T cell priming in vivo. This translates into enhanced tumor protection upon prophylactic and therapeutic vaccination via intradermal injection against B16-OVA melanoma and HPV-related TC1 tumors. These results highlight the potential of CRX-527 as an adjuvant for molecularly defined cancer vaccines, and support the design of adjuvant-peptide conjugates as a strategy to optimize vaccine formulation.

The paper presents the first analysis of crowdsourcing data of all observations of fungi (including lichens) and myxomycetes in Northwestern Siberia uploaded to iNaturalist.org to date (24.02.2022). The Introduction presents an analysis of fungal diversity crowdsourcing globally, in Russia, and in the region of interest. Materials and methods describe the protocol of uploading data to iNaturalist.org, the structure of the crowdsourcing community, initiative to revise the accumulated data, procedures of data analysis, and compilation of a dataset of revised crowdsourced data. The Results present the analysis of accumulated data by several parameters: temporal, geographical and taxonomical scope, observation and identification efforts, identifiability of various taxa, species novelty and Red Data Book categories and the protection status of registered observations. The Discussion provides data on usability of crowdsourcing data for biodiversity research and conservation of fungi, including pros and contras. The Electronic Supplements to the paper include an annotated checklist of observations of protected species with information on Red Data Book categories and the protection status, and an annotated checklist of regional records of new taxa. The paper is supplemented with a dataset of about 15 000 revised and annotated records available through Global Biodiversity Information Facility (GBIF). The tradition of crowdsourcing is rooted in mycological societies around the world, including Russia. In Northwestern Siberia, a regional mycological club was established in 2018, encouraging its members to contribute observations of fungi on iNaturalist.org. A total of about 15 000 observations of fungi and myxomycetes were uploaded so far, by about 200 observers, from three administrative regions (Yamalo-Nenetsky Autonomous Okrug, Khanty-Mansi Autonomous Okrug, and Tyumen Region). The geographical coverage of crowdsourcing observations remains low. However, the observation activity has increased in the last four years. The goal of this study consisted of a collaborative effort of professional mycologists invited to help with the identification of these observations and analysis of the accumulated data. As a result, all observations were reviewed by at least one expert. About half of all the observations have been identified reliably to the species level and received Research Grade status. Of those, 90 species (195 records) represented records of taxa new to their respective regions; 876 records of 53 species of protected species provide important data for conservation programmes. The other half of the observations consists of records still under-identified for various reasons: poor quality photographs, complex taxa (impossible to identify without microscopic or molecular study), or lack of experts in a particular taxonomic group. The Discussion section summarises the pros and cons of the use of crowdsourcing for the study and conservation of regional fungal diversity, and summarises the dispute on this subject among mycologists. Further research initiatives involving crowdsourcing data must focus on an increase in the quality of observations and strive to introduce the habit of collecting voucher specimens among the community of amateurs. The timely feedback from experts is also important to provide quality and the increase of personal involvement.

Molecularly thin films are important in material sciences but their use in a wide range of applications requires control over their chemical functionalities, which is difficult to achieve. Here, the authors use decacyclene to form such freestanding and mechanically stable molecular films held together by supramolecular interactions without requiring covalent crosslinking of any kind

Background. The currently existing techniques for dissection the anterior tibial vascular bundle in the proximal third of the lower leg do not provide sufficient length of the vascular pedicle to rotate the tibial bone graft to the level of the middle third of the thigh. The aim of the study to substantiate the possibility of pedicled transfer to the level of the thigh middle third of two blood-supplied bone autografts on a common permanent pedicle, including the anterior tibial vascular bundle. Material and Methods. The study was conducted on 62 lower limbs of non-fixed (native) corpses. We studied the topographic and anatomical relationship between the anterior tibial vascular bundle and the deep peroneal nerve at the level of the proximal third of the leg. Results. The distance between the tip of the greater trochanter of the femur and the distal edge of the anterior tibial bone graft using a combination of grafts at the same level in men was Me 176.7 [173.7; 193.9] mm, in women Me = 151.6 [146.9; 159.9] mm. An analysis of limb lengths ratios in men and women indicates standard level that can be achieved with graft rotation in each person. Conclusion. Dissection of the anterior tibial vascular bundle at the level of the proximal third of the lower leg allows rotation of the complex of the anterior tibial bone autograft and the autograft of the second metatarsal bone into the area of the middle third of the femur on a single vascular bundle. Prevention of injury to the deep peroneal nerve branches during dissection of the vascular pedicle requires the use of microsurgical techniques and preoperative preparation.

