The aim of the review. To analyze the prevalence of sarcopenic obesity among elderly and senile people, to assess its causes, and to present modern methods for its prevention and physical rehabilitation.
This review article discusses the most recent evidence on age-related changes in fat and muscle tissue, and on calorie restriction and exercise that have positive effect on physical performance in older people with sarcopenic obesity. In addition, potential gaps in clinical practice guidelines that merit attention in future research are identified and analyzed.
Search strategy. We used the following key words to define participation in the review:
“sarcopenic obesity”, “sarcopenia with obesity”, “sarcopenia”, “elderly/old age”. Inclusion and exclusion criteria. The review included original research results (reviews, meta-analyses). Editorials, proceeding of the conferences, and research protocols were excluded. The study sample included women and men of any race aged ≥ 60 years with a diagnosis of sarcopenic obesity and with preserved locomotion function. Articles involving hospital patients were also excluded. Non-human studies and studies that did not report precise intervention criteria (e. g., nutrition, exercise, duration, etc.) were excluded.
The literature search was conducted in four electronic databases: PubMed, Cochrane Library, Springer, Scopus, for the period from 2013 to August 1, 2023. There were no restrictions on the language of the publication.

There is an insufficiency of data on the characteristics of physical performance of schoolchildren in the critical period of ontogenesis associated with pubertal development.
The aim of the study. To determine the factors and level of physical performance of schoolchildren aged 13–14 years, taking into account pubertal development.
Methodology. The study involved healthy male adolescents aged 13–14 years (n = 165). Five stages of puberty were determined. To diagnose the level of physical performance, a complex of functional and ergometric tests and a battery of motor tests were used. The structure of performance was determined based on the factor analysis.
Results and discussion. We determined the factors characterizing physical performance: aerobic capacity; absolute aerobic power; anaerobic alactic performance; anaerobic glycolytic performance; relative aerobic power. The identified factors are associated with zones of relative power. It has been established that during puberty, changes in indicators combined into different factors occur non-linearly and non-simultaneously. The results of the study show that subjects of the same age with stages II, III and IV of puberty differ in the level of key bioenergetic performance criteria. Transition to higher stages of puberty is accompanied with progressive dynamics of most indicators associated with factors of anaerobic performance, while indicators of aerobic power and capacity change in different directions, showing in some cases a tendency to temporarily decrease.
Conclusion. It is advisable to use the results of the study when organizing various types of monitoring the functional state and regulation of aerobic and anaerobic physical activity in adolescents aged 13–14 years at different stages of puberty. The obtained materials can serve as a scientific basis for improving the physical education system in order to increase the functional capabilities of children’s bodies during the critical period of ontogenesis associated with pubertal development

Background. Chronic endometritis (CE) is an inflammatory hysteropathy causing miscarriage and infertility. High invasiveness of the main method of CE diagnosis and vague clinical picture necessitate the need for the development of less invasive approaches to establish the presence of this disease.
The aim of the study. To establish a significant association of the concentration of pro- and anti-inflammatory interleukins in the blood serum with the presence of chronic endometritis in premenopausal women without concomitant endocrine diseases.
Materials and methods. This re-analysis of the data is based on the results of a cross-sectional study conducted between May 2017 and December 2019 which included 198 premenopausal women. In all participants, body weight and height were measured with the calculation of the body mass index, the concentration of Creactive protein, pro- and anti-inflammatory cytokines in the blood serum was determined, and a pipelle biopsy was performed to determine the CD138 expression in the endometrial stroma. Non-parametric methods, as well as ROC analysis, were used for statistical analysis.
Results. 86 women were included in the re-analysis of the data, 37 of them had a confirmed diagnosis of chronic endometritis. Statistically significantly higher values of interleukin 1 (IL-1) concentration (p = 0.0028) and IL-1/tumor necrosis factor α ratio (p < 0.001) were determined in women with CE and normal body weight; threshold values of these parameters were ≥ 1.35 pg/ml (sensitivity 75 %, specificity 83 %; 95% confidence interval (95% CI): 0.88–2.15) and ≥ 1.03 (sensitivity 85 %, specificity 78 %; 95% CI: 0.81–1.27) respectively. Such a relationship was not revealed in women with overweight.
Conclusions. The obtained results can be the basis for conducting a larger-scale study with determining the concentration of cytokines not only in the blood serum, but also in the endometrium of women with CE, which will allow the development of a minimally invasive method for determining the risk of the presence of chronic endometritis in premenopausal women.

The polycystic ovarian morphology (PCOM) is a generally accepted ultrasound marker for ovulatory dysfunction, is one of the criteria for polycystic ovary syndrome (PCOS) and is established based on the assessment of ovarian volume (OV) and the follicle number per ovary (FNPO), taking into account the upper normal values determined in healthy premenopausal women. However, there is a necessity for regular revision of the PCOM characteristics depending on ethnic and age characteristics.
The aim. To develop differentiated standards for assessing the ultrasonographic ovary structure in premenopausal women of various ethnicity.
Materials and methods. From March 2016 to December 2019, a multicenter cross-sectional prospective study was conducted in Eastern Siberia (Irkutsk region) and in the neighboring Republic of Buryatia. The study included 1134 participants: 715 women of Caucasian origin, 312 Asian women, 107 women of mixed ethnic subpopulation.
Results. It has been established that for Caucasians, it is advisable to diagnose PCOM when the ovarian volume is 9 cm3 and/or FNPO ≥ 12; for women of the Asian population – when the ovarian volume is 7 cm3 and/or FNPO ≥ 11; for women of mixed ethnicity – when the ovarian volume is 8 cm3 and/or FNPO ≥ 9. An important advantage of our study is that all participants were recruited from a non-selective multi-ethnic population of women with comparable socio-demographic characteristics living in the same geographical conditions.
Conclusion. Differentiated approach for identifying the polycystic ovarian morphology in premenopausal women of different ethnic groups requires using ethnically differentiated normative readings

