Background. Approximately 5–10 % of cases of Parkinson’s disease (PD) are monogenic, in other cases the pathology has a multifactorial etiology. One of recognized pathogenetic pathways of PD is mitochondrial dysfunction, in particular the accumulation of damage in mitochondrial DNA. Hence, the genes of DNA repair proteins are promising candidate genes for multifactorial forms of PD.
The aim. To study the involvement of genes of DNA repair proteins in the development of Parkinson’s disease.
Materials and methods. The associative analysis was carried out while comparing a group of patients with PD (n = 133) with a Tomsk population sample (n = 344). SNaPshot analysis was used to study 8 SNPs in genes of DNA repair proteins (rs560191 (TP53BP1); rs1805800 and rs709816 (NBN); rs473297 (MRE11A); rs1189037 and rs1801516 (ATM); rs1799977 (MLH1); rs1805321 (PMS2)).
Results. Common alleles and homozygous rs1801516 genotypes in the ATM gene predispose the development of PD (odds ratio (OR) – 3.27 (p = 0.000004) and OR = 3.46 (p = 0.00008) for risk alleles and genotype respectively) and rs1799977 in the MLH1 gene (OR = 1.88 (p = 0.0004) and OR = 2.42 (p = 0.00007) respectively); heterozygotes have a protective effect (OR = 0.33 (p = 0.0007) and OR = 0.46 (p = 0.0007) for ATM and MLH1, respectively). The rare rs1805800 allele in the NBN gene (OR = 1.62 (p = 0.019)) and a homozygous genotype for it (OR = 2.28 (p = 0.016)) also predispose to PD. Associations with PD of the ATM, MLH1, NBN genes were revealed for the first time.
Conclusion. Mitochondrial dysfunction is one of the key factors in the pathogenesis of PD, while at least two of the three protein products of associated genes are involved in the development of mitochondrial dysfunction. Accordingly, it can be assumed that associated genes are involved in the pathogenesis of PD precisely through mitochondrial dysfunction.

Taking into account the significance of the HLA complex in the inflammatory and immune responses, we can assume that the potential for limiting or developing pathology in the next generation will be determined at the stage of selection of certain alleles in the spousal genotype.
The aim. To study the role of HLA assortativity in couples with healthy children and couples with children with congenital heart diseases (CHD) through the prism of immunogenetic mechanisms of mutual olfactory choice.
Materials and methods. We studied the distribution of HLA-DRB1 alleles in married couples with healthy children and with children having CHD. To identify the associations of HLA-DRB1 alleles with odor preferences, we also studied the group included young males and females. HLA-DRB1 gene typing was carried out in all participants.
Results. The combination of HLA-DRB1 alleles in couples with healthy children was similar to the combination of these alleles in the mutual olfactory sympathy between unfamiliar young males and females. Allele combinations in the spouses from the experimental group differ from the group of random selection. The frequency of matches for HLA-DRB1 alleles in married couples with children having CHD without was significantly higher than in the control group.
Conclusion. The first stage of selection, associated with olfactory selection, is aimed to the whole population, and it is significantly manifested in the control group (married couples with healthy children). At the same time, in the experimental group (couples with children having CHD), some deviations from the main selection were discovered. Generally, specific HLA-DRB1 allele combinations obtained on the basis of olfactory assessments, indicate the involvement of HLA molecules in pheromone reception.

Background. Chronic obstructive pulmonary disease is a socially significant disease affecting patient’s quality of life. Assessment of endogenous intoxication in patients with chronic obstructive pulmonary disease will allow to understand pathogenetic features of different phenotypes of this disease, which can be taken into account when predicting its course.
The aim of the study. To determine the prognostic value of levels of mediumand low-molecular-weight substances and oligopeptides in patients with chronic obstructive pulmonary disease.
Materials and methods. One hundred and four patients with chronic obstructive pulmonary disease (COPD) and 110 somatically healthy individuals were examined. Molecular weight medium and low molecular weight substances (LMWSM) and oligopeptides (OP) were determined in blood plasma, erythrocytes and urine. Based on these indicators mathematically calculated indices of endogenous intoxication and coefficient of elimination were defined. Statistical processing of the data was performed using the SPSS 26.0 software package (IBM Corp., USA).
Results. In all biological fluids, the levels of average molecules and calculated indices in the COPD patients’ group were statistically significantly different from those in the control group. The indices characterizing endotoxin accumulation were statistically significantly higher, while those characterizing toxin elimination were lower. The level of endotoxemia was correlated with the frequency of exacerbations, clinical manifestations severity, quality of life, COPD group and phenotype.
Conclusions. Frequent exacerbations, groups C and D, bronchitic and mixed COPD phenotypes are characterized by more severe endotoxicosis manifested by high levels of LMWSM, OP and calculated indices.

Inflammatory bowel diseases (ulcerative colitis and Crohn’s disease) tend to increase in frequency and prevalence worldwide and lead to a significant reduction in quality of life with a complicated course. Intravenous administration of corticosteroids in acute severe ulcerative colitis is effective in 60–70 % of cases. Rescue therapy for patients with steroid‐refractory and steroid-dependence attacks is effective for reducing colectomy or colproctectomy and improves long-term treatment outcomes. Despite the proven efficacy of infliximab, limitations to the use of monoclonal antibodies are adverse reactions to the administration of genetically engineered biologic therapy (GEBT), both well-known and studied, and rare.
The aim of the study. To analyze a case of an extremely rare and paradoxical incurable hyperergic reaction that occurred after using genetically engineered biological therapy with tumor necrosis factor alpha blockers in a patient suffering from ulcerative colitis.
Materials and methods. We carried out the search in the PubMed, Embase, Scopus and Medline databases until November 1, 2022 using the following keywords: inflammatory bowel disease, ulcerative colitis (UC), anti-tumor necrosis factor α (antiTNFα), infliximab, fever, adverse events. In the scientific electronic library eLIBRARY, a search was made for Russian-language publications using similar queries in Russian. We analyzed the patient’s medical records from 03.06.2013 up to the present day; the patient signed an informed consent for the publication and discussion of the presented data.
Conclusion. The widespread use of GEBT in the treatment of autoimmune and autoinflammatory diseases leads to the accumulation of both positive and negative experience of clinicians in real clinical practice. The officially described adverse events in the appointment of any drug suggest options for their prevention and treatment. Atypical manifestations or casuistic cases must be systematized for further fundamental pathophysiological studies.

This literature review presents the role of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO), as well as arginine, the enzyme substrate, in the disease of metabolic syndrome and COVID-19 (SARS-CoV-2 virus). Metabolic syndrome is a combination of obesity, insulin resistance, hyperglycemia, dyslipidemia and hypertension. It has been shown that in elderly people, patients with obesity, metabolic syndrome, type 2 diabetes mellitus (DM2), and patients with COVID-19, endothelial dysfunction (ED) and vascular endothelial activation are detected. ED is the main cause of a number of pathological conditions during the development of COVID-19 and earlier in patients with metabolic syndrome, while a sharp drop in the level of nitric oxide (NO) is detected due to a decrease in the expression and activity of eNO synthase and enzyme depletion, which leads to a violation of the integrity of blood
vessels, that is, to vasoconstrictive, inflammatory and thrombotic conditions, followed by ischemia of organs and edema of tissues. It should be noted that metabolic syndrome, DM2, hypertension and obesity, in particular, are age-related diseases, and it is known that blood glucose levels increase with age, which reduces the bioavailability of NO in endothelial cells. Defects in the metabolism of NO cause dysfunction in the pulmonary blood vessels, the level of NO decreases, which leads to impaired lung function and coagulopathy. The review presents possible mechanisms of these disorders associated with ED, the release of eNO synthase, changes in phosphorylation and regulation of enzyme activity, as well as insulin resistance. A modern view of the role of the polymorphism of the eNO synthase gene in the development of these pathologies is presented. To increase the level of endothelial NO, drugs are offered that regulate the bioavailability of NO. These include arginine, agonist NO – minoxidil, steroid hormones, statins, metformin. However, further research and clinical trials are needed to develop treatment strategies that increase NO levels in the endothelium.

Background. Currently, there are two main areas of study of the impact of a new coronavirus infection on mental processes: the first is in connection with the regime of self-isolation and restrictions in a pandemic; the second – with the impact of the pathological process itself and the post-covid syndrome on the central nervous system. The results of the studies indicate the relationship of this infection with local lesions of the brain and the corresponding disturbances in the functioning of mental processes.
The aim of the research. To systematize and analyze the results of studies on the main routes of penetration of the SARS-CoV-2 virus into the central nervous system, cognitive and emotional disorders in people who have recovered from COVID-19, and to discuss the areas of psychological rehabilitation for this group of patients.
Materials and methods. Information search was carried out using Internet resources (PubMed, Web of Science, Scopus, bmj.com, eLibrary.ru, frontiersin.org, sciencedirect. com, ncbi.nlm.nih.gov), literature sources were analyzed for the period from May of 2020 to November of 2021 for the following keywords: COVID-19, SARS-CoV-2, cognitive functions, cognitions, cognitive impairments, emotional dysfunction, affective dysfunction.
Results. According to the analysis of the literature, most researchers identify the neurogenic pathway of SARS-CoV-2 penetration into the CNS, as well as penetration through the bloodstream or through cerebral lymphatic drainage, which are a possible cause of mental disorders of a neurological nature. Correction of these violations involves the creation of a comprehensive system of rehabilitation with the inclusion of psychotherapeutic methods.
Conclusions. Despite the lack of a single picture describing the specifics of cognitive and affective symptoms in COVID-19, in the most general terms, there is a certain consensus. So, quite often, post-COVID cognitive symptoms are characterized by impaired memory and attention, and post-COVID affective symptoms are characterized by increased levels of anxiety, depression, and fatigue. The issues of diagnosis and correction of disorders in post-COVID syndrome and the admissibility of the existence of this diagnosis are still relevant.

Background. Russian Federation is included in the list of 30 countries with the highest burden of tuberculosis, including MDR tuberculosis. The most important part of this problem is the primary MDR/XDR TB in children.
The aim: a comparative analysis of the phenotypic and genotypic profile of drug resistance to anti-tuberculosis drugs (ATP) according to whole genome sequencing of M. tuberculosis strains from children.
Materials and methods. Whole genome sequencing (WGS) results of 61 M. tuberculosis isolates from children with tuberculosis in 2006–2020 in the Russian Federation were analyzed for anti-TB drug resistance mutations, according to the WHO catalog and were compared with the results of phenotypic drug sensitivity.
Results. The M. tuberculosis belonged to two genetic groups: Beijing genotype – 82 % (50/61) dominant Central Asian Russian (31/50) and B0/W148 (16/50) subtypes, and non-Beijing (Ural, S, LAM) – 18 % (11/61). Three isolates belonged to Asian Ancestral subtype (3/50). Of the 61 isolates, only 14.7 % (9/61) were sensitive to antiTB drugs, 49.2 % (30/61) were MDR and 14.7 % (9/61) were pre-XDR. Comparison of the resistance profile (MDR/pre-XDR) with genotype revealed an upward shift for Beijing isolates, in particular Beijing B0/W148 (15/16) subline compared to other Beijing (19/34) (Chi-square with Yates correction = 5.535; p < 0.05) and nonBeijing (5/12) (Chi-square with Yates correction = 6.741; p < 0.05) subtypes. Discrepancies between genotypic and phenotypic drug resistance profiles were found in 11.5 % (7/61) of cases.
Conclusions. Based on the analysis of WGS data, the genotypic characteristics of M. tuberculosis and the most complete set of drug resistance mutations were obtained, indicating a significant prevalence in MDR and pre-XDR TB of cases caused by epidemic subtypes of Beijing (B0/W148 and Central Asian Russian). The molecular mechanisms of adaptation of M. tuberculosis to the treatment of anti-TB drugs are not unique for the child population but reflect the general processes of the spread of MDR/XDR in Russia.

Testosterone assessment is essential for detecting biochemical hyperandrogenism, one of the important diagnostic criteria of polycystic ovary syndrome (PCOS) both in clinical practice and in epidemiological studies. Currently, tandem liquid chromatography-mass spectrometry (LC-MS/MS) is the most preferred technique to measure testosterone level in women. Its validation is important to reproducibility of androgen tests results for clinical practice and for epidemiological studies of the prevalence PCOS.
The aim of the study. To develop and validate a method for determining total testosterone in blood serum using highly efficient LC-MS/MS to assess androgenemia in the epidemiological study of the prevalence of PCOS and its phenotypes in Eastern Siberia (ESPEP STUDY).
Materials and methods. We determined a total testosterone level in serum blood using triple quadrupole mass spectrometer LCMS-8060 (Shimadzu, Japan). The protocol of technique was developed using self-prepared purified human testosteronefree serum with a known concentration of analyzed compound. We used the serum samples of women of reproductive age to test the developed method.
Results. Optimum chromatographic conditions were obtained with a Kromasil 100-2.5-C18 column (2.1 mm × 100 mm; AkzoNobel, Netherlands), and an isocratic elution mode using a mobile phase consisting of acetonitrile and 0.1 % aqueous solution of formic acid. The total flow rate was 0.35 ml/min. The lower limit of quantification was 5 ng/dl with an average accuracy of 100.2 %. During the approbation of the method in a test population sample of 1138 premenopausal women (mean age – 34.3 ± 6.3 years), the median testosterone concentration was 26.9 ng/dl.
Conclusion. It was found that the proposed method for determining testosterone in blood serum has acceptable linearity and reproducibility and meets the requirements for bioanalytical methods under the regulatory documentation. This method can be used for clinical practice and epidemiological study of the prevalence of PCOS.

Background. The participation of immune responses in the pathogenesis of degenerative-dystrophic diseases of the synovial joints determines the feasibility of using more rational approaches to assessing the immune status of patients with this pathology. Despite the ongoing immunological studies in patients with degenerative-dystrophic diseases of the hip joint, there are questions related to the functioning of the immune system as a whole, which require additional research.
The aim of the study was to establish the features of the relationship between the indicators of the immune status and to identify the factors that determine the nature and severity of immunological disorders in patients with coxarthrosis.
Material and methods. The study is based on the results of immunological parameters in 73 patients (mean age – 45.3 ± 2.56 years) with stage III dysplastic coxarthrosis. The data obtained using cluster analysis made it possible to distribute patients into two groups. The first clinical group included 46 patients, the second one – 27 patients. The control group consisted of 28 clinically healthy individuals. Mathematical processing of the results was carried out using the Statistica 6.0 software package (StatSoft Inc., USA) and the mathematical package Mathcad 2001 Pro (MathSoft Inc., USA).
Results. The levels of CD4+ and CD8+ cells and IgA were determined as the classification features that make the greatest contribution to the division of the studied groups. Model experiments have shown that a specific combination of the magnitude of each of the noted factors with a certain degree of probability makes it possible to assess the state of the initial immunological reactivity and verify the nature and severity of immunological disorders.
Conclusion. The information obtained is of great importance, since it allows predicting the course of the recovery period after surgery and assessing the risk of developing possible postoperative complications in patients with severe articular pathology.

Background. Epidemiological and epizootological monitoring of natural plague foci requires an integrated approach to solving problems, taking into account the phenotypic and genetic variability of Y. pestis and zoning of natural plague foci. The introduction of a new molecular genetic methodology aimed at studying the genomic polymorphism of the plague pathogen provides reliable results for the differentiation of not only groups, but also individual strains.
The aim. To determine the genotypes of the plague microbe from different autonomous foci of the Republic of Kazakhstan.
Materials and methods. 105 strains of Y. pestis isolated from various natural plague foci of Kazakhstan in 1951–2015 were studied. The phenotypic properties of the strains were studied using standard microbiological methods. A polymerase chain reaction (PCR) was used to detect fragments of the cafl, pst and YPO2088 genes. Multilocus variable number tandem repeat (VNTR) analysis (MLVA) was performed for 25 VNTR loci.
Results. The phenotypic properties of the strains were preliminarily studied and the strains of the plague microbe were tested for specificity using the Pest-Quest test system (Kazakhstan). The PCR study confirmed the species-specific affiliation of Y. pestis strains. A variety of strains with typical phenotypic characteristics was revealed. MLVA for 25 key loci (MLVA25) revealed that the studied strains of the plague microbe are phylogenetically closest to the Mediaevalis biovar representatives. A phylogenetic tree of the studied strains has been obtained. It was found that 9 genotypes circulate on the territory of Kazakhstan, and their distribution in certain natural plague foci was determined.
Conclusions. The resulting clustering indicates the relationship between the strain groups obtained on the dendrogram by the MLVA25 method and the territories of certain natural plague foci.

Background. Aptamers are small single-stranded DNA or RNA molecules that have an affinity for a specific target molecule. The main method of aptamers construction is the technology of systematic evolution of ligands with exponential enrichment (SELEX). However, the exact approach depends on the nature of target molecules, and is selected and optimized by each researcher independently. The article describes the technique of production of aptamers to the tick-borne encephalitis virus (TBEV) using membrane ultrafiltration with a molecular weight cut-off of 100 kDa. As a result, the pool of aptamers with observable affinity for TBEV is successfully selected and enriched.
The aim. To develop the technique suitable for selection of specific DNA aptamers to a live, crude TBEV suspension directly in cell culture supernatant.
Materials and methods. The selection of aptamers was carried out using a modified SELEX DNA aptamer technology in combination with semipermeable membrane ultrafiltration using Vivaspin 6 (Sartorius, Germany) concentrators of molecular weight cut-off of 100 kDa. Enrichment of a specific pool of aptamers was performed using real time polymerase chain reaction. Aptamers were sequenced with automated Sanger sequencing method. The direct virucidal effect of the aptamers was determined by the decrease in the titer of the infectious virus after incubation with the aptamer.
Results. The pool of aptamers to TBEV was selected and enriched. This aptamer pool expressed affinity both to the infectious TBEV and to the TBEV antigen. Sixteen aptamers were sequenced from this pool and four of them were synthesized and tested for antiviral activity against TBEV. No antiviral activity was observed.
Conclusions. The technique developed that can be successfully used to select aptamers to a live virus culture for the viruses comparable in size to TBEV or larger.

Obesity is associated with a high risk of cardiovascular diseases. Therefore, an urgent task of preventive medicine is to search for markers indicating the early development of cardiovascular pathology in young people in order to develop preventive measures.
The aim of the study. To study macro- and microhemodynamics in young people with normal and elevated body mass index (BMI).
Methods. After receiving informed consent, we evaluated microhemodynamics using Doppler ultrasound (Angiodin-PC (BIOSS, Russia); 16 MHz sensor) and macrohemodynamics by daily blood pressure monitoring (MnSDP-3 (BPLab, Peter Telegin LLC, Russia)) in students (20.05 ± 1.46 years old) who did not play sports in the period from 2019 to 2021. The subjects were divided into 2 groups according to their BMI: group 1 (control) – BMI ≤ 25 (average age 20.5 ± 0.7 years; average weight 59.47 ± 8.26 kg); group 2 – BMI ≥ 25 (average age 20.12 ± 1.73 years; average weight 83.8 ± 9.59 kg).
Results. It has been proven that already at a young age, an increased BMI adversely affects the elasticity of the vascular wall. We registered a statistically significant increase in the peripheral resistance index (RI; Purcello index) (p = 0.022,) and the Stewart index (SD) (p = 0.0034) which are reflecting vascular wall remodeling. There is also a statistically significant increase in average blood pressure per day, day/night against the background of increased BMI. An insufficient degree of nocturnal decrease in systolic blood pressure is revealed, as well as an increase in pressure load and blood pressure variability.
Conclusion. Since changes in the structure and function of the vessels of the microcirculatory bed are a precursor to preclinical disorders of systemic blood flow, the introduction of high-frequency Doppler ultrasound into the protocol of examination of people having metabolic syndrome will allow us to assess the functional status of large and small arteries and to identify early vascular disorders.

Background. The results of treatment of the elderly patients operated for spinal stenosis allow us to suggest that a cascade of degenerative changes in the spinal motion segments causes the formation of an adjacent level syndrome, pseudarthrosis, and in some cases – the instability in the fixing structure.
The aim of the study. To determine the prognostic factors for the adjacent level syndrome in patients after decompressive and stabilizing spinal surgeries.
Methods. We carried out a retrospective cohort study of the surgical treatment of 129 elderly patients (over 60 years of age) for the period from January 2018 to March 2022, who underwent surgery at the lumbosacral level of spine for degenerative spinal stenosis.
Results. The outcomes of surgical treatment of 129 patients and the results of discriminant analysis of morphometric studies of computed tomography data indicate that the most significant indicators for the development of the adjacent level syndrome are the lordosis angle in the segment adjacent to the operated one (the mean value in the analyzed group is 12.87 ± 2.22°; in the control group – 11.92 ± 2.97°); the anterior height of the adjacent intervertebral disc (the mean value in the analyzed group is 12.70 ± 2.44 mm; in the control group – 11.46 ± 3.58 mm) and the difference of anterior and posterior disc heights at the adjacent level (the mean value in the analyzed group is 5.48 ± 2.84 mm; in the control group – 6.27 ± 2.71 mm).
Conclusion. When analyzing the treatment outcomes of 129 elderly patients operated for degenerative spinal stenosis using instrumented spinal fusion, we revealed that in 16 patients, the adjacent level syndrome developed with an increase in the lordosis angle at the level adjacent to the operated segment. An increase in the anterior height of the adjacent intervertebral disc and the decrease in the difference of anterior and posterior disc heights at the adjacent level can be considered as unfavorable prognostic factors (p = 0.83).

Examination of the spine using radiological methods remains the most frequently conducted study in the outpatient practice of almost any radiologist. In most cases, changes in the spine are degenerative and dystrophic in nature. These changes in the spine are the leading cause of loss of activity among adults and the elderly, and cover a wide range of age-related structural changes. It is of great importance to understand the possibilities and limitations of radiological methods of diagnostics. The description of morphological changes observed in degenerative and dystrophic changes requires the use of unified terminology and classifications among clinicians and radiologists.
The aim. To present modern concepts in the assessment of degenerative changes of the spine using radiological methods. A description of the standardized international nomenclature of intervertebral disc pathology and current classifications of spinal canal stenosis are presented.
Material and methods. For literature search, we used electronic databases MEDLINE (PubMed), eLibrary, EMBASE and Cochrane Library with a selection of sources published from 2000 to 2021. We analyzed the works devoted to the diagnosis of degenerative changes in lumbar spine and to degenerative stenosis.
Conclusion. The key to productive communication between physicians is the uniformity or standardization of terminology and definitions used. It is important that the protocol of description, its terms, semantic expressions be uniform and understandable to specialists who are involved in the diagnosis and treatment of the spine. Magnetic resonance imaging is a valuable method in the diagnosis of degenerative changes of the spinal column, but it has its limitations.

In order to find out the mechanisms of pathogenesis of degenerative-dystrophic diseases of the spine, it is of particular interest to search for body parameters which are directly or indirectly interrelated with the key factors of peripheral conversion of nidus iodothyronines and constitute a system of network interactions, affecting metabolic indicators at the local and systemic level.
The aim. To search for correlations of local key factors of peripheral conversion of Ligamentum flavum iodothyronines with indicators of biochemical, hematological and hormonal blood profiles of patients with stenosing processes of the spinal canal and dural sac in the lumbar spine.
Materials and methods. 33 patients (15 males, 18 females) with stenosing processes of the spinal canal and dural sac in the lumbar spine were examined (mean age – 45.73 ± 1.95 years). The expression of deiodinase genes and other candidate genes was determined in Ligamentum flavum biopsies collected during surgical treatment. Biochemical, hematological and hormonal parameters were determined in peripheral blood. The resulting data array was processed in order to find correlations between the parameters of systemic and local metabolism.
Results. The relationships of deiodinases with the expression of GDF5, MMP1, MMP3 and TIMP1 in Ligamentum flavum (p < 0.05) were found. Of the hormonal profile of the blood serum, the most significant indicators were thyreotropin, free triiodothyronine and thyroperoxidase antibodies. In the biochemical profile, levels of direct bilirubin, total cholesterol, HDL and LDL cholesterol and triglycerides changed along with the expression of deiodinases. Correlative relationships with the expression of deiodinases were found for the following hematological analytes of whole peripheral blood: hemoglobin, mean corpuscular hemoglobin concentration, numbers of granulocytes, lymphocytes, eosinophils, monocytes, band neutrophils, red cell distribution width and platelet crit. The data obtained indicate the involvement of peripheral conversion factors in the pathogenetic process and provide information to form a new view on the pathogenesis of degenerative-dystrophic processes in the Ligamentum flavum of patients with stenosing processes of the spinal canal and the dural sac in the lumbar spine.

Background. This study was carried out due to persistent increase in the incidence of ischemic stroke in people of working age and insufficient knowledge of risk factors affecting its clinical course in the early recovery period in young and middle-aged patients.
The aim. To identify and to study variants of the clinical course of the early recovery period of ischemic stroke in young and middle-aged patients; to determine the risk factors for its unfavorable course.
Materials and methods. We carried out a longitudinal prospective study, which involved 145 patients with ischemic stroke in its early recovery period. The main risk factors for cardiovascular diseases were analyzed. Dynamic observation of these patients allowed us to determine five variants of the clinical course of the ischemic stroke early recovery period – regressive, regressive with residual mild focal neurological symptoms, stable, slowly progressive and rapidly progressive.
Results. Regressive course was observed in 58 (40 %) patients; regressive course with residual mild focal neurological symptoms – in 66 (45.5 %) patients; stable course – in 9 (6.2 %) patients; slowly progressive course – in 8 (5.5 %) patients, rapidly progressive course – in 4 (2.8 %) patients. The following risk factors had statistically significant affect on the unfavorable course of the disease: more pronounced motor, sensory and speech disorders at the time of patient’s admission to the hospital and at the end of the ischemic stroke early recovery period; severity of ischemic stroke according to the National Institutes of Health Stroke Scale (NIHSS); damage to the carotid basin of the brain; ischemic heart disease; irregular intake or patient’s refuse of taking prescribed antiplatelet, lipid-lowering, antihypertensive therapy (p < 0.05).
Conclusions. Defining the variant of the clinical course of the ischemic stroke early recovery period in young and middle-aged patients and risk factors for its unfavorable course is important in determining tactics and further neurorehabilitation measures.

The analysis of literature data on ischemic damage to the brain and the organ of vision was carried out in order to study etiological factors, pathogenetic processes, parallel flow and mutual influence of two nosological forms: dyscirculatory encephalopathy and vascular optic neuropathy. According to the World Health Organization, there is much more people suffering from cardiovascular diseases: atherosclerosis, hypertension, diabetes mellitus and coronary heart disease. These diseases result in ischemic damage to a number of vital organs, including the central nervous system and the visual analyzer. Chronic vascular pathology of both the brain and the eye is one of the leading causes of patients’ life quality decrease of and their disability. The “triggering” causes of brain and eye damage, according to researchers, are cerebral atherosclerosis, elevating/fluctuating blood pressure, coronary heart disease, and carbohydrate metabolism disorders. Disorders of the systemic blood supply caused by these etiological factors lead to a progressive lack of oxygen supply to organs and tissues, followed by the development of intracellular and cellular hypoxia, and an ischemic intracellular cascade of biochemical disorders leading to dysfunction and sometimes cell death.
In addition to direct hypoxic-ischemic damage of the nervous and visual systems cells, endothelial dysfunction contributes to the progression of these diseases, leading to a pronounced change in the wall at the level of small vessels, a change in its reactivity and a violation of the coagulation properties of blood, and as a consequence, to a gradual accumulation of ischemic and secondary degenerative changes in brain and eye cells.
Knowledge of etiological factors and patterns of development of brain and eye combined ischemic damage can allow clarifying the complex of diagnostic measures, developing preventive measures, as well as prescribe pathogenetically justified treatment of existing pathology.

The human cornea – the anterior fibrous membrane of the eye, is a unique ordered optical-biological system that is avascular, saturated with nerve endings, includes tissue-specific cells, consists mainly of various types of collagen. An exceptional feature of the collagen layers of the cornea, including the collagen plates of the stroma, is transparency, which provides physiological refraction and light transmission due to the stable supporting properties of the cornea. The data on the morphological structure of the cornea, which is an important element of the optical system of the eye, are of considerable interest not only from theoretical, but also from practical positions. This is due to the fact that the identification of the first signs of deviation from normal physiological morphological and ultrastructural criteria in the cornea allows us to establish the nature of its pathological changes, which can be caused by both hereditary predisposition and local and general disorders. It has been shown that the thinning of the layers of the cornea, a decrease in the density of endotheliocytes or keratocytes signal the development of dystrophic processes in it. In addition to evaluating quantitative morphometric data, changes in qualitative ultrastructural indicators play an important role. In particular it was found that a decrease in the density of endothelial cells is accompanied by an increase in their size and a decrease in the cell nucleus. In addition, a number of degenerative pathological conditions are characterized by a decrease in the diameter of collagen fibrils and a change in the density of fibrillary packaging.
This literature review presents basic information, features of morphology, ultrastructural organization and functional purpose of layers and cells of the human cornea.

Background. Cognitive impairment (CI) is one of the important disability factors in the elderly. The role of CI in prognosis of the frailest patients with limited mobility is uncertain.
The aim. To determine the influence of the initial cognitive status in the group of patronage patients aged 60 years and older on the risk of mortality within one year.
Materials and methods. Study group consisted of 450 patients from patronage group with one-year period of observation (from July 2019 till July 2020). Initial physical, functional, neuropsychiatriac and social statuses were evaluated by comprehensive geriatric assessment. Cognitive impairment was screened by Mini-Mental State Examination (MMSE), with dividing patients into dementia group (MMSE ≤ 24) and no-dementia group (MMSE > 24). The mortality rate after one year was assessed.
Results. Of the 450 patients included in the study, dementia was present in 44.2 %. Patients with dementia were more prone to greater severity of chronic pain, sleep disturbances, depression, malnutrition and anemia. After one year of observation 34 out of 196 patients (17.3 %) in the group of patients with dementia and 18 out of 248 patients (7.3 %; p = 0.002) in the no-dementia group died. According to multivariate analysis, independent risk factors for death in patients with dementia were anemia, hearing impairment and a history of bone fractures.
Conclusion. Thus, the assessment of the cognitive status of frail patients with limited mobility is important for the purpose of identifying the most vulnerable individuals with a high risk of adverse outcomes.

Background. The neuropsychological approach suggests that differences in cognitive processes are associated with the variability of combinations of signs of partial dominance of certain brain structures, manifested in the form of individual laterality profiles. However, the problem of identifying and studying the relationship between interhemispheric asymmetry and cognitive functions in adolescents with a high level of intelligence remains not fully resolved, which determines the relevance of this study.
The aim of the research was to describe the relationship between the type of profile of interhemispheric asymmetry with the characteristics of cognitive functions in adolescents with average and high levels of intelligence.
Materials and methods. The sample included 52 people aged 12–15 years: 26 adolescents with high level intelligence (main group), 26 adolescents with an average level of intelligence (control group). The following research methods were used: Wechsler test (WISC-IV), method for studying the profile of interhemispheric asymmetry (Khomskaya E.D., Efimova I.V.); method “Correction test” by B. Bourdon; method ”Story on a given topic”.
Results. The majority of adolescents with a high level of intelligence revealed the severity of right-lateral features, which were traced in the manual, auditory and visual spheres of sensorimotor asymmetry. At the same time, the severity of right-lateral and ambilateral features is accompanied by more pronounced indicators of the development of cognitive functions. Adolescents with the type of profile of interhemispheric asymmetry “Left-handed” were characterized by an insufficient level of attention stability and a reduced ability for detailed speech utterance, regardless of the level of intelligence.
Conclusions. The data obtained show that the peculiarity of individual profiles of interhemispheric asymmetry determines the uneven development of a number of mental functions in adolescence and the different readiness of brain mechanisms to support various cognitive processes. We assume that the results of the work will expand the understanding of the role of interhemispheric asymmetry of the brain in the organization of cognitive functions in adolescents with a high level of intelligence.

Stress fractures are an actual problem of modern medicine. A fracture associated with insufficiency of the bone tissue of the knee condyles is a new type of stress fracture that occurs in people aged 50–55 years in response to a normal daily activity, but with damage to the weakened subchondral bone tissue of the joint caused by various reasons. This literature review is mainly based on data from foreign medical sources, since there is very little information on this type of fracture in Russian sources. This is primarily due to the fact that initially the world and Russian medical communities designated this type of fracture as a spontaneous osteonecrosis of the knee (SONK). In recent years, this term has been revised abroad and replaced by a more suitable one – subchondral insufficiency fracture of the knee (SIF/SIFK). According to modern concepts, it is necessary to clearly distinguish among the concepts of osteonecrosis and subchondral insufficiency fracture of the knee. The reason for this is not only differences in the pathogenesis of these pathologies, but also fundamentally different approaches to managing these patients. Thus, taking into account the fundamental differences in the treatment of patients with stress fracture associated with bone insufficiency and patients with osteonecrosis, and also the relevance of stress fracture of the knee condyles, we state the following aim – to study the available literature on this problem.

Background. To date, the problem of choosing the optimal graft for anterior cruciate ligament (ACL) reconstruction and the methods for its formation is one of the main trends in the surgical treatment of patients with anterior knee joint instability.
The aim. To compare the results of the anterior cruciate ligament reconstruction using the known method and the new proposed method for autograft formation.
Materials and methods. The results of treatment of ACL injury in 44 patients were assessed. In the main group (19 patients), an original technique of ACL reconstruction from 1/2 of the width of m. peroneus longus tendon was used. In the control group (25 patients), ACL reconstruction was performed using a graft from the m. semitendinosus tendon prepared by the Lubowitz method.
Results. The mean difference in the circumference of the distal third of the hip in the main group was 1.57 ± 1.162 cm and was statistically significantly better than in the control group, where the mean difference in the hip circumference was 4.74 ± 1.7207 cm.
The range of motion of the knee joint in the main group 3 months after the surgery was 128.42 ± 9.287°, and in the control group mean flection was 109.6 ± 9.120°.
The functional results in the main group were assessed by the Lisholm scale and were statistically significantly better than the results in the control group. The functional results by the AOFAS (American Orthopedic Foot & Ankle Society) scale in the main group were 100 points before the surgery and at all terms after the surgery: this indicates that the use of 1/2 of the width of m. peroneus longus tendon does not cause the its functional impairement.
Conclusion. Anterior cruciate ligament plasty with use of 1/2 of the width of m. peroneus longus tendon prepared by the proposed method showed statistically significantly better results compared to the preparation of autograft from semitendinous muscle tendon using known method.

The aim of the study. To establish the possibility of using the X-ray method for determining the position of the metatarsal heads for preoperative planning in the treatment of patients with forefoot deformities.
Material and methods. The proposed radiological method for determining the position of the metatarsal heads includes performing radiography on a special platform. On the X-ray image, the relative position of the metatarsal heads is determined. Using the proposed X-ray method, we examined 15 patients with transient metatarsalgia under the 3rd metatarsal head, which developed after surgical treatment of hallux valgus and hammertoe (2nd toe), and 28 patients with similar forefoot deformity without postoperative metatarsalgia.
Results. As a result of the proposed X-ray method, we found that in in 86.67 % of patients with transient metatarsalgia, the 3rd metatarsal head was below the adjacent 2nd and 4th metatarsal heads. In 82.14 % of patients without postoperative complications, the 3rd metatarsal head was higher or at the same level as the adjacent 4th metatarsal head. The clinical application of the proposed method made it possible to determine the position of the 2nd, 3rd or 4th metatarsal heads and to establish normal variants and deviations from the norm.
Conclusions. The proposed X-ray method makes it possible to effectively determine the relative position of the metatarsal heads and to choose the optimal surgical tactics for the treatment of patients with forefoot deformities. The proposed method for determining the position of the metatarsal heads is advisable to be included in the preoperative examination along with the standard X-ray of the foot bones, due to its reproducibility, as well as the value of the information obtained.

Rotator cuff ruptures are the most common injuries of shoulder joint with an incidence of about 20 %. This pathology is more common in adults over 60 years of age because it is caused by degenerative changes in the tendon. Massive injuries account for 10–40 % of all rotator cuff injuries. Currently, there is no unified surgical tactics for the treatment of patients with massive ruptures of rotator cuff tendons.
The aim. To assess the efficiency of transposition of the latissimus dorsi tendon in patients with massive ruptures of the rotator cuff tendon.
Materials and methods. The study included 15 patients with Patte stage III massive ruptures of the rotator cuff who had transposition of the latissimus dorsi tendon.
Results. The article presents clinical cases of surgical treatment of patients. The following criteria were assessed: mean age; time since injury; duration of the surgery; blood loss volume; functional results by the ASES (American Shoulder and Elbow Surgeons) Shoulder Score. Taking into account the ASES Shoulder Score indicators 1 year after the surgical treatment, the following results were obtained: excellent results – in 9 (53.3 %) cases; good results – in 1 (13.4 %) case; satisfactory results – in 5 (33.3 %) cases.
Conclusion. When preserving the articular cartilage, the method of choice in the treatment of patients with massive ruptures of rotator cuff tendons is transposition of the latissimus dorsi tendon. At the same time, an incomplete restoration of the function of the injured limb was registered in 33.3 % of patients, which requires further study and modification of the known method of transposition of the latissimus dorsi tendon.

Background. Sporadic multigland parathyroid disease (MGD) account for 1/4 of all cases of primary hyperparathyroidism (PHPT). There are no specific signs of MGD in comparison with single-gland parathyroid disease in PHPT. The only radical treatment is surgical, therefore, determining the number of excessively functioning parathyroid glands at the preoperative stage is important for choosing the extent of the operation and the success of the treatment in general.
The aim. To identify the specific signs of multigland parathyroid disease in patients who underwent surgery for primary hyperparathyroidism.
Methods. We conducted a single-center prospective study including 126 cases of surgical treatment of PHPT from December 2019 to June 2021. The study included an analysis of demographic, clinical, laboratory parameters and visual methods of topical diagnosis of parathyroid glands (ultrasound, scintigraphy, multislice computed tomography). The main endpoint of the study was the identification of characteristic signs of MGD in patients with PHPT.
Results. Lower values of creatinine (p ≤ 0.01; Mann – Whitney U-test), albuminadjusted calcium (p ≤ 0.05; Mann – Whitney U-test), parathyroid hormone (p ≤ 0.01; Mann – Whitney U-test), glomerular filtration rate (p ≤ 0.01; Mann – Whitney U-test) and inconsistency of two methods of preoperative imaging (p ≤ 0.01; χ2) were set as specific signs of multigland compared with single-gland parathyroid disease.
Conclusion. The results of preoperative biochemical and imaging studies can become the basis for differentiating single-gland and multigland parathyroid disease in primary hyperparathyroidism.

Background. Appendicitis-like diverticulitis is considered a rare disease and is usually the subject of clinical reports. Clinical manifestations of this pathology is similar to those of appendicitis, which is why a preoperative diagnosis is made quite rarely. When carrying out the study, we considered a clinical case of acute phlegmonous appendicitis with a rare variant of the appendix wall diverticulum.
Material and methods. To assess clinical cases, a retrospective analysis of medical documentation (medical records of patients with diverticulitis in particular) was used. The assessment of clinical symptoms was accompanied by using general clinical, histological and microbiological methods.
Results. Patient I., 62 years old, was diagnosed with acute appendicitis. An urgent appendectomy was carried out, during which the vermiform process was removed. It was located retrocecally, in the adhesive process and loose infiltrate. The length of the process is 7–8 cm, its diameter is 1–1,5 cm. 6 diverticula up to 0,7 cm in size are visible. When the process is cut, the pyoid contents protrudes from its lumen. In addition, the appendix removed during appendectomy was sent for pathological study. A standard histopathological study was carried out with the step-like sectioning and hematoxylin and eosin staining.
Conclusion. From the results of a pathological study, it was found that the layers of the vermiform process wall with diverticula are diffusely infiltrated by polymorphonuclear leukocytes. The mucous membrane is anesthetized and had ulcerative defects. The patient was diagnosed with phlegmonous appendicitis, periappendicitis, diverticulitis.
Vermiform process diverticulitis is not a common pathology, however a timely diagnosis can cause quite severe complications.

In recent history, the functions and forms of health care remain insufficiently analyzed, despite the fact that the incentives invested in medicine determine not only the volume and structure of medical care, but also the reasons for its provision, which are becoming wider, and costs are increasing. The COVID-19 pandemic, as well as the global geopolitical, ideological and economic crisis that emerged in 2022, will require changes in both the structure and economics of the health care system in accordance with its main mission – providing conditions in which people can be healthy.
The aim of this article is to analyze the concept of a modern health care system.
Materials and methods. Statistical materials of the Russian Research Institute of Health, methods of content analysis, analytical materials of Russian and foreign researchers, including those posted on the Internet, were used.
Results. The materials presented in the article allow us to talk about the emergence of a new form of healthcare organization during the life of just one generation of people, where economic incentives are dominant, characteristic of the market and commodity production, the vector of development of which is largely determined by the interests of international financial institutions, clinical corporations, as well as enterprises, manufacturing medical and pharmaceutical products. The expansion of the resource base in this model can occur by attributing epidemic character to certain diseases, as well as by turning social phenomena into medical problems. Therefore, there is always a shortage of resources, and it is not possible to eliminate it without changing the paradigm of the development of the industry and qualified management.
Findings. Radical changes in the structure and economics of health care need to be made in line with the industry’s core mission of providing conditions in which people can stay healthy. The basis of these changes is the displacement of market self-regulation and the genesis of a mixed public-private (hybrid) healthcare economy.

Background. The discovery of new pharmacological agents for myocardial protection during reperfusion injury is an urgent goal of modern physiology and pharmacology.
The aim of the study. To identify the potential for protecting the myocardium from reperfusion injury by administering the delta-2 opioid receptor agonist deltorphin-II prior to reperfusion in old rats with diet-induced metabolic syndrome.
Materials and methods. The study was performed on Wistar rats aged 60 days (young rats) and 450 days (old rats) before the onset of a study. Metabolic syndrome (MetS) was modeled for 84 days with a high-carbohydrate high-fat diet (16 % protein, 21 % fat, 46 % carbohydrate) with the replacement of drinking water with 20 % fructose solution. Myocardial infarction was performed by 45-min coronary occlusion followed by 120-min reperfusion; the size of the area of the necrotic myocardium was determined relative to the size of the hypoperfusion zone. The delta-2 opioid receptor agonist deltorphin-II was administered once intravenously 5 minutes before the end of ischemia.
Results. It was found that coronary occlusion and subsequent reperfusion both in groups of young and old rats led to the formation of myocardial infarction (necrosis), the size of which was 45 % of the size of the risk zone. Administration of deltorphin-II in old rats led to a limitation of infarct size to 30 % of the size of the risk zone, i. e. 1.7-fold. The use of deltorphin-II in old rats with MetS contributed to a decrease in infarct size to 27 % of the size of the risk zone (1.5 times). The obtained results demonstrate the cardioprotective efficacy of the delta-2 opioid receptor agonist deltorphin-II in aging and metabolic syndrome in rats.
Conclusions. These data may serve as a basis for conducting preclinical studies of deltorphin-II as a drug for treatment of acute myocardial infarction.