Kefir has attracted interest in the scientific community due to its beneficial properties, such as: improving digestion, antimicrobial action, hypocholesterolemic, antihypertensive, and anti-inflammatory effects, control of plasma glucose levels, antioxidant, anticarcinogenic, and antiallergic activity. The comparative characteristics of the microbiomes of kefir grains (KG) obtained from the regions of their historical origin (Caucasus and China) is given. The diversity of their compositions was shown using classical microbiological and molecular genetic methods, including high-throughput sequencing of V4-region of bacterial 16S rRNA genes and the ITS1 region of the 18S-ITS1-5.8S-ITS2-28S complex of yeast rRNA. The species of the Lactobacillus genus are the most common of the bacterial cultures in kefir grains, while the most common of the yeast cultures is Pichia fermentans, as well as the rarer species of Yarrowia lipolytica and Galactomyces candidus.

Background. Sore throat of infectious and inflammatory origin is one of the most common reasons for the prescription of antimicrobial drugs. The use of antimicrobial peptides (AMPs) for topical therapy may be a promising solution, due to the peculiarities of AMPs’ mechanism of action, taking into account the high importance of microbial resistance spread problem in relation to systemic etiotropic drugs.
The aim of the study was to assess the formation of resistance to AMP Gramicidin S (GS) of clinical isolates of Streptococcus pneumoniae and Staphylococcus aureus, including strains resistant to antimicrobial drugs during repeated exposure, in the setting close to their actual use in clinical practice.
Materials and methods. The object under study is AMP GS. The test microorganisms are reference strains of S.pneumoniae (ATCC 6303), S.aureus (ATCC 6538–P), and 10 strains of clinical isolates of each type of microorganisms, types with antimicrobial resistance (including MRSA). At the first stage, the antimicrobial activity of GS was evaluated by the method of microdilutions in plates by estimating the value of the minimum inhibitory and the minimum bactericidal concentrations (MIC and MBC, respectively). At the second stage, using reference strains and 4 clinical isolates of each microorganism, including types with antimicrobial resistance, resistance was formed in two ways simultaneously (with liquid and solid media) for 7 consecutive passages over 7 days with GS at concentrations equal to 0.5 and 1.0 MIC. The number of surviving microorganisms was estimated and the MIC and MBC were determined at each passage.
Results. At the first stage, the MIC of GS in relation to S.pneumoniae was 8 µg/ml for 5 strains, 16 µg/ml for 5 strains, and 4 µg/ml for one. For 10 out of 11 strains of S.aureus, including MRSA, the MIC of GS was 4 µg/ml (for 1 strain — 8 µg/ml). For 4 strains of S.pneumoniae, MBC of GS was equal to MIC (16 µg/ml), for 7 strains MBC was 4–8 times higher than MIC, and mostly amounted to 32 µg/ml (for 1 strain — 64 µg/ml). MBC for 6 strains of S.aureus was equal to MIC (4 µg/ml), for the 5 remaining strains MBC was 2–8 times higher than MIC, but did not exceed 64 µg/ml. At the second stage, it was found that the estimated values of GS MIC and MBC with repeated exposure to GS remained at the same level for 7 passages in all strains, including those resistant to antibiotics in liquid and solid media.
Conclusions. Gramicidin S demonstrated high bactericidal activity against reference strains and clinical isolates of leading pathogenic microorganisms S.pneumoniae and S.aureus, including strains resistant to systemic antimicrobial drugs, while MIC and MBC did not exceed concentrations contained in single doses of drugs used in clinical practice. During repeated exposure (7 passages in 7 days), there were no signs of the formation of resistance of test strains of pathogens, including those resistant to systemic antimicrobial medicines from the groups of beta-lactams, macrolides, fluoroquinolones, tetracyclines, aminoglycosides, etc.

Influenza and coronavirus infections are especially dangerous due to being capable of causing pandemics and clinical complications in the nervous and cardiovascular systems, as well as exacerbation of chronic diseases (diabetes mellitus, heart failure, chronic obstructive bronchopneumonia, etc.), which can cause delayed death, especially in children under two years of age, the elderly, and individuals with poor health. The aim of the study was to search for compounds effective against these two topical viruses which possess constant epidemic activity — influenza virus and betacoronavirus — among new adamantane derivatives containing a NO-donor fragment or a dopamine residue. Another purpose of the study was determination of cytotoxicity and antiviral activity of compounds on cell lines permissive for influenza virus and betacoronavirus. The antiviral activity of 6 adamantane derivatives against strains of the influenza virus (H1N1) and betacoronavirus was studied. It was established that the NO-donor derivative of aminoadamantane succinate and the dopamine derivative of adamantanebenzoic acid had the greatest ability to suppress the development of the influenza virus with a chemotherapeutic index above 60. No promising compounds against betacoronavirus were identified.

The general toxicity was studied with an assessment of local tolerability, immunotoxicity, and pharmacological safety of the new medicine Dioxidine®, a solution for topical and external use, 0.25 mg/ml (0.025%) for the treatment of acute tonsillopharyngitis (JSC «Valenta Pharm», Russia). The experiment included 48 rabbits (divided in equal proportion by sex) randomized into 3 groups (n=16 in each group), whose back wall of the pharynx was irrigated with the studied substances for 28 days. Group 1 — control (aqueous solution of NaCl 0.9% for infusions at a daily dose of 4.0 ml/animal); group 2 — dioxidine (1.8 ml/animal); group 3 — dioxidine (4.0 ml/animal). The animals were observed for the entire period of drug administration — up to the 28^th day of the experiment, as well as during the delayed observation period — up to the 58^th day. The following indicators were recorded: lethality, daily monitoring of general condition and behavior, weight, feed and water consumption, respiratory rate, heart rate, blood pressure, electrocardiogram, mass coefficients of internal organs. Immunotoxicity, poisoning symptoms, adrenal insufficiency, as well as animal autopsy results were assessed. Clinical and biochemical blood tests, blood coagulation system analysis, urine analysis, macroscopic and histological examination of internal organs were performed. The absence of statistically significant differences in all evaluated indicators between the group of animals receiving dioxidine solution for topical and external use, 0.25 mg/ml (0.025%) at a dose of 1.8 ml/animal (equivalent to 15 therapeutic doses for humans), the group receiving dioxidine at a dose of 4.0 ml/animal (equivalent to 35 therapeutic doses for humans) and the control group allowed us to draw conclusions concerning the absence of signs of general toxicity, including toxic effects on the adrenal glands, cardiotoxicity, immunotoxicity, and toxic effects on other organs and organ systems, as well as local irritant and toxic effects after repeated irrigation of dioxidine on the back wall of the pharynx in rabbits for 28 days and during the period of delayed observation.

Background. Patients with autoimmune and inflammatory rheumatic diseases (AIRDs) are at high risk of developing COVID-19. Vaccination is an effective method of preventing this disease, which may be unsafe for patients with AIRDs.
The aim of the study is to assess the safety of Gam-COVID-Vac in patients with IVRD in real clinical practice.
Material and methods. A cross-sectional study was carried out. The main group consisted of patients with AIRDs, the control group consisted of individuals without AIRDs. All participants were interviewed by the research physician using a unified questionnaire, additional information was obtained from medical records.
Results. The study included 222 patients with AIRDs (119 with rheumatoid arthritis, 36 with ankylosing spondylitis, 17 with psoriatic arthritis, 17 with Sjögren's disease, 10 with undifferentiated spondyloarthritis, 8 with systemic lupus erythematosus, 4 with metabolic arthritis, 3 with systemic scleroderma, 3 with systemic vasculitis, 2 with polymyalgia rheumatica, 2 with undifferentiated systemic connective tissue disease, 1 with adult Still's disease) and 111 patients without AIRDs. The number of patients with AIRDs who had a combination of local and systemic adverse events (AE) on the introduction of the first component of the vaccine was significantly less than in the control group (22.1 and 44.1%, respectively, P<0.001). Similar differences were also noted after the introduction of the second component (14.0 and 29.7%, respectively, P<0.001). AEs such as pain at the injection site without restriction of movement, weakness, fever, arthralgia/myalgia, headache, and chills were significantly more common in the control group after the introduction of the first component of the vaccine. After complete immunization, AEs were absent in 35.6% of patients with AIRDs and in 21.6% of control group patients (P=0.01). Exacerbations of AIRDs and new autoimmune phenomena were not registered in any cases.
Conclusions. According to preliminary data, immunization of patients with AIRDs with the Gam-COVID-Vac combined vector vaccine appears to be quite safe.

The aim of the study. To analyze formation features of the epidemic situation for tuberculosis (TB) in the context of the COVID-19 pandemic in order to predict the further actions of medical organizations.
Materials and methods. The data for the region for the last 5 years (2017–2021) were analyzed, including 1,762 newly diagnosed cases of patients with TB and comorbidities (according to the data of the Regional Public Health Organization «Regional Clinical Anti-Tuberculosis Dispensary»). All cases were verified using standard diagnostic methods, including molecular genetic methods, to determine the resistance of pathogens to antibacterial drugs.
Results. It was revealed that the epidemiological situation in the region was multidirectional: thus, during the COVID-19 epidemic, the most pronounced incidence decrease was observed among cases of chronic course hepatitis (by 16.4 times), while among patients with tuberculosis the incidence decreased by 2.75 times, and among patients with acute hepatitis — only by 1.5 times (P<0.05). Among the cases of comorbid infection, the most severe course was observed in patients with combined (TB + HIV) infection: there was both a more severe general condition, and the development of adverse (undesirable) reactions to anti-TB drugs, which required an extension of maintenance therapy.
Conclusions. The results of the study showed that against the background of the COVID-19 pandemic in the region, there was no tendency towards a worsening of the epidemic situation, primarily for the more socially significant infection — tuberculosis. At the same time, there was an increase in the number of cases of comorbid pathology, including HIV + TB. In the treatment of patients with comorbid forms of infection, it is necessary to take into account the possibility of developing hepatotoxic reactions and, as a result, the appointment of accompanying drugs with hepatoprotective and detoxification effects in therapy.

The aim of the study was to assess the association of polymorphic variants CYP3A5*3 6986 A>G rs776746 and CYP3A4*22 rs35599367 C>T with the safety parameters of remdesivir therapy in patients with COVID-19.
Material and methods. The study included 156 patients admitted to the City Clinical Hospital No. 15 of the Moscow Health Department with COVID-19 diagnosis, who received remdesivir as an antiviral drug. The frequency of adverse reactions (bradycardia, dyspeptic disorders), as well as various laboratory parameters (ALT, AST, creatinine, ferritin, interleukin-6, and d-dimer levels) were compared between the carriers of wild-type and polymorphic variants of the studied genes.
Results. Carriers of CYP3A5*3 polymorphic variants (GA+AA) had higher ALT levels after the treatment with remdesivir than carriers of the wild variant (GG). When comparing the level of interleukin-6 after therapy with remdesivir, carriers of the polymorphic variant of the CYP3A4*22 (CT) gene had a significantly higher level of this cytokine.
Conclusion. An association between the carriage of polymorphic variants of CYP3A5*3 and an increase in the level of liver enzymes was found. Polymorphic variants of CYP3A4*22 were associated with higher levels of interleukin-6. Additional pharmacogenetic studies are required to assess the possibilities of personalizing antiviral therapy for COVID-19.

Background. Asthma is one of the most common diseases in the world that affects more than 300 million people worldwide. Helicobacter pylori is one of the most common infection worldwide and its colonization in the gastric mucosa releases acute phase proteins that may reveal the pathogenic relationship between the infection and inflammatory diseases. The aim of this study was to evaluate of H.pylori infection in asthmatic children and its relationship with the severity of asthma.
Methods. In this case-control study, 94 patients (aged 2 to 18 years) were divided in two equal groups of asthmatic and non-asthmatic patients. H.pylori infection was assessed in two groups using serum anti-Helicobacter pylori antibody (IgG). Data were analyzed using SPSS 16 software. Chi-square test and T-test were performed. P<0.05 was considered statistically significant.
Results. 36.2% of cases in asthmatic group and 48.9% of cases in control group had positive H.pylori test (P=0. 211). There was a significant relationship between H.pylori infection and the duration of asthma (P=0.002), as well as the age of patients (P=0.04). There was no significant relationship between Helicobacter pylori infection with patients’ gender severity of asthma, family history of asthma and pulmonary function tests.
Conclusion. Results of this study showed that the incidence of H.pylori infection was lower in asthmatic children than the control group but this difference was not statistically significant. Also, there was a significant relationship between H.pylori infection with duration of asthma and age of the patients.

Introduction. The article explores the innovative method of ABA-therapy, as well as the projective method «Children's Drawing» used in the rehabilitation complex of children with delayed psychoverbal development within the autistic spectrum.
The aim of the study was to find new effective methods for the rehabilitation of children with delayed psychoverbal development and autistic personality traits.
Materials and methods. 180 patients were examined in the period from 2019–2021, the age range was 3–5 years.
Results. Significant improvements in fine and gross motor skills, social adaptation, cognitive sphere, as well as improvements in psychological experiences in young patients were observed in patients who underwent ABA therapy as part of a complex of rehabilitation measures in 2–3 courses.

One of the most discussed issues in environmental science and society is plastic pollution of natural ecosystems and its impact on living organisms. This is evidenced by the flow of numerous publications that have appeared in recent years. The results of the studies confirm that the pollution of aquatic ecosystems with plastic waste is considered one of the most severe global environmental problems. The wide distribution of photooxidation and biological degradation products of micro- and nano-sized plastic particles (MP and NP) in the World Ocean is of particular concern, which make the main contribution to biological effects. Catastrophic environmental consequences of marine ecosystems contamination with microplastics are associated not only with economic damage, but also with human health and the biosecurity of mariculture. Human-made plastisphere is a new ecosystem that plays an increasingly significant role in the life of marine microorganisms. Biofilms formed on the rough and hydrophobic surfaces of the plastisphere consist of various taxa of microorganisms and differ in composition from the surrounding marine communities. In addition, they act as depositories and carriers of intra- and extracellular antibiotic resistance genes (ARGs). The purpose of the review is to summarize current information on environmental pollution by microplastics in the context of its role in the conservation and spread of pathogenic bacteria and antibiotic resistance genes in natural environments with an emphasis on marine ecosystems.

Some bacterial infections may become persistent and lead to chronic conditions when treatment was stopped prior to desired efficacy being achieved or when the treatment regimen was not optimized from the start. In such cases, the patient becomes a carrier of a population of resistant microorganisms, which are very hard to fight against. This prompts the scientific community to search for novel, more effective medicines. Untimely, the development of antibiotic resistance to new drugs spurs a vicious cycle. New approaches are needed to develop medications with greater efficacy, with their mechanism(s) of action directed not at the pathogen per se, but rather at the protective functions of the host organism. The purpose of this review is to summarize the literature on the role of the host immune system in elimination of bacterial pathogens. The paper discusses the main targets of antibacterial therapy, describes the structure and function of proteins of the major histocompatibility complex (MHC), and provides examples of studies using candidate molecules with mechanisms of action aimed at enhancing the host immune response. The article discusses mechanisms of bacterial influence on the expression of MHC class I and class II molecules and antigen presentation, as well as options to consider when targeting these molecules as an alternative approach in the treatment of bacterial infections. The authors suggest that MHC molecules are unique targets in the treatment of bacterial infections through the activation of the innate and the adaptive immune response of the host. This approach can serve as a platform for development of a new class of drugs that can be used in addition to the conventional antibacterial therapy.

Antibiotics are widely used in animal husbandry for livestock treatment, as well as in feed additives, as growth promoters. Antibiotics are sometimes used to preserve food and extend shelf life in the food industry. One can often encounter the falsification of agricultural raw materials and finished products with antibiotics for the same purposes. Antibiotics can get into food through animals. Milk and dairy products occupy an important place among food products; they are especially necessary for the younger generation. Currently, antibiotics are considered a serious factor in the contamination of food products, as well as a source of antibiotic resistance and food allergies. The international community is concerned about the problem associated with the steady development of pathogenic microorganisms’ resistance to the drugs currently in use. According to expert estimates, about 700 thousand people die every year globally due to the resistance of pathogenic microorganisms. As a result, the problem of negative impact of antibiotics on humans becomes crucial. Different countries, the WHO, the WTO, and the EAEU, which includes the Russian Federation, adopt regulations and special laws that limit the use of antibiotics in the agro-industrial complex. Therefore, the problem of studying the risks of contamination of food and dairy products with antibiotics is a pressing matter.