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Liver cirrhosis continues to be an acute problem of modern medicine due to the high rates of its prevalence and mortality. The high mortality rate is caused by the development of the number of life–threatening complications in decompensated forms of liver cirrhosis – hepatorenal syndrome, infections and varicose bleeding. Hepatorenal syndrome and infections are the result of immunological shifts occurring during decompensation of liver cirrhosis. Currently available literature data do not allow us to create a complete picture of the functional state of various links of adaptive immunity with decompensated liver cirrhosis. The aim of the research was to study the characteristic features of adaptive immunity in patients with decompensated liver cirrhosis. Material and methods. The prospective cohort study included 136 patients with decompensated liver cirrhosis, who received inpatient treatment in the hepatological department of the multidisciplinary hospital. The cohort of examined patients was divided into two groups, one of which included patients with liver cirrhosis of viral origin (n = 78), the other – patients with alcoholic liver cirrhosis (n = 58). In addition to the generally accepted standard methods, the patient examination program included immunological tests: identification of T- and B-lymphocytes, immunoregulatory and activated subpopulations of T-lymphocytes by the method of immunophenotyping peripheral blood mononuclear cells using monoclonal antibodies. The serum levels of immunoglobulins IgM, IgG, IgA, circulating immune complexes were determined by immunoturbidimetric method. Results. The study of indicators of the humoral link of adaptive immunity revealed an increase in the number of B cells, an increase in IgM, IgG, IgA and circulating immune complexes in patients with decompensated liver cirrhosis. The cellular link of adaptive immunity was characterized by an increase in the relative content of T helper cells, activated T cells against the background of a decrease in the number of immature T cells and T regulatory cells. Conclusions. The distinctive features of adaptive immunity in patients with decompensated liver cirrhosis are simultaneous activation of both humoral and cellular components, which, apparently, supports the systemic inflammatory process and the associated progressive liver fibrosis.

Aim. To study the indicators and regional specifics of morbidity associated with temporary disability in the Subjects of the Far Eastern Federal District (FEFD) of Russia.Materials and methods. A descriptive epidemiological study was performed based on retrospective data on the morbidity associated with temporary disability of the working population in FEFD as of January 01, 2021. A unified inter-agency information and statistical system was used to study the indicators of temporary disability (TD), including the number of TD cases per 100 employees and the number of TD days per 100 employees during 2005–2020. The methods of descriptive statistics were applied to differentially calculate the average annual indicators for the periods of 2005–2014 and 2015–2019 due to the adoption of the Rosstat order No. 723 dated December 25, 2014.Results. The average long-term value of the indicators of morbidity associated with temporary disability in most FEFD subjects was found to be statistically significantly higher than that in the entire Russian Federation, with higher values o bserved in 2005–2014 compared to 2015–2019. The indicators of morbidity associated with temporary disability demonstrated a more stable trend during 2015–2019. The indicators for 2020 were statistically higher than for 2015–2019, largely due to the COVID-19 pandemics.Conclusions. In view of the specific nature of the main economic sectors in FEFD (shift and seasonal work), as well as the lack of a developed social, road transport, and engineering infrastructure, data on temporary disability of the working population (including migrants) should be continuously monitored. The results obtained at this research stage can be used to develop optimal measures aimed at protecting the health of people living in the Far East of Russia.

The article deals with the phenomenon of dialogical speech activity in foreign language. Much attention is given to the notion of dialogic communication. A number of definitions of the dialogue are given. The article features communicative interaction. The key functions of dialogical speech communication are described. The article presents the main type of dialogue among which the authors highlight the ones of great importance for students to master professionally-oriented foreign language communication. Fundamental characteristics of dialogic discourse are analyzed. The article provides the definition to the concept of “ability”; groups of abilities necessary to carry out oral communication are outlined, the authors examine their most significant properties. The questions of division of abilities of foreign language dialogical speech activity development and theoretical justification of their typology are considered. The tree-phase structure of speech actions is revealed the elemental composition of the exercise is determined. The existing typologies of communicative tasks in domestic and foreign linguodidactics are analyzed, each type is characterized. The article provides a system of exercises aimed at developing communicative skils and abilities in the process of learning a foreign language.