Ovarian reserve is the basis of female fertility. The main markers of ovarian reserve are the level of anti-Mullerian hormone and the number of antral follicles. In addition to the natural age-related loss of follicles, many women experience a premature diminished ovarian reserve associated with a number of factors. This can be caused by both various diseases and environmental factors, lifestyle, and social aspects.
The aim of this review was to examine the influence of external factors on the ovarian reserve and women fertility. A systematic analysis of data from modern scientific literature, domestic and foreign sources was carried out. The search involved such resources as PubMed, MEDLINE, Science Direct, eLibrary, Scopus, Cyberleninka. A detailed analysis of the influence of environmental pollution, lifestyle (sleep, nutrition, physical activity), previous surgeries, bad habits, obesity, psychological and social factors on the ovarian reserve and reproductive function of women was carried out. Significantly diminished ovarian reserve was noted with low sleep quality, excessive physical activity, and an unbalanced diet poor with animal proteins. Regular consumption of alcohol, smoking and exposure to certain chemical environmental pollutants cause premature follicle apoptosis and the onset of menopause. Circadian dysrhythmia, chronic stress and obesity can lead to the ovarian menstrual cycle disorders and the development of infertility in women. Previous parovarium surgeries are a significant risk factor for diminished ovarian reserve. Further population-based studies are needed to determine the precise mechanisms of influence of various factors on female fertility.

According to recent data, vitamin D is classified as a substance with hormonal activity, which, in addition to classical, has “non-classical” effects caused by the complex relationship between vitamin D and effector cells of the immune system. This relationship is based on the expression of the vitamin D receptor (VDR) on immune cells, which is encoded by the corresponding VDR gene. Vitamin D receptor specifically binds the active form of vitamin D (1,25(OH)2D3). As a result, a D3-VDR complex is formed, which mediates the effects of vitamin D through the formation of intracellular signaling pathways that transform the activity of certain target genes. However, it is not entirely clear how vitamin D realizes its effects at the cellular and receptor levels. According to the literature, studies of recent decades have revealed a significant role of vitamin D and immune checkpoint receptors (PD-1 (programmed cell death), PD-L (PD ligand), CTLA (cytotoxic T lymphocyte associated protein)) in autoimmune diseases. This review outlines possible mechanisms for the interconnection of these pathways. A deeper understanding of the intercellular interactions mediated by ligand-associated activation of vitamin D receptors, D3-VDR complex and immune checkpoint receptors (PD-1, PD-L, CTLA) in inflammation may become the basis for the development of new strategies for the diagnosis, prognosis and treatment of various diseases

Background. Fatal familial insomnia is a rare genetically determined neurodegenerative disorder from the group of prion diseases. Its main cause is the autosomal dominant D178N mutation of the PRNP gene, which leads to the synthesis of the pathological prion protein PrP.
The aim. Using the example of a clinical case to describe an example of the early onset of fatal familial insomnia in a teenager, a clinical example of its management.
Materials and methods. Female patient V., 16 years old, of hyposthenic constitution, undernourished, with negative family history (multiple sclerosis in her paternal grandmother) for the first time consulted a neurologist in Tver for the complaints of superficial sleep, shortened to 4–5 hours, unspecific pain all over the body, periodic numbness in the upper limbs. Six months later, retardation of speech and movements, changes in gait, and intentional tremor occurred; sleep was shortened to 2 hours. In the future, the teenager lost the ability to independently maintain the vertical body position, the ability to walk without assistance, speech was reduced to syllable answers to questions. In order to verify the diagnosis and to carry out differential diagnosis with other neurodegenerative diseases, the girl underwent auxiliary research methods: detection of antibodies to nuclear antigens, magnetic resonance imaging, computer electroencephalography, polyexomal genome sequencing.
Results. Based on the anamnesis, complaints, clinical picture and results of genetic research the final diagnosis of fatal familial insomnia was made. Due to the lack of etiological and pathogenetic therapy, the patient was subsequently provided with palliative medical care. The fatal outcome occurred 19 months after the onset of the disease.
Conclusions. The presented clinical case reflects the complexity of managing patients with rare genetic diseases, confirms the need for mandatory polyexomal genome sequencing in order to verify the diagnosis, which allows timely palliative care