The relevance of the research is caused by the fact that the presence of natural fracturing in complex carbonates reservoirs is the main factor that affects the shape and propagation of the network of hydraulic fractures. In such cases, when a hydraulic fracture collides with natural fracturing, there may be a different nature of their interaction, for example, displacement, intersection, etc. Consequently, hydraulic fracturing in complex carbonate reservoirs, characterized by the presence of natural fracturing, can lead to the formation of not a symmetric fracture in its classical sense, but their complex network. Based on field observations (microseismic monitoring and studies of the void space of rocks), various degrees of complexity of hydraulic fractures have been established: from a simple relatively flat single fracture to a rather complex network of fractures. The main aim of the study is to assess the formation of complex networks of hydraulic fractures in naturally fractured carbonate reservoirs. Object: complex carbonate reservoir with a system of natural fractures. Methods: analysis of production, technological, hydrodynamic data and the results of microseismic monitoring in the process of hydraulic fracturing. Results. It was found that hydraulic fracturing in complex carbonate reservoirs often does not lead to the formation of a fracture in its classical sense – two wings propagating symmetrically from the wellbore, which is confirmed by the results of the analysis of the pressure build-up curves in diagnostic logarithmic coordinates. Hydraulic fractures can propagate into the formation directly from wells – targets of influence (classical representation), or through the existing network of natural fractures located in the drainage zone. To involve a significant number of natural fractures and other types of voids in the filtration process during hydraulic fracturing, it is advisable to pump the fracturing fluid at low speeds. Control over the development of hydraulic fractures should be based on reliable information about the natural fracturing of the reservoir before the event, and regulation – through monitoring the dynamics of pressure and injection rate, which confirms the research results.

This paper provides a demonstration-of-concept of a new methodology for comparing field electron emission (FE) theory and experiment. It uses the parameter κ in the mathematical equation Im = CVmκ exp[–B/Vm] (where B and C are weakly varying or constants) that is taken to describe how measured current Im depends on measured voltage Vm for electronically ideal FE systems (i.e. systems that (i) have constant configuration during voltage application and (ii) have Im(Vm) given by the emission physics alone). Experimental parameter values (κm) are used to compare two alternative FE theories, for which allowable (but different) κ ranges have been established. At present, contributions to the ‘total theoretical κ’ made by voltage dependence of notional emission area are not well known: simulations reported here provide data about four commonly investigated emitter shapes. The methodology is then applied to compare 1928/1929 Fowler–Nordheim (FN) FE theory and 1956 Murphy–Good (MG) FE theory. It is theoretically certain that the 1956 theory is ‘better physics’ than the 1928/1929 theory. As in previous attempts to reach known correct theoretical conclusions by experimentally based argument, the new methodology tends to favour MG FE theory, but is formally indecisive at this stage. Further progress needs better methods of establishing error limits and of measuring κm.

The new coronavirus infection COVID-19 from the moment of the first message to the present has spread rapidly in more than two hundred countries around the world, posing a serious threat to the life and health of the population. Most patients who have recovered from COVID-19 continue to complain of shortness of breath, increased fatigue, chest pain, palpitations and other symptoms. Currently, the presence of symptoms 12 weeks after the acute phase of the new coronavirus infection COVID-19 is collectively referred to as post-covid syndrome. Studies have shown that this syndrome occurs frequently in recovered patients with COVID-19, regardless of their age and severity of the disease. This feature significantly distinguishes post-covid syndrome from other syndromes after an infection, and therefore the study of the mechanisms of its development, methods of diagnosis and treatment is an important public health problem. Particular attention is paid to patients with comorbidities, especially those with hypertension and cardiovascular diseases, since they have a more severe outcome after infection and higher case mortality rate. The current drug regimens for patients with post-covid syndrome and concomitant diseases are symptomatic. The most common manifestations of post-covid syndrome from the cardiovascular system are an increase in blood pressure and heart rate. In this regard, this review discusses the prospects for the use of a fixed combination of bisoprolol and amlodipine in the treatment of patients with post-covid syndrome, accompanied by an increase in blood pressure and heart rate.

Background Amplivant is a molecularly optimized Toll-like receptor 2 ligand that can be covalently conjugated to tumor peptide antigens. In preclinical models, amplivant-adjuvanted synthetic long peptides (SLPs) strongly enhanced antigen presentation by dendritic cells, T cell priming and induction of effective antitumor responses. The current study is a first-in-human trial to investigate safety and immunogenicity of amplivant conjugated to human papillomavirus (HPV) 16-SLP.Methods A dose escalation phase I vaccination trial was performed in 25 patients treated for HPV16 positive (pre-)malignant lesions. Amplivant was conjugated to two SLPs derived from the two most immunodominant regions of the HPV16 E6 oncoprotein. The vaccine, containing a mix of these two conjugates in watery solution without any other formulation, was injected intradermally three times with a 3-week interval in four dose groups (1, 5, 20 or 50 µg per conjugated peptide). Safety data were collected during the study. Peptide-specific T cell immune responses were determined in blood samples taken before, during and after vaccination using complementary immunological assays.Results Toxicity after three amplivant-conjugated HPV16-SLP vaccinations was limited to grade 1 or 2, observed as predominantly mild skin inflammation at the vaccination site and sometimes mild flu-like symptoms. Adverse events varied from none in the lowest dose group to mild/moderate vaccine-related inflammation in all patients and flu-like symptoms in three out of seven patients in the highest dose group, after at least one injection. In the lowest dose group, vaccine-induced T cell responses were observed in the blood of three out of six vaccinated persons. In the highest dose group, all patients displayed a strong HPV16-specific T cell response after vaccination. These HPV16-specific T cell responses lasted until the end of the trial.Conclusions Amplivant-conjugated SLPs can safely be used as an intradermal therapeutic vaccine to induce robust HPV16-specific T cell immunity in patients previously treated for HPV16 positive (pre-) malignancies. Increased vaccine dose was associated with a higher number of mild adverse events and with stronger systemic T cell immunity.Trial registration numbers NCT02821494 and 2014-000658-12.

PARG and ARH3 are the main hydrolases to reverse serine poly(ADP-ribosylation) yet their activities in the process differ. Here, the authors synthesise linear and branched poly(ADP-ribose) molecules, perform structure-function analysis and elucidate the mechanistic differences between PARG and ARH3.

The case of primary splenic lymphoma, the uncommon type of non-Hodgkin lymphoma presenting with prominent splenomegaly, is reported. The disease is characterized by long asymptomatic stage and splenic abscess found during splenectomy.

Over the past few decades, there have been significant changes in approaches to the management of patients with pulmonary arterial hypertension (PAH). From the moment when the classification of this disease was first published, new diagnostic capabilities and new drugs have appeared that have improved the quality of life and survival of patients. The article is devoted to the issues of rapid diagnosis of PAH in the case of its high probability. Particular attention is paid to the rapid referral of such patients to an expert center, where it is possible to perform catheterization of the right heart. The importance of risk stratification of patients is also noted, which allows prescribing combination specific therapy at an early stage, which can significantly improve the quality of life and reduce the risk of adverse outcomes. Risk assessment is indicated for all patients at both regional and expert level by determining the risk of 1-year mortality in PAH. The article also discusses the issues of dispensary observation of such patients and dose titration when prescribing specific therapy by an expert center. Recommendations are given for non-specific therapy for PAH, the use of oxygen support, anticoagulants, and other drugs. It is emphasized that ACE inhibitors, angiotensin receptor blockers, betablockers, and ivabradine are generally not used to treat PAH, and their use may limit the possibilities of specific therapy. Occasionally, patients with PH at the regional level require dose titration of PAH-specific therapy, as well as regular follow-up, which requires specialized knowledge. This dictates the need to create pulmonary hypertension rooms in each region or manage this group of patients in high-risk rooms, where medical workers will have the necessary knowledge and will regularly undergo training in expert centers. The described clinical case demonstrates the effectiveness of combination therapy of pulmonary arterial hypertension using an innovative selective agonist of prostacyclin receptors for oral administration – Selexipag. Practical recommendations are given for dose titration and its use in patients with PAH.

Aim. To study the relationship between the indicators of dynamic capnography and pulse oximetry with the indicators of the 6-minute walk test (6MWT) in patients with chronic obstructive pulmonary disease (COPD). Materials and methods. 67 patients of both sexes were examined: 45 patients with COPD (age 60.02.74 years) and 25 patients of the control group (age 47.603.46 years). The study of the functional capabilities of the patients respiratory system was carried out before, during and after the 6MWT on the equipment LifeSense LS1-9R capnograph-pulse oximeter (MedAir AB). Results and discussion. In the comparison group, the parameters of dyspnea at rest were higher than the control group (p0.05), the spirometry indices were significantly lower (p0.05). Shortness of breath as a reason for stopping/slowing down the pace during the 6MWT was noted by patients of both groups (p0.05). When analyzing the PETCO2 trend graphs, periodic breathing (PВ) was revealed. In the group of patients with COPD, signs of PВ in the analysis of the PETCO2 trend were found in 80.95% (p0.05). Regression analysis of Cox proportional risks of mortality in patients with COPD revealed the prognostic value of the following parameters of a comprehensive assessment of the patient: body mass index (BMI), BODE index, dyspnea index on the mMRS scale, Borg, forced expiratory volume in 1 second (FEV1), index Tiffno, signs of PВ, distance 6MWT, signs of PВ and desaturation during 6MWT. At the same time, the total contribution of these indicators to the risk of a lethal event was assessed (p=0.003). Conclusion. When analyzing the correlation dependence, it was revealed that the presence of PВ was a prognostically unfavorable sign in patients with COPD. Predictors of an unfavorable course of COPD were BMI (23.0 kg/m2), BODE index, dyspnea indices on the mMRS, Borg, FEV1 scales, Tiffnos index, signs of PH, distance 6MST, signs of PD and desaturation during 6MST (reliability of the model coefficient p=0.003) in terms of forecast.