Background. For many years the primary aim of treatment strategy for ph-negative myeloproliferative neoplasms has been to restrain disease progression, with lasting relief and management of symptoms to improve patients’ quality of life. Generally, this did not lead to a significant increase in life expectancy with primary myelofibrosis and didn’t decrease the risk of fibrosis in patients with polycythemia vera and essential thrombocythemia. To date a new class of targeted drugs has been developed, it is JAK2 inhibitors with pathogenetic effects. The results of clinical trials showed the high efficacy of the first registered drug of this its kind – ruxolitinib – that includes a faster reduction in the symptoms of tumor intoxication and in symptoms associated with the development of splenomegaly and increase in the overall survival rates. It is known that the data obtained during clinical trials of medicines may differ from the results obtained in routine clinical practice. In actual practice drugs are used in a much wider heterogeneous population of patients, less limited first of all by age and comorbid characteristics. It is possible to analyze cohorts of patients including a larger number of clinical cases with a longer follow-up period. In this regard of great interest is the actual clinical experience of long-term use of ruxolitinib in patients whose set is limited only by clinical contraindications for prescribing the drug.Aim. To present our own actual experience of targeted therapy of myelofibrosis and compare the results obtained with the data of clinical trials.Materials and methods. Our analysis includes data from 141 patients (67 (47.5 %) men and 74 (52.5 %) women) in a chronic phase myelofibrosis. All patients received ruxolitinib. Of these, 109 (69 %) patients had primary myelofibrosis, 26 (16 %) – postpolycythemia myelofibrosis, 6 (4 %) – postessential thrombocythemia myelofibrosis. The median age at the start of therapy was 62 (18–84) years. The median disease duration before ruxolitinib was prescribed – 79 (1–401) months. According to the dIpSS (dynamic International prognostic Scoring System) criteria, 13 % of patients were assigned to the low risk group, 38 % – to the intermediate-1, 36 % – to the intermediate-2, 13 % – to the high risk group. Most patients (52 %) had grade 3 bone marrow fibrosis.Results. The median duration of treatment was 18 (range from 1 to 115) months. Symptoms of intoxication were relieved 74 (81 %) of 91 patients, the spleen size decreased in 81 % of patients (the spleen size returned to normal in 25 % of patients). The increase in the median hemoglobin level was 15 %. The proportion of patients requiring blood transfusion decreased by 4 times (from 39 to 9 %). Mean platelet levels normalized in most patients with baseline high and low platelet levels. A complete clinical and hematological response was achieved in 16 % (n = 23) of cases, a partial response – in 26 % (n = 37) of cases, clinical improvement – in 21 % (n = 30), disease stabilization – in 33 % (n = 46) of cases. No response was received in 1 (1 %) patient and in 3 (3 %) cases there was progression of the disease. At the time of analysis, 81 (57 %) of 141 patients were continuing the ruxolitinib treatment. The fatal outcome in 33 (22 %) patients was associated with concomitant diseases, among which 20 (14 %) died from proven COvId-19 infection. Overall survival: 1-year 81 %, 2-year 73 %, 5-year 50 %. Overall survival excluding deaths due to COvId-19: 1-year 92 %, 2-year 85 %, 5-year 70 %. Massive splenomegaly and a high degree of fibrosis were unfavorable predictors of prognosis of overall survival.Conclusion. Target therapy with Janus kinase inhibitor ruxolitinib has demonstrated high efficacy in patients with myelofibrosis in routine clinical practice. The most rapid effect ruxolitinib had on the spleen size and the symptoms of intoxication. Tolerability of ruxolitinib therapy was generally satisfactory. The overall and progression-free survival rates in patients with myelofibrosis, receiving ruxolitinib in the clinical setting was consistent with the results of international multicenter clinical trials.

The article discusses the problem of waste management relevant for the Russian Federation and its Arctic regions on the example of a number of Arctic states – the countries of Northern Europe. The existing waste management system, features of the relevant regulatory framework and competition development in this area are considered. The legislative framework of waste management in the northern countries is heavily influenced by the European Union directives and international law. The northern countries have much in common, including cultural and legislative traditions, however there are significant differences between them. In most northern countries, existing laws and other regulations to some extent limit competition in waste management. It imposes obligations, but at the same time provides broad waste management rights. Within the current legislative framework, there are opportunities to increase competition in the field of waste management. However, the existing regulatory framework may not be sufficient to improve the market structure or create new waste markets.