Introduction. Influenza remains a serious viral infection in children and has consequences for the organism.
The aim of the study. To analyze the lipid peroxidation products and antioxidant defense (AOD) components level in children of two age groups with seasonal influenza.
Materials and methods. We examined 141 children aged from 1 month to 6 years with a diagnosis of influenza (subgroup 1 – 1 month – 2.11 years (n = 78); subgroup 2 – 3–6 years (n = 63)), 47 children of control group (subgroup 3 – 1 month – 2.11 years (n = 17); subgroup 4 – 3–6 years (n = 30)). Spectrophotometric, fluorometric and statistical methods were used.
Results. In subgroup 1 of children with influenza, there were higher levels of compounds with double bonds (p = 0.001), conjugated dienes (CDs) (p < 0.0001), ketodienes and conjugated trienes (KD and CT) (p = 0.004); in subgroup 2 of children with influenza – increased values of CDs (p < 0.0001), KD and CT (p < 0.0001) and thiobarbituric acid reactants (p < 0.0001) compared to the control. The AOD system in subgroup 1 was characterized by a decrease in the level of α-tocopherol (p < 0.0001), retinol (p < 0.0001) and higher oxidized glutathione (GSSG) values (p = 0.002) compared to the control. Children of subgroup 2 had lower values of the level of α-tocopherol (p < 0.001), retinol (p = 0.012) and total antioxidant activity (p < 0.0001) and higher values of GSSG (p = 0.035) compared to the control.
Conclusion. In children with influenza, regardless of age, there is a higher level of production of lipid peroxidation indicators, a lack of fat-soluble vitamins and higher values of oxidized glutathione than in healthy children

Therapeutic drug monitoring is the practice of measuring the concentration of a drug in patient’s biological fluids to assess the effectiveness and safety of drug therapy. The results of determining the drug level in biological fluids can also indicate noncompliance of therapy regimen and low adherence to therapy.
The aim. To compare the concentrations of some antiretroviral drugs (lopinavir, ritonavir, lamivudine, abacavir, zidovudine) in children living with HIV infection of different age groups.
Methods. We examined 184 children with perinatal HIV infection who underwent therapeutic drug monitoring of nucleoside reverse transcriptase inhibitors (lamivudine, abacavir, zidovudine) and protease inhibitors (lopinavir, ritonavir). Children were divided into four age groups. Group 1 included children 1–2 years old (n = 7); group 2 – children 3–5 years old (n = 14); group 3 – children 6–11 years old (n = 78); group 4 – children 12–17 years old (n = 85). The concentration of antiretroviral drugs in blood plasma was determined using high-performance liquid chromatography with mass selective detection.
Results. The lowest lopinavir concentration was found in children 12–17 years old (3782 [2117–5046] ng/ml), which was statistically significantly different from the similar values in children 6–11 years old (5614 [3521–7264] ng/ml; p = 0.011). For other antiretroviral drugs, no statistically significant differences in blood plasma concentrations were found in children of different age groups.
Conclusion. The lowest lopinavir concentrations are detected in children older than 11 years. For the other studied antiretroviral drugs, this pattern was not revealed

Background. Despite the high evidence level of the currently existing international recommendations on stable coronary heart disease (CHD) and chronic coronary syndrome, their implementation in domestic clinical practice is insufficient.
The aim of the work. To analyze the choice of diagnostic tactics (non-invasive and invasive) in patients with suspected obstructive coronary heart disease in real clinical practice.
Methods. The study included outpatients with suspected obstructive CHD, in whom the pre-test probability (PTP) of obstructive CHD was determined; if PTP = 5–15 %, clinical probability was assessed based on CHD risk factors. Based on the results of coronary angiography, the following groups were identified: group I – obstructive lesion of the coronary arteries (≥ 70 %) (n = 50); group II – non-obstructive lesion of the coronary arteries (< 70 %) (n = 32); group III – intact coronary arteries (n = 40). Results. According to the results of coronary angiography, the frequency of detection of obstructive lesion of the coronary arteries was 42 % (in patients without past medical history of myocardial infarction – 31 %). Before performing coronary angiography, non-invasive tests were performed in 2.5 % of cases. Pain in the chest was represented by typical angina in 74 % of patients, with no difference in frequency in all groups. PTP values were statistically significantly higher in the group with obstructive CHD (median – 32 %), however, in the other two groups, PTP values corresponded to a high risk of obstructive CHD (median – 27 % and 21 %, respectively). PTP was an independent predictor for obstructive CHD and subsequent myocardial revascularization.
Conclusion. In the cohort of outpatients with suspected coronary heart disease we examined during invasive coronary angiography, the frequency of obstructive lesion of the coronary arteries remains low. Non-invasive tests were performed in isolated cases, while PTP was an independent predictor for obstructive CHD and subsequent myocardial revascularization. To increase the frequency of detection of obstructive coronary heart disease, we should adhere to the diagnostic algorithms of the European Society of Cardiology and make wider use of non-invasive imaging tests.

Background. In recent years, special attention has been paid to the studying the consortia of probiotic bacteria. In these associations, the properties of individual microorganisms can be enhanced, in particular, their antagonistic activity which is an effective indicator for screening of probiotic potential. The development of probiotics based on such consortia with antibacterial properties is critical in the light of the growing problem of drug resistance in microorganisms.
The aim of the work. To study the antagonistic activity of monocultures and consortia of lactobacilli against multidrug-resistant isolates of opportunistic bacteria. Materials and methods. The antagonistic activity of lactobacilli monocultures and their consortia was assessed simultaneously by two methods: the cross streak method and the well diffusion method.
Results. All strains of lactobacilli and their consortia, depending on the research method, had varying degrees of antagonistic activity. Five consortia had stronger antagonism to test cultures as compared to monocultures, while in one consortium, the effect of antagonistic activity was reduced compared to monocultures. The results of studying the antagonistic activity of two consortia (Limosilactobacillus fermentum 44/1 and Lacticaseibacillus rhamnosus 12L, Latilactobacillus curvatus LCR-111-1 and Lactiplantibacillus plantarum 8PAZ) contradict data on the biocompatibility of strains in these consortia. Differences in the degree of antagonistic effects of lactobacilli on gram-positive and gram-negative species of opportunistic bacteria were revealed.
Conclusion. The study showed that both the biocompatibility of the probiotic strains and the antagonistic activity of the consortium are the important requirements for creating a probiotic consortium with effective probiotic potential. To study the antagonistic properties of lactobacilli, the number of isolates of target gram-positive and gram-negative bacteria and normobiota should be increased. This will allow us to determine effective strategies for using probiotics in conditions of the spread of drug resistance of microorganisms.