Disclaimer The EAC Guidelines represent the views of the EAC, and were produced after careful consideration of the scientific and medical knowledge, and the evidence available at the time of their publication. The EAC is not responsible in the event of any contradiction, discrepancy, and/or ambiguity between the EAC Guidelines and any other official recommendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies. Health professionals are encouraged to take the EAC Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic, or therapeutic medical strategies; however, the EAC Guidelines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient’s health condition and in consultation with that patient and, where appropriate and/or necessary, the patient’s caregiver. Nor do the EAC Guidelines exempt health professionals from taking into full and careful consideration the relevant official updated recommendations or guidelines issued by the competent public health authorities, in order to manage each patient’s case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations. It is also the health professional’s responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription.

A clinical observation of an integrated approach to surgical reconstruction of multisystem trauma complications is presented. A man came to the Department of Reconstructive Surgery with the complication of a multisystem injury as a result of a fall in the subway on the way 6 months before his visit. An individual treatment plan was developed based on the characteristics of anatomical and functional disorders and pathological tissue changes. As a result of staged surgical treatment, functional rehabilitation of the patient was achieved with the restoration of the function of the upper and lower extremities and the achievement of a stable remission of osteomyelitis. The observation period was 11 years.

The article is devoted to topical issues of management of patients with pulmonary arterial hypertension and strategies for switching to riociguat therapy in patients with insufficient clinical response against the background of phosphodiesterase type 5 (PDE-5) inhibitors. The role of the NO metabolic pathway in the development of pulmonary arterial hypertension (PAH) was shown. From the standpoint of pathogenesis, the importance of the effect of medication on this pathway through soluble guanylate cyclase (sGC) has been assessed. The effects of the drug riociguat, the only member of the sGC stimulant class approved for the treatment of PAH, are associated with a dual mechanism of action: riociguat sensitizes the sGC enzyme to endogenous NO by stabilizing the NO-sGC bond, and also directly stimulates the latter through another site of the bond, regardless of NO. The favorable efficacy and safety profile of riociguat has been demonstrated in the PATENT-1,2 studies. During therapy, patients showed an improvement in exercise tolerance, functional class, and a number of other indicators. Studies that indicate the feasibility of using a change in therapy in clinical practice are reviewed. In particular, the article provides a detailed analysis of the REPLACE study. It demonstrated a significantly greater likelihood of achieving clinical improvement and a significant decrease in the rate of development of clinical deterioration when switching patients with PAH from PDE-5 inhibitors to riociguat. This therapy was well tolerated and can be considered as a strategy for managing patients at intermediate risk with insufficient patient response to PDE-5 inhibitors. In conclusion, the need to plan the need for specific therapy for pulmonary arterial hypertension in the region is noted in order to rapidly escalate therapy to achieve a low risk of mortality in these patients.

Introduction. Heel bone fractures account for about 3 % of the total number of fractures. Various methods of surgical treatment were used depending on the features of a fracture, the condition of soft tissues in a damage area, the general condition of a patient and co-morbidity.The objective was to improve the results of treatment of heel bone fracture by using screws made of glycosylated lactic acid.Methods and materials. The examination and treatment methods as well as the results of surgical treatment of 89 patients diagnosed with a heel bone fracture were analysed. Depending on the type of fractures, all the patients were divided into 4 groups according to Sanders.Results. We studied the short-term (100 %) and long-term (82.5 %) results of treatment of patients using the point-based assessment systems - the Foot Function Index (FFI) scale, and the Clinical rating system for the Ankle and Hindfoot scale.Conclusion. The current study showed that the use of bioimplants along with classical osteosynthesis is one of the advanced technologies in traumatology and orthopedics, which allows to expand the possibilities of surgical fixation of heel bone fractures.

The initiatives on data mobilization in biodiversity science have been steadily on the rise throughout the past few decades. The Global Biodiversity Information Facility (GBIF) supports this development and enables open access to biodiversity data on an international scale. In Russia, with its immense territory, the initiative is following a unique course; while some regions are well-represented, others are hardly ever mentioned. The operational unit in the GBIF network is a GBIF Participant Node, which coordinates a country or organization to collectively develop an infrastructure for delivering biodiversity information. The Nodes, however, are formally established in countries which become Voting or Associate participants in GBIF, which is not yet the case for Russia. The large size of our country would justify the need to create sub-nodes of the next level. This publication is describing process of establishing a regional initiative in the northern part of West Siberia – within the administrative boundaries of the Khanty-Mansi Autonomous Okrug-Yugra, Yamal-Nenets Autonomous Okrug and Tyumen region. The regional initiative started in 2018, although some biodiversity information initiatives had been developing earlier (since 2012). The work currently covers four main areas of GBIF-nodes responsibilities and services: coordination the landscape of initiatives, support of biodiversity data mobilization, biodiversity data analysis and use, and support of data management and curation. These services are described in more detail in the present paper, and problems in the development of individual services are discussed. By the end of 2020, there are 11 registered publishing organizations and 37 published datasets from the Siberian Northwest. The total number of published records is about 120 000, with 30% published by the Yugra State University; 20% are observations from iNaturalist.org; all organizations in Northwestern Siberia as a whole represent about 50% of the published records.

The Neisseria meningitidis serogroup A capsular polysaccharide (MenA CPS) is a component of commercial vaccines, but is unstable. Here, the authors generate glycomimetic oligomers that demonstrate higher stability than their natural counterparts and induce protective antibodies in mice.

Relevance. The Russian Federation is one of the largest states in the world, includes 85 subjects of the Federation located in two hemispheres of the Earth (Western and Eastern). The geographical location of the country, as well as the differences in territories according to the epidemiological situation, allow each subject, in accordance with the law, to develop regional schedules of vaccination. Aim. To analyze the trends in improving the regional schedule of routine vaccination, as well as to outline the directions of its development. Materials and methods. The analysis of regional schedules of vaccination in different years, including a descriptive stage based on the study of regulatory documents for the period from 2001 to 2019, was carried out. Results. The regional vaccination schedule was first introduced in Moscow in 2001. Infectious diseases against which vaccination was carried out, basically repeated the National calendar. Over time, the Regional Schedule has changed depending on the epidemic and economic situation in the capital. For the period from 2001 to 2019, the calendar had 4 editions - the number of infections against which residents of Moscow are vaccinated increased from 10 infectious diseases to 17. Vaccination schemes also undergo changes: the age of measles and mumps booster vaccination, the tactics of vaccination against viral hepatitis B, the introduction of combined vaccines, as well as changes in composition persons at risk to be vaccinated. The stages of introducing vaccination against rotavirus infection, meningitidis, pertussis, human papillomavirus infection, varicella, viral hepatitis A, pneumococcal infection into the Regional Schedule are described. A brief overview got of the regional schemes of vaccinations in some regions of the Russian Federation. Conclusion. The article describes an almost 20-year history of improving the Regional Schedule of Routine Vaccination in Moscow in the context of the development of the National Schedule of Routine Vaccination of the Russian Federation, as well as in comparison with immunization calendars from other countries of the world and constituent entities of the Russian Federation. Achievements and directions for further improvement of the Regional schedule of preventive vaccinations in the city of Moscow are indicated.

Supraventricular arrhythmias, including atrial fibrillation (AF), are a current problem for patients in the older age group due to the possibility of lifethreatening complications. Elderly patients have pre-conditions for the development of supraventricular rhythm disturbances (age-related structural and functional changes in the myocardium, concomitant diseases).Aim. To study the features of structural and functional changes in the myocardium of the left heart in elderly patients, depending on the presence of supraventricular arrhythmias.Material and methods. The cross-sectional study included 200 individuals aged 60 to 89 years. All participants underwent echocardiographic examination and 24-hour electrocardiogram (ECG) monitoring. The patients of the study cohort were divided into 3 groups: group 1 consisted of patients with coronary heart disease (CHD) without heart rhythm disturbances (n=80); group 2 consisted of patients with CHD and paroxysmal AF (n=40); group 3 consisted of patients with CHD and supraventricular extrasystoles (n=40). The control group consisted of patients of the older age group without CHD and rhythm disturbances (n=40).Results. In patients with paroxysmal AF and frequent supraventricular extrasystoles, large sizes of the left atrium were revealed (anteroposterior dimension: 4.30±0.07 and 4.12±0.12 cm; upper-lower: 6.15±0.03 and 5.96±0.10 cm; medial-lateral: 4.15±0.11 and 3.87±0.09 cm, respectively). In patients with CHD and rhythm disturbances, the presence of a combined increase in the size of the left atrium and a decrease in myocardial contractility was revealed (ejection fraction of the left atrium in groups 2 and 3 – 27.2±0.1% and 27.9±0.1%, respectively, vs 36.3±0.1% and 38.20±0.02%, respectively in group 1 and control). The duration of ischemic changes during 24-hour ECG monitoring was also greater in group 3 compared with groups 1 and 2 (249.6 vs 27.1 and 66.4 min, respectively). In groups 2 and 3, a discordant effect of the sympathetic and parasympathetic nervous systems on heart rate variability was revealed.Conclusion. For elderly patients, morphological and functional changes are characteristic, which consist in the restructuring of the myocardium and changes in heart rate variability with a prevalence of the sympathetic part of the autonomic nervous system.

