Background. The vaccine preventable diseases outbreaks have become more frequent in recent decades and the lack of global vaccine awareness has been increasing and deteriorating vaccine compliance.
   The aim. To assess the attitude towards vaccination of parents from India and Russia.
   Methods. 1620 parents from Russia (Irkutsk city) and 214 parents from India (Kerala state) took part in the international cross-sectional multicenter study via survey method.
   Results. Parents from both countries showed good adherence to vaccination, only 1 % of Indians and 2 % of Russians did not vaccinate their children. More than 90 % of Russians took information from pediatricians compared with other sources with a prevalence of pediatricians working in the public health system 91.7 % (95 % CI: 90.2–92.9), whereas only 50 % of Indians were informed about vaccination from pediatricians (p < 0.0001). The main source of vaccine information for Indian parents was Internet (52.8 %; 95 % CI: 46.1–59.3) and mass-media (83.6 %; 95% CI: 78.1–87.9), whereas Russians resorted to this source much less (0.3 %; 95 % CI: 0.1–0.7 for Internet; and 4.3 %; 95 % CI: 3.4–5.4 for mass-media; p < 0.0001). Interestingly, while the vast majority of Russians received information about vaccination from a pediatrician, 71.2 % (95 % CI: 68.9–73.3) wanted to know more. Indians suffered from a lack of information too, but not as much (63.1 %; 95 % CI: 56.4–69.3; p = 0.01).
   Conclusion. Despite of a good attitude to vaccination of parents from India and Russia the lack of vaccine information was registered.

   Background. Human serum albumin (HSA) is a natural buffer of amyloid-β peptide (Aβ), a key factor in the development of Alzheimer’s disease (AD). A promising approach to the AD prevention is to reduce the concentration of free Aβ by targeted stimulation of the interaction between HSA and Aβ. This approach can be implemented by increasing the affinity of HSA to Aβ through the action of HSA ligands, which was previously demonstrated for some low molecular weight ligands.
   The aim of the study was to search for peptide and protein ligands of human serum albumin capable of affecting its interaction with Aβ.
   Materials and methods. To perform a systematic search for peptides/proteins, HSA ligands that are capable of affecting Aβ-HSA interaction, we analyzed the DrugBank, BioGRID, and IntAct databases. As criteria for selecting candidates, along with physicochemical characteristics (molecular weight, solubility, blood-brain barrier passage, molar concentration), we used the requirements of extracellular proteins localization and strict association with AD, according to the DisGeNET and Open Targets Platform databases as well as Alzforum online resource. The algorithms for searching and analyzing the obtained data were implemented using the high-level programming language Python.
   Results. A candidate panel of 11 peptides and 34 proteins was formed. The most promising candidates include 4 peptides (liraglutide, exenatide, semaglutide, insulin detemir) and 4 proteins (S100A8, transferrin, C1 esterase inhibitor, cystatin C).
   Conclusions. Selected peptide and protein candidates are subject to experimental verification regarding their effect on the HSA-Aβ interaction and can become the basis for the development of first-in-class drugs for the prevention of Alzheimer’s disease.

   Uterine fibroid is one of the most common gynecological diseases in women of reproductive age and many aspects of this disease remain the subject of investigation. In particular, the role of the metabolic syndrome is of interest as a potential predictor of uterine fibroid or a comorbid condition that has pathogenetic significance.
   The aim of this literature review is to systematize current data on the prevalence and associations of the metabolic syndrome and uterine fibroid in women of reproductive age.
   Literature search was carried out using the scientific literature databases eLIBRARY, PubMed, NCBI, CyberLeninka, and the official IDF website for the period from 2010 to 2022. In PubMed search, we used the following terms: uterine fibroid, metabolic syndrome, uterine fibroid and metabolic syndrome, uterine myoma and metabolic syndrome, uterine myoma and metabolic disorders, uterine myoma and MetS. A total of 439 sources were analized, 32 sources met the search criteria.
   Results. An analysis of the largest epidemiological studies conducted in recent years, both in non-selective populations and in hospital samples, demonstrates a significant prevalence of both uterine fibroid and metabolic syndrome among women. The results presented in the publications which were included in the review indicate that there is a relationship between the presence of uterine fibroid and the manifestations of the metabolic syndrome.
   Conclusions. Uterine fibroid and metabolic syndrome are mutually aggravating conditions. Women with uterine fibroid have a worse risk profile for cardiovascular disease, and the presence of metabolic syndrome increases the risk of uterine fibroid. One of the ways to reduce the risk of occurrence and growth of uterine fibroid is the timely correction of the metabolic syndrome and its components. On the other hand, the presence of uterine fibroid should be considered as a basis for active detection of metabolic disorders and cardiovascular risks.