Background. Setting of norms for the parameters of P300 cognitive auditory evoked potentials (EP) in elderly people with intact cognitive functions considering their residence in certain climatic and geographical regions is an urgent problem.
The aim of the study. To determine age-related parameters of P300 cognitive auditory evoked potentials in elderly people aged 60–69 and 70–74 years, living in the European North of Russia (using the example of Arkhangelsk).
Methods. The parameters of P300 auditory EP were determined in randomly selected urban residents in the age groups of 60–69 years (n = 284) and 70–74 years (n = 115) with normal scores on the Montreal Cognitive Assessment Scale (MoCA), without depression (according to Beck Depression Inventory), with preserved ability to work and/or social functions. We calculated the 5th–95th percentile values (P5– P95) of the P300 EP parameters and assessed the relationships of these parameters with socio-demographic characteristics, lifestyle and the results on the MoCA scale and Beck Depression Inventory.
Results. Statistically significant differences in latency indicators of P300 EP were determined between groups of 60–69 and 70–74 years (P25–P90) in all studied brain regions (frontal, central). In the group of 60–69 years, the range of P25–P75 values of P300 EP latencies was 342.5–401 ms, in the group of 70–74 years – 358.5–443 ms. Age differences in P300 EP amplitudes were minimal with an interquartile range of 4–13 μV in the total sample. Participants who smoked had higher latency scores and lower amplitude scores; former smokers had higher latency scores compared to never-smokers.
Conclusion. Latency above 400 ms at the age of 60–65 years and above 443 ms at 70–74 years can be considered as a criterion for reduced cognitive reserve and an increased risk of developing cognitive disorders in elderly people living in the European North of Russia.

Background. Carotid atherosclerosis is one of the urgent problems due to the high risk of developing ischemic stroke and cognitive impairment. The dynamics of clinical disorders in patients with carotid stenosis is determined by a complex of neurophysiological, angiological, tissue and biomolecular reactions, the characteristics of which can act as predictors of the course of the pathology.
The aim of the work. To determine the neurophysiological parameters and predictors of cognitive dysfunction in patients who underwent carotid endarterectomy.
Materials and methods. The study included 59 people with carotid atherosclerotic disease. All included patients underwent carotid endarterectomy. We assessed the degree of stenosis of the internal carotid artery and cognitive status using the FAB (Frontal Assessment Battery) scale and MoCA (Montreal Cognitive Assessment) Test and recorded electroencephalogram (EEG), P300 cognitive evoked potentials and heart rate variability in patients at various terms (before surgery, 6 months after the surgery). Patients were divided into groups based on the dynamics of cognitive tests using cluster analysis (k-means) with identification of elements included in the clusters: patients of cluster 1 had a “preserved” profile of cognitive status; patients of cluster 2 – moderate cognitive dysfunction.
Results. Patients of cluster 1 had a higher power of beta oscillations in the frontal lead, a higher amplitude of the P3 component of the P300 potential, and a greater variability of R-R intervals in terms of the total indicator and high-frequency power. We proposed a model that allows us to classify patients into groups according to the dynamics of cognitive function scores. According to the data obtained, the most significant predictors of the dynamics of cognitive status were the initial characteristics of the EEG and the P300 cognitive evoked potential.
Conclusions. We determined the clinical and neurophysiological correlates of cognitive dysfunction: an association with greater preservation of activating effects on the EEG, processes of recognition and decision-making in the associative zones of the cortex, and less pronounced activity of stress-implementing mechanisms. Indicators of EEG spectral analysis and characteristics of the P300 cognitive evoked potential are predictors of the cognitive status dynamics.

Despite the wide choice of antiepileptic drugs (AEDs), a third of patients remain resistant to the effects of modern AEDs. Drug-resistant epilepsy (DRE) is characterized by the inability to control seizures in a patient when using at least two adequate AED regimens at an effective daily dose as monotherapy or in combination. In this case, the mechanisms responsible for drug resistance are mainly either increased excretion of AEDs by transporters from epileptogenic tissue (the multidrug transporter hypothesis) or a decrease in the sensitivity of drug receptors in epileptogenic brain tissue. It is assumed that there are other mechanisms, but they remain understudied. A number of factors are associated with the risk of DRE developing in patients with diagnosed epilepsy, including genetic, iatrogenic, brain malformations, and others. Patients with DRE have a higher probability of developing psychopathological disorders (depression, anxiety, psychosis), the proportion of which is significantly higher than in the general population. They have a 10-fold increased risk of death due to injury, cognitive decline, and sudden unexpected death in epilepsy (SUDEP). The priority treatment method for DRE is surgery. Early identification of DRE is critical for identifying potential treatment alternatives and determining whether a patient is a surgical candidate. Analysis of data from clinical and instrumental research of operated patients with DRE in the early and late postoperative period will allow us to identify factors of unfavorable outcome and to increase the effectiveness of treatment for this category of patients.
The aim was to study and to summarize literature data on the pathogenesis and risk factors of drug resistance to antiepileptic drugs in patients with epilepsy, justifying the need for timely identification of drug resistance and referral of patients with drugresistant epilepsy to specialized centers for possible surgical treatment.

