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Background: Despite advances in surgery and pharmacotherapy, there remains significant residual ischemic risk after coronary artery bypass grafting surgery. Methods: In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial), a multicenter, placebo-controlled, double-blind trial, statin-treated patients with controlled low-density lipoprotein cholesterol and mild to moderate hypertriglyceridemia were randomized to 4 g daily of icosapent ethyl or placebo. They experienced a 25% reduction in risk of a primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina) and a 26% reduction in risk of a key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) when compared with placebo. The current analysis reports on the subgroup of patients from the trial with a history of coronary artery bypass grafting. Results: Of the 8179 patients randomized in REDUCE-IT, a total of 1837 (22.5%) had a history of coronary artery bypass grafting, with 897 patients randomized to icosapent ethyl and 940 to placebo. Baseline characteristics were similar between treatment groups. Randomization to icosapent ethyl was associated with a significant reduction in the primary end point (hazard ratio [HR], 0.76 [95% CI, 0.63–0.92]; P =0.004), in the key secondary end point (HR, 0.69 [95% CI, 0.56–0.87]; P =0.001), and in total (first plus subsequent or recurrent) ischemic events (rate ratio, 0.64 [95% CI, 0.50–0.81]; P =0.0002) compared with placebo. This yielded an absolute risk reduction of 6.2% (95% CI, 2.3%–10.2%) in first events, with a number needed to treat of 16 (95% CI, 10–44) during a median follow-up time of 4.8 years. Safety findings were similar to the overall study: beyond an increased rate of atrial fibrillation/flutter requiring hospitalization for at least 24 hours (5.0% vs 3.1%; P =0.03) and a nonsignificant increase in bleeding, occurrences of adverse events were comparable between groups. Conclusions: In REDUCE-IT patients with a history of coronary artery bypass grafting, treatment with icosapent ethyl was associated with significant reductions in first and recurrent ischemic events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01492361.

Difficulties in prescribing antibiotics for lower urinary tract infections (UTI) are associated with a fact that such patients can be treated not only by urologists, but also by general practitioners, internists, pediatricians, and gynecologists. Therefore, it is important to adapt the practical recommendations for the treatment of cystitis for different medical disciplines. When creating clinical guidelines, experts take into account the different factors in choosing antibiotic therapy. First of all, pharmacokinetics is of importance and drugs with renal excretion should be preferred. Secondly, the natural activity of the antibiotic against the pathogens, which cause cystitis, has to be considered. In uncomplicated infections, E. coli predominates, while in complicated and recurrent infections E. coli and other enterobacteria are commonly isolated, as well as Enterococci. In addition, local resistance pattern is reviewed. In the Russian Federation E. coli has minimal resistance to nitrofurans and fosfomycin. Lastly, antibiotics can negatively affect the gastrointestinal and urinary tract microbiota and contribute to the increase of antibiotic resistance and the selection of antibiotic-resistant strains, therefore the environmental safety of therapy should be considered. The effect of antibiotics on the resident flora of the gastrointestinal tract, urinary tract and vagina is called collateral effect, or concomitant (parallel) damage, and it may exceed the therapeutic effect of some antibiotics. Cephalosporins and fluoroquinolones can cause ecologically unfavorable effects with the risk of selection of resistant strains; therefore, these drugs are currently considered as second-line agents for UTI. When choosing an antibiotic, preference should be given to drugs with the narrow spectrum and minimal collateral damage, i.e., the principle of "minimum sufficiency" is of importance. Nitrofurans and fosfomycin trometamol are the optimal drugs in terms of efficiency and environmental safety in UTI. WHO experts consider nitrofurans as the most environmentally safe antibiotics with a minimally sufficient spectrum of activity. The environmental safety of antimicrobial therapy is an important component of preventing antibiotic resistance at the global and local levels.

Noise minimization and suppression is one of the most important problems in image processing. Background correction and detection of weak reflections were performed using the well-known algorithms implemented in the ImageJ and Digital Micrograpph (GATAN) programs and developed in this paper for experimental electron diffraction patterns obtained from a nanocrystalline 10-nm-thick hafnium oxide layer. An algorithm for processing electron diffraction patterns is proposed, which is based on a multiscale Retinex filter and Hough transform. It is also devised to present electron diffraction patterns in polar coordinates, which is often more visual and convenient for indexing reflections.

The demand for future semiconductor devices with enhanced performance and lower cost has driven the development of epitaxial growth of high quality, free-standing semiconductor thin film materials without the requirement of lattice matching to the substrate, as well as their transfer to other substrates and associated device processing technology. This work presents a study on the van der Waals epitaxy based molecular beam epitaxy of CdSe thin films on two-dimensional layered mica substrates, as well as related etch-free layer transfer technology of large area, free-standing layers and their application in flexible photodetectors for full-color imaging. The photoconductor detectors based on these flexible CdSe thin films demonstrate excellent device performance at room temperature in terms of responsivity (0.2 A·W−1) and detectivity (1.5 × 1012 Jones), leading to excellent full-color imaging quality in the visible spectral range. An etch-free and damage-free layer transfer method has been developed for transferring these CdSe thin films from mica to other substrate for further device processing and integration. These results demonstrate the feasibility of van der Waals epitaxy method for growing high quality, large area, and free-standing epitaxial layers without the requirement for lattice matching to substrate for applications in low-cost flexible and/or monolithic integrated optoelectronic devices.

Introduction. Pure white cell aplasia (PWCA) is a rare hematologic disorder characterized by the absence of neutrophil lineages in the bone marrow, with intact megakaryopoiesis and erythropoiesis. PWCA is commonly associated with several immune pathologies. Cytopenia in patients with thymoma is a paraneoplastic syndrome, along with other manifestations. The two major clinical issues in PWCA are various infectious complications and ulcerative-necrotic lesions of the skin and mucosa membranes. Case presentation. We present a rare case of a patient with thymoma and PWCA, as paraneoplastic syndrome. On the background of agranulocytosis, the patient developed sepsis and infective endocarditis (IE) caused by a rare agent, carbapenem-resistant Klebsiella pneumoniae. Conclusions. The rarity of endocarditis caused by Klebsiella species limits its recognition and awareness of its often severe course. Most cases of endocarditis with Klebsiella pneumoniae are associated with prosthetic heart valves. In patients with immunosuppression, such as PWCA associated with thymoma, and endocarditis, rare microorganisms must be considered.

