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Typhoid fever is an acute infectious disease caused by Salmonella enterica subsp. enterica serovar Typhi (S. Typhi), which is still extremely common in endemic low- and middle-income countries of Asia and Africa. Industrialised countries may also be affected by typhoid fever outbreaks due to booming international tourism, and natural disasters. Given S. Typhi progressive resistance to antibiotics, high epidemiological burden, and lack of adequate sanitation and hygiene in a number of regions, the introduction of new treatment protocols and the improvement of preventive vaccination are critical tasks in global healthcare. The aim of the study was to highlight the main historical aspects of the typhoid vaccine development, to summarise data on the licensed vaccines and promising approaches to the development of new typhoid vaccines. The paper describes the current epidemiological situation of typhoid fever globally and in the Russian Federation. It dwells upon the global experience in typhoid vaccine development from the production of an inactivated vaccine to the development of conjugated vaccines. The paper summarises data on Russian and foreign-made typhoid fever vaccines currently available in the global pharmaceutical market. It outlines the main trends in the development of vaccines against the disease caused by S. Typhi. The paper demonstrates the need for improving the efficacy of existing vaccines and development of new typhoid combination vaccines.

Objective: to analyze the roles of undifferentiated connective tissue dysplasia (UCTD) in the development of cartilage and ligamentous apparatus diseases.Material and methods. This paper presents the results of analyzing the literature on fundamental and clinical studies of relationships between chondroitin sulfate (CS) and connective tissue (CT) disease. A total of 922 publications on the relationship between CT dysplasia and CS and 2249 publications on CS receptor molecules were analyzed. These arrays of publications were analyzed using topological and metric approaches to data analysis.Results and discussion. The genetic predisposition to UCTD is substantially aggravated by inadequate nutrition that leads to deficiency of certain micronutrients that support CT reconstructive processes. The paper presents the results of a systematic analysis of prospects for the use of drugs based on standardized CS substances in patients with UCTD. CS is a material for CT reconstruction. CS increases the activity of growth factors and reduces CT inflammatory destruction (inhibition of the secretion of histamine, pro-inflammatory chemokines, Toll-like receptors, and the NF-κB cascade through exposure to the CD44 receptor).Conclusion. The pharmacological effects of CS indicate the importance of using standardized CS forms in the treatment of patients with UCTD.

The paper is devoted to frontotemporal dementia (FTD), one of the most common forms of frontotemporal degeneration. The main symptoms of the disease include disinhibition, lack of empathy, obsessive-compulsive symptoms, apathy, cognitive impairment, appetite changes, and progressive changes in social behavior. In parallel, there are personality changes that are characterized by lower levels of self-awareness and by progressive psychological and social maladaptation of patients in society.The paper describes a clinical case of FTD in a female patient with marked behavioral changes and personality disorder. A 52-year-old woman was admitted to the alcoholism treatment department for alcohol intoxication and symptoms of mental confusion. According to her relatives, drinking too much alcohol every day, she was found to become rude, indifferent to others and her own duties, sharply limited the range of her activities and communication, and showed a decline in memory for current events. Psychopathological examination determined a distinct motivational-volitional decrease, the patient’s inability to mobilize mental activity, non-critical thinking, and indifference. X-ray diagnosis revealed the changes characteristic of frontotemporal neurodegeneration (atrophy of the frontal and temporal lobes prevails). The described case confirms that alcohol abuse can mask organic disorders that develop in systemic cerebral atrophy.

The paper analyzes various viewpoints on applicability of preprints used to exchange data on the following: how a non-peer-reviewed paper affects the way preprints are perceived in various sciences, how the academic community tackles the issue of evaluating preprints, how publishers treat preprints, how external factors affect the development of preprints, and who is responsible for the quality of preprints. The timeline has been identified for the development of preprints between 1940s and 2020. The development of preprints has been analyzed during the COVID-19 pandemic. Data has been provided on current platforms and tools that can be used to work with preprints and to evaluate them.

One of priority issues of the present-day healthcare system is development of new vaccines and improvement of existing ones due to decreasing immunocompetence of the population, emergence of new infections and reemergence of old ones which were previously thought to be under control. Adjuvants have proven to be integral and important components of modern vaccines, as they enhance immune response to the vaccine antigen. However, despite a lot of effort put into their development, only a small number of adjuvants are currently used in clinical practice.The aim of the study was to systematise literature data on the adjuvants’ mechanisms of action, their specific structure, composition, and stimulation effects that mediate their immunoadjuvant properties. The paper summarises data on adjuvants used as components in licensed vaccines, describes their characteristics, analyses molecular mechanisms of their action in order to establish correlation between their structure and activity, which is important for the development of more efficacious and safe adjuvants. The paper cites advanced developments aimed at enhancing stimulation effects of existing adjuvants. It concludes by stating that the key research area aimed at improving vaccination efficacy is the study of mechanisms that contribute to the development of effective protection against infectious agents, as well as analysis of how to use adjuvants to stimulate the body’s defensive mechanisms, primarily by impacting the innate immunity.

Herbal medicines make up a large part of all medicinal products in the Russian market. Complex combinations of biologically active substances that are used as components in herbal medicines not only determine their therapeutic efficacy, but can also cause adverse reactions. The aim of this review was to analyse data on adverse effects of herbal medicines, and reasons and mechanisms behind their development. Special attention should be given to hepatotoxic and nephrotoxic effects of biologically active substances that are used as components in herbal medicines, because liver and kidney failure may lead to life-threatening conditions. The paper addresses hepatic adverse effects, including sinusoidal obstruction syndrome, caused by toxic biologically active substances of the pyrrolizidine alkaloids group. The paper summarises data on herbal medicines and toxic biologically active substances causing acute kidney injury and chronic kidney disease. It analyses potential clinically significant interactions that may occur during co-use of herbal and other types of medicines due to their pharmacokinetic and pharmacodynamic interactions. Further research involving collection, systematisation, and analysis of adverse effects of herbal medicines used alone or in combination with other medicinal products is needed to improve the safety of pharmacotherapy.

The review is devoted to specific aspects of the development of post-vaccination immunity following immunisation with different types of antiviral vaccines, as well as to ways of increasing immunogenicity of vaccines and effectiveness of preventive vaccination. Vaccines containing highly purified and recombinant antigens obtained using modern technologies have lower reactogenicity and a higher safety profile, but are less immunogenic compared to live vaccines. Effective vaccines have not been developed for many viral infections yet. Therefore, it is critical to search for ways to enhance immunogenic properties of vaccines in order to increase the efficiency of vaccination, and to develop new vaccine formulations that provide reliable protection of the body against infection. The aim of the paper was to analyse specific aspects of immune response development following immunisation with antiviral vaccines, and approaches to increasing their immunogenicity using adjuvants. It reviews different types of antiviral vaccines, as well as specific aspects of immune response development depending on the nature of a specific antigen. The paper substantiates the use of adjuvants to enhance and regulate the induced immune response. It analyses mechanisms that determine the stimulating effect of adjuvants and summarises data on the adjuvants used in the licensed vaccines for human use. The authors highlight the need for further research to increase the efficiency of vaccination and suggest that one of potential solutions is the use of adjuvants based on recombinant human cytokines.