   Background. Smell disorder is a recognized clinical symptom of COVID-19 infection. The problem of the loss of sense of smell in the structure of COVID-19 pathogenesis during pregnancy remains unresolved.
   The aim of the study. To determine the sense of smell and taste in pregnant women with COVID-19, as well as to evaluate the relationship between the sense of smell and the number of SARS-CoV-2 genome equivalents in the nasopharyngeal secretion.
   Material and methods. In the case-control study, 121 pregnant women participated: 40 of them were infected with COVID-19; 81 were not infected with COVID-19 earlier and at the time of the study. The survey was conducted in July 2021. Sense of smell was assessed using the Connecticut Chemosensory Clinical Research Center (CCCRC) olfactory test, which includes olfactory threshold determination and odor identification assessment. Taste was measured according to the O. Massarelli method. Viral load was calculated using a standardized method for determining the number
of SARS-CoV-2 RNA copies in 1 ml of nasopharyngeal secretion.
   Results. The incidence of olfactory disorders (moderate / severe and anosmia) in pregnant women with COVID-19 is 62.5 % compared to 22.23 % among pregnant women who have never had COVID-19 (p = 0.002). No significant taste disorders were identified. The threshold value for the manifestation of olfactory disorders was 17794 RNA copies of the SARS-CoV-2 virus, which corresponds to the 37th threshold cycle (Ct).
   Conclusion. During pregnancy in the acute phase of COVID-19, sense of smell is significantly impaired, but not sense of taste. Decreased sense of smell is associated with SARS-CoV-2 viral load.

   Background. Disruption of the energy balance of erythrocytes under conditions of a decrease in the glycolysis level can cause a change in the ion permeability of their membrane.
   The aim. To study Ca²⁺-dependent potassium permeability of the erythrocytes membrane in the presence of SH group modifiers under conditions of glucose deficiency.
   Materials and methods. The study used precipitated erythrocytes obtained from the blood of 20 male Wistar rats. The change in the Ca²⁺-dependent potassium conductivity of the erythrocyte membrane was determined using the potentiometric method. The A23187-and redox-induced hyperpolarization responses of erythrocytes were evaluated.
   Results. Glucose deficiency in the medium, as well as the use of the glycolysis inhibitor 2-deoxyglucose, led to an increase in the amplitude of A23187-stimulated membrane hyperpolarization by the opening of the Gardos channels. At the same time, the redox-dependent hyperpolarization of the erythrocyte membrane turned out to be insensitive to a decrease in the glucose content in the medium and to the glycolysis inhibition. The effects of SH group modifiers in the normal incubation medium and under glucose deficiency turned out to be multidirectional and depended on the method of stimulation of Gardos channels.
   Conclusion. The results obtained indicate that metabolic disorders in erythrocytes under conditions of glucose deficiency lead to a change in the mechanisms of control of Gardos channels with the participation of SH groups of the proteins of these channels or their regulatory proteins.

   Polymorphic variants of the multidrug resistance gene (ABCB1 or MDR1) are associated with changes in the absorption and transport of drugs in the body. One of the substrates of the ABCB1 transporter is an antiretroviral drug from the class of protease inhibitors, lopinavir.
   The aim. To research the effect of polymorphic variants C1236T and C3435T in the ABCB1 gene on the plasma concentration of lopinavir / ritonavir in children and adolescents living with HIV infection.
   Methods. The genotypes of polymorphic variants of the ABCB1 gene were identified in 136 HIV infected children and adolescents; median age – 10 [7–12] years. The plasma concentration of lopinavir / ritonavir was measured from blood taken during the next scheduled appointment as part of dispensary observation at the Irkutsk Regional AIDS Centre using high performance liquid chromatography.
   Results. The average duration of lopinavir/ritonavir use as part of an antiretroviral therapy was 55 months. Median viral load in patients was 1 [1–2.03] log 10  copies/ mL; the number of CD4 +  T cells – 38.36 %. The frequency of occurrence of the 3435T and 1236T alleles of the ABCB1 gene was ~50 %. In carriers of the 3435TT genotype, the median lopinavir concentrations 2 and 12 hours after drug intake were 5050.8 [3615.8–5847.7] and 2665.5 [216–4896.3] ng/mL, respectively. In carriers of the 1236TT genotype, median lopinavir concentrations 2 and 12 hours after drug intake were 4913.5 [3355.1–5733.7] and 3290.6 [159.1–4972.5] ng/mL, respectively.
   Conclusions. The study did not reveal a significant relationship between the carriage of the C3435T and C1236T genotypes of the ABCB1 gene and the concentrations of lopinavir and ritonavir 2 and 12 hours after drug intake.

   One of the delayed consequences of SARS-CoV-2 infection is post-acute COVID-19 – polymorphic disorders of various organ systems that affect COVID-19 convalescents and persist for more than four weeks after an acute infection. Due to the infectious nature of the COVID-19, we would like to pay special attention to complications from the immune system, especially concomitant and new-onset autoimmune pathology. This review analyzes the current state of the issue of post-acute COVID-19 complications, discusses the molecular features of the SARS-CoV-2 virus and the mechanisms underlying the impaired immune response during acute COVID-19 infection and the occurrence of autoimmune and autoinflammatory conditions during convalescence. Particular attention is paid to the molecular mimicry of antigenic determinants of the SARS-CoV-2 virus, which are structurally similar to the epitopes of human autoantigens. The current data on post-acute COVID-19 autoimmune complications from humoral immunity and the endocrine system, as well as reproductive disorders faced by male patients are presented. For the first time, we hypothesize a role of the structural homology of the human SOX13 autoantigen (HMG box factor SOX13) associated with diabetes mellitus and SARS-CoV-2 envelope (E) protein in the development of the post-acute COVID-19 autoimmune pathologies. Due to the structural similarity of the two proteins and the overlap of their immunogenic regions, we suggest that the increased risk of developing diabetes mellitus and reproductive disorders in men after suffering from COVID-19 may be associated with immunological cross-reactivity.

   The aim. To assess the general condition, laboratory parameters, quality of life of women of post-reproductive age after asymptomatic COVID-19 and 12 months after moderate COVID-19.
   Material and methods. We examined 47 women (45–69 years old), divided into 3 groups: those who did not have COVID-19, not vaccinated (group 1 – control; n = 15); women 12 months after moderate COVID-19, accompanied by pneumonia (group 2; n = 19); women with IgG in their blood who deny any symptoms of COVID-19 (group 3; n = 13).
   Results and discussion. An assessment of the general condition of women in post-reproductive age was carried out. In women 12 months after COVID-19 we found a lower level of total bilirubin compared to the group with asymptomatic COVID-19 (p = 0.004). An increase in thrombin time was determined in the groups of patients with symptomatic (p = 0.014) and asymptomatic (p = 0.025) COVID-19 course compared with the control group. Patients with asymptomatic COVID-19 course had a higher level of high-density lipoprotein cholesterol compared with the control group (p = 0.016) and the group 2 (p = 0.006). Compared with the control group, the group 2 had lower scores for general health (p = 0.006), vital activity (p = 0.013), general physical well-being (p = 0.039), physical functioning (p = 0.046); and the group 3 had higher scores in role functioning due to physical condition (p = 0.049). When comparing groups 2 and 3, lower scores in the group of women who recovered from the moderate COVID-19 were found in physical functioning (p = 0.002), pain intensity (p = 0.034), role functioning due to physical condition (p = 0.049), general health (p = 0.003), vital activity (p = 0.018), general physical well-being (p = 0.001).
   Conclusion. 12 months after moderate COVID-19, there is a pronounced deterioration in physical and emotional health; and in asymptomatic patients, better protective functions of an organism can be assumed.

   Background. The incidence of diseases associated with impaired transport and oxidation of fatty acids is from 1:5,000 to 1:9,000 newborns. High morbidity, risk of death in the absence of timely correction, non-specificity of clinical manifestations define the importance of their timely laboratory diagnosis based on the determination of free carnitine and acylcarnitines in the blood. Reference values for free carnitine and acylcarnitines vary in different populations.
   The aim. To determine the reference intervals of free carnitine and acylcarnitines in newborns of the Irkutsk region and to compare them with similar reference intervals in newborns in other countries.
   Methods. The analysis of 229 samples of drу blood spots of healthy newborn children of the Irkutsk region aged from 0 to 7 days was carried out. Analysis of acylcarnitine concentrations was performed using high performance liquid chromatography with tandem mass spectrometry.
   Results. 2.5 and 97.5 percentiles (µmol/l) were calculateed for 13 acylcarnitines: C0 – [8.78; 38.08]; C2 – [3.55; 19.09]; C3 – [0.33; 1.96]; C4 – [0.08; 0.51]; C5 – [0.06; 0.44]; C5DC – [0.03; 0.17]; C6 – [0.01; 0.07]; C8 – [0.01; 0.07]; C10 – [0.02; 0.07]; C12 – [0.04; 0.51]; C14 – [0.07; 0.24]; C16 – [0.58; 3.25]; C18 – [0.35; 1.16].
   Conclusion. Differences in acylcarnitine reference intervals were found: compared with other countries, the concentrations of reference intervals for C0, C2, C3, C5DC, C8, C10, C14, C16 and C18 were lower in our study, reference intervals for C5 and C12 were higher in our country.

   Background. The widespread use of copper oxide nanoparticles (CuO NPs) increases their release into the environment, which leads to accumulation in trophic chains. Bacterial biofilms are more resistant to physico-chemical factors compared to planktonic cells due to an exopolymer matrix (EPM) consisting of polysaccharides, proteins, lipids and nucleic acids. Rhodococcus actinobacteria are promising for environmental biotechnology due to biodegradation of petroleum products, pesticides and other organic pollutants, as well as bioaccumulation of heavy metals.
   The aim. To investigate effects of CuO NPs on the viability of Rhodococcus ruber IEGM 231 cells in biofilms and the dynamics of EPM components.
   Methods. R. ruber biofilms were grown on microscopy cover glass with CuO NPs and EPM components were studied using confocal laser scanning microscopy (CLSM) by differentiating staining with LIVE/DEAD to determine the number of living and dead cells, Nile Red for lipids, FITC for proteins and Calcofluor White for betapolysaccharides.
   Results. It was found that R. ruber biofilms grown in a mineral medium with
1.0 vol.% n-hexadecane are more resistant to CuO NPs compared to biofilms growing in a rich culture medium (meat-peptone broth). This was due to more intensive EPM formation, which plays a major role in protecting cells from the bactericidal action of nanometals. A weak stimulating effect of a low (0.001 g/l) concentration of CuO NPs on biofilm formation was registered. Dynamics and localization of main EPM components were monitored during prolonged (24–72 h) biofilm cultivation with CuO NPs. When exposed to high (0.01–0.1 g/l) concentrations of CuO NPs, a consistently high lipid content and an increase in concentrations of polysaccharides and proteins were revealed.
   Conclusion. Understanding the complex interaction mechanisms of nanometals and biofilms will contribute to the development of effective biocatalysts based on immobilized bacterial cells. Also, the obtained data can be used to combat unwanted biofilms with the help of metal nanoparticles.