In recent years, the important role of disturbances in the intestinal microbiota and its possible correction in children with oncological and autoimmune diseases has been established. The aim of the article is to review the literature data on the issue and to describe own experience of fecal microbiota transplantation (FMT) in children with an intestinal form of acute graftversus-host disease (GVHD). Materials and methods of research: a prospective single-center study included 7 patients aged 3 to 10 years with gut GVHD developed after transplantation of allogeneic hematopoietic stem cells (allo-HSCT). The clinical effects of FMT have been studied in children using rating scales during 120 days after this procedure. Time-dependent changes in the composition of fecal microbiota were assessed by the method of multiplex polymerase chain reaction test-system (PCR). Results: the literature data show a significant role of the content and ratio of of the main bacterial classes of Firmicutes and Bacteroides in the development of the immune response in cancer and autoimmune processes, as well as the possibility of correcting disorders using FMT. The first-hand experience of FMT in children with gut GVHD and antibiotic-resistant colitis is presented. Complete or partial response to GVHD therapy after 120 days was achieved in 6 (86%) patients in the absence of serious adverse events after FMT. From day +3 after FMT, increased amounts of B. fragilis gr., F. prausnitzii and E. coli were registered in fecal microbiota (p

Aim.The presented study aims to assess threats to national spatial development, determining the significance of each threat.Tasks.The authors identify factors that influence the specific aspects of the national socioeconomic system's spatial organization; propose and test methodological tools for assessing parameters that make it possible to determine the scale of such threats.Methods.This study uses a proprietary methodology to assess the features of spatial transformations by determining the values of a set of indicators. These can be interpreted by comparing the obtained values with threshold values, each determined individually, making it possible to calculate the significance of the estimated risk (red, yellow, or green zone).Results.By summarizing the scientific literature, the authors identify factors of spatial development in the Russian Federation related to the parameters of spatial integrity, connectivity, uniformity, and efficiency of use. An algorithm for analyzing threats to national spatial development is proposed, which makes allowance for these specific factors. Indicators that characterize the state of each factor and criteria that make it possible to interpret each of the considered parameters are selected. Testing of the proposed methodology shows the significance of threats to spatial development in the Russian Federation. The threat of disrupting sustainable infrastructure connections between territories has a high degree of risk. The prospect of losing certain elements of the country's spatial framework, increasing spatial fragmentation, reducing connectivity and efficiency of the socio-economic space have a moderate degree of risk (although gradual deterioration of parameters associated with these threats could complicate the situation in the future, moving these threats to the "red" zone).Conclusions. Testing of the proposed methodological tools makes it possible to identify threats to national spatial development and assess their significance for Russia. The results obtained can be useful to federal authorities responsible for implementing regional policies and setting guidelines for the country's spatial development.

The aim of the study was to evaluate the effectiveness of cefepime/sulbactam in patients with intra-abdominal infection, nosocomial pneumonia (NP) or ventilator-associated pneumonia (VAP) in actual clinical practice. Material and methods. The study was conducted in 14 Russian Clinics from October 2019 to March 2020. Study design: an open-label, prospective, non-comparative, multicenter, observational study. The study included patients who met the inclusion/exclusion criteria and signed a written informed consent. The studied antibiotic: cefepime/sulbactam (Maxictam®-AF). The primary parameter for effectiveness evaluation was the clinical effect after the conclusion of cefepime/sulbactam therapy — recovery/improvement or no effect. Results. The study included 140 patients (average age — 60.8 years) who received at least one dose of cefepime/sulbactam; 37 of them had intraabdominal infection, 72 — NP, and 31 — VAP. Most of the included patients were in the ICU department (82.1%) and their condition was severe: the average APACHE II score was 15.5 points, SOFA — 5.4 points, the Mannheim peritonitis index value in patients with intra-abdominal infection was from 14 to 35 points, with an average of 24.3 points. The majority of patients treated with cefepime/sulbactam (68.6%) had one or more risk factors for multi-resistant pathogens upon hospital or ICU admission. Cefepime/sulbactam was prescribed as the 1st or 2nd line of empirical therapy at a daily dose of 4 g (in 68.3%), 6 g (2.9%) or 8 g (28.8%); most patients were prescribed cefepime/sulbactam in monotherapy (72.3%). The average duration of therapy with cefepime/sulbactam was 9.6±3.5 days. The final assessment of treatment effectiveness was carried out in 132 patients: recovery or improvement was noted in 80.6% of patients with intra-abdominal infection, the effectiveness in NP and VAP was slightly higher — 95.6 and 89.3%. The effect was absent in 5.3% of patients, relapse or superinfection was noted in 3.0 and 1.5%. The majority of patients (81.3%) treated with cefepime/sulbactam were discharged from the hospital. No serious side effects were observed. In patients with a positive effect, age and values of APACHE II were significantly lower (59.58 years and 14.79 points) compared to those with no effect (67.95 years and 18.39 points). A multivariate analysis found that the probability of recovery of patients treated with cefepime/sulbactam did not depend on the diagnosis of infection, ICU admission, the presence of sepsis or septic shock. Conclusion. The multicenter study has established a high clinical efficacy of cefepime/sulbactam in real clinical practice in the treatment of patients with severe intraabdominal infection, nosocomial pneumonia or ventilator-associated pneumonia.

This article proposes an improved methodology for the development of decision support systems, developed on the basis of a situational scheme for solving behavioral problems by a person. The proposed methodology proposes an approach to solving the problem of decision support based on the ontological model of an organization (business process), containing information about typical situations, their features, options (scenarios) of decisions and indicators for choosing these decisions. An intelligent mechanism for “recognition” of the states of typical situations has been developed on the basis of categorization and the use of the obtained hierarchy of their states and features. A general approach to keeping the ontological model up to date is proposed. The examples of the application of the methodology for the enterprise of the aircraft industry are considered.