Epilepsy affects more than 70 million people worldwide. From 30 to 40% of the patients are resistant to existing medication. This paper describes the current state of the treatment of epilepsy and proposes a future approach to preventative treatment at earlier stages of epileptogenesis. For preventative treatment biomarkers are needed that predict the development of epilepsy at its earlier stages. Pathological high frequency oscillations are the only acceptable biomarker of epileptogenesis. However, the main limitation of this biomarker is the necessity of implanting of recording electrodes. The search for noninvasive biomarkers of epileptogenesis is one of the hot topics in epilepsy research. There are two potentially interesting directions in this area: search for inflammatory biomarkers in the peripheral blood and analysis of different parameters of imaging methods. In this paper we present approaches for identification of potential epileptogenesis biomarkers by magnetic resonance imaging. Some of magnetic resonance imaging parameters correlate with the existence of pathological high frequency oscillations, may indirectly reflect ongoing inflammation process in the brain and be potential biomarkers of epileptogenesis.

Modern food culture and ecological environment lead to metabolic failures. Cardiovascular and digestive diseases, as well as obesity and diabetes, are becoming younger and younger. The present research featured the development of medical science by promoting the scientific platform of ‘preventive environment’. The priority of the platform is to assess the impact of individual bioactive nutrients on morbidity. The paper starts with a brief overview of the main directions in dietetics. Imbalanced nutrition leads to metabolic syndrome, which results in weight gain and cardiovascular diseases. Scientists associate metabolic disorders with hereditary predisposition, i.e. the presence of polymorphism of certain genes, and with the effect of environment and diet. Modern science knows few medical options for obesity treatment, which means that both pharmaceutical and nutraceutical methods of weight-reducing treatment remain understudied. Functional foods with a modified carbohydrate profile can improve the chemical composition of the diet. The study involved ranking of dairy products according to the obesity risk. The paper describes the effect of various biologically active substances of plant origin on metabolism of an obesity-affected organism. Thypakoids were found to affect satiety and fullness of the gastrointestinal tract through hormones of appetite. They also affect the microbial composition of the gastrointestinal tract without causing side effects, such as steatorrhea. The research results indicate that thylakoids are a new means of natural origin for the prevention and treatment of obesity. A single dose of black tea containing flavonoids was found to reduce peripheral blood flow in the upper and lower extremities after glucose loading, which was accompanied by a lower reaction to insulin. A mixture of curcumin and piperine can increase fat loss and suppress inflammation caused by high fat content. The paper also features the phenomenon of oxidative stress: antioxidant ingredients, such as vitamins, trace elements, and minor biologically active components are mandatory for a balanced diet. The analysis of scientific data made it possible to create a formula for a preventive product – an oat milk with a modified carbohydrate composition and various fruit, berry, and vegetable fillers.

Investigations have been carried out in respect of structural steel and titanium alloy fatigue at various cyclic loading frequencies and these investigations have made it possible to reveal regularities in changes of parameters pertaining to fatigue resistance and stability behaviour of the tested materials. A change in cyclic loading frequency affects duration of a single (during one cycle) stay of the material in the loaded state and it has an impact on its durability. In addition, with an increase in frequency of load cycles, deformation rate becomes higher, and stress build-up time is decreasing, while distortion of a crystal lattice is increasing due to reduction of time for development of a weakening process. This process is accompanied by an increase in intensity of grain crushing into fragments and blocks, and their disorientation. Tests on cyclic strength of the studied material samples have been carried out at various frequencies and at a room temperature according to the following loading schemes: cantilever cyclic transverse bending of a flat sample; cantilever bending with rotation of a cylindrical sample; axial tension on a pulsating cycle. Quantitative estimates of a fatigue resistance index in the form of slope tangent in a left branch of the fatigue curve to a cycle axis have been used in order to analyze and evaluate performance and stability of the tested materials. Methods for mathematical statistics have been applied to process the obtained results. Graphic dependences of fatigue curves have been plotted in logarithmic coordinates that allowed to obtain straightening of approximating lines for experimental data. The investigations have revealed that loading frequency has an ambiguous effect on fatigue resistance due to some differences in materials in respect of their reaction to changes in a load spectrum within different areas of the fatigue process, but at the same time it has been found that an increase in fatigue strength leads to a slope decrease in the fatigue curve regardless of a decrease or an increase in a load frequency. The paper proposes a new approach to assess a cyclic strength and durability of materials, and it comprises a system of parameters including a relative coefficient of limited endurance, a correlation coefficient and a slope tangent of the fatigue curve. Behavior dynamics for real machine parts and structures made of these alloys under operating conditions has been indicated in the paper.

The paper reviews of the data available in the literature on the clinical efficacy and safety of tofacitinib (TOFA) in the treatment of psoriatic arthritis (PsA). It considers the mechanism of action of TOFA, which is mainly in the selective inhibition of signal transmission due to its effect on the activity of JAK3 and/or JAK1, the enzymes that ensure the function of turning on and turning off the signals transmitted by cytokines. TOFA is noted to directly or indirectly act on a wide range of a number of molecules that play an important role in the pathogenesis of PsA.The paper analyzes the current data on the clinical efficacy of TOFA in treating PsA, which have been obtained in the 12-month OPAL Broaden study including patients with PsA and an inadequate response to synthetic disease-modifying anti-rheumatic drugs and in the 6-month OPAL Beyond study enrolling those with PsA and an inadequate response to tumor necrosis factor-α (TNF-α) inhibitors. It is noted that the results of these studies confirmed the efficacy of the drug in treating PsA not only according to the data of objective (medical) monitoring, but also to the subjective characteristics of pain, to the global assessment of disease activity, fatigue, as well as the mental and physical components of the SF-36 quality of life questionnaire.It is concluded that the current findings allow JAK inhibitors to be recommended as a new pathogenetically sound approach to treating PsA and suggest that TOFA has benefits in managing patients unresponsive to therapy with TNF-α inhibitors.

Today, within the context of harmonisation of requirements in the international pharmaceutical market, there is a trend towards development of common standards, including in the field of preclinical studies. The reliability and reproducibility of experimental data obtained in various laboratories using animals cannot be guaranteed unless the 3Rs principles are observed (the principles of humane experimental technique) to ensure the welfare of animals. The present paper analyses Russian and foreign recommendations on different administration routes and administered volumes as applied to mice, rats, guinea pigs, and rabbits – the most frequently used laboratory animals. The paper systematises literature data on oral/intragastric, subcutaneous, intramuscular, intravenous and intraperitoneal routes of administration. It assesses potential complications of each route of administration, and negative effects on both health and well-being of laboratory animals, as well as on the results of experiments. The paper also touches upon some anatomical and physiological characteristics of laboratory animals, potential opportunities for feed and water deprivation, ways of reducing pain in animals. The results of comparison of administered volumes helped to determine optimal recommended and maximum administered volumes.