   Background. The study of the mechanisms of action of antibiotics requires the integrated use of traditional microbiological and physicochemical methods.
   The aim. To study the response of Escherichia coli bacteria to the action of four antibiotics, inhibitors of protein synthesis, using combined approach.
   Methods. Bacteria were grown under aerobic conditions on minimal M9 medium with glucose. Tetracycline, kanamycin, streptomycin and chloramphenicol have been tested. The effect of antibiotics on survival (CFU) and growth rate was determined. Respiratory activity, sulfide production, extracellular potassium, as well as pH and Eh of the medium were measured using electrochemical sensors directly in a growing culture in the “real time”, membrane potential was measured using a DiBAC dye and a Leica DM2000 fluorescent microscope.
   Results. The tested antibiotics were divided into two groups according to their properties. Tetracycline and chloramphenicol showed a pronounced bacteriostatic effect, growth inhibition began immediately after the addition of antibiotics and occurred at a high rate. Both antibiotics inhibited respiration, stimulated sulfide production and an Eh jump. Bacteria treated with tetracycline and chloramphenicol retained the ability to maintain membrane potential and intracellular potassium better. Inhibition of respiration led to a decrease in glucose catabolism, as evidenced by a lower rate of acidification of the medium compared to the control. Growth inhibition with streptomycin and kanamycin was initiated with a 30-minute delay. Both antibiotics showed a bactericidal effect, did not stimulate sulfide production and Eh jump, did not inhibit respiration, but caused a drop in membrane potential and intracellular potassium. High respiratory activity promoted glucose catabolism, as evidenced by the rapid acidification of the medium. Of interest is the detection of kanamycin-induced sulfide production during E. coli growth on MOPS medium.
   Conclusion. An analysis of the data obtained indicates that the use of electrochemical sensors in combination with traditional methods is a promising approach to studying the mechanisms of action of antibiotics.

   Background. The formation of biofilm structures by microorganisms living in the hospital environment is a serious medical problem. To conduct correct experimental studies, it is necessary to know the speed and efficiency of biofilm formation by clinically significant species of opportunistic bacteria.
   Aim: to study the kinetics of plankton culture growth and the rate of biofilm formation by clinically significant pathogens of infections associated with medical care to substantiate the methodology of further research.
   Materials and methods. The strains from the working collection of the Laboratory for Microbiome and Microecology of the Scientific Сentre for Family Health and Human Reproduction Problems were used. Experiments were carried out with conditionally pathogenic microorganisms of the Enterobacteriaceae family and non-fermenting gram-negative bacteria. The optical density was measured, the total microbial number of the cell suspension was determined, and the morphological structure of the biofilm was evaluated using a light microscope on sterile cover glasses for the
species Pseudomonas aeruginosa, Klebsiella pneumoniae and Serratia marcescens.
   Results. The duration of the lag phase of the kinetic curve of cell growth varied in isolates of S. marcescens, P. aeruginosa and K. pneumoniae from 1 to 4 and 6 hours of cultivation, respectively. Despite this, the exponential growth phase was the same for all tested isolates and amounted to 4 hours. Thus, isolates of clinically significant species entered the stationary growth phase after 5–10 hours of cultivation and were characterized as fast-growing. On abiotic surfaces, after 8 hours of incubation of the tested cultures, the initial stages of the formation of biofilm structures were observed, after 20 hours the formed multilayer biofilm was visualized, after 24 hours succession occurred, new single cells were attached to the place of the detached structures.
   Conclusion. The data obtained on the duration of the main stages of growth kinetics compared with the visualization of the formation of biofilm structures on abiotic surfaces should be taken into account when studying the effects of disinfectants, antiseptics and antibacterial drugs on planktonic cells and biofilm associations of clinically significant opportunistic microorganisms.

   Background. There is no current generally accepted classification and clinical approaches to assess the clinical course severity of tick-borne encephalitis.
   The aim is to develop models for the quantitative severity scores of the febrile form of tick-borne encephalitis using the most informative predictors.
   Materials and methods. In accordance with clinical criteria of the height and duration of fever, two groups of 9 and 30 patients (52.2 ± 4.3 and 49.5 ± 3.9 years old) with severe and non-severe febrile form of tick-borne encephalitis were formed. The study design was a retrospective case-control study. Statistical significance assessment of variables was carried out using the chi-square test. The odds ratios were also calculated. The development of logistic regression models was carried out using Statistica 12.0 modules.
   Results. A questionnaire of febrile form of tick-borne encephalitis severity score was developed using the height of fever and 11 most informative clinical predictors including arthralgia, chills, sleep disturbance, dizziness, orbital pain, nausea, photophobia, myalgia, severe headache, vomiting and meningism. To predict the severe clinical course of febrile form of tick-borne encephalitis, two logistic regression models were developed with or without severity score assessment of fever syndrome (coefficients α and β were –12.13 and 0.94 and –5.78 and 0.75 for models 1 and 2, respectively). Models 1 and 2 demonstrated a high predicted probability for cut-off values equal to 14 and 9 points and excellent quality of prediction test (AUC are equal to 0.99 and 0.98, respectively).
   Conclusions. The models of severity score demonstrated high predicted probabilities to predict severe clinical course of febrile form of tick-borne encephalitis, which can be used in clinical practice and for scientific purposes.