The adverse effects of the construction from the perspective of reducing greenhouse gas emissions are becoming increasingly important in terms of sustainable development and the growth of construction output. Construction actors involved in the process of creating buildings are responsible for the deterioration of the environmental situation. Flexible tools to motivate construction participants to actively and purposefully decarbonize construction and maintain the production and use of low-carbon technologies should be established. Multilevel institutional tools for regulating extended responsibility of construction participants through organizational and economic incentives for low-carbon design and construction and optimization of building design solutions are presented in the article. Recommendations are also provided to improve the environmental safety of construction, including the establishment of the of low-carbon certification institute for developers, based on a cost estimate of the carbon impact of buildings used in the development of compensatory and incentive measures. The proposed methodological aspects of rational low-carbon design and construction of buildings with minimal carbon footprint will allow to formulate the basic principles of functioning of the low-carbon certification institute of builders as a tool to improve their bid competitiveness.

Recently, unmanned aerial vehicles are being used more often for reconnaissance in combat conditions. Communication with unmanned aerial vehicles must be carried out in a confidential mode to protect against the interception of control, while being fast and resistant to attacks from outside. A new algorithm for transferring confidential data, based on the properties of extremal uniform hypergraphs, is proposed.

The pandemic of new coronavirus infection COVID‑19 has become a serious challenge for the national health systems, including Russia, setting ambitious goals aimed at preventing the spread of infection and maintaining the availability of medical care in environment of increasing pressure. The aim of the study was to develop, based on the principles of lean production, a set of measures to increase the availability of emergency medical services for patients diagnosed with or suspected of a new coronavirus infection COVID‑19 in the Tomsk Region. Standard tools of lean manufacturing are applied to the work process of the admission department of the respiratory center in RSBHI «Medical sanitary station № 2». As a result of implementation of target state map, which provides for the optimization of process of transferring a patient diagnosed or suspected of a new coronavirus infection COVID‑19 to admission department, a positive dynamics of local (5.4 times increase in the proportion of calls completed within 15 minutes after the patient was delivered to the admission department) and system (an increase of 1.3 times in the proportion of calls with the time the ambulance team reaches the patient within 20 minutes) indicators of the ambulance service was achieved. The study confirms the effectiveness of lean manufacturing tools for optimizing the work of ambulance and allows us to recommend them for use in a pandemic and other risks of emergency.

— Aim of the study: to assess the level of dental pathology in Penza Region (Russia) and estimate the impact of the industrial environment. Materials and methods: A clinical examination and analysis of the frequency of enamel erosion, fluorosis and hypoplasia, wedge-shaped defect and multiple enamel cracks were carried out among the main professional groups of the region's population — workers of the machine-building and timber processing industries in the Penza region. Results and Discussion. Among the residents of Penza region, the frequency of enamel erosion was 4.0%, pathological tooth wear — 7.1%, wedge-shaped defect — 6.1%, multiple enamel fractures — 11.1%. There is a high frequency of noncarious tooth defects that occur before teething. In patients working in the machine-building industry, a high frequency of pathological tooth wear was noted (24,5%); in workers of the timber processing industry, it was 2 times lower (12,6%), as well as a high frequency of wedge- shaped defects, enamel erosion and multiple enamel cracks — all this was 2–2.5 times higher compared to similar indicators in patients from agricultural populations. However, the prevalence of dental fluorosis and hypoplasia was almost the same as in the agricultural population. Conclusion: Penza region has a high prevalence of dental fluorosis and hypoplasia. At the same time, the influence of industrial environment on the incidence of various types of non-carious dental pathology in workers of machine-building and timber processing industries in Penza region was established.

The article presents a rare case of congenital diaphragmatic hernia (Bohdalek's hernia) in a 1.5 month old child. There are indications of the difficulty of diagnosing this pathology. SKT, as well as the presence of a well-organized telemedicine consultation has made it possible to make the diagnosis in a timely manner and prescribe a propper treatment

The issues of the visible lights non-visual impact on the human body during work, the circadian efficiency of lighting installations are considered, the analysis of fluorescent lamps used to illuminate industrial facilities according to their circadian characteristics is carried out, the need to take them into account when creating an effective industrial lighting installation is substantiated. Lighting systems design is one of the main components of the electric power systems formation for any industrial facility. When choosing equipment for the projects implementation, it is necessary to be guided not only by electrical parameters, but also by lighting technical parameters, since in addition to the power load, lighting is a means necessary for the successful implementation of the planned technological process. It is important to note that the illiterate implementation of the lighting network is a harmful factor and has a detrimental effect on the work and personnel health. Thus, ensuring light comfort, subject to the observance of the standardized illumination for each room, is one of the key tasks that must be solved when calculating and designing a lighting system. A properly designed lighting system has a direct impact on productivity, fatigue, visibility and visual discomfort during work. When choosing light sources to provide a given standardized illumination, various well-known calculation methods are used, but none of them takes into account the factors affecting the provision of visual comfort. The spectral composition of light is an important parameter of artificial light sources, which affects not only visual function, comfort, but also human health. When developing new lighting standards, standards for light sources and assessment of their quality, it is necessary to take into account the parameters that affect human health and well-being.

The possibility of utilizing the used magnesia-silicate reagent as an active additive to foam silicates based on a silica-containing matrix was studied. Foamed materials with an ordered structure and improved physical and technical characteristics were obtained, which can be recommended for use as heat-insulating materials to increase energy conservation in adverse climatic conditions.