The problem of the structural and functional effectiveness of episcleral and endovitreal treatment methods of rhegmatogenous retinal detachment remains open to this day.
The aim of the study. To assess the clinical effectiveness of surgical treatment of rhegmatogenous retinal detachment using episcleral and endovitreal methods.
Material and methods. An analysis of the electronic database and a detailed assessment of the treatment of 285 patients with rhegmatogenous retinal detachment for 2005–2022 were carried out. A comparative analysis was made in two groups: group 1 – patients after episcleral surgery (n = 155); group 2 – patients after endovitreal surgery (n = 130). The initial condition and the extent of surgery were comparable. Results. From 2005 to 2009 in 65.9 % of cases, episcleral buckling predominated; from 2009 to 2021 – posterior closed vitrectomy (in 64.8–88.7 % of cases). The incidence of primary retinal reattachment was 74.2 % and 71.5 %. The number of relapses after vitreoretinal surgery slightly exceeded the values in the group 1 – 28.4 % versus 25.7 %, and in 20% of cases the first relapse occurred before silicone aspiration as a result of subsilicone proliferation. The total number of surgical interventions per person, taking into account mandatory silicone aspiration, in the group 1 was 1.3, in the group 2 – 2.25 for the entire observation period. The visual acuity of patients in group 1 was 2 times higher than that of the comparison group – 0.21 ± 0.02 and 0.1 ± 0.03, respectively (p < 0.05).
Conclusion. Episcleral treatment methods of rhegmatogenous retinal detachment are characterized by better anatomical, reconstructive and functional effects with fewer re-operations

Background. Cataract is one of the main causes of decreased visual acuity in the world, and therefore scientists are continuing researches on the mechanisms of development of this ophthalmic pathology.
The aim. To study metabolic changes in a cloudy lens using an experimental model.
Materials and methods. The study was carried out on adult male Wistar rats (n = 60), which were divided into control (n = 30) and experimental (n = 30) groups. Experimental cataract were simulated by daily ultraviolet irradiation (λ = 300–350 nm) during 6 months for 20 minutes. At the months 2, 4 and 6 of the study, we carried out a biomicroscopic examination of the anterior eye of animals using a slit lamp to monitor the development of cataract. Lenses were collected to determine the content of stearoyl-coenzyme-A desaturases and melatonin using enzyme immunoassay.
Results. At the stage of initial cataract, the content of the stearoyl-coenzyme A desaturase was statistically significantly lower than the control values by 38 %; at the stage of immature cataract – by 30 %; at the stage of mature cataract – by 15.4 %. It was revealed that at the month 6 of the study, the concentration of melatonin in lens homogenates was 17 % lower when compared with the control. A statistically significant correlation was established between stearoyl-coenzyme A desaturase and melatonin (r = 0.32).
Conclusion. Melatonin and stearoyl-coenzyme A desaturase play an important role in a number of biochemical processes that ensure the proper functioning of the visual analyzer. Changes in the concentration of these biological molecules can play a key role in the pathogenesis of cataract and a number of other ophthalmic diseases

The aim. To study the predisposing factors for the development and timing of development of intraventricular hemorrhage (IVH) in extremely premature newborns.
Materials and methods. We carried out retrospective analysis of 32 case histories of children born at a gestational age of less than 32 weeks. The children were divided into three groups: group 1 (n = 13) – children death was caused by non-traumatic IVH; group 2 (n = 12) – surviving infants with IVH; group 3 (comparison group; n = 7) – premature infants without IVH. We assessed risk factors for the development of IVH, their severity, and main indicators predisposing to death in newborns of these groups.
Results. Children of the group 1 had statistically significantly low values of body weight – 670 [640–860] g (р1–2 = 0.007; р1–3 = 0.012), head circumference – 23 [22–24] cm (р1–2 = 0.008; р1–3 = 0.049), gestational age – 24.5 [23.5–25.5] weeks (р1–2 = 0.002; р1–3 = 0.007). Gender differences were revealed: in the group 1, there were 92.3 % of boys, in the group 2 – 33.3 % (p1–2 = 0.008). Maternal smoking increased the risk of fatal IVH by 3.5 ± 0.15 times, polyhydramnios – by 3.3 ± 0.37 times, chorioamnionitis – by 12.8 ± 0.47 times, placenta previa – by 3.2 ± 0.15 times. In newborns of the group 1, seizures developed on the day 1 of life in 84.6 % (more often than in group 2; p = 0.00001), and shock in the first 3 hours of life was recorded in 46.1 % of cases (р1–2 = 0.034), which increased the risk of death by 4.3 ± 0.47 times. In newborns of group 1, compared with newborns of groups 2 and 3, pulmonary hypertension was more often detected (60.8 [50.1–69.2] mm Hg; p1–2 = 0.028; p1–3 = 0.047).
Conclusion. Confirmed infectious diseases in the mother, clinical manifestation of convulsions, pulmonary hypertension, development of multiple organ failure and shock in extremely premature newborns increase the risk of intraventricular hemorrhage and the frequency of deaths.