Investigation of the influence of external fields on living systems is one of the most interesting and rapidly developing areas of modern biophysics. However, the mechanisms of such an impact are still not entirely clear. One approach to the study of this issue is associated with modeling the interaction of external fields with internal mobility of biological objects. In this paper, this approach is used to study the effect of external fields on the motion of local conformational distortions - kinks, in the DNA molecule. Realizing and taking into account that on the whole this task is closely connected with the problem of the mechanisms of regulation of vital processes of cells and cellular systems, we set the problem - to investigate the physical mechanisms regulating the motion of kinks and also to answer the question whether permanent and periodic fields can play the role of regulators of this movement. The paper considers the most general case, when constant and periodic fields are switching on and off asynchronously. Three variants of asynchronous switching on/off are studied in detail. In the first variant, the time intervals (or diapasons) of the actions of the constant and periodic fields do not overlap, in the second - overlap, and in the third - the intervals are putting in each other. The calculations were performed for the sequence of plasmid pTTQ18. The kink motion was modeled by the McLaughlin-Scott equation, and the coefficients of the equation were calculated in a quasi-homogeneous approximation. Numerical experiments showed that constant and periodic fields exert a significant influence on the character of the kink motion and regulate it. So the switching on of a constant field leads to a rapid increase of the kink velocity and to the establishment of a stationary velocity of motion, and the switching on of a periodic field leads to the steady oscillations of the kink with the frequency of the external periodic field. It is shown that the behavior of the kink depends on the mutual arrangement of the diapasons of the action of the external fields. As it turned out, events occurring in one of the two diapasons can affect the events in the other diapason, even when the diapasons are sufficiently far apart. It is shown that the overlapping of the diapasons of action of the constant and periodic fields leads to a significant increase in the path traversed by the kink to a complete stop. Maximal growth of the path is observed when one diapason is putting in each other. In conclusion, the question of how the obtained model results could be related to the most important task of biology - the problem of the mechanisms of regulation of the processes of vital activity of cells and cellular systems is discussed.

Relevance. In 2005 International Health Regulations, the plague, is on the list of dangerous infectious diseases that can cause emergency situations of interstate importance. Even single cases of human plague are considered as the basis for carrying out preventive measures. The paper presents the results of immunological monitoring conducted on the territory of the Republic of Kalmykia in order to assess the immunological efficacy and safety of the plague live vaccine The paper presents the results of immunological monitoring in the territory of the Kalmyk Republic over the individuals vaccinated against plague due to epidemiological reasons. Materials and methods. Studies of immunological efficacy of live plague vaccine were conducted alongside stepwise assessment of cellular and humoral components of innate and adaptive immunity in persons revaccinated against plague, using a complex of advanced informative tests. Results and conclusions. It is established that before the second revaccination all the surveyed persons retained expressed immune response by the mixed or cellular type, characterized by high level of spontaneous and induced production of Th1-associated cytokines. Activation of Th1 immune reaction was registered one month after the scheduled revaccination; immune response change-over from Th1 to Th2 type – after 6 months of observation, and retention of adaptive immunity by mixed type at the moderate level – in a year. Specific humoral immunity developed in 85% of the surveyed persons, but throughout the whole investigation the dynamics of antibody titers to plague microbe F1 individualized and did not coincide with cellular immunity indicators. Performed complex study has confirmed the relative safety of the live plague vaccine.

Despite the recent achievements in searching for the causes of monogenic human diseases, there is still a massive gap in understanding the molecular causes of phenotypic variability. At the moment, it is evident that the pathogenic genetic variant often acts together with the other genetic and non-genetic factors that can reduce or, on the contrary, aggravate the severity of the disease. Thus, to completely understand the disease, we shall consider the entire set of mechanisms leading to the resulting phenotype. This paper reviews the current state of the art in identifying genetic and non-genetic phenotype modifiers for rare monogenic cardiovascular diseases.

The paper presents an analysis of West Nile Fever incidence in the Russian Federation in 2020, summarizes the results and identifies problematic issues of the pathogen monitoring. Manifestations of West Nile Fever in 2020 were characterized by a low incidence rate (10 times lower than the average long-term value) with sporadic cases registration in the endemic areas of the Southern (9 cases) and Central (1 case) Federal Districts. A discrepancy between the morbidity structure (distribution by age, sex, social status) and the trends that have developed in Russia in recent years is shown. The analysis of officially recorded cases doesn’t characterize the epidemic process of West Nile fever in Russia during 2020-season as a whole. The generalized results of monitoring of the West Nile virus circulation in environmental objects in 2020 indicate a decrease in the effectiveness of its implementation and a low detectability of pathogen markers. A decrease in the volume of diagnostic studies for the active detection of patients with West Nile fever in the epidemic season (5.7 times lower compared to 2019), as well as serological screening of healthy population samples (1.6 times) has been established. The results of a molecular-genetic study of the pathogen showed that lineage 2 of the pathogen was circulating in the European part of Russia. The circulation of the lineage 4 of the virus in the enzootic cycle in the Republic of Kalmykia was found out. The genome sequences of 11 West Nile virus isolates allocated in 2019 and 2020 were obtained. Phylogenetic analysis revealed that all isolates allocated in the Volgograd Region and isolates from the Rostov and Astrakhan regions belong to the Volgograd clade of the lineage 2 of the West Nile virus. Based on the assessment of abiotic and biotic factors, possible local increases in the incidence of West Nile fever in 2021 in the regions of the Southern and North Caucasian Federal Districts and in the south of Western Siberia have been substantiated.

The aim of the work was to substantiate the forecast of the epidemiological and epizootiological situation in natural foci of plague in the Russian Federation, countries of the near and far abroad for the year of 2021. Characteristics of the distribution of Yersinia pestis strains of the main subspecies (subspecies pestis) of medieval and antique biovars, Caucasian (ssp. caucasica) and central Asian (ssp. central asiatica) subspecies by 45 natural foci of the CIS countries are presented in the paper. The persistence of a multidirectional trend in the dynamics of epizootic activity of natural foci of the CIS countries with the circulation of Y. pestis pestis strains of the medieval biovar of the 2.MED1 phylogenetic branch and the antique biovar of the 0.ANT5, 4.ANT phylogenetic branches in the current decade has been outlined. For the Russian Federation, the development of epizootics is predicted in the Gorno-Altai highland and Tuva mountain natural foci caused by the circulation of Y. pestis pestis strains of the antique biovar 4.ANT and Y. pestis of the Altai biovar of the Central Asian subspecies 0.PE4a in 2021. For the Republic of Kazakhstan, there is a high probability of preserving epizootic activity in the North Aral, Aral-Karakum, Balkhash, Mojynkum, Taukum desert and Ili intermountain natural foci with the circulation of Y. pestis pestis strains of the medieval biovar of the phylogenetic branch 2.MED1. For the Kyrgyz Republic, the forecast for the development of plague epizootics caused by Y. pestis pestis strains of the antique biovar 0.ANT5 phylogenetic branch in the Sarydzhaz and Upper Naryn high-mountain natural foci has been substantiated. A high epidemic risk of epizootic manifestations caused by highly virulent strains of Y. pestis pestis of antique biovars 0.ANT5, 4.ANT and medieval biovar 2.MED1 for the entire territory of the CIS countries is noted. The relevance of implementing forecasts of the epidemiological situation into practice, taking into account the molecular-genetic and epidemiological characteristics of Y. pestis strains circulating in areas of expected epizootic manifestations of plague, is highlighted.

Some scientific publications contain data suggesting the “return” or “resurgence” of pertussis. Prevention and elimination of pertussis can only be achieved by extensive immunisation of susceptible populations with a highly effective vaccine. The aim of the study was to characterise available whole-cell and acellular pertussis vaccines and to assess the feasibility of improving their quality, for instance, to demonstrate the role of lipooligosaccharide (LOS)—Bordetella pertussis cell wall antigen—in the induction of adaptive immunity. The paper summarises pathogenesis of pertussis, development of post-infection and post-vaccination immunity, and potential ways of improving pertussis vaccines. Improvement of quality of available vaccines can be achieved by reducing reactogenicity of whole-cell pertussis vaccines and enhancing immunogenic activity of acellular pertussis vaccines. One way to reduce reactogenicity of a whole-cell vaccine is to reduce the number of pertussis cells in the vaccine dose, provided that this does not affect the immunogenic activity of the product. Another possible way of reducing reactogenicity is to select vaccine strains based on the LOS endotoxin content. Improvement of acellular vaccine quality involves addressing many issues, such as identification and isolation of new protective antigens. Literature review demonstrated that LOS is a key antigen, because it is involved in the body’s immune response and ensures Th1 and Th17 cell responses to pertussis, which is crucial for protection from B. pertussis bacteria. Considering the evolutionary stability of the LOS structure, this antigen (i.e. its non-toxic oligosaccharide part) can be considered as a candidate for acellular pertussis vaccine.

One of the major public health challenges today is development of new vaccines and technologies to optimize the vaccination process. There is a growing scientific interest in vaccine adjuvants that enhance vaccine immunogenicity. At present, numerous studies are underway to develop COVID-19 vaccines, including inactivated and subunit vaccines which contain adjuvants for efficient induction of immune response and solid immunity. The aim of the study was to systematise literature related to the analysis of the structure, mechanisms of action and stimulating properties of vaccine adjuvants (synthetic oligodeoxynucleotides, virosomes, polyoxidonium, sovidone), as well as to summarise data on the effects of adjuvants used in SARS-CoV, MERS-CoV, and SARS-CoV-2 vaccine development studies. The paper analyses the prospects for enhancing the stimulating effect of the adjuvants when used in combination with compounds having a different mechanism of action. It also analyses the results of studies of adjuvanted vaccines against SARS-CoV and MERS-CoV, which may be useful when selecting adjuvants with optimal efficacy and safety profiles to be used in SARS-CoV-2 vaccines under development. It was concluded that understanding of the mechanisms of action of adjuvants that mediate their stimulating effect on the body’s immune system will contribute to safe and effective use of adjuvants to enhance the immunogenicity of both authorised and new vaccines.

The aim of the study was to develop a unified approach to a comprehensive risk assessment of the anthrax situation deterioration based on the ranking of territories by epidemiologically significant factors.Materials and methods. For a comprehensive risk assessment of the situation complication, the statistical principles of ranking of the estimated indicators were used. These indicators comprise the presence and activity of soil foci of anthrax, the prevailing soil types and their main characteristics, as well as social risk factors associated with the peculiarities of animal husbandry and the possibility of infection of the population. The proposed assessment method has been tested on a national scale, and its content and results are described in this paper by the example of the Volga Federal District. The materials of the study were federal and regional cadastres of stationary hazardous as regards anthrax areas, an atlas and maps of soils, data of statistical accounting and reporting of Federal Service for Veterinary and Phytosanitary Surveillance, Federal Service for State Registration, Cadastre and Cartography and Rospotrebnadzor.Results and discussion. It has been established that in all constituent entities of the district there are potential risks of the situation deterioration that are associated with the presence of soil foci. In terms of the sum of ranks, the greatest potential disadvantage is noted in a number of republics and regions of the Volga Region. At the same time, the real danger is mainly due to social factors, which include the characteristics of animal husbandry, as well as the degree of susceptibility of the population. The maximum risks are currently identified in the territories of the republics of Bashkortostan and Tatarstan, as well as in the Saratov Region. The study is aimed at improving the efficiency of anthrax epidemiological surveillance in the Russian Federation, and the proposed methodology can be used at all levels of surveillance.

The paper attempts to analyze the problems of adjusting the educational process in the EurAsEC countries that have arisen in recent decades in case of unforeseen circumstances. At the end of the 20th century, the ideas of globalization of all areas of the world community's activity led in the field of higher education to a thirst for immediate changes. What prompted the concern of the leading universities in Europe, which train highly qualified for the real sectors of the economy? An analysis of the current situation showed that the realities existing at that time pushed people to action, since analysts of higher education have repeatedly noticed that in the field of many areas of fundamental research, Europe is significantly inferior to the United States. Also noteworthy is the identity of the Nobel laureates. Independent commentators, beyond any emotion, pointed out that the United States has always invested significant amounts of money in the development of science. These problems gave rise to the Bologna process of reforming higher education in Europe. In this regard, the problems are considered and the prospects for the creation and development of a single educational space on the territory of the member states of the Eurasian Economic Union, considered by the authors as an important component of economic integration in the post-Soviet space, are identified. From the standpoint of taking into account foreign experience, as well as existing elements of educational integration within the framework of such associations. as EurAsEC, SCO, CIS, the main directions of integration interaction in the field of education of the EAEU countries are highlighted. The authors made attempts to formulate ways out of the current situation in the Eurasian educational space, especially in cases of unforeseen environmental conditions, such as a pandemic. Although in the educational space under consideration, the state of affairs with the organization, and in particular with funding, research and science is worse, this should not lead to ignoring the interests of both the students themselves and educational organizations in general. Insufficient funding is aggravated by many other factors, which together lead to the conclusion that EurAsia needs innovations designed to “modernize” the structure of education.

Combination of neoadjuvant chemoradiotherapy with subsequent total mesorectum excision and 6-months of adjuvant chemotherapy remains a standard approach to treatment of locally advanced rectal cancer (T3 or T4 and / or N1–3; M0) for more than 15 years, which is reflected in practical guidelines of most leading oncological societies. However, recent data suggests possibilities of more individualized treatment conceptions with a potential of further improvement of long-term therapy outcomes and patient’s quality of life. In this paper we present review of results of clinical trials which investigated new approaches to treatment of locally advanced rectal cancer.

One of the directions of apple breeding in the Middle Urals is the development of varieties with a long-term storability. The ability of apples to maintain their consumer qualities for a long period is one of the most important indicators of the variety. A significant role in the storage of apples is played by the amount of ethylene produced in them. The paper presents the results of identification of genes involved in the control of ethylene biosynthesis in apple varieties selected by the Sverdlovsk horticultural breeding station. A total of 21 apple varieties were analyzed. The main objective of the study was to detect Md-ACO1-1 and Md-ACS1-2 alleles in the homozygous state. The combination of these alleles in one genotype reduces the production of ethylene in fruits, which contributes to their long-term storability. The analysis showed the availability of polymorphism in the two studied genes. The Md-ACO1 gene is characterized by the availability of two alleles in most varieties. The homozygous Md-ACO1-1 allele was identified in the Isetskoe pozdnee variety. Analysis of the Md-ACS1 gene revealed the predominance of the Md-ACS1-1 allele form. The Md-ACS1-2 allelic form was observed only in heterozygous samples. No combination of Md-ACO1-1 and Md-ACS1-2 alleles was found in the homozygous state. However, heterozygous forms are also of interest for breeding. They can serve as a source of a character of reduced ethylene biosynthesis when creating varieties with a long-term storability. Such varieties are Sokol yasnyy, Aksena, Rozovatoe zimnee, Sverdlovchanin, Isetskoe pozdnee, Blagaya vest'. The comparison of fruit storage periods and the genotype of the variety has been made. Allelesassociated with a reduced level of ethylene biosynthesis are typical both for the varieties with low and high storability.

Idiopathic normal pressure hydrocephalus (NPH) is cerebral ventriculomegaly characterized by a wide range of controversial issues related to the prevalence of the disease, the mechanisms of its development, and nosological independence. Developing in old age, NTH is often concurrent with other neurodegenerative or cerebrovascular diseases, posing certain diagnostic difficulties. The paper describes a clinical case of a patient initially diagnosed with NTH, followed by amyloid angiopathy signs detected during magnetic resonance imaging after bypass surgery. It discusses the diagnostic features of NTH and amyloid angiopathy and the possible common mechanisms of these diseases.

Colistin and polymyxin B are the “last reserve” antimicrobials for the treatment of extensively drug-resistant Gram-negative bacterial infections. The rapidly increasing prevalence of polymyxin resistance mediated by the mcr gene localized on plasmid DNA currently poses a high epidemiological threat. In order to control a distribution of mcr genes, it is necessary to develop highly accurate, highly sensitive and easy-to-use diagnostic tools. This paper provides a review of the most relevant studies on the molecular epidemiology as well as current approaches to microbiological and molecular detection of mcr group genes.

Axial skeletal injury is observed in 25–70% of patients with psoriatic arthritis (PsA). Spondylitis frequently occurs subclinically, which leads to serious structural and functional disorders over time. An update shows that axial skeleton involvement in PsA is characterized by a more severe clinical course: these patients are observed to have a greater severity of peripheral arthritis, enthesitis, and dactylitis, skin and nail psoriasis, a higher CRP level, and worse functional status. In addition, the disease is more severe according to the patients' subjective assessment, as evidenced by questionnaires. Synthetic disease-modifying antirheumatic drugs used to treat peripheral PsA are not recommended for axial injury. When nonsteroidal anti-inflammatory drugs are ineffective, biological drugs (tumor necrosis factor-α inhibitors or interleukin-17A (IL-17A) inhibitors) should be prescribed immediately to patients with psoriatic spondylitis. The paper describes two clinical cases demonstrating the successful use of the IL-17A inhibitor secukinumab (SEC) in patients with axial PsA (axPsA). Given the positive experience with SEC in real clinical practice, it seems reasonable to prescribe it to patients at earlier stages of axPsA.

Psoriatic arthritis (PsA) is a chronic immune-mediated disease from a group of spondyloarthritis, which is characterized by damage to the musculoskeletal system with a wide range of different clinical manifestations and is usually associated with psoriasis. Activation of the interleukin (IL) 23/IL17 axis plays a key role in the pathogenesis of PsA and psoriasis. When non-steroidal and synthetic disease-modifying antirheumatic drugs are insufficiently effective, biological drugs are recommended. In recent years, there have been considerable advances in PsA treatment with tumor necrosis factor-α (IFN-α) inhibitors and IL-12/23 inhibitors. However, in some cases, this therapy fails to provide the desired effect and a search for new treatments for PsA seems to be an urgent task. The paper desctibes a clinical case demonstrating the efficacy of the IL17A inhibitor ixekizumab in a patient with high PsA activity and recurrent uveitis in both eyes. Ixekizumab therapy resulted in positive changes as the reduced severity of articular syndrome and psoriasis and normalization of acute phase parameters. Assessing the activity of PsA over time when using ixekizumab during a year showed an average decrease in ESR from 72 to 19 mm/h, in CRP from 162.1 to 0 mg/L, BSA from 51 to 0.25%, PASI from 43. 6 to 0, DAPSA from 78.2 to 2, ASDAS-SRB from 5.11 to 1.12, BASDAI from 4.85 to 1, BASFI from 5.3 to 0.7, BASMI from 5.0 to 2.6, MASES from 6 to 0, LEI from 2 to 0, SPARCC from 6 to 0, and NAPSI from 28 to 8. Thus, this clinical case is an example of successful treatment with the IL17 inhibitor ixekizumab for PsA with recurrent uveitis in the patient who has previously received three drugs from the TNFα group without any effect.

Gastrointestinal (GI) manifestations, such as abdominal pain, nausea, vomiting, and diarrhea, are common autoinflammatory disease (AID) symptoms. The abdominal symptomatology reflecting serositis is one of the most important classification and diagnostic criteria for the classic monogenic AID (MAID) – familial Mediterranean fever (FMF). Failure to timely diagnose FMF frequently leads to unjustified surgical interventions. Other periodic fevers may also present as abdominal symptoms; however, the latter are outside their diagnostic features. These diseases include, first of all, tumor necrosis factor receptor-associated periodic syndrome (TRAPS). Interleukin 1 (IL1) inhibitors serve as the major targeted drugs for the treatment of TRAPS. Russia has registered the IL1 inhibitor canakinumab that prevents the development of organ damages, including those in the GI tract. The paper describes a clinical case of the classic manifestations of TRAPS (fever, rash, periorbital edema, arthritis, and elevated levels of acutephase inflammatory markers) concurrent with severe abdominalgia during attacks and with the development of severe peritoneal adhesions, which led to bowel perforation and emergency surgical intervention. The prolonged persistence of inflammatory attacks before the initiation of therapy, as well as violation of the IL1 inhibitor administration regimen facilitated the development of an urgent exacerbation. Thus, TRAPS should be included in the differential diagnostic circle for patients with severe gastrointestinal manifestations characterized by an attack-like course. These patients need timely prescription of targeted therapy, strict adherence to the dosing and intervals between drug administrations, and careful monitoring to prevent serious complications with the visceral organs, including the gastrointestinal tract, and their immediate correction.

Introduction. The market of dietary supplements is actively developing due to the general deterioration of public health and the fact degenerative diseases affect younger population. Functional foods and biologically active additives can prevent and treat various pathological processes. Unlike pharmaceuticals, they provoke neither addiction nor allergic reactions and do not accumulate in the human body. Therefore, consumer interest in dietary supplements is a relevant research issue. The research objective was to conduct marketing research in order to study the current state of the market of dietary supplements. Study objects and methods. This research was based on a systematic approach and abstract-logical, statistical-economic, and graphical methods. Results and discussion. The marketing research made it possible to classify biologically active additives on the pharmaceutical market of Kemerovo (Russia). The market included 45 organizations and 15 brands. A sociological survey of 100 respondents revealed that the younger participants were familiar with the concept of dietary supplements. All respondents monitored the state of their health; however, their attitude to functional food additives was quite neutral. They used supplements for general health promotion and to solve particular problems, e.g. acne. On average, they took one course of administration per year based on medical prescriptions and recommendations of close relatives. The survey identified the most popular brands and producers of dietary supplements in Kemerovo. Most supplements were purchased in pharmacies and specialized stores. Packaging appeared to be the least important factor that affected the consumer behavior. The paper introduces some recommendations on attractive packaging. Conclusion. Biologically active additives replenish the necessary amount of nutrients to maintain health, which makes them a popular product on Kemerovo market. Further study is required, despite the obvious benefits of functional additives.

Anti-glutamic acid decarboxylase (GAD) antibody-associated ataxia is a rarely diagnosed but potentially curable disease associated with autoimmune damage to and death of Purkinje cells in the cerebellar cortex. In Russia, the authors have provided for the first time descriptions of three own observations of this disease, which had a number of clinical features, such as slow progression, mild ataxia, stroke-like episodes with stem symptoms, concomitant gluten sensitivity, onset of ataxia after hepatitis C with cerebellar hemiataxia and hemiatrophy. In the all patients, the diagnosis was verified based on the determination of high anti-GAD antibody titers in serum and cerebrospinal fluid. All the patients lacked intrathecal synthesis of oligoclonal antibodies; protein levels and cytosis were normal. Pulse therapy with methylprednisolone at a total dose of 3–5 g led to a slight reduction in ataxia in one case (a female patient with subacute onset of the disease); the treatment was ineffective in two other cases (patients with a primary chronic course). The paper analyzes the literature covering the pathogenesis and clinical presentations of this type of ataxia, and difficulties in its diagnosis and treatment.

The paper proposes to improve the quality of butter with flavoring components during storage through the use of prescription ingredients containing natural antioxidants. The composition of the flavor component includes: tomato flakes; salt; olives, basil, onions, oregano, garlic, sugar, sage. According to the results of the scoring of the samples, the optimal dose of adding a flavoring component of 1.0% was established. Taking into account the recommended standards according to GOST 32899, the salt in the composition of the flavor component contains an insufficient amount, so it was added to the oil in addition to a total content of 1% in the product. In tomato flakes, which make up more than half of the entire mixture of the flavoring component, a high content of beta-carotene, vitamin C, PP, B1, B2, B6 is noted. Also, a high content of vitamin E in olives, basil, oregano; vitamin C - in sage; vitamin PP - in basil, oregano, sage; Vitamin B1 - in oregano, garlic, sage, Vitamin B2 - in basil, oregano and sage, B6 - in basil, onion, oregano, garlic, sage. Amperometric method found an indicator of the antioxidant activity of the taste component of 0.382 mg / g The resistance of fat oil with flavoring components was determined. The sample passed the test for 8 hours, no spoilage of fat was noted. Microscopic studies of oil samples were carried out using a Altami BIO digital microscope at a magnification of 200 times. The microstructure of butter with flavoring components is characterized as granular, plasma drops are evenly distributed in the sample. Some consistency indicators are identified. A good cut-through consistency was established and good heat resistance of the oil with taste components. Organoleptic characteristics of butter with flavoring components: taste and smell creamy, salty, piquant, aroma and taste of the introduced component; plastic consistency with inclusions of the added component, glossy surface; color light cream with grains of the introduced component. The main physicochemical parameters of butter with flavoring components were established experimentally: mass fraction of fat 62.0%; mass fraction of moisture 32.5%; salt - 1%. Microbiological indicators comply with regulatory requirements. The addition of a flavoring component to butter contributes to the formation of its dense structure, stable storage of the fat fraction, and uniform distribution of the oil plasma. The product has improved quality indicators.

All current challenges and concerns associated with rheumatoid arthritis (RA) in the elderly are analyzed from the point of view of a practicing rheumatologist, including issues of terminology and diagnostics, the need to develop classification criteria for RA presenting at old age. This paper also discusses RA management in the elderly during the coronavirus disease 2019 (COVID-19) pandemic. A multicenter international study, initiated by the League of Eurasian Rheumatologists, can provide necessary insight to develop unified recommendations for RAP.

Inflammation and coagulation are key basic mechanism of protection against all potentially pathogenic mechanical and biological factors targeting human organism from inner and outer environment. On the other hand, uncontrolled inflammation results in hypercoagulation, inhibition of anticoagulation and alteration of mechanisms responsible for resolution of inflammation, while production of “procoagulant” mediators (thrombin, tissue factor and others), activation of platelets and of vascular endothelial cells maintains inflammation. All factors taken together serve as the basis for a pathological process called thromboinflammation or immunothrombosis. Currently thromboinflammation is considered in the broad sense as a universal pathogenetic mechanism of numerous widespread acute and chronic conditions, including immune-mediated (autoimmune) inflammatory rheumatic diseases, oftentimes complicated by severe irreversible damage to vital organs. Thromboinflammation gained specific attention during СОVID-19 (coronavirus disease 2019) pandemic, caused by SARS-Cov-2 (severe acute respiratory syndrome Coronavirus-2). COVID-19 is considered currently as systemic thromboinflammation syndrome, manifesting via generalized thrombosis of arterial and venous macro- and microvasculature, termed as COVID-19-coagulopathy. The paper discusses common pathogenetic coagulopathy mechanisms in COVID-19 and immune-mediated (autoimmune) inflammatory rheumatic diseases (IMRDs), associated with overproduction of antiphospholipid antibodies, activation of the complement system, and dis-regulated synthesis of proinflammatory cytokines, etc. Delineating the autoimmune subtype of thromboinflammation, identification of genetic (i.e., genes encoding the complement system and others) and molecular-biologic biomarkers associated with higher occurrence of COVID-19-coagulopathy are the most relevant undertakings for the current practice. Gaining insights into mechanisms of thromboinflammation and converting them into potential pharmacotherapies of IMDs would facilitate and accelerate the drafting of effective therapeutic strategies for COVID-19.

The paper highlights the relationship between HLA-B27-associated uveitis and spondyloarthritis (SpA). It presents the genetic aspects of inflammation of the eyes and musculoskeletal system, the role of the HLA-B27 histocompatibility antigen, and the contribution of other genes to the development of uveitis and spondylitis. The authors characterize the general pathogenetic mechanisms of the development of these diseases: the importance of factors of innate immunity, proinflammatory cytokines in the initiation of inflammation of the eyes and joints. The detection rate of SpA is analyzed in various forms of uveitis; the predictors of SpA development are identified in the patients. An algorithm is presented, which makes it possible to timely diagnose SpA in the presence of acute anterior uveitis. HLA-B27, inflammation in the ocular anterior chamber, unilateral alternating eye lesions, an acute recurrent course, and uveitis onset at the age of less than 30 years are singled out as the most significant signs associated with SpA in patients with uveitis. The features of the course and the frequency of complications in uveitis with and without SpA are compared. It is shown that exacerbations of uveitis and associated complications occur statistically significantly more frequently in SpA. There is evidence for the need for a close interaction between ophthalmologists and rheumatologists in the management of patients with uveitis.

Neurotoxic effects are one of the common reasons for discontinuation of preclinical and/or clinical studies. Preclinical evaluation of neurotoxic effects is complicated due to a wide range of manifestations and degrees of severity. Current experimental approaches to neurotoxicity assessment are cumbersome, laborious and not adapted enough for preclinical studies in the early stages of drug development. The aim of the study was to review existing approaches to experimental assessment of neurotoxic potential of new drugs and to discuss the need for and feasibility of developing and using integrated rapid neurotoxicity tests for early assessment of a pharmacological project’s potential. The authors reviewed scientific literature and guidance documents and analysed current approaches to chemical compound neurotoxicity assessment in laboratory animals. The paper analyses the main issues of neurotoxicity assessment for new drugs and compares Irwin tests with the functional observation battery. It analyses issues related to assessment of drugs’ effects on the development and maturation of central nervous system functions at pre- and postnatal stages. It was determined that the current practice is not sufficient for assessment of potential adverse effects on cognitive functions. The authors assessed factors affecting cognitive functions of rodents during studies. The “Acute suppression of the exploratory and orientation response” and “Extrapolation escape task” tests were proposed for validation as potential rapid tests for detection of an array of organic and functional neurotoxic disorders at early stages of preclinical studies.