Objective: to analyze the 3-year experience of vacuum-assisted aspiration biopsy under ultrasound guidance in patients with focal mammary neoplasms in categories BIRADS 2–5.Materials and methods. The totals of 121 interventions were performed in 121 patients. In 9 (7.4 %) cases there were more than 1 node in the mammary gland.Results. In 97.7 % cases the removed formations were benign. The breast cancer was detected in 5 (2.3 %) cases; there were cases of malignant tumors in each category according to the BIRADS scale. The complications were registered in 15 (12.3 %) cases and did not require surgical treatment. In 77 (63.3 %) cases the results of ultrasound monitoring were obtained in 6 months after the removal of formations, residual tissue was detected in 6 (4.9 %) patients.Conclusions. The vacuum-assisted aspiration biopsy, thus, has a high diagnostic accuracy; the number of completely removed benign formations allows us to consider the method as an alternative to sectoral resection. It is worth saying that a high percentage of complications is associated with the stage of mastering the method; all complications were resolved conservatively.

With the interaction of drugs belonging to different pharmacotherapeutic groups – nonsteroidal anti-inflammatory and antihypertensive – against the background of comorbid arterial hypertension with rheumatoid arthritis, the activity and safety of drugs may change with their combined use. Changes in the analgesic activity of nonsteroidal anti-inflammatory drugs, different in their selectivity to the types of cyclooxygenase (diclofenac, nimesulide and celecoxib), under the conditions of their long-term combined use with amlodipine in different periods of inflammation against the background of hypertension should be studied. Using the model of adjuvant arthritis comorbid with hypertension, in experiments on nonlinear mature white rats, the threshold of pain sensitivity has been determined by means of the “tail flick” test. Hypertension was caused by salt load with 1% sodium chloride solution for drinking with free access to it. Adjuvant arthritis was induced by the introduction of complete Freund’s adjuvant into the plantar aponeurosis of the hind limb of each animal with the established arterial hypertension. Against the background of arterial hypertension and comorbid pathology, there was an increase in the threshold of pain sensitivity observed in rats, which indicated the development of hypoalgesia. When combined, amlodipine enhanced the analgesic activity of diclofenac during 60 days of observation, slightly heightened the analgesic effect of nimesulide – up to 42 days, the effect of Celecoxib – in the acute period and the period of manifestation of adjuvant arthritis against the background of hypertension. The antinociceptive effect of diclofenac with amlodipine and celecoxib with amlodipine exceeded the analgesic effect of the combined nimesulide with amlodipine use against the background of comorbid pathology. The results obtained can be taken into account under the conditions of prescribing drugs belonging to the studied pharmacotherapeutic groups. It is likely that the use of diclofenac for analgesia against the background of comorbid conditions is only appropriate in the acute period of rheumatoid arthritis. The use of nimesulide to achieve an analgesic effect in the recurrence of rheumatoid arthritis against the background of hypertension is appropriate in the acute period and in the period of the inflammatory process attenuation. A highly selective coxib group cyclooxygenase-2 inhibitor, celecoxib, can reduce pain during the acute period of arthritis and during the manifestation of an inflammatory reaction that has developed against the background of arterial hypertension.

BACKGROUND: In the XXI century, the frequency of pancreas diseases increased 2–3 times. The expectation that causes a pandemic lead to the development of a number of diseases. The results of studies on the relationship of overweight, obesity with the risk of developing pancreas diseases (acute pancreatitis (AP), chronic pancreatitis (CP) and pancreas cancer (PC)) are very heterogeneous (for AP and PC) and not numerous (for CP). AIMS: to identify the frequency of obesity in AP patients (APр), CP patients (СPр) and PC patients (PCр) and compare these parameters. MATERIALS AND METHODS: at the observational multicenter clinical cross-sectional uncontrolled case-study 44 APp, 97 CPp and 45 PCp were examined; the groups were comparable by sex/age. Informed consent form for participate in the study was obtained from all patients. The main outcome of the study: the frequency of obesity in APp, CPp; PCp. RESULTS: The frequency of obesity in APp (13,6%), CPp (24,7%) and PCp (20,0%) did not differ significantly. Among the examined patients, the lowest average BMI (24,2±0,7 kg/m2) was observed in APp (p=0,049). BMI ≥22,5 kg/m2 was found to be associated with AP (OR=0,398; 95%CI 0,195–0,812; p=0,011). An inverse relationship was shown between the BMI and “definite” CP (Exp (B)=0,772; 95%CI 0,632–0,942; p=0,011). In men with CP and in CPp alcoholic etiology, weight deficit was observed significantly more often than in women with CP and in CPp biliary etiology, respectively. Earlier (a year before the present survey), obesity was more common in PCp (55,6%) than in APp (13,6%, χ2=3,3; p=0,000) and CPp (25,8%, χ2=12,0; p=0,001). A history of obesity (in our study one year before PC detection) and PC (OR=4,435; 95% CI 2,180–9,025; p=0,000) direct relationship was shown. CONCLUSIONS: the frequency of obesity in APp, CPp and PCp was similar. The average BMI was higher in APp, than in CPp and PCp. BMI≥22,5 kg/m2 was a protective factor for AP. BMI was inversely associated with “defined” CP. A history of obesity was directly associated with PC.