   Background. In spring and summer, the population of the Baikal region regularly comes into contact with the pathogens transmitted through the bites of ixodid ticks. In the Center for Diagnosis and Prevention of Tick-Borne Infections (Irkutsk, Russian Federation), we annually detect anaplasmas of the Anaplasma phagocytophilum species, as well as Ehrlichia chaffeensis/E. muris in both ixodid ticks and blood samples from people who have been bitten by ticks. At the same time, there are no data in open sources on the incidence of human granulocytic anaplasmosis and human monocytic ehrlichiosis in the Baikal region. Currently, there is very little information on the studies of intensity of the immune response to anaplasmas and ehrlichia in people living in the surveyed area, although this information is critical for assessing the frequency of contacts and the risk of infection of people in a territory endemic for tick-borne infections.
   The aim. To update information on the presence and prevalence of specific immunoglobulins M and G to A. phagocytophilum and Ehrlichia sp. among the population of the Irkutsk Region affected by tick bites.
   Materials and methods. In total, 204 samples of blood serum from the residents of the Irkutsk Region who were registered to be bitten by ticks were analyzed for the presence of IgM and IgG to human monocytic ehrlichiosis and human granulocytic anaplasmosis agents.
   Results. IgG to A. phagocytophilum were found in 9 samples, IgG to E. chaffeensis/E. muris – in 1 sample; no IgM to both pathogens were found in any sample.
   Conclusions. The results obtained indicate regular infection of the population with anaplasmas and ehrlichia which is a testifies to the existence of active natural foci of human monocytic ehrlichiosis and human granulocytic anaplasmosis in the Baikal region. To clarify the real epidemic role of these infections, a detailed study of the immune status is required both among healthy individuals and among patients with symptoms of an infectious disease.

   Background. The problem of antibiotic resistance has remained significant for the medical community for more than half a century, since the first cases of resistance to penicillin were registered.
   The aim. Analysis of the long-term dynamics of changes in the antibacterial resistance of microorganisms and the creation of a collection of multi-resistant strains of opportunistic microorganisms.
   Materials and methods. The study included data from 3173 bacteriological samples of various loci of the human body for 2010 and 2020–2021. The sensitivity of isolated cultures was determined by the disk diffusion method to antimicrobial drugs of the following groups: penicillins, cephalosporins, fluoroquinolones, aminoglycosides, carbapenems, tetracyclines, macrolides, lincosamides, oxazolidinones, glycopeptides and others.
   Results. In the general structure of conditionally pathogenic microorganisms, a significant increase in the frequency of isolation of multidrug-resistant representatives of the genus Staphylococcus by two or more times was observed in 2021 compared to 2010 and 2020. We also observed a significant increase in the proportion of multidrug-resistant Streptococcus spp. and non-fermenting gram-negative bacteria. These changes marked the beginning of the creation of a collection of conditionally pathogenic microorganisms with multiple antibacterial resistance. In the structure of multiresistant microorganisms included in the “Collection of human microbiota of the Irkutsk region”, the leading positions belong to Klebsiella pneumoniae (23.81 %), Escherichia coli (19.05 %) and Staphylococcus aureus (22.22 %).
   Conclusion. Antibiotic resistance monitoring is an important measure to control the resistance of community-acquired and nosocomial (nosocomial) microorganisms both within a particular country and globally.

   Background. The balance of TNF receptor expression on immune cells is a key factor determining cytokine-induced activation of proapoptotic or proliferative signaling pathways. As a result, the changes in cytokine level and in expression of its receptors may be one of the mechanisms that regulate the level of systemic and local inflammation in rheumatoid arthritis (RA) and determine the degree of therapy effectiveness.
   The aim. To study the effect of rheumatoid arthritis therapy on the change in the patterns of TNF receptors expression in terms of co-expression and the number of receptors on the main subpopulations of immunocompetent cells.
Materials and methods. A comparative analysis of the profiles of TNF receptors type 1 and 2 (TNFR1/2) co-expression was carried out in patients with RA (n = 16) before and after having inpatient effective therapy and in comparison with a group of healthy individuals (n = 21). We compared the number of receptors and the proportion of cells expressing the corresponding receptor using flow cytometry and studied the subpopulations of regulatory T cells, T cells, B cells, and monocytes.
   Results. In patients with RA, there is a significant redistribution of TNFR1 and TNFR2 expression on immunocompetent cells, while the intensity of changes is associated not only with disease severity indicators, but also with the therapy received. The key adaptive mechanism of the TNF system in long-term treatment refractory course of RA is a change in the proportion of double-positive TNFR1+TNFR2+ cells, while the effectiveness of therapy and clinical indicators of the disease severity are associated with individual variability in the parameters of type 2 receptors expression.
   Conclusions. The data obtained confirm the existence of a relationship between an imbalance in the expression of type 1 and type 2 TNF receptors on immunocompetent cells and the effectiveness of response to therapy. The identified patterns of typical changes in TNFR1/2 co-expression in RA can be used as potential therapeutic targets and predictive factors for the effectiveness of therapy.

   Background. Memory CD4⁺ T cells proliferation is the basis for accelerated secondary immune response. The characteristics of memory CD4⁺ T cells providing their faster division compared to naive CD4⁺ T lymphocytes are poorly understood. T cells proliferative ability is determined by their metabolism. The metabolic features of proliferating memory CD4⁺ T cells remain elusive.
   The aim. To compare the metabolic features of naive and memory CD4⁺ T cells in quiescence and during proliferation.
   Methods. Peripheral blood mononuclear cells were analyzed using flow cytometry. Dividing cells were identified by CD71 expression. Cellular glucose and fatty acid uptake was assessed using fluorescent glucose (2-NBDG) and palmitate (BODIPY-FL-C16) analogs, respectively. Glutamine transporter expression was analyzed by staining the cells with anti-ASCT2 antibodies. Mitochondrial mass and membrane potential were measured using MitoTracker Green and MitoTracker Orange, respectively.
   Results. Quiescent memory CD4⁺ T cells exhibited elevated levels of glucose and palmitate uptake when compared to naive CD4 + T lymphocytes (p < 0.001). Both subsets had increased substrate consumption when proceeding to proliferation (p < 0.001). When dividing, naive CD4⁺ T cells consumed more glucose and palmitate than memory CD4⁺ T cell (p < 0.001). Proliferation caused an increase in mitochondrial mass in naive (p < 0.001) and memory CD4⁺ T lymphocytes (p < 0.05). In memory CD4⁺ T cells, unlike naive CD4⁺ T lymphocytes, an increase in mitochondrial mass wasn’t accompanied by an increase in membrane potential.
   Conclusion. In memory CD4 + T cells, compared to naive CD4⁺ T lymphocytes, the metabolic change induced by proliferation is moderate and affects the mitochondrial activity to a lesser extent. Lower bioenergetic expenses of memory CD4⁺ T cells can contribute to their rapid proliferation during secondary immune response.

   Introduction. Bone marrow erythroblasts produce a wide range of cytokines with opposite biological effects. This may be due to a change in the spectrum of production of immunoregulatory mediators during differentiation and small qualitative and quantitative differences in the spectrum of cytokines produced at each stage of differentiation, which may be important for the regulation of hemo- and immunopoiesis.
   The aim. To study the spectrum of production of mediators by erythroblasts at different stages of differentiation.
   Methods. Erythroblasts were obtained from CD34+ bone marrow cells of healthy donors in the presence of recombinant cytokines. Phenotype assessment was performed using flow cytometry for erythroid (CD45, CD71, CD235a, CD44) and lymphoid markers (CD3, CD4, CD8, CD16, CD19). Blocking of erythroblast differentiation at different stages was carried out using specific blocking monoclonal antibodies to melanocortin receptors (MCR) of types 1, 2 and 5. Cytokine analysis in conditioned erythroblast media was performed using the Bio-Plex Pro Human Cytokine 48-Plex Screening Panel (Bio-Rad Laboratories, USA). Cytokine production was analyzed using the CytokineExplore online tool.
   Results. The resulting erythroblasts are divided into positive and negative populations according to the CD45 marker, carry markers of erythroid cells CD71, CD235a and do not express linear markers of lymphoid cells. In type 1 MCR blockage, polychromatophilic erythroblasts predominate, in type 2 MCR blockage, basophilic erythroblasts predominate, and in type 5 MCR blockage, orthochromatophilic erythroblasts accumulate. According to the production of cytokines, it was shown that when using any of the blocking antibodies, we obtain cells that differ qualitatively and quantitatively in a number of mediators from the initial population of induced erythroblasts.
   Conclusion. Thus, we have shown qualitative and quantitative differences in the production of mediators by erythroblasts depending on the stage of differentiation, which can lead to different regulatory effects.

   Background. It is known that adaptation to chronic continuous hypoxia leads to a pronounced cardioprotective effect. The efficiency of acute adaptation to hypoxia is reduced in metabolic syndrome. However, the effectiveness of the myocardial infarct size-limiting effect of chronic continuous hypoxia in metabolic syndrome remains an understudied fact.
   The aim. To study the effectiveness of the development of the myocardial infarct size-limiting effect of chronic continuous hypoxia in rats with metabolic syndrome.
   Materials and methods. The study was carried out on 43 Wistar rats. Adaptation of animals to chronic hypoxia was performed during 21 days in a hypoxic chamber (12 % O2, 0.3 % CO₂). Metabolic syndrome was modeled by keeping rats on a high-carbohydrate and high-fat diet (proteins 16 %, fats 21 %, carbohydrates 46 % (including fructose 17 %), cholesterol 0.125 %, cholic acid 0.5 %) for 12 weeks with replacement of drinking water with 20% fructose solution. Coronary occlusion-reperfusion was performed in vivo. The effect of chronic hypoxia and metabolic syndrome on myocardial infarct size was assessed.
   Results. It was found that myocardial infarct size in rats after chronic continuous hypoxia was 38 % less than in animals of the control group. In rats which were kept on a high-carbohydrate and high-fat diet we observed the obesity, decreased glucose tolerance, increased serum triglycerides level, and hypertension. Adaptation to chronic continuous hypoxia in animals on a high-carbohydrate and high-fat diet improved carbohydrate metabolism, but did not affect the severity of other metabolic disorders. At the same time, the myocardial infarct size-limiting effect of chronic hypoxia was not observed in rats with metabolic syndrome.
   Conclusion. Metabolic syndrome eliminated myocardial infarct size-limiting effect of chronic continuous hypoxia.

   The aim of the study was to assess the functional state of glutathione system in menopausal women of the Buryat ethnic group with insomnia.
   Methods. The study involved 94 women aged 45 to 60 years who were divided into perimenopause (n = 44) and postmenopause (n = 50) groups. In each period, a control group and an insomniac group were identified. The reduced (GSH) and oxidized (GSSG) glutathione levels in erythrocyte lysate, the glutathione-S-transferase π concentration and glutathione reductase activity in blood serum were determined.
   Results. An increase of the GSH level (p < 0.05) and GSH/GSSG ratio (p < 0.05) both in perimenopausal and postmenopausal women with insomnia were found as compared to controls. There were no differences in the glutathione-depends enzymes parameters. Comparative analysis of the main groups showed an increase GSH/GSSG ratio (p < 0.05) in the postmenopausal period compared with perimenopause.
   Conclusion. The study results demonstrate the glutathione link activation in Buryat menopausal women with insomnia. In this regard, the appointment of glutathione preparations for the correction of free radical homeostasis in these groups of women cannot be recommended.

   Introduction. According to the literature, it is known that clinical signs and symptoms of influenza may differ depending on age, the state of the human immune system, the serotype of the virus and its virulence. Intoxication, catarrhal and hyperthermia are main symptoms of influenza, but the disease does not always proceed classically, it may hide under the mask of other infections.
   The aim was to conduct a comparative analysis of clinical, laboratory and instrumental parameters in children with influenza A(H1N1) and A(H3N2).
   Materials and methods. A single-stage retrospective comparative study was carried out with the participation of 96 children from 1 month of age up to 13 years old with a diagnosis of influenza, who were hospitalized at the Irkutsk Regional Infectious Clinical Hospital from December 2018 to January 2019. Clinical and laboratory features of the course of influenza in children were determined depending on a viral strain.
   Results. The structure of morbidity: influenza A(H1N1) – 70 people (73 %), influenza A(H3N2) – 20 children (21 %), influenza A clinically unvaccinated – in 3 people (3 %), mixed viral infection influenza H1N1 + adenovirus infection – 2 cases (2 %), mixed viral infection H1N1 flu + RS-virus – 1 case (1 %). In the clinic of both strains of the virus, symptoms prevailed: runny nose, dry cough, fever, intoxication. Muscle pain and pharyngeal hyperemia were significantly more common in influenza A(H1N1), the duration of symptoms did not differ. Lymphocytosis was more often observed in influenza A(H1N1), monocytosis – in influenza A(H3N2) (р < 0.05). In 64 % of cases, patients with influenza A(H1N1) had a high leukocyte index of intoxication (odds ratio – 2.2).
   Conclusion. The symptoms of different influenza A viral strains virus in children are the same, however, muscle pain and hyperemia of the pharynx prevails in children with influenza A(H1N1).

   The gut microbiota is the largest human microbial community, comprising more than 1000 species of various microorganisms. It has been established that these are the gut microorganisms that play a decisive role in maintaining health, participating in the metabolism of proteins, carbohydrates, lipids, bile acids and the synthesis of vitamins. It has been shown that changes in the balance in the gut microbiocenosis lead not only to pathologies of the gastrointestinal tract, but also increase the risk of developing diseases of the cardiovascular and endocrine systems, and cause disturbances in the psycho-emotional state.

   To restore, correct and maintain the gut microbiota, probiotic preparations are recommended. In connection with the obvious relevance of the use of probiotics, this review aimed to describe the history of the emergence of the first probiotic products, current trends in the development of the concept of functional foods enriched with probiotics, as well as the prospects for developing probiotic preparations in the Russian Federation and abroad.

   This article presents an analysis of the market for probiotic preparations and dietary supplements, as well as functional food products that are produced in the Siberian Federal District. For an objective assessment of the development of the market for probiotic products, a generalization of analytical data from marketing services that monitor the movement of medicines in pharmacy chains and analyze consumer reviews was carried out.

   The issues of psychological adaptation of a person to the extreme conditions of the Arctic continue to be relevant at the present time. Dynamic monitoring of human functional states is an effective technology that allows timely identification of the level of human adaptation to the conditions of the North and implementation of preventive measures to maintain health in extreme working conditions.
   The aim of the study is to identify and describe the relationship of individual-personal qualities and the dynamics of the functional states of the participants of the marine Arctic expedition.
   Methods. Psychophysiological testing using the device UPFT-1/30-«Psychophysiolog» (variational cardiointervalometry, complex visual-motor reaction); color preference test (M. Luscher, adapted by L. N. Sobchik) with calculation of interpretation coefficients by G. A. Aminev; Five-factor personality questionnaire (R. McCrae and P. Costa, adapted by A. B. Khromov); statistical methods: descriptive statistics, frequency analysis, correlation analysis using Spearman’s rank correlation coefficient. The study was conducted daily in the morning and evening for 20 days on the research vessel Mikhail Somov in June 2021. The study involved 39 people, including participants in the scientific and educational expeditionary project “Arctic Floating University–2021”.
   Results. The dynamics of psychophysiological and projective psychological parameters of the functional states of the expedition members as a whole is characterized by favorable levels, which indicates their adaptation to the conditions of high latitudes. According to the results of the correlation analysis, statistically significant relationships were revealed between the dynamics of functional states and such individual-personal qualities as: extraversion − introversion and attachment − separation.
   Conclusion. The results of the study are consistent with the data of previous expeditions of the “Arctic floating university” and other polar expeditions. The revealed interrelations of functional states with different personality characteristics of the participants testify in favor of the complex nature of the study using different groups of diagnostic methods.

   An analysis of modern research has shown insufficient study of the labor factors that influence the development of various functional states of non-departmental security officers which allow to develop the recommendations to improve their psychological safety.
   The aim of the study. To identify and to describe psychosocial factors at work in relation to the general functional state of the body, stress and performance of non-departmental security officers.
   Methods. We used the General Nordic Questionnaire for Psychological and Social Factors at Work (QPSNordic), psychophysiological testing using “Psychophysiologist” device, M. Lüscher color preference test, multivariate statistical methods. The study involved 74 non-departmental security officers of the Arkhangelsk region.
   Results. The general functional state of the body, stress and performance, measured by objective and projective methods, are differentially interconnected with psychosocial factors at work. The general functional state of the body is related with the personal attitude to the work performed; stress and performance – with factors of social support, organizational culture and work requirements. The general functional state of non-departmental security officers is favorably influenced by such factors as understanding the goals of the work performed and the expected results, satisfaction with the quality of work and labor safety. Insufficient ability to maintain good relations with the team unfavorably influences the general functional state of the officers. The factors of work intensity include one-type tasks, tight schedule, increased alertness during work and greater precision in movements. Risk factors are associated with strict working hours and insufficient attention of the manage-
ment to the opinion and interests of subordinates. At the same time, the environmental resource is the possibility of realizing professional motives and demonstrating mastery in work, as well as a favorable organizational culture.

   Background. Due to their very small size, nanomaterials, in particular cucurbiturils, have unique physical and chemical properties that find their application in medicine. However, the toxicity of cucurbiturils is not fully understood; in particular, we are interested in the immunological safety of their use. One of the mechanisms of nanotoxicity is the formation of reactive oxygen species (ROS) by macrophages and neutrophils. Hyperproduction of ROS can lead to oxidative stress and further damage to cell DNA with loss of physiological function and development of pathology.
   The aim. Evaluation of the effect of cucurbit[n]urils (n = 6, 7, 8) on the production of reactive oxygen species by mice macrophages and neutrophils.
   Materials and methods. F1 hybrid mice (CBAxC57Bl/6) aged 2 months (n = 11) were used in the work. Evaluation of superoxide radical production by peritoneal mouse neutrophils and macrophages was carried out by spectrophotometric method for determining the reduction of p-nitroblue tetrazolium (NBT) to formazan.
   Results. It was shown that CB[6] and CB[7] at concentrations of 0.5 and 0.3 mM do not have an inhibitory effect on ROS synthesis, but, on the contrary, significantly increase ROS production by macrophages. In addition, CB[6] 0.3 mM increases the level of ROS in neutrophils.
   Conclusion. Cucurbiturils can lead to an increase in the production of ROS in immunocompetent cells, depending on the concentration used (0.3 mM and higher).

   Background. A high percentage of people in the world suffer from acute or chronic pain, the treatment of which is based on the introduction of morphine and its derivatives, agonists of the µ-opioid receptors, leading to the development of addiction in patients. An urgent task is to study the properties of endogenous opioid peptides, which are capable of showing not only pronounced analgesic activity, but also have a number of other effects on the periphery, while having a much smaller spectrum of side effects. Of particular interest are the immunomodulatory effects of peptide agonists of µ-receptors – endomorphins, tetrapeptides, the effects of which are not described in detail in the literature. Due to their structure and properties, endorphins can be considered as potential substitutes for low-molecular-weight opiates.
   The aim. To investigate the effect of endorphins-1,2 on the synthesis of oxygen radicals and the absorption activity of innate immunity cells in vitro, in vivo.
   Materials and methods. The object of the in vitro study is peripheral venous blood leukocytes from donors aged 22–40 years; the object of the in vivo study is peritoneal flush cells of Swiss white male mice. Oxygen-dependent microbicidal activity was evaluated using a luminol-dependent chemiluminescence reaction. Phagocytic activity was evaluated by flow cytometry.
   Results. It has been found that endomorphins inhibited spontaneous production of reactive oxygen species in vitro, in vivo. Endomorphin-2 reduced the intensity of respiratory explosion in stimulated cultures of peritoneal macrophages. Blockade of opiate receptors with naloxone in vitro, in vivo did not cancel the effects of endomorphins. Both peptides and naloxone had no effect on the phagocytic activity of macrophages of the peritoneal cavity of mice in vivo, but in vitro endomorphins led to an increase in the percentage of phagocytosis of peripheral blood leukocytes.
   Conclusions. The effects of endomorphins in vitro, in vivo are predominantly depressive.