The paper considers the problems of the early glaucoma diagnosis before the development of the marked glaucomatous optic neuropathy. Special attention is paid to the methods of computer perimetry, which are important in diagnosing the presence or progression of glaucoma.Purpose. To create the computer program “perimetric calculator” that performs mutual recalculation of perimeter data of HFA and HEP without additional perimetric studies, as well as calculation of diagnostic information content of perimeter parameters with different “cut-off points” of HFA and HEP parameters.Patients and methods. 56 patients (85 eyes), including 16 men and 40 women aged 55 to 84 years (mean age 64.9 ± 6.4 years). All patients were divided into 2 groups: group I — 23 healthy subjects (40 eyes) without any signs of glaucoma; group II — 33 patients (45 eyes) diagnosed with the initial stage of primary open-angle glaucoma.Results and discussion. The study revealed the comparability of the standard automated perimetry (HFA) results and Heidelberg edge perimetry (HEP), determined the most informative diagnostic criterion (MD/HEP). According to the obtained results, a computer program was created, it included two modules: the first — diagnostic information content of perimeter parameters with different “cut-off points”, the second-mutual recalculation of HFA and HEP parameters.Conclusions. This computer program allows calculating the main indices of diagnostic information content of the perimeter parameters (sensitivity and specificity) at different “cut-off points”, gives the results of calculating the values of sensitivity, specificity and accuracy for at least 150 threshold values, allows performing mutual recalculation of the parameters of the standard automated perimeter (HFA) and Heidelberg perimeter (HEP).

The main target for COVID-19 is the lung with the development of acute respiratory failure. But the virus also displays tropism to the central nervous, muscle, and immune systems. The paper gives the data available in the literature on nervous system damage and the characteristics of clinical and magnetic resonance imaging manifestations of brain damage in COVID-19. Among the neurological symptoms of COVID-19, there may be stroke, encephalitis, and neuropathy. An account is given of the features of multiple sclerosis patient management during the COVID-19 pandemic depending on the risk of developing coronavirus infection.

Exudative otitis media in childhood is most often associated with chronic inflammation in the nasopharyngeal area, with immediate participation of phagocytic cells. Our paper presents the data on evaluation of clinical and immunological efficacy of intranasal Imunofan use included into complex therapy of exudative otitis media. Dynamic observation (before treatment, 1 and 3 months after treatment) of these parameters included regular evaluation of the neutrophil and monocyte amounts in peripheral blood and in smear imprints from nasal mucosa, determination of myeloperoxidase activity in circulating neutrophils, and the content of interleukin IL-8 and IL-18 in the nasal washouts. The clinical status was assessed using a scoring system, which subjectively reflected the state of the nasopharynx and auditory function. Fourty-three children aged from 3 to 7 years with exudative otitis media associated with chronic adenoiditis were examined. Patients of the first group (22 children) were treated using only conventional approaches (basic therapy). The patients from the second group (21 children) received Imunofan in addition to the basic therapy. The control group consisted of 16 relatively healthy children. Before treatment of the children with exudative otitis media, an increase in the relative content of monocytes in their blood, a decreased activity of myeloperoxidase and lower concentration of IL-8 and IL-18 in the nasal wash was observed in comparison with healthy controls. No differences in severity of clinical symptoms were revealed between the groups of patients. Baseline therapy was not accompanied by positive dynamics in the clinical pattern of the disease. Relative monocytosis and reduced activity of neutrophilic myeloperoxidase persisted in peripheral blood; the concentration of IL-8 and IL-18 in the nasal washings remained low. Following intranasal use of Imunofan, the number of circulating monocytes was restored by the third month from the start of treatment, there was an increased activity of myeloperoxidase registered in blood neutrophils, as well as higher IL-8 and IL-18 concentrations in the nasal washings. Normalization of the phagocytos-related parameters, according to this scoring, was associated with clinical remission of the disease. The revealed relationships between clinical data and the results obtained in the course of laboratory research suggest a positive effect of Imunofan as an agent that may enhance effectiveness of conventional basic therapy of otitis media in children.

Dangerous viral infectious diseases pose a serious threat to human life and health, as their uncontrolled spread leads to the development of major outbreaks and epidemics. Rapid and accurate detection of the pathogen is an essential component of the fight against infectious diseases. This review is devoted to loop-mediated isothermal amplification (LAMP), which is one of the simplest and most reliable methods of molecular-genetic research that meets modern requirements. The simplicity of the analysis and registration of the obtained results, which is necessary under conditions with minimal laboratory capacities, makes it possible to consider this type of diagnostic technology as the most promising, which allows us to identify genetic markers (DNA or RNA) of pathogens of dangerous infectious diseases in the shortest possible time. Objective of the review is to summarize and systematize the data available to date on the use of LAMP for detecting RNA of dangerous infectious diseases caused by the Ebola,Marburg and Lassa viruses. The paper discusses the basic principles of the loop isothermal amplification reaction, the components that make up the reaction mixture and are used for the analysis, as well as methods for detecting the results obtained. When studying the information available in the literature sources about the advantages and disadvantages of LAMP, it is shown that in many cases, isothermal amplification is not inferior in sensitivity and specificity to the main molecular-genetic diagnostic methods currently used. Modifications that can be used for accelerated diagnostics of RNA-containing viruses are also considered.

The authors focus on the controversial situation of a large number of theoretical and practical works on psychological aspects of education, the high importance of hardiness for productive life of individuals in modern society and the absence of works exploring how parents influence the formation of hardiness in their children. The paper presents results of the study of the relationship between hardiness in young male and female students and the features of their subjective childhood image of family and current attitudes of their parents. The sample of the study was 119 students (43 males and 76 females).Methodological support of the research included the following: Hardiness test (Hardiness Survey by S. Muddi, adapted by D.A. Leontiev); two scales of the BIV questionnaire (Biographisches Inventar zur Diagnose von Verhaltenstörungen) revealing the nature of childhood image of family; the Operationalized Psychodynamic Diagnostics technique assessing the key aspects of relationships. The results of the study showed that the level of hardiness in the subjects is closely related to the nature of their childhood images of family: the more positive the image is, the higher the hardiness. The relationship between hardiness and the current attitude of parents has both common and gender-specific trends. Parental care and high interest in preserving the child’s attachment impede the manifestation of hardiness in the young people. The gender specifics of those aspects of parental attitude that promote hardiness does not coincide with the generally accepted patterns.

The results of the analysis of epidemiological and epizootiological situation on anthrax in the Russian Federation and in the world in 2019 are presented in the paper. The forecast of morbidity rates in the Russian Federation for 2020 is made. In 2019, five cases of cutaneous anthrax were registered in the Russian Federation in two regions of the North Caucasian Federal District – Republic of Dagestan (4) and Stavropol Territory (1), which is two cases plus as compared to 2018. Outbreaks of infection among livestock animals and humans were recorded in such neighboring countries as Azerbaijan, Armenia, Belarus, Kazakhstan, Kyrgyzstan and Tajikistan. The unfavorable epizootiological situation on anthrax was observed almost everywhere. The highest incidence rates among wild and livestock animals were found in a number of countries in Asia and Africa. Anthrax among people was registered mainly in African countries, infection occurred mainly by alimentary route, less often – through contact with carcasses, meat of animals. Anthrax morbidity rates among animals and humans in the Russian Federation in 2020 will be largely determined by the completeness of registration and coverage with specific immunization of livestock animals and groups of people under professional risk of infection and, if measures are fully implemented, incidence will not exceed single cases.

Hereditary angioedema (HAE) is a genetically caused orphan disease with a high risk of developing life-threatening attacks, thus requiring availability for up-to-date information on this problem for the doctors of any specialties. A limited number of observations determine the value of the analysis for each clinical case. Many facets of clinical manifestations, a list of predisposing and triggering factors, as well as limitations of some diagnostic and therapeutic algorithms, require the development of individual management schemes under distinct clinical situations. In this paper, we present the unique clinical cases with certain limitations, describing unexpected onset of the disease in the course of pregnancy, management aspects during delivery and post-delivery periods in a women with a previously confirmed HAE diagnosis. Adapted diagnostic algorithms of postnatal diagnostic verification are presented for children with burdened genetic history. We express some assumptions about involvement of a multidisciplinary team of specialists, personalized approach to building a management plan with an “online” correction depending on observation stage of НАЕ patient.

Continuing trends of antimicrobial resistance growth require a set of countermeasures, of which antimicrobial resistance surveillance at the global, national, and local levels plays one of the most important roles. Local surveillance systems are the most significant in controlling the changes in susceptibility of microorganisms in specific settings and contribute to the necessary activities, including prevention of epidemics. This paper presents basic principles and recommendations for handling antimicrobial resistance surveillance data, provides examples of table completion and metadata quick guide. A focus is made on specific issues and problems associated with surveillance data handling and the ways to resolve those problems are proposed.

The growing interest in metabolite circulating in the blood is associated with the accumulation of factual material on the involvement of low-molecular compounds in the development of a number of serious diseases. This review reveals the effect of a whole class of chemical compounds― tryptophan metabolites― on various pathological processes. The following keywords were used to find papers published in the PubMed database for the last 10 years: names of natural indole compounds, methods for their detection, nosology of diseases and critical ill patients. The data is presented in sections, which provide data on the study of tryptophan metabolites in a variety of groups of diseases, such as cancer, cardiovascular disease, kidney disease, bowel, mental disorders, atherosclerosis, etc. Particular attention is paid to the role of indole compounds that enter the systemic circulation as a result of microbial biotransformation of tryptophan, serotonin and other indole metabolites, which can be attributed to the "common metabolites" of humans and microbiota. The most interesting clinical studies are summarized in summary tables and figures. A number of indole metabolites are considered as potential biomarkers. The authors of the review substantiate the metabolomic approach to the study of a number of oncological, septic, mental and other intractable diseases, which opens up new possibilities of influence on the pathological process by targeted regulation in the metabolome/microbiome system.

The paper discusses the issues of morphofunctional variability of sapronoses pathogens in stressful environment. In the current century, sapronoses infections attract increasing attention. Under unfavorable environmental conditions the pathogens use the strategy for the formation of resting (stable) states, that is: viable but non-culturable cell formes and persistent bacteria, which are characterized by reduced metabolism and changes in the morphology and physiology of the microorganisms, termination of replication. Possibility of sapronoses pathogens survival in interepidemic period and antibiotic resistance formation, which play an important role in chronic infections, are associated with the formation of persistent forms of bacteria. The literature extensively discusses mechanisms and conditions of the pathogenic bacteria stable states formation and their pathogenetic contribution to infectious pathology, whereas ultrastructural organization and morphological variability of persistent cell forms, as well as their differentiation, causing the pathogens population heterogeneity, is still insufficiently illuminated. Based on the analysis of current data and their own experience, the authors evaluate the morphological and functional changes of bacteria stable cellular forms and their role in sapronoses pathogens adaptation strategies.

According to world statistics, 15 % of married couples do not reach pregnancy within one year and seek medical help. At the same time, an important component of the complex problem of infertility, in addition to not getting pregnant, are also pregnancy losses. According to modern ideas, one of the reasons for termination of pregnancy is sperm DNA fragmentation (SDF). According to the European Association of Urology guidelines on male infertility, SDF reduces the chances of natural conception and increases the risk of pregnancy loss. In the European Society of Human Reproduction and Embryology guideline on the management of recurrent pregnancy loss, the definition of SDF is recommended in the algorithm for examining a couple after a single episode of miscarriage. The causes, mechanisms and approaches to correcting increased SDF are the subject of active research; according to PubMed, more than 2,500 papers have been published on this problem to date. Given the huge amount of factual material, the purpose of this review is to highlight the key points of etiology, pathogenesis and approaches to the correction of increased levels of SDF

The review provides the data on the epidemic condition of tularemia foci in countries neighboring Russia and ongoing preventive measures in these territories. The highest tularemia incidence in the stated countries and in the world as a whole is observed in Finland. In 2019, 42 cases of human infection with tularemia pathogen were recorded in the territory of the Russian Federation, 85 % of which occur in three Federal Districts: North-Western, Central, and Siberian. Epizootic manifestations of infection of varying degrees of intensity were detected in 51 entities of the Federation. Against this background, sporadic cases of tularemia are registered in 17 regions of the country. The most severe epidemic complications continue in Karelia – 9 patients. Seventeen Francisella tularensis cultures were isolated from environmental objects in the Tver, Yaroslavl, Vologda Regions, in the Altai Territory and the Altai Republic. The paper gives an opinion on the regions in which epidemic complications of tularemia are most likely to occur in 2020.

The annual Interregional research and practical conference “Epilepsy and Paroxysmal Conditions as an Interdisciplinary Problem” was held in Moscow 19/02/2020, bringing together neurologists and epileptologists from Russia. The event was dedicated to the memory of Gagik N. Avakyan, who was President of Russian League Against Epilepsy (RLAE) for many years. The paper contains key messages of the plenary session.

Objective of the study was to review the current normative-methodological documentation on the matters of safe handling of pathogenic biological agents (PBA) of the III–IV pathogenicity groups. Materials and methods. We used analytical method for the study. We carried out comparative analysis of the provisions contained in the current regulations approved at different times for different agencies on the matters of air filtering system equipping, usage of microbiological safety cabinets, ensuring hand washing station provision for laboratories, inspection of disinfectants entering a lab, and waste decontamination procedures. Results and discussion. We have considered the provisions of the current documentation that require further refinement and clarification for the future editions of sanitary regulations. Two aspects draw increasing attention: the problem of regulating the inlet and exhaust ventilation system setup in the laboratories of microbiological specialization for work with PBA and the need to devise a consistent coordinated regulatory framework. Examples provided in the paper demonstrate the necessity of adhering to the integrated unified approach to the requirements for biosafety provision in the documents of various agencies; clear wording; harmonized system of normative and technical specifications for laboratory equipment, stating the basic characteristics of microbiological safety cabinets and ventilation systems. The documents should be in compliance with the requirements of various agencies. The maintenance of technical-engineering systems should be performed by the specialists with an appropriate qualification on a regular basis.

The paper presents data on the pathogenesis of systemic lupus erythematosus (SLE), and depicts various molecular mechanisms for the development of SLE and lupus-like syndromes. It describes groups of diseases, such as apoptotic defects; NETosis; interferonopathies; complement deficiency; autotolerance disorders associated with mutations in the RAG1/RAG2 genes; hereditary metabolic diseases (prolidase deficiency, deficiency of adenosine deaminase 2; lysinuric protein intolerance; and α-mannosidase deficiency). The table summarizes clinical data on most of the known lupus-like syndromes and their molecular mechanisms.The pathogenesis of many forms of monogenic lupus-like diseases is being studied. The main sign suggesting in favor of the possible monogenic disease in a patient with SLE is its onset in infancy, especially in males. Attention should be also paid to a compromised family history, including to the marriage between close relatives, the resistance of disease to standard therapy, as well as atypical symptoms.