Was to evaluate clinical efficacy, adverse events and changes in the gut microbiome after fecal microbiota transplantation (FMT) in patients with gastrointestinal (GI) form of graft-versus-host disease (GVHD).The prospective single-center study in R.M. Gorbacheva institute included 27 patients with GI GVHD after allogeneic stem cell transplantation. 19 patients received FMT, 8 patients received placebo. Clinical scales for GI autoimmune diseases were used to evaluate response. Microbiome alterations were assessed with multiplex PCR.After FMT higher overall bacterial mass (р=0.00088), higher bacterial numbers ofBifidobacteriumspp. (р=0.021),Escherichia coli(р=0.049) andBacteroides fragilisgr. (р=0.000043) compared to placebo group. Also higher bacterial mass was observed in patients with clinical response (р=0.0057). The bacterial mass after procedure in non-responders was compared to the placebo group (р=0.31). Partial response of GVHD was achieved faster in the FMT group compared to placebo (median 4 days vs 48 days,p=0.014). Complete response was observed in 8 (42%), 14 (74%) and 16 (84%) at 30, 60 and 90 days respectively, while in the placebo group only 0%, 1 (13%) and 4 (50%) achieved complete response at the same time points. The incidence and severity of adverse events was comparable between FMT and the placebo group.FMT in patients with refractory GI GVHD was associated with favorable clinical outcomes and recovery in certain marker bacterial populations. Multiplex PCR can be used to assess an engraftment of a donor microbiota. FMT in GI GVHD was not associated with life-threatening adverse events, but further studies are required to validate clinical efficacy.Цель.Оценка клинической эффективности, спектра побочных эффектов и динамики микрофлоры после трансплантации фекальной микробиоты (ТФМ) у пациентов с кишечной формой реакции трансплантат против хозяина (РТПХ). Материалы и методы.Проспективное одноцентровое сравнительное исследование в НИИ детской онкологии, гематологии и трансплантологии им. Р.М. Горбачевой включало 27 пациентов с кишечной формой РТПХ после трансплантации аллогенных гемопоэтических стволовых клеток. ТФМ выполнена 19 пациентам, плацебо получали 8 человек. По оценочным шкалам изучены клинические эффекты и безопасность ТФМ у пациентов. Изменения состава фекальной микробиоты оценивали методом мультиплексной полимеразной цепной реакции. Результаты.После ТФМ по сравнению с группой плацебо выявлены статистически значимо более высокие средние значения общей бактериальной массы (р=0,00088),Bifidobacteriumspp. (р=0,021),Escherichia coli(р=0,049) иBacteroides fragilisgr. (р=0,000043). При этом изменения в бактериальной массе наблюдались у пациентов с клиническим ответом (р=0,0057), а бактериальная масса у пациентов без полного ответа сопоставима с группой плацебо (р=0,31). Частичный ответ по тяжести РТПХ достигался быстрее в группе ТФМ, чем в группе плацебо (медиана 4 дня против 48 дней;р=0,014). Полный ответ наблюдался у 8 (42%), 14 (74%) и 16 (84%) больных через 30, 60 и 90 дней в группе ТФМ соответственно против 0%, 1 (13%) и 4 (50%) в группе принимавших плацебо. Частота и выраженность нежелательных явлений после ТФМ сопоставима с группой плацебо. Заключение.ТФМ у пациентов с резистентными формами кишечной РТПХ сопровождается позитивной динамикой клинических проявлений наряду с восстановлением кишечной микробиоты по ряду маркерных бактерий. Метод мультиплексной полимеразной цепной реакции можно использовать для оценки приживления фекального трансплантата. ТФМ пациентам с резистентной формой кишечной РТПХ не сопровождается жизнеугрожающими побочными эффектами. Однако требуются дополнительные исследования для уточнения клинической эффективности ТФМ.

The number of dialysis patients is increasing every year and is estimated to be more than 2 million, with an annual increase of 6–12% in dialysis programs. There is a high correlation between cognitive impairment and mortality in dialysis patients, which suggests the relevance of screening cognitive functions in dialysis patients using different neuropsychological scales.Aim of the study was to test the cognitive status and identify cognitive impairment in patients with terminal stage of chronic kidney disease treated using program hemodialysis, as well as to evaluate risk factors for cognitive impairment in this category of patients.Material and methods. 83 patients aged 28 to 78 years (mean age 56.7±13.7 years) were examined. The main group included 53 people who received program hemodialysis, of them 23 men and 30 women. The mean age of patients in this group was 58.3±13.3 years. The control group composed of 30 individuals without kidney diseases, including 13 men and 17 women. The mean age in the control group was 53.6±14.9 years. The MoCA and SLUMS scales were chosen for detecting cognitive impairment and assessment of neuropsychological status. We used mathematical methods of research data processing such as inductive statistics and correlation analysis.Results. Cognitive impairment was found to be significantly more frequent in dialysis patients (75.5–81.1% of cases, P=0.05) compared to those without kidney pathology. The SLUMS scale was shown to be more sensitive than MoCA (P=0.05, CI 95.0%). The risk factors of cognitive impairment in dialysis patients included increased dialysis duration, age (rs=–0.298) and low estimated urea dialysis adequacy index (Kt/V less than 1.2).Conclusion. A high risk of cognitive impairment is common in dialysis patients. For its timely detection, the screening neuropsychological test are recommended to be used by clinicians. Cognitive impairment, diagnosed by the tests, is an indication for a specialist consultation.

Summary Fecal microbiota transplantation (FMT), as any other medical procedure, requires standardization of results, approaches, monitoring of its dynamics and microbiota engraftment evaluation. The aim of the present study was to compare efficiency and results of PCR and 16S RNA-based sequencing in order to trace the dynamics of microbiota composition after FMT. Patients and methods The prospective, single-center study included 27 patients with acute intestinal and chronic (overlap syndrome) graft-versus-host disease (GvHD) developed after allogeneic hematopoietic stem cell transplantation (HSCT). FMT in 19 cases was performed, mostly, with ingestible capsules, eight placebo-treated patients were included into control group. Quantitative changes of different bacterial groups in fecal microbiota were assessed by means of real-time multiplex PCR, being compared with16S rRNA sequencing technique at the terms of D+3, D+16, D+30, D+60 and D+120 following FMT. Clinical response was determined by 4 scales evaluating intestinal syndrome and GvHD grade. Results When evaluating stool consistence according to Bristol scale as an index of GvHD therapy efficiency, we have observed complete clinical response by the D+120 after FMT in nine cases (47% with Bristol score of ≤4 points), and nine patients (47%) showed improved stool properties (>4 points). In the placebo group, complete or partial response was revealed, respectively, in one (13%), and four cases (50%) on the D+120. Multiplex PCR of fecal microbiota has shown a different time course in FMT- and placebo-treated patients, when compared to their initial (pre-FMT) levels. Total bacterial mass and copy numbers of distinct microbial species exhibited sufficient increase after FMT. Such shifts were demonstrable on D+30 for total microbial mass (p=0.002); Escherichia coli (p=0.001); Bacteroides fragilis group (p=0.05); Faecalibacterium prausnitzii (p=0.005). Meanwhile, the numbers Lactobacillus spp., and Bacteroides thetaiotaomicron, generally, were not changed over this time period. Moreover, in the control group (placebo) we have not found significant fecal microbiota changes against initial levels during 120 days monitoring period. Over 120 days of observation, we have also found some differences of the microbiota dynamics for the subgroups with complete response and partial/no response: Bifidobacterium spp. (р

It is well known that regular physical activity has a beneficial effect on thecardiovascular system and reduces the risk of heart disease; however, numerous studies have shown an increase in heart troponin levels after exercise, which indicates damage to themyocardium in apparently healthy people. The prevalence of these results in various exercise conditions and population groups, as well as the potential underlying mechanisms and clinical significance of exercise-induced cardiac troponin release, has not yet been fully determined. This review discusses the effect of exercise on cardiac troponin levels and possible mechanisms for increasing these biomarkers.