Dioxolenium ion intermediates formed from remote positions are hypothesized to direct stereoselective glycosylations. Herein we combine infrared ion spectroscopy, DFT calculations and synthetic work to characterize and study these dioxolenium ions and their role in stereoselective glycosylation reactions.

The relevance of the researchis caused by significant contribution of oil produced as a result of hydraulic fracturing at the wells to its total production. Correct assessment of the results of actually carried out measures for hydraulic fracturing will make it possible to develop clear recommendations on the further application of this method of intensifying oil production for geological and physical conditions of specific fields. The main aim of the research isto evaluate the effect of hydraulic fracturing in relation to the element of the development system in which the well is located – the object of impact. Object: oil producing wells that make up an element of the reservoir development system. Method: geological field research, correlation analysis, schematization of the interaction between wells. Results. It was found that the hydraulic fracturing of the well 221 of the Shershnevskyfield led to a change in the nature of interaction between the wells within the entire element of the development system, which began to work as a single, unidirectional coordinated system. As a result of hydraulic fracturing, there was no redistribution of drainage volumes, but a synergistic effect arose when holding an event in one well led to an increase in flow rates and consistency of the entire element of the development system. Probably, the conduction of hydraulic fracturing in the well 221 led to a significant change in the reservoir filtration parameters in more significant limits than the volume of the drainage zone of this well, and rather large system of channels with reduced filtration resistance appeared in rather large area of ​​the reservoir, as it is customary in classic presentation.

The objective: safety assessment of chemotherapy regimens compiled in accordance with the recommendations of World Health Organization (WHO), 2019, in patients with multiple drug resistant tuberculosis (MDR) in clinical practice settings.Subjects: Frequency, patterns, severity and risk factors of adverse events (AE) of chemotherapy regimens compiled in accordance with the WHO recommendations as of 2019 were analyzed in 122 patients with MDR and XDR respiratory tuberculosis within programmatic use of new anti-tuberculosis drugs.Results. The frequency of AE made 64.8% (95% CI 55.9-72.7%), gastrointestinal, cardiovascular and allergic events prevailed, the comorbidity was the risk factor of AE development (OR 6.44; 95% CI 1.91-21.76). AEs of with severity degrees 3-4 were observed in 24.6% (95% CI 17.8-33.0%), neurotoxic, ototoxic and hepatotoxic reactions prevailed; risk factors included female sex (OR 3.15, 95% CI 1.32-7.53) and complications of chemotherapy in the past (OR 3.50%, 95% CI 1.49-8.70). At least one anti-tuberculosis drug was canceled due to AE in 26.2% (95% CI 19.2-34.7%), and any of Group A drugs was canceled during the first 6 months of chemotherapy in 13.9% (95% CI 8.8-21.3%) of patients.

We present the results of an experimental and analytical study of the structural and dynamic properties of a monolayer consisting of dust grains in an electrostatic trap in an RF discharge plasma. The possibility of forming a monolayer with an isotropic distribution for interparticle distance and kinetic energy of particles in the structure has been experimentally shown. Isotropy has crucial importance for the study of various processes in such systems, including the kinetics of phase transitions, the formation of directed flows, wave propagation, and others.

We demonstrate the peculiarities of the magnetization process in the ferrimagnetic intermetallic compound (Nd0.5Dy0.5)2Fe14B, which has been studied theoretically and experimentally using ultrahigh magnetic fields. We observe phase transition induced by external ultrahigh magnetic fields (up to 170 T) and also describe the magnetization process analytically in terms of critical transition fields. In this work, the first and second critical fields of the field-induced magnetic transitions, Hc1 and Hc2, were estimated, and the results were verified against experimental data for Hc1. Critical field Hc2 predicting the place of transition to the forced-ferromagnetic state was estimated for the first time for (Nd0.5Dy0.5)2Fe14B compound. A comparison of the magnetization behavior for (Nd0.5Dy0.5)2Fe14B with the basic systems Nd2Fe14B and Dy2Fe14B is also performed. We demonstrate that, in the Dy2Fe14B compound, the field-induced transition type is changed from the first to the second order due to the replacement of the Nd atom by Dy one.

Aim. To study the effectiveness and benefits of blood pressure (BP) remote monitoring in outpatients with hypertension.Material and methods. The study included 100 patients with a verified diagnosis of hypertension, who didn’t achieve target BP pressure levels. The patients measured their BP twice a day over 6 months with facilities with automatic data transmission over GSM-channel to a remote monitoring center. BP parameters were being transmitted online to the remote monitoring center, where they were being processed and transferred to the personal account planner (created by the Web interface based on the software and hardware complex) of the attending physician and operator of the remote monitoring center. It is important that doctor received information only on clinically significant measurement results, based on which he determined the urgency of contact with the patient and the further tactics of his management.Results. No malfunctions in the work of communication facilities, technical failures in the software and hardware complex were registered over the entire period of the study. After 6 months of the monitoring it was possible to achieve target BP levels less than 135/85 mm Hg in 70% of patients. The proportion of patients with a high level of normal BP increased from 10% to 19%, while the proportion of patients with grade 1 and 2 of hypertension decreased significantly (from 33% to 7% and from 54% to 3%, respectively). At the beginning of telemedicine monitoring 3% of patients had stage 3 of hypertension, at the end of the study – 1%.Conclusion. The technology of telemedicine monitoring has shown itself as a simple, affordable and reliable way of management of outpatients with hypertension in conditions of real clinical practice. It was possible to achieve BP levels less than 135/85 mm Hg in 70% of patients by the method of remote outpatient monitoring. BP remote monitoring changed fundamentally the decision-making strategy of the patients management: it was not the patient who independently determined the need for consultation with a medical professional, but the attending physician made a decision on the method and urgency of contact with the patient on the basis of the data of objective monitoring indicators.

Given the significant increase in the frequency of atrial fibrillation (AF) in elderly and senile patients with confirmed coronary heart disease (CHD), the study of the relationship between the polymorphisms responsible for the functioning of the renin-angiotensinaldosterone system and the presence of this disease becomes relevant. Purpose of the study. To study the genetic polymorphism of the CYP11B2 gene in elderly patients with ischemic heart disease, as well as to identify the role of aldosterone synthetase in the development of AF in this category of patients. Materials and methods. The study included 140 patients of both sexes (54,3% – men), over the age of 60 years, with confirmed coronary artery disease and any form of AF (the last episode no later than 12 months from the date of inclusion in the study). 84 patients agreed to participate in the study of aldosterone synthase polymorphisms. The control group consisted of 34 patients who had no diagnosed non-infectious diseases at the time of the survey. Both groups were comparable in age and sex characteristics. Results. Comparative evaluation of the distribution of genotypes and alleles – C344/T of the aldosterone synthase gene among patients with AF+CHD and relatively healthy individuals revealed that in the first group, most patients had the CYP11B2 T/T genotype in 38,1% of cases, the incidence was higher, than in patients of the comparison group – 14,7% (OR = 3.44, CI 1.07-11.07, p = 0.038). The frequency of detection of genotypes of CYP11B2 С/T and CYP11B2 С/С did not significantly differ in the compared groups. In the group with AF+CHD, the T allele was significantly more common (53,6% vs. 35,3%; p

Coronary artery disease (CAD) can manifest as a classic chest pain, or atypical angina. At the same time, the prevalence of CAD in a group of male patients with atypical angina over the age of 60 can reach 59--78%. It should be noted that the clinic manifestation of the chronic heart failure (CHF), which will be the main limiting factor, may take centre stage in diffuse coronary artery atherosclerosis. In patients with coronary artery disease and heart failure, who take atorvastatin, one should expect a decrease in the risk of adverse outcomes and hospitalizations due to heart failure. However, this does not negate the need for treatment and optimization of heart failure, if necessary. The therapy of these patients is based on the administration of high doses of angiotensin converting enzyme inhibitors (ACE inhibitors), beta-blockers (BB) and statins. The routine use of statins in heart failure with low ejection fraction (EF) is not recommended for the management of patients with heart failure from clinical guidelines point of view. This conclusion is based on two multicenter randomized clinical trials that have purposefully studied the use of statins in heart failure (CORONA and GISSI-HF). However, this document recommends the use of statins to prevent heart failure in patients with coronary artery disease. Continuing statin therapy in patients, who are already receiving these drugs for coronary artery disease or hyperlipidemia, should also be discussed. Thus, the use of atorvastatin in patients with coronary artery disease and systolic left ventricular myocardial dysfunction can reduce the risk of adverse outcomes and hospitalizations due to heart failure. In patients with non-ischemic heart failure, taking statins is not associated with improved survival. Thus, the decision to prescribe this group of drugs in patients with chronic heart failure should take into account the specific clinical situation and be strictly individualized.

The continuous field measurements of net ecosystem exchange (NEE) of CO2 were provided at ridge-hollow oligotrophic bog in the Middle Taiga zone of West Siberia, Russia in 2017-2018. The model of net ecosystem exchange of CO2 was suggested to describe the influence of different environmental factors on NEE and to estimate the total carbon budget of the bog over the growing season. The model uses air and soil temperature, incoming photosynthetically active radiation (PAR) and water table depth, as the key factors influencing gross primary production (GPP) and ecosystem respiration (ER). The model coefficients were calibrated using the data collected by automated soil CO2 flux system with two transparent long-term chambers placed at large hollow and small ridge sites.Experimental and modeling results showed that the Mukhrino bog acted over the study period as a carbon sink, with an average NEE of –87.7 gC m-2 at the hollow site and –50.2 gC m-2 at the ridge site. GPP was – 344.8 and –228.5 gC m-2 whereas ER was 287.6 and 140.9 gC m-2 at ridge and hollow sites, respectively. Despite of a large difference in NEE estimates between 2017 and 2018 the growing season variability of NEE were quite similar.

Despite the decline in cardiovascular mortality in Russia over the past 15 years, it remains relevant to study the possibilities of its further reducing. And preventive measures of risk factors reducing play the main role. However, before developing preventive measures, it is necessary to study the prevalence and structure of risk factors in a particular region, since Russia is a huge country and each region is different from another. The study of this issue needs large-scale epidemiological studies, the conduct of which is very difficult in organizational terms. This article presents our own experience in successfully organizing a regional phase of epidemiological research.

Aim. To assess the incidence of adverse outcomes and the role of main risk factors in their development.Material and methods. Prospective, long-term study was conducted with observation period of 36 months. The sample in the MERIDIAN-RO study was formed from the urban and rural population. It included 1622 people aged 25-64 years. The response to the study was 86,1%. Observation and screening of endpoints continued for 36 months. The endpoints were: all-cause death, ischemic stroke, myocardial infarction, coronary artery revascularization.Results. When studying the relationship between various risk factors and outcomes, it was found that they had a significant impact on the combined endpoint (all-cause death + nonfatal ischemic stroke + nonfatal myocardial infarction): risk SCORE >5% (odds ratio (OR) 5,80, 95% confidence interval (CI) 2,31-14,58, p=0,0001, Wald — 23,040), excessive alcohol consumption (OR 714, 95% CI 1,41-36,31, p=0,018, Wald — 2,908), arterial hypertension (OR 4,77 95% CI 1,91-11,90, p=0,01, Wald — 9,000), combination of coronary artery disease/myocardial infarction/stroke in history (OR 11,16, 95% CI 3,98-31,31, p=0,0001, Wald — 22,607) and an apolipoprotein B increase more than 180 mg/dL (OR 28,57 95% CI 732-111,42, p=0,0001, Wald — 24,509).Conclusion. The most significant effect on the combined endpoint (all-cause death + nonfatal myocardial infarction + nonfatal stroke) made: SCORE risk >5%, excessive alcohol consumption, hypertension, combination of coronary artery disease/myocardial infarction/stroke in history and an apolipoprotein B increase more than 180 mg/dL. That should be considered when choosing aims and preventive strategies.

An expression and the analysis of the external quantum efficiency (EQE) for for inverted flat heterojunction based on copper phthalocyanine and fullerene. The analysis of the external quantum efficiency of photovoltaic cells has shown that the averaging EQE over the spectrum of solar radiation for the inverted cell interference redistribution has little effect on the EQE and optimization of cells to the thickness of its layers does not lead to a significant increase in quantum efficiency.

Over the past 20 years, the burden of atrial fibrillation (AF) has increased. AF is associated with increased risk of death, ischemic stroke and disability, hospitalization rates, and reduced quality of life. Treatment for this pathology is based on the correction of risk factors, underlying disease and anticoagulant therapy. The review considers strategies to minimize the risk of complications during oral anticoagulant therapy.

The objective of the study: to determine the efficacy and safety of chemotherapy regimens with bedaquiline in patients with respiratory tuberculosis in the context of everyday clinical practice with minimal non-inclusion criteria. Subjects and methods. In a prospective, open-label, non-randomized, single-center trial which included 315 patients, the efficacy and safety of chemotherapy regimens were evaluated, when prescribing a regimen the priority was given to bedaquiline, linezolid, levofloxacin/moxifloxacin, and cycloserine/terizidone. Patients were followed up for at least 24 months, 52.4% suffered from extensive drug resistance of M. tuberculosis (MTB), the majority of patients (50.8%) had a failure of the previous course of treatment, and serious co-morbidities were found in 89.5% of patients. Results. In 104 patients, the duration of treatment with bedaquiline was limited to standard 24 weeks, in 42 patients, it lasted for 36 weeks, in 56 patients – 48 weeks, and 94 patients received bedaquiline for more than 48 weeks. The increased duration of treatment with bedaquiline for more than 24 weeks provided a significant increase of treatment efficacy (regardless of drug resistance profile) from 66.2% (95% CI 54.4-77.9%) to 84.3% (95% CI 80.0-89.7%). The used regimens were well tolerated: serious adverse events (AE) were observed only in 27.6% of patients, and bedaquiline contribution to their development was not significant (bedaquiline had to be discontinued due to AE in 2.2% of cases). The range of AE practically did not differ from that when using only traditional anti-tuberculosis drugs.