The results of analytical research on the use of methods for calculating the size of inflows of cylindrical casts from steels 40ХЛ and Х12МЛ weighing 200 - 16000 kg and a diameter of 0.25 - 0.7 m, hardening in metal form (mold) in electroslag heating of the melt and creating atmospheric gas pressure in the overflow part. Schemes of construction of the corresponding device and realization of technology are resulted. The use of the refrigerator design in the form of a metal housing with an insert of refractory material, graphite electrodes and a flux insert, which works on the principle of floating filling insert in the combined technology of gas-dynamic impact and electroslag heating, allows more efficient use of melt casting ingot by keeping the metal in a liquid state throughout the curing time of the main mass of the casting (ingot), thereby reducing the amount of melt required to feed the shrinkage and, accordingly, the mass of the overflow. This is especially true for alloy products that contain high-cost base components and / or alloys. It is also an urgent task to be able to determine the size of a particular filling when using technology for castings of different weights and sizes in the most convenient way without the implementation of cumbersome calculation schemes. It is shown that the peculiarity of determining the size of overflows of castings made using combined technology is to take into account changes in the size of the insert of refractory material (especially wall thickness), which occupies a certain share of the overflow part of the cast or ingot, which, in turn, will change the size of the filling. Calculations and nomograms for determining the height of the filling by its diameter and the mass of casts at the ratios of the diameters of the casting and filling 0.6, 0.65 and 0.7.

The objective. To increase the effectiveness of cardioprotection during coronary artery bypass grafting (CABG) by using a modified technique of remote ischemic preconditioning (RIPC).Subjects and Methods. A prospective randomized study included 119 patients (aged 18 to 75 years) undergoing on-pump CABG. Patients were divided in 5 groups: Group 1 ‒ Sevoflurane control (ContrSevo), RIPC was not used, sevoflurane anesthesia (n = 24); Group 2 ‒ RIPC1 sevoflurane (RIP1Sevo), RIPC with ischemia-reperfusion of one lower limb, sevoflurane anesthesia (n = 26); Group 3 ‒ RIPC2 sevoflurane (RIP2Sevo), RIPC with ischemia-reperfusion of two lower limbs, anesthesia sevoflurane (n = 23); Group 4 ‒ Propofol control (ContrProp), RIPC was not used, propofol anesthesia (n = 22); Group 5 ‒ RIPC2 propofol (RIP2Prop), RIPC with ischemia-reperfusion of two lower limbs, propofol anesthesia (n = 24). The serum troponin I concentration (cTnI) (baseline, and 30 minutes, 12, 24, 36 and 48 hours after СPB weaning). Hemodynamic parameters and indicators of the clinical postoperative course also were evaluated. The impact ischemic-reperfused tissue mass of RIPC on the cardioprotection was assessed by comparing the groups of ContrSevo, RIPC1Sevo, and RIPC2Sevo. To assess the impact of propofol on the RIPC-induced cardioprotection, the groups of ContrProp and RIPC2Prop were compared.Results. Statistically significant differences in cTnI were found between the ContrSevo and the RIPC2Sevo at points of 12, 24 and 36 hours: ContrSevo 1.83 (1.3; 2.24) ng/ml, RIP2Sevo 1.28 (0.75; 1.63) ng/ml after 12 hours (p = 0.02), ContrSevo 1.44 (0.98; 2.26) ng/ml, RIPC2Sevo 1.17 (0.55; 1.66) ng/ml after 24 hours (p = 0.046), ContrSevo 1.26 (0.86; 1.72) ng/ml, and RIPC2Sevo 0.81 (0.47; 1.24) ng/ml after 36 hours (p = 0.035). No differences in the cTnI were found between the groups of ContrSevo and RIPC1Sevo, RIPC1Sevo and RIPC2Sevo at any stage of the study. There were no statistically significant differences between the groups when comparing hemodynamic parameters. In the RIPC2Sevo Group, arrhythmias requiring cardioversion or drug therapy were significantly less frequent compared to ContrSevo (1 vs. 6) (p = 0.047). There were no other significant differences in the postoperative clinical course. When comparing the groups of ContrProp and RIP2Prop, no significant differences were found in cTnI and hemodynamic parameters as well as in the postoperative clinical course.Conclusions. A greater mass of ischemic-reperfused peripheral tissue is accompanied by greater RIPC-induced cardioprotection. A modified protocol for RIPC with ischemia-reperfusion of two lower limbs with sevoflurane anesthesia enhances cardioprotection during on-pump CABG. The modified RIPC protocol with ischemia-reperfusion of two lower limbs with sevoflurane anesthesia reduces the risk of arrhythmias requiring cardioversion or drug therapy. Propofol inhibits the RIPC-induced cardioprotection with ischemia-reperfusion of two lower limbs.

The issues of preliminary constitutional review are not thoroughly researched in the scientific field of constitutional law mainly due to relatively small volume of relevant practice both in the Russian Federation and in affairs of competent bodies of foreign states. At the same time, the changes in the legal regulation of the powers of the Constitutional Court of the Russian Federation, which occurred within the framework of the constitutional reform of 2020, indicated once again the relevance of the study of preliminary constitutional review. Whereas prior to these transformations the competence of the Constitutional Court of the Russian Federation in the field of preliminary review encompassed only international treaties (of the Russian Federation) that did not enter into force and issues on referendums of the Russian Federation, now it also includes verification of the constitutionality of federal legislative acts of all types, including laws on amendments to the Constitution of the Russian Federation, as well as the laws of the constituent entities of the Russian Federation prior to their promulgation. In this regard, it seems important to refer to the relevant experience of other countries and above all of those that are historically and geographically close to the Russian Federation. The article provides a brief overview of the concepts of preliminary constitutional review developed in constitutional and legal science, its merits and controversial points. Using the comparative legal method, the authors investigate the state of constitutional and legislative regulation of preliminary constitutional review carried out by constitutional courts and other similar bodies of the post-Soviet states. The subject of the analysis includes approaches to determining the objects of such review, as well as practice and features of the regulation of the constitutional review procedures under study. Despite the sufficient development and high quality of legal regulation of these issues in the Russian Federation, the authors come to a conclusion that it is advisable to adopt certain aspects from the relevant experience of the states from the former USSR.

Introduction. Olfactory dysfunction is considered to be an early and relatively important marker of Parkinson's disease (PD). Olfactory studies using objective neurophysiological methods may become one of the diagnostic tests to identify individuals with a high risk of developing PD. The aim of the study was to assess the spectral and topographic characteristics of bioelectrical brain activity in patients with PD during directional perception of olfactory stimuli. Materials and methods. This study included 30 patients with PD (mean age was 66.5 6.5 years). The control group consisted of 20 people without PD (mean age was 65.3 8.5 years). Lavender oil, clove oil, camphor oil and -mercaptoethanol solution (an aversive stimulus) were used for olfactory stimulation, while distilled water was used as a control test. The test subject sat with their eyes closed and inhaled the presented smell for 30 seconds, while an EEG recording was made during this time. Study results. Olfactory stimulation in patients with PD showed increased synchronicity of the 3 rhythm in the right hemisphere, as well as the rhythm in the parieto-occipital regions of both hemispheres. These changes indicate significant activation of internal (endogenous) attention, increased overall, non-specific readiness potential, as well as the involvement of the limbic-reticular complex in olfactory perception. Olfactory perception in the control group was accompanied by reduction in the 1 rhythm amplitude in the parieto-occipital regions bilaterally, which may indicate moderate activation of external (exogenous) attention and the posterior attention system responsible for simple perception processes. Conclusion. Increased 3 rhythm amplitude in the right hemisphere and increased rhythm amplitude, observed during directional olfactory perception, may indicate olfactory dysfunction and should be viewed as an additional indicator when establishing a diagnosis of Parkinsons disease.