The article considers an instrument of influence on the economic development of the Russian Federation in the form of creating special economic zones. The current state of Russian enterprises is described in terms of the theory of techno-economic paradigm. The problem of technological backwardness of Russia is revealed. In this regard, the authors consider special economic zones as an engine for the development of the Russian Federation. The principles of functioning of these zones are described, privileges for enterprises registered in the territory of special economic zones are listed. The types of zones are also characterized, among which four are distinguished by the legislation of Russia: industrial-production, technical-innovative, tourist-recreational and port. Examples are given for each type of special economic zone. The authors examined the stages of construction of these zones, and the legislation that determines their functioning. The article also provides an example of the Innopolis special economic zone: its specialization, what benefits it gives residents and what is located on its territory. The article’s conclusion provides a list of benefits that an enterprise can count on if it is registered as a resident in the territory of a special economic zone. It also proves the existence of a direct relationship between the effective functioning of special economic zones and the acceleration of the economic development of the state, which allows it to enter the next techno-economic paradigm.

This work demonstrates a controlled van der Waals growth of two-dimensional SnTe nanoplates on mica substrates and their applications in flexible near-infrared photodetectors. The growth of nonlayered rock-salt structured SnTe crystals into two-dimensional SnTe nanoplate structures is mainly caused by the two-dimensional nature of the mica surface, which also results in the ultrathin nanoplates obtained (3.6 nm, equivalent to 6 monolayers). Furthermore, it is found that the shape of the SnTe nanoplates can be well engineered by changing their growth temperature due to the competition between the surface energy of the {100} crystallographic plane and that of the {111} plane. As a result of the favorable physical properties of topological crystalline insulators such as metallic surface (high electron mobility) and narrow bandgap, near-infrared photodetectors based on single SnTe nanoplate with the thickness of 3.6 nm present excellent device performance with a responsivity of 698 mA/W, a specific detectivity of 3.89 × 10

Background. Tuberculosis therapy can lead to considerably dissimilar outcomes among individual patients. Some patients benefit from anti-tuberculosis chemotherapy leading to a desired therapeutic effect, while other patients show insufficient or absent response, or develop adverse side effects. Individual response to isoniazid is affected by mutations in the gene encoding N-acetyltransferase 2 (NAT2). Wide variations were observed in distributions of polymorphic NAT2 alleles in human populations depending on race, ethnicity, or geographical origin. No data are available to date on prevalence of NAT2 gene polymorphic variants and acetylation types in Yakut (Sakha) patients with newly diagnosed pulmonary tuberculosis. Aims: the frequencies of NAT2 polymorphic SNPs as well isoniazid acetylation phenotypes were evaluated in the patients cohort of Yakut ethnicity with newly diagnosed pulmonary tuberculosis (PTB). The comparison with, other ethnic groups of Asian origin was done. Methods. Cross-sectional study was conducted among Yakut patient cohorts with newly identified pulmonary tuberculosis. Using real-time PCR the following SNPs were explored: NAT2*5 (rs1801280, Т341С), NAT2*6 (rs1799930, G590A), NAT2*7 (rs1799931, G857A), NAT2*11 (rs1799929, C481T), NAT2*12 (rs1208, A803G), NAT2*13 (rs1041983, C282T). Genetically determined metabolic rates were calculated using NATpred online tool. Results. NAT2 SNPs were assessed, namely *5, *6, *7, *11, *12, and *13. The most frequent in Yakut patients were NAT2*6 and NAT2*13 SNPs (40.9% and 64.4%, respectively). Significant differences were detected in frequencies of NAT2 *5, *11, *12 polymorphisms; all studied NAT2 gene polymorphisms showed meaningful differences in genotype and minor allele prevalence rates after comparison between Yakut population and other Mongoloid ethnic groups (populations of China, Japan, Vietnam). High prevalence of intermediate acetylation type among ethnic Yakuts (58.3%) was established. Conclusions. Certain distinct differences in allelic variants of NAT2 gene and acetylation type prevalence in patients of Yakut ethnic origin newly diagnosed with pulmonary tuberculosis let conclude that the existing genotyping and phenotyping data from studies among other Mongoloid populations cannot be implicitly extrapolated on Yakut people. Pharmacogenetic data on individual response to drugs in Yakut patients should be made use of in clinical practice, to develop personalized isoniazid administration algorithms, with a final goal to make treatment more effective and safe.

Aim. To analyze the associations of health care system resources utilization and temporary disability (TD) with the main cardiovascular risk factors (RF) at the population and individual level in working age population based on ESSE-RF study data.Material and methods. The analysis was based on ESSE-RF study data. Standard epidemiological survey methods and evaluation criteria were used. Analysis of probability and number of outpatient visits, hospitalizations, ambulance calls and TD was conducted by using hurdle model. Hypertension, obesity, hypercholesterolemia, hyperglycemia and tobacco consumption were independent variables.Results. A total of 21923 individuals aged 25-64 years were included: men – 8373 (38%) and women – 13550 (62%). The probability of outpatient visits significantly determined in group with tobacco consumption and with hypercholesterolemia for men, and for women – in the smoking group, with obesity and with hyperglycemia. Numbers of outpatient visits has doubled for patient with hyperglycemia. The numbers of outpatient visits were higher among women smokers compared to non-smokers. Chance to be hospitalized significantly associate with smoking, obesity, hypercholesterolemia for men and with obesity, hyperglycemia – for women. Hypercholesterolemia was associated with a smaller number of inpatient treatment cases among men. The probability of ambulance calls increased for smoking men, for male group with hypertension, hypercholesterolemia, obesity and with hyperglycemia, at the same time, the likelihood increased in female group with hypertension, hyperglycemia, smoking and with obesity. In addition, numbers of ambulance calls were higher in 1.55 times for women with obesity (pConclusion. So, there is a significant association of probability of using and consumption level of healthcare recourse with the RF depending on the type of medical care, sex and RF.