Background. Coronary heart disease (CHD) ranks first among the causes of death, morbidity, and disablement. The development of innovative methods for predicting CHD will reduce these losses.
The aim of the work. To assess the quality of the screening test for predictors of coronary heart disease using statistical quality control of a verifiable diagnostic test (with binary outcomes).
Materials and methods. In 2008–2013, 70 cases of CHD were registered in a group
of 7959 initially healthy men 18–66 years old who were the members of locomotive crews. Statistical analysis identified CHD predictors: arterial hypertension; psychosocial stress; hyperglycemia; dyslipidemia; excessive alcohol consumption; obesity of degree I–III; age 34–66 years; microalbuminuria; thickening of the intima- media complex/atherosclerotic plaque (IMC/ASP); pulse wave velocity (PWV) > 12 m/s; left ventricular hypertrophy; grade I–II retinopathy; atherosclerosis of aorta. DiagStat (Russian Federation) software determined their predictive ability when used in screening tests to predict CHD. We demonstrated the use of this method to assess the predictive ability of risk factors for any disease.
Results. CHD predictors have high to moderate specificity for the absence of CHD in individuals who test negative for the above-listed factors. IMC/ASP, microalbuminuria, PWV > 12 m/s, grade III obesity moderately increase the posterior odds of developing CHD versus its absence in comparison with the prior odds after receiving a positive result of the verifiable diagnostic test for these factors. Age 34–66 years moderately increases the posterior odds in favor of the absence of CHD versus its occurrence compared with the prior odds after receiving a negative result of the verifiable diagnostic test.
Conclusion. When assessing the result of the verifiable diagnostic test, we should focus on both the probability of occurrence and the absence of CHD in the presence or absence of a predictor in the patient. Since the determination of PWV > 12 m/s, atherosclerosis of aorta, microalbuminuria, stress, and excessive alcohol consumption among workers of locomotive crews is not mandatory, it is necessary to conduct a targeted search for them

Background. The etiological structure of implant-associated infection and antibiotic resistance of pathogens are important when choosing empirical antibiotic therapy. COVID-19 pandemic and increased consumption of antibiotics by the population could provoke an increase in antibiotic resistance.
The aim of the work. To compare the spectrum of leading pathogens of implantassociated infection in the pre- and post-Covid period and to assess antibiotic resistance.
Materials and methods. A continuous retrospective study of biomaterial samples from traumatology and orthopedic patients with implant-associated infection was carried out for 2018–2019 and 2021–2022. The sample consisted of 548 microorganism strains (n = 237 and n = 317, respectively) in 442 cases of infectious complications. The antibiotic resistance of all isolated microorganisms, including those from microbial associations, was assessed.
Results. The leading pathogen of monomicrobial implant-associated infection in both study periods was Staphylococcus epidermidis (33–37 %). In 2021–2022, the proportion of microbial associations increased (from 12.5 to 17.5 %; p = 0.147) with the appearance of fungi in the microbial landscape. In the post-Covid period, the increase in Staphylococcus aureus resistance to tetracycline and doxycycline was revealed; the isolation of methicillin-resistant strains among Staphylococcus aureus decreased from 4 cases (out of 187) to 3 (out of 232); 100 % sensitivity to rifampicin and co-trimoxazole was maintained. An increase in Staphylococcus epidermidis resistance to all tested antibiotics was detected (statistically significant increase in resistance to fluoroquinolones; p = 0.002–0.003) with the isolation of methicillin-resistant strains in 80.5% and 80.9% of cases, respectively. All staphylococcal isolates were susceptible to vancomycin and linezolid. Enterobacteriaceae representatives showed a decrease in resistance to carbapenems and an increase in resistance to co-trimoxazole; in Pseudomonas aeruginosa and Acinetobacter baumannii, there is an increase in resistance to carbapenems and fluoroquinolones. All gram-negative microorganisms were sensitive to colistin.
Conclusion. The high frequency of isolation of methicillin-resistant staphylococci determines the choice of vancomycin for empirical therapy. Increasing resistance of staphylococci to fluoroquinolones may limit their use. Increasing resistance of gram-negative bacteria and a narrow spectrum of antibiotics acting on carbapenemase producers may reduce the effectiveness of therapy.

Background. Orostachys spinosa (L.) Sweet. – a perennial plant of a wide habitat and contains various metabolites (amino acids, flavonoids, polysaccharides, etc.). Extracts from the aerial part of the plant are used in traditional medicine as an anticonvulsant and sedative.
The aim of the work. To study the neuroprotective effect of O. spinosa in cholinergic deficiency.
Materials and methods. The studies were carried out on 52 Wistar rats. The animals were administered scopolamine (1 mg/kg) daily for 21 days, followed by O. spinosa dry extract per os at a dose of 100 mg/kg for 14 days. On the day 32, the animals developed a conditioned passive avoidance reflex (CPAR), the integrity of which was checked after 1, 24 and 72 hours; on the day 35 they were tested in an “open field”. On the day 36, biochemical and histological studies of the brain were carried out.
Results. It has been established that O. spinosa, against the background of scopolamine intoxication, reduces the anxiety of animals, stimulates exploratory activity in the open field test, improves the production and preservation of the CPAR, and also reduces the number of functionally inactive neurons (pyknotic and shadow cells) in the cerebral cortex. The extract reduces the lactate/pyruvate ratio by 47 %, intensifies the activity of mitochondrial complexes I and II by 54–64 %, and increases the concentration of adenosine triphosphate by 1.6 times compared to the control. O. spinosa exhibits antioxidant properties by reducing malondialdehyde and increasing the activity of catalase, glutathione peroxidase and glutathione reductase in the brain.
Conclusion. O. spinosa dry extract has a neuroprotective effect in cholinergic deficiency. The studied extract exhibits antioxidant properties and stimulates energy processes in the brain

Background. It is known that COVID-19 can be followed by a shift in the hemostatic system towards hypercoagulation, which is more pronounced in the presence of diabetes mellitus (DM). Tuberculosis process is often accompanied with hypercoagulation syndrome. Of great interest is the study of the state of hemostatic systems in patients with pulmonary tuberculosis (TB) with concomitant DM who have had COVID-19.
The aim. To study the relationship between the state of the hemostatic and fibrinolysis systems and moderate and severe COVID-19 in patients with pulmonary tuberculosis and diabetes mellitus.
Methods. 32 patients with TB and DM were divided into two groups. Group 1 included 16 patients with TB and DM who have previously had COVID-19 (TB-DM-COVID). Group 2 included 16 patients with TB and DM who did not have COVID-19 (TB-DM).
Results. It was found that TB-DM-COVID patients were more likely to develop a hypercoagulable shift compared to TB-DM patients. This was evidenced by a more frequent shortening of such indicator as activated partial thromboplastin time (43.7 % and 25.0 % of cases, respectively; χ2 = 7.22; p = 0.01), an increase in fibrinogen levels (43.7 % and 25.0%, respectively; χ2 = 7.22; p = 0.01) and D-dimer (43.7 % and 18.7 %, respectively; χ2 = 14.74; p = 0.0001). These changes were closely associated with the systemic inflammatory response, as strong and positive correlations were found between fibrinogen and C-reactive protein levels (r = 0.420; p = 0.01), and erythrocyte sedimentation rate (r = 0.433; p = 0.01) in TB-DM-COVID patients.
Conclusion. In patients with pulmonary tuberculosis and diabetes mellitus after moderate and severe COVID-19, compared to patients who have not had COV ID-19, a hypercoagulable shift associated with the development of more pronounced systemic inflammation develops more often.

Background. One of the priority areas of modern medicine, which unites the interests of various specialists (therapists, cardiologists, gastroenterologists, endocrinologists), is the study of the pathogenesis and clinical manifestations of nonalcoholic fatty liver disease (NAFLD), which is widespread and of unconditional social significance. The search for adequate experimental models of NAFLD that reflect the severity of liver damage is of paramount importance for studying its etiology and pathogenesis.
The aim of the study. To compare biochemical and histological changes in experimental models of NAFLD of varying severity.
Materials and methods. Two NAFLD model versions were used: a light one – nonalcoholic steatosis (NAS) and a severe variant – non-alcoholic steatohepatitis (NASH). The following biochemical parameters were measured: enzyme activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (AP), plasma glucose concentration, total protein (TP), total bilirubin (TBil) and its conjugate fraction (CB), plasma concentrations of homocysteine (HC), total cholesterol (TC), triacylglycerides (TG), catalase (Cat), superoxide dismutase (SOD) and malondialdehyde (MDA).
Results. When used in a model of steatohepatitis, liver function was impaired to a significantly greater extent than in the model of steatosis; this difference was manifested in a statistically significant increase in ALT, AST, AP, TC, Tbil, MDA (p < 0.001) and a decrease in Cat, SOD (p < 0.05). This is confirmed by the development of more pronounced symptoms of disorders of pigment and lipid metabolism, cytolytic and cholestatic syndromes, significant activation of lipid peroxidation and depression of the antioxidant system when modeling non-alcoholic steatohepatitis. Various degrees of severity of morphological changes in the experimental groups were revealed.
Conclusion. The study showed the priority of determining biochemical markers, including the levels of ALT, AST, OBIL, TG, MDA and SOD to optimize laboratory methods for diagnosing the severity of liver dystrophy.
The practical originality of the results lies in the optimization of the methodology for laboratory diagnosis of the severity of the pathological process in NAFLD.

Background. Continuous lighting contributes to the development of desynchronosis, which is stressful for the body. As a result, the normal functioning of the immune system is disrupted, which in turn can shift the physiological balance towards pathology and endotoxemia. It is relevant to develop innovative drugs based on a sorbent matrix, which can be modified with biologically active molecules that extendedly leave the sorbent surface. At the same time, the sorbent retains the properties of a detoxifier, fixing toxic agents on the surface and removing them from the body, which helps restore the internal environment and normalizes the overall reactivity of the body in extreme conditions.
The aim. To study the effect of aluminum- and silicon-containing enterosorbent (based on aluminum oxide and polydimethylsiloxane) on the cellular composition of the thymus and the distribution of thymocytes in the organ according to the cell cycling state in C57Bl/6 mice kept under the all-night lighting.
Materials and methods. Animals received sorbent (0.665 g per 1 kg of body weight in 200 μl of distilled water) through an intragastric tube once a day for 14 days against the background of continuous lighting. Intact mice and placebo animals composed control group. We used flow cytometry to assess the percentage of CD3hi and CD3low lymphocytes of the thymus, the CD3low/CD3hi ratio, viability and distribution of cells across according to the cell cycling state.
Results. Continuous lighting inhibited the differentiation and maturation of young CD3low lymphocytes into mature forms of CD3hi, reduced the proliferation of thymic epithelial cells, and activated apoptosis of lymphocytes and epithelial cells in the organ. The introduction of the sorbent restored the content and viability of young CD3low lymphocytes and contributed to the preservation of the viability and proliferation of thymic epithelial cells.
Conclusion. Using an enterosorbent based on aluminum oxide and polydimethylsiloxane under conditions of continuous lighting helps maintain the functional activity of the thymus, preventing its involution, and is advisable against the background of circadian disruption.

One of the important directions for increasing the immunogenic properties of vaccine strains against highly dangerous infections is the search for adjuvants that not only stimulate the immunological effectiveness of vaccination, but can also provide a metabolic correction of the vaccination process. Organoselenium compounds have immunotropic properties and an antioxidant effect, and therefore, the study of the effect of the organoselenium compound 2,6-dipyridinium-9-selenabicyclo[3.3.1]nonane dibromide (974zh) on the activity of the TLR2 and TLR4 gene expression by macroorganism cells of experimental animals immunized with Yersinia pestis EV NIIEG vaccine strain, is a current area of research.
The aim of the work. To assess the TLR2 and TLR4 gene expression by cells of the immune phagocyte system of experimental animals immunized with the Y. pestis EV vaccine strain against the background of immunomodulation with the organoselenium compound 974zh.
Materials and methods. The study was carried out on 125 certified outbred white mice. Biological material (blood, spleen) was disinfected, and the spleen was homogenized. RNA isolation and reverse transcription were performed using commercial reagent kits. The expression level of the TLR2 and TLR4 genes was determined using real-time polymerase chain reaction with specific primers.
Results. When assessing innate immunity using the example of blood and spleen cells of animal models, features of the TLR2 and TLR4 gene expression were revealed in response to the introduction of the Y. pestis EV vaccine strain against the background of immunomodulation with the 974zh. It was found that 974zh induces a statistically significant increase in TLR2 gene expression when co-administered with Y. pestis EV at a dose of both 104 CFU and 103 CFU.
Conclusion. Y. pestis EV against the background of immunomodulation with 974zh, stimulates the expression of the TLR2 and TLR4 genes, which may indicate an increase in the immunogenic properties of the Y. pestis EV vaccine strain under the influence of this preparation.

Background. Immunological studies are impossible without long-term storage of cryopreserved biomaterial. There are no standard procedures for working with cryopreserved mononuclear leukocytes.
The aim of the study. To optimize the protocol for culturing T lymphocytes thawed after cryopreservation by assessing their viability and proliferative capacity.
Methods. Mononuclear leukocytes were isolated from the peripheral blood of relatively healthy volunteers (n = 18). Cells were subjected to controlled freezing down to –80 °C and were transferred to liquid nitrogen. First step: after thawing, the cells were stained with CFSE (carboxyfluorescein succinimidyl ester), were divided into two parts and cultured in the presence/absence of interleukin 2 (IL-2). Cell proliferation was stimulated with phytohemagglutinin (type P). Cells were incubated for 7 days. Sample analysis was performed using flow cytometry. Second stage: thawed cells were divided into three parts. Two parts were resuspended in a full growth medium with IL-2 and were placed in a thermostat (+37 °C) to “rest” for one hour or overnight. After “resting”, the cells were stained with CFSE. One third of the thawed leukocytes were stained with CFSE immediately after thawing. Cells were stimulated, cultured and analyzed the same way at both stages of the study.
Results. It has been established that adding IL-2 to the culture medium contributes to a better cell survival. In the presence of IL-2, stimulated CD4+ and CD8+ T lymphocytes produced more daughter cell generations. At the end of the 7-day incubation “rested” samples had reduced leukocyte counts compared to the samples that were cultured immediately after thawing. The number of daughter cell generations formed by stimulated CD4+ and CD8+ T cells decreased when the “rest” stage was included into the study protocol.
Conclusion. Adding IL-2 into culture medium can increase the viability and mitotic capacity of thawed T cells, making their state more similar to that of freshly isolated lymphocytes. Cell “rest” after thawing negatively affects the viability and proliferative activity of T lymphocytes during their weekly incubation.

Background. The severe course of parenteral viral hepatitis and their further chronicity are associated with the presence of immunodeficiency disorders, frequency of which increases significantly in harsh climate. The article discusses the spread of parenteral viral hepatitis in the Arctic zone of the Republic of Sakha (Yakutia) and the issues of organizing medical care for patients with chronic viral hepatitis at the regional level.
The aim of the study. To analyze the incidence rates of parenteral viral hepatitis in the Arctic regions of Yakutia in order to improve the health care system using the example of remote areas of hard access.
Methods. The work uses materials from official statistics of the territorial department of Rospotrebnadzor for the Republic of Sakha (Yakutia) for 2000–2022 and information from the “Chronic viral hepatitis in the Republic of Sakha (Yakutia)” register. Results. In the Arctic regions of Yakutia, problems are observed in chronic forms of viral hepatitis B, C and D, as well as in their outcomes, such as cirrhosis and liver cancer, leading to early disability and mortality. In the general structure, hepatitis B infection prevails, which indicates the presence of family foci of infection. All this requires a complex of not only therapeutic, but also advanced anti-epidemiological measures.
Conclusion. The difficult epidemiological situation regarding parenteral viral hepatitis, caused by extreme natural and climatic conditions, genetic characteristics of the indigenous population and the lack of medical institutions specializing in the treatment of chronic viral hepatitis, dictates the need to strengthen systematic on-site monitoring studies and telemedicine consultations in the Arctic zone of Yakutia. Thanks to this, residents of hard-to-reach areas of the Arctic zone of the Republic of Sakha (Yakutia) will be able to receive targeted subsidized care for the treatment of chronic hepatitis without traveling to Yakutsk.