Seismic monitoring in the region in 2015 was carried out by a seismic network consisting of 59 stations. Digital equipment was installed at all stations in the second half of the year. The network capability was assessed by the level of seismic noise at the stations: in most of the region, the network provided registration of an earthquake from КR7.0, in the central (including the Greater Sochi region) and eastern parts of the region – КR6.0, and in some local zones with КR5.5. 2,276 earthquakes were registered, 17 earthquakes were felt in the settlements of the Caucasus. The maximum intensity VII at MSK-64 (SSI-17) scale was noted from the earthquake in the territory of Azerbaijan. The earthquake on November 3, which occurred on the platform territory within the Stavropol arch, felt IV at MSK-64. The strongest earthquakes were recorded in the Terek-Caspian and Kura troughs and in the eastern part of the Greater Caucasus. The seismicity of the North Caucasus in 2015 in accordance with the seismicity scale "SOUS-09" was set as the "background average" for the observation period from 1962 to 2015.

X-ray imaging of virus particles at European XFEL could eventually allow solving their complete structure, potentially approaching resolution of other structural virology methods. To achieve this ambitious goal with today’s technologies, several mL of purified virus suspension containing at least 1012particles per mL are required. Such large amounts of concentrated suspension have never before been obtained for enveloped viruses. Tick-borne encephalitis virus (TBEV) represents an attractive model system for the development of enveloped virus purification and concentration protocols, given the availability of large amounts of inactivated virus material provided by vaccine manufacturing facilities. Here we present the development of a TBEV vaccine purification and concentration scheme combined with a quality control protocol allowing substantial amounts of highly concentrated non-aggregated suspension to be obtained. Preliminary single particle imaging experiments were performed for this sample at European XFEL, showing distinct diffraction patterns.

Various definitions of the notion of translation are given. Special attention is paid to components of the procedural aspect in teaching translation of scientific texts that enable molding theoretical and applied knowledge, abilities and skills by means of special exercises. The article provides examples of pre-translation and translation exercises aimed at developing skills of translation of professionqlly-oriented texts.

Tick-borne encephalitis virus (TBEV) is a RNA-containing enveloped virus, a member of the Flaviviridae family. Here we describe a detailed analysis of the size and structure of inactivated TBEV (the Sofyin-Chumakov TBEV strain, used in vaccines). Four analytical methods were used to analyze individual TBEV particles—negative staining TEM, cryo-EM, AFM, and NTA. All methods confirmed that the particles were monodisperse, and their mean size was ~50 nm. Cryo-EM data were used to obtain a 3D electron density model of the virus with clearly distinguishable E-proteins. STEM-EELS analysis detected phosphorous in the particles, which was interpreted as the RNA signal. Altogether, the described analytical procedures can be valuable for the further analysis of vaccine inactivated virus samples.

The author of the article shows the research results of the popularity of tattoos among young people (15-30 years old). The author examines the most popular tattoo styles, reveals the details of tattooing in such styles as realism, minimalism, new school, trash polka, watercolor. Finally, the author concludes that it is necessary to train highly qualified masters of art tattoo who meet the high requirements of professional competencies, who have professional ethics, know the historical aspects of the development of this art, styles of tattoos, the technique of its application, the technical aspect of the issue, who are aware of art, psychology, medicine, and can provide a first aid. The author notes that these specialists should be trained in organizations of supplementary vocational training. The author also notes the importance of developing a competent educational program for a master of art tattoo. So, the author says that such training should be carried out by qualified teachers in the fields of knowledge, training should be fully immersed in the educational process, and training of these specialists should be carried out only in accredited educational organizations.

This article presents the results of a sociolinguistic electronic survey conducted in 2017–2019 in Finland. The purpose was to reveal the attitude of children towards their names in bilingual and polylingual families living in Finland. The questionnaire was answered by 19 children (4 interviews was taken additionally) aged from 10 to 16 years old (born between 2002–2010). The research methods were: the method of sociolinguistic questionnaire, focused interviews, the method of verification, the case study method. As a result, socio-psychological motives determining the orientation of variants of children’s names both at the culture of their parents (family) and the Finnish society. The novelty of the pilot study is an analysis of bilingual children’s reflections on their personal name as a significant part in self-identification processes.

Tick-borne encephalitis virus (TBEV) is an enveloped RNA virus, a member of the genus Flavivirus (family Flaviviridae). Here, we provide a detailed analysis of the size and structure of the inactivated TBEV vaccine strain Sofjin-Chumakov. Four analytical methods were used to analyze individual TBEV particles—negative staining TEM, cryo-EM, atomic force microscopy (AFM), and nanoparticle tracking analysis (NTA). All methods confirmed that the particles were monodisperse and that their mean size was ~50 nm. Cryo-EM data allowed us to obtain a 3D electron density model of the virus with clearly distinguishable E protein molecules. STEM-EELS analysis detected phosphorus in the particles, which was interpreted as an indicator of RNA presence. Altogether, the described analytical procedures can be valuable for the characterization of inactivated vaccine virus samples.

Background. With the growing role of economic environment in the socialization of a modern person, there is an increasing interest in understanding the socio-psychological mechanisms of human behavior when choosing goods. Economic realms are refl ected in the self-identifi cation of the individual in relation to other people and social structures. Th e study of the relationship between social identity and the features of consumer behavior when choosing goods is relevant. At the same time, various aspects of social identity in connection with the peculiarities of consumer preferences remain poorly studied in social psychology. Objective. Th e study is aimed at identifying the relationship between the components of social identity and the characteristics of consumer preferences (using the example of locally produced food). Design. Th e study was conducted online by presenting respondents with a questionnaire that included questions about consumer preferences and components of social identity. Th e sample was targeted by experts: consumers of food products of local production, citizens of the Russian Federation, aged 25 to 67 years (N = 200). Results. Th e interrelation of cognitive and value components of social identity with the peculiarities of consumer preferences concerning general attitude to products, their characteristics and selection criteria is revealed. More significant connections were found between value components and all manifestations of consumer preferences. Th e interrelation between local and world identity and preference for food products of domestic production, as well as the features of the criteria for choosing food products among consumers with diff erent severity of the cognitive component of social identity, has been revealed. Conclusion. New data on the relationship between cognitive and value components of social identity and the characteristics of consumer preferences were obtained. Th ey can serve as a basis for a deeper analysis of the identity structure, understanding the role of identity in consumer behavior. Th e main limitations of the study relate to the sample and the methods used.

The proposed scientific work considers and substantiates an effective method for selecting interference fit on smooth cylindrical surfaces of parts, which can be successfully applied in automated design of fit. Based on the analysis of numerical and analytical research of the results of calculation and design of the considered joints, a flat image of a mathematical model of the area of existence of geometric parameter values in a two-dimensional coordinate system (diameter and working length of the fit) was first obtained. At the next stage of modeling many alternative i-th standard interference fits were built. Within each i-th object centers of grouping rational values of geometric parameters were defined. They are formed by crossing the largest segments of allowable ranges of changing values of diameter and working length in each of the models of sets. The position of such centers is analytically described using the mathematical apparatus of the theory of R-functions. On the considered specific example of this research, the criterion for choosing a rational standard interference fit is formulated depending on the values of geometric parameters. The meaning of this criterion is that within the flat geometric image of the model, the shortest distance is analytically determined - the segment between the points of the grouping centers of the model of set of the �-th fit and the model of the area of existence of values. The effectiveness and advisability of the formulated criterion is illustrated by comparison with other criterions obtained in previous researches of the authors. As a result of the research, it was revealed that the task of choosing a single rational design solution is significantly simplified if several criterions of one of the alternative fits coincide.

The article highlights the main provisions of corporate culture role in business system human resource management. It is determined, that human resource management is aimed at maximum adaptation and disclosure of human potential, taking into account the positive social and economic effect for the company. The result of human resource management is expressed in the effectiveness of human capital attracting. An analysis of the approaches to human resource management covered in the scientific literature found, that today many people have an approach to human resource management, which contains four concepts and is developed in accordance with three main approaches to human resource management. During the study of approaches to human resource management in modern conditions of economic relations, it was found that one of the areas of providing companies with qualified personnel is the development and implementation of policies in the field of training and development of their own personnel. In this case, the leaders of the organization will have the opportunity to get highly qualified, motivated and creative professionals from among their employees, who will be ready to bring new approaches to the company's business processes that meet the mission and objectives of its operation. Another area of providing the company with professional staff is the formation of an effective recruitment system, which is a set of measures to find and select the necessary specialists for the organization. Modern human resource professionals use a variety of techniques and the latest advances at every stage of their work to develop the company and improve the human resource management system, taking into account that personal qualities of the employee mainly affect his behavior in the organization and performance of professional and social roles in the team. The paper contains proposals for improving approaches to the formation and implementation of corporate culture as an effective tool for human resource management in terms of the main trends in post-industrial society and models of new technologies and tools development. Such tools can also be called Headhunting, HR-brand, social networks, remote or automatic selection.

The immunomodulatory properties of immunobiological drugs Glutoxim and Phosprenyl we well as vesicular stomatitis virus and inactivated tick-borne encephalitis vaccine virus were studied using human diploid fibroblast cell line from the collection of M. P. Chumakov Federal Research Center for Research and Development of Immunobiological Products. All tested preparations exhibited immunomodulatory activity in human diploid fibroblast cell line. Glutoxim in doses of 0.1 and 0.25 μg/ml stimulated production of IL-6 and IL-10 during 24-48 h of culturing, but did not stimulate production of IL-1β. Phosprenyl, on the contrary, increased production of IL-1β and the levels of IL-6 and IL-10. Vesicular stomatitis virus stimulated the production of IL-1β, IL-6, and IL-10, while inactivated tick-borne encephalitis vaccine virus stimulated the production of cytokines IL-8 and IL-18. Immunomodulatory activity of inactivated tick-borne encephalitis vaccine virus was first demonstrated in the in vitro system.

Here we present a protocol for the isolation, purification, and inactivation of the yellow fever virus (YFV) aimed to facilitate high-resolution structure determination using cryo-electron microscopy (cryo-EM). Cryo-EM studies require the concentration of viral particles to be at least 1012 particle/mL. The concentration of the sample was evaluated by a combination of methods, including the plaque-forming assay, spectrophotometry, and protein polyacrylamide gel electrophoresis. High purity of the sample was confirmed by electrophoresis and transmission electron microscopy. The cryo-EM data set was collected and the 2D classification of viral particles was performed.

Hepatorenal syndrome is a life-threatening complication of liver cirrhosis. 90% of patients with liver cirrhosis die within 2 months since the onset of hepatorenal syndrome development. For many years the hypothesis of the hemodynamic mechanism of hepatorenal syndrome development was accepted as the only true one, according to this hypothesis compensatory systemic vasodilation in response to portal hypertension causes renal ischemia and the development of functional specific acute kidney damage, the so-called “hepatorenal syndrome – acute kidney damage”. In recent years some works were published that substantiate the role of a systemic inflammatory reaction in the development of hepatorenal syndrome; this inflammatory reaction being associated with activation of innate immunity cells in response to a bacterial infection, including that to the microflora of the intestine which is adjacent to the liver. Data has been obtained which indicated that Toll-like receptors (TLRs), in particular TLR4 and TLR9 are involved in the development of hepatorenal syndrome.

The purpose of this study is assessing informative capability of the most frequently used scales and neuropsychological tests evaluating cognitive function for mild cognitive impairment (MCI) and vascular dementia (VD). A total of 104 patients with cerebrovascular disorder including 39 male and 65 female were divided into two subgroups depending on severity of the cognitive impairment. The first group consisted of 51 patients with MCI and the second one consisted of 53 patients with VD confirmed by MMSE and MoCA-test. The obtained correlation analysis data testifies to difficulties in the interpretation of these routinely used scales not only because of the differences between investigated parameters of the patients with MCI and VD, but also because of the main goal of their creation. Most of the scales were created for patients with dementia and now their sensitivity for MCI is doubtful. The MoCA test, Clock Drawing Test (CDT) and ADAS-cog subscale are more sensitive and has greatest informative capability for patients with MCI and dementia, while MMSE is more informative mostly for patients with dementia. Neuropsychological tests DAD and NPI remain informative in varying degrees of cognitive impairment. In the diagnosis and differential diagnosis of the degree of cognitive impairment of vascular genesis, one should use not only a complex of scales and neuropsychological tests, but also methods that comprehensively reflect the vascular genesis of the process of formation of cognitive impairment.

Carfilzomib, lenalidomide, and dexamethasone (KRd) have been approved for the treatment of relapsed and refractory multiple myeloma (RRMM) based on ASPIRE clinical trial.Analysis of efficacy and safety of KRd in routine clinical practice.The prospective analysis included patients with MM who received at least one line of previous therapy. The inclusion criteria were relapse/progression; refractoriness; lack of very good partial response (VGPR) and more after the first line of therapy. Since February 2016, we used KRd like in ASPIRE trial, since October 2019, carfilzomib has been used at a dose of 56 mg/m2 on days 1, 8 and 15. Autologous hematopoietic stem cell transplantation (autoHSCT), consolidation (KRd) and maintenance therapy (Rd) were regarded as one line of therapy.We evaluated 77 patients with median age at the time of diagnosis is 55 (3072) years. For 56% (n=43) of patients KRd was applied as the second line (group 1), for 44% (n=34) as the third and more (group 2). In 23/43 patients from group 1, an early change in therapy was made due to insufficient effectiveness (after 24 courses of VCD or PAD). KRd served as a "bridge" to autoHSCT in 25 (32%) patients (21 of 25 in group 1). Another 7 patients underwent collection of autoHSC (all from group 1). The overall response rate (ORR) was 80.5%, with 33.8% complete response (CR) and 26% VGPR. ORR in group 1 was 98% versus 65.6% in group 2; 24-month overall survival (OS) was 70%, progression free survival (PFS) 49.8%. In group 1, 24-month OS was 85.6% versus 50.0% in group 2, 24-month PFS was 67.8% versus 25.5% (p=0.01).Our analysis confirmed the high efficiency of KRd in the treatment of RRMM in real-life practice. Early correction of therapy with insufficient effectiveness of the first line made it possible to implement the strategy of high-dose consolidation and autoHSCT in a larger percentage of patients with MM.Обоснование. Комбинация карфилзомиба, леналидомида и дексаметазона (KRd) одобрена для лечения пациентов с рецидивом и рефрактерным течением (РР) множественной миеломы (РРММ) на основе результатов исследования ASPIRE. Цель. Анализ эффективности и безопасности применения схемы KRd в условиях реальной клинической практики. Материалы и методы. В проспективный анализ включены пациенты с ММ, получившие не менее одной линии предшествующей терапии. Критериями включения служили: рецидив/прогрессия; рефрактерность; отсутствие очень хорошей частичной ремиссии (ОХЧР) и более после 1-й линии терапии. С февраля 2016 г. использовался стандартный режим KRd (ASPIRE), с октября 2019 г. карфилзомиб применяли в дозе 56 мг/м2 в 1, 8 и 15-й дни. Трансплантация аутологичных стволовых кроветворных клеток (аутоТСКК), консолидация (KRd) и поддерживающая терапия (Rd) расценивались как одна линия терапии. Результаты и обсуждение. Проанализирована терапия 77 больных. Медиана возраста на момент диагноза 55 (3072) лет. У 56% (n=43) схема KRd применена во 2-й линии (группа 1), у 44% (n=34) в 3-й и более (группа 2). У 23/43 пациентов из группы 1 произведена ранняя смена терапии из-за недостаточной эффективности (после 24 курсов VCD или PAD). Схема KRd послужила мостом к аутоТСКК у 25 (32%) больных (21 из 25 в группе 1). Еще 7 пациентам выполнен сбор аутоСКК (все из группы 1). Общий ответ (ОО) достигнут у 80,5%, полный ответ 33,8%, ОХЧР 26%. Частота ОО в группе 1 составила 98% против 65,6% в группе 2; 24-месячная общая выживаемость составила 70%, выживаемость без прогрессии 49,8%. В группе 1 24-месячная общая выживаемость составила 85,6% против 50,0% в группе 2; 24-месячная выживаемость без прогрессии 67,8% против 25,5% (р=0,01). Заключение. Наш анализ подтвердил высокую эффективность схемы KRd в терапии РРММ в реальной практике. Ранняя коррекция терапии при недостаточной эффективности 1-й линии позволила реализовать стратегию высокодозной консолидации и аутоТСКК у большего числа больных ММ.