Results of studying different-scale ionospheric irregularities on the basis of multi-instrumental data, obtained in the East Siberian region of Russia during the geomagnetic storm of May 27–28, 2017, are presented. Spatial inhomogeneities of electron density in the ionosphere were observed through data from ground-based receivers of signals of global navigational satellite systems and on the basis of direct measurements of electron density in low-orbit satellites. An intense radio aurora was seen in UHF radar data just after the initial phase of geomagnetic storm. At the same time, we recorded fluctuations of the total electron content from data of GPS receivers and the presence of E-layer irregularities by data of the ionosonde in Norilsk. The time of irregularity recording by different instruments is consistent with the spatiotemporal changes in field-aligned currents of the second zone, obtained from data of AMPERE low-orbit satellite system.

The subject of this research is the formation of skills of the architecture of speech that corresponds to the norms of the Russian literary language among students majoring nonlinguistic specialties. The object of this research is the process of teaching language subjects using the “crib notes” method. The goal consist in testing the effectiveness of such teaching method. Methodological substantiation of the methods of pedagogical research consists in the activity, personal and systemic approaches. Methods of pedagogical research contain empirical (study and generalization of pedagogical experience, analysis of students’ performance, observation, conversation), data processing methods (mathematical, statistical). A pedagogical experiment was conducted as method of studying the pedagogical process in the modified and accurately considered conditions. The described in the article “crib notes” method applicable to studying language disciplines not only structures the knowledge, but also helps the students to memorize easily reproduce the learnt material, develops creative abilities of future engineers, even in the area of cognition and development of literary and formalized speech architecting skills. The scientific novelty consists in combination of language material and the competences of future engineers to present information in the form of diagrams, tables, and systems. This allows employing this method in studying not only the selected language topics, but entire disciplines as well.

The international educational migration as a resource of «soft power» of the state has been analyzed in the article. Based on comprehensive analysis of the existing definitions of educational migration the author’s interpretation of this concept have been proposed. Based on the data of UNESCO, the Institute of international education of the United States, the Ministry of Science and Higher Education of the Russian Federation the statistics of international educational migration has been presented and analyzed. The main emphasis has been made on such categories of international educational migrants as students (bachelors, masters), postgraduate students. The reasons for the popularity of foreign students in countries such as Canada and the United States have been described. Based on the study two groups of factors have been highlighted: external and internal (motivational) factors, influencing decision-making in choosing the country of study.Based on the data of the Ministry of Science and Higher Education of the Russian Federation, the advantages of education in Russia have been analyzed. The issue of adaptation of foreign students in Russian universities has been considered: first-year curatorial programs, the Institute of student fellowships. It has been concluded hat Russian universities have a wealth of experience in teaching and adaptation of foreign students.The concepts and projects to attract foreign students to the Russian Federation also have been described in detail. Special attention to two projects “5–100” and “Export of Russian education” has been paid. The Federal Agency for the Commonwealth of Independent States Affairs, Compatriots Living Abroad, and International Humanitarian Cooperation (Rossotrudnichestvo) as one of the main institutions in the export of Russian education has been designated. The measures to attract foreign students to Russian universities have been proposed.

The understanding of economic polarization as one of the possible sources of economic development is rooted in a number of scientific papers and in strategic planning documents. This understanding requires the revision of the implications that emerge due to the formation and development of growth poles. The goal of our present research is to develop an approach that will help assess the impact of growth poles on the surrounding space. Scientific novelty of the work consists in the justification of an approach to the identification of direct and reverse effects of the development of growth poles, which allows us to measure the scale of the impact they have on the territories concentrated around. Theoretical and methodological basis of the study is formed by a set of scientific ideas in the field of regional economics, spatial analysis and modeling. Using the assessment of spatial autocorrelation (by determining the values of Moran’s Global Index and Moran’s Local Index) and the implementation of cartographic analysis, we assess the relationships between individual constituent entities of the Russian Federation according to the resulting parameters of territory development such as “permanent population” and “gross regional product”. According to the calculations we prove that the influence of growth poles on the surrounding space is ambiguous: the territories located near large-scale socio-economic systems do not receive a significant impetus to their own development; moreover, they lose the resources they already have. The revealed pronounced reverse effect of economic polarization determines the importance of applying a balanced approach to the use of growth poles as a tool of economic development. The results of our research can be used in the work of public authorities at different levels and can also form the basis for further studies related to the measurement of the effects of development of growth poles and the development of priorities and mechanisms of regional policy, taking into account the interests of the territories that surround them

Objective:The objective is to assess the influence of cardiac rehabilitation (CR), represented by self-controlled walking in middleaged men with different onsets of coronary heart disease (CHD), on the muscular strength of the hand flexors, muscle mass and 6-minute walking distance.Methods:90 men aged from 45 to 65 with the same prescriptive CHD with different onsets: myocardial infarction (MI) – 56 patients, or stable angina – 34 patients were examined. After 9 months of CR we have assessed the muscular strength of the hand flexors (MSHF), have run the bioelectrical impedance analysis and 6-minute walking test, have determined the level of testosterone in blood serum.Results:In patients with CHD with MI as an onset, MSHF of the right hand increased from 43 to 49 DAN at the average, and from 41 to 46 DAN – of the left hand; equity proportion of muscle tissue increased from 48.4 to 48.8% , 6-minute walking distance – from 450 to 500 meters. In patients with CHD with stable angina as an onset, the proportion of muscle tissue decreased from 48.2 to 47.3 %, 6-minute walking distance – from 405 to 400 meters without significant improvement of MSHF.Conclusions:9-month CR in patients after MI had a positive effect on MSHF, muscle tissue and stamina as opposed to the patients with stable angina.

The article consists of analyze of one of the innovational pedagogical technologies — "the flipped classroom". The history of development, didactical opportunities and methodical features of this technology are presented in the article. The example of using "the flipped classroom" technology on informatics lesson is given, its positive aspects and difficulties encountered, as well as possible ways to overcome them, are analyzed.

The article develops the methodological approach to coordinating the priorities of scientific, technological and spatial development of regions. The relevance of the study is due to the significance of choosing the benchmarks for the transformation of regional economic systems. These systems are based on the principles of harmonisation of the social and economic interests of individuals, business entities, territories of different levels, and modern prospects for the development of science and technology. The study aims to substantiate the methodology for assessing and selecting priorities for coordinating scientific, technological and spatial development of the economies of industrialised regions. The methodology is based on a combination of the individual territories’ interests due to their joint participation in integrated investment projects of interregional significance. We applied general scientific methods of theoretical and empirical knowledge, including a causal method, a method of analysis and synthesis, a method of scientific abstraction. We substantiated the role of macro-regions in the process of integration of the local territories’ initiatives with the national development guidelines. Then, we identified the characteristics of integrated investment projects with significant potential, which can be the basis for determining the criteria for assessing and selecting projects and project initiatives proposed for implementation at the supra-regional level. Further, we offered an algorithm for developing an integrated investment project that determines the sequence of events. Such events allow realisation of opportunities of scientific and technological development available for industrialised regions, taking into account the priorities of their spatial transformations. We tested the algorithm using the industrial Ural-Siberian macro-region as an example, identifying key aspects of the “Ural Highway” pilot project. A specific feature of the developed approach is the proposal of a “bipolar” system for determining priorities. It allows integration of the national guidelines for scientific, technological and spatial development with the prospects for transformation defined by individual territories (industrialised regions). The proposed approach can be used to substantiate proposals and strategic measures aimed at implementing the priorities of spatial development and the development of science and technology in industrialised regions. © 2019 Institute of Economics, Ural Branch of the Russian Academy of Sciences. All rights reserved. The article has been prepared in accordance with the plan of Institute of Economics of the Ural Branch of RAS for 2019-2021. We would like to thank Averina Lidiya Mikhailovna, Research Assistant of the Institute of Economics of the Ural Branch of RAS for helping to develop methodological recommendations for creating an integrated investment project "Ural Highway".

Summary Background Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe (requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19. Methods We did a 60-day, randomised, double-blind, placebo-controlled, multinational phase 3 trial at 45 hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain. We included adults (≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomly assigned (2:2:1 with permuted blocks of five) to receive intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the course of the study. The primary endpoint was time to clinical improvement of two or more points (seven point scale ranging from 1 [death] to 7 [discharged from hospital]) in the modified intention-to-treat population. The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This study is registered with ClinicalTrials.gov, NCT04327388; EudraCT, 2020-001162-12; and WHO, U1111-1249-6021. Findings Between March 28 and July 3, 2020, of 431 patients who were screened, 420 patients were randomly assigned and 416 received placebo (n=84 [20%]), sarilumab 200 mg (n=159 [38%]), or sarilumab 400 mg (n=173 [42%]). At day 29, no significant differences were seen in median time to an improvement of two or more points between placebo (12·0 days [95% CI 9·0 to 15·0]) and sarilumab 200 mg (10·0 days [9·0 to 12·0]; hazard ratio [HR] 1·03 [95% CI 0·75 to 1·40]; log-rank p=0·96) or sarilumab 400 mg (10·0 days [9·0 to 13·0]; HR 1·14 [95% CI 0·84 to 1·54]; log-rank p=0·34), or in proportions of patients alive (77 [92%] of 84 patients in the placebo group; 143 [90%] of 159 patients in the sarilumab 200 mg group; difference −1·7 [−9·3 to 5·8]; p=0·63 vs placebo; and 159 [92%] of 173 patients in the sarilumab 400 mg group; difference 0·2 [−6·9 to 7·4]; p=0·85 vs placebo). At day 29, there were numerical, non-significant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +8·9% [95% CI −7·7 to 25·5]; p=0·25) for patients who had critical disease. No unexpected safety signals were seen. The rates of treatment-emergent adverse events were 65% (55 of 84) in the placebo group, 65% (103 of 159) in the sarilumab 200 mg group, and 70% (121 of 173) in the sarilumab 400 mg group, and of those leading to death 11% (nine of 84) were in the placebo group, 11% (17 of 159) were in the sarilumab 200 mg group, and 10% (18 of 173) were in the sarilumab 400 mg group. Interpretation This trial did not show efficacy of sarilumab in patients admitted to hospital with COVID-19 and receiving supplemental oxygen. Adequately powered trials of targeted immunomodulatory therapies assessing survival as a primary endpoint are suggested in patients with critical COVID-19. Funding Sanofi and Regeneron Pharmaceuticals.

Hypothyroidism is one of the most common pathological conditions in modern clinical practice. Due to the fact that the targets of thyroid hormones are virtually all organs and tissues, the morphological and clinical manifestations arising with a deficiency of thyroid hormones are quite diverse. Experimental models of hypothyroidism in laboratory animals are widely used for preclinical study of the fundamental pathophysiological mechanisms underlying hypothyroidism, as well as for assessing the effectiveness of treatment-and-prophylactic effects. Currently, several groups of effective models of hypothyroidism have been developed: dietary, surgical, medicamentous, genetic, radioactive and immunological. Each of the specified models is based on different principles, has advantages and disadvantages, and can be used depending on the goals and objectives of the experiment. In this review, we will consistently consider hypothyroidism modeling methods and indicate some promising areas of their use in cardiology.