Aim. To study the effects of a high-fat, high-carbohydrate diet on erythrocytes and platelets of rats.
Materials and methods. Male Wistar rats (n = 23) were used for the study. The rats were divided into a control group and an experimental group. The rats from the control group were fed with standard rat chow. The rats from the experimental group had received a high-fat and high-carbohydrate diet for 12 weeks. In the rats, body weight and blood pressure (BP) were measured, an oral glucose tolerance test was carried out, and hematological and lipid metabolism parameters were analyzed. The conductance of erythrocyte KCa-channels was measured by the potentiometric method, and platelet aggregation was determined by the turbidimetric method.
Results. Feeding the rats with a high-fat, high-carbohydrate diet for 12 weeks resulted in obesity, BP elevation, hyperglycemia, impaired glucose tolerance, and dyslipidemia with pronounced triglyceridemia. In the experimental group, a rise in the number of leukocytes, mainly due to granulocytes, and an increase in the number of platelets and their collagen-induced aggregation were observed. The red blood cell count in the rats of the experimental group did not significantly differ from that of the control group. In the experimental group, multidirectional changes in the membrane potential were observed in response to the stimulation of the KCa-channels in the erythrocyte membrane with the Ca2+ ionophore A23187 or artificial redox systems.
Conclusion. The obtained data indicate that a high-fat, high-carbohydrate diet leads to metabolic and hemorheological disorders that are typical of metabolic syndrome.

Aim. To evaluate the prognostic value of pAKT1 expression by tumor cells in patients with diffuse large B-cell lymphoma.
Materials and methods. The study included 90 patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL), who were treated at the clinic of Kirov Research Institute of Hematology and Blood Transfusion from 2014 to 2017 and received standard first-line polychemotherapy according to the R-CHOP regimen. Using immunohistochemical and morphometric methods, the relative number of tumor cells expressing pAKT1 was determined. Using the two-sided Fisher’s exact test, the relationship of different levels of marker expression with clinical and laboratory parameters of patients and long-term treatment results was analyzed. The impact of pAKT1 on the risk of an adverse event was assessed using the Cox regression analysis.
Results. Overexpression of pAKT1 is associated with unfavorable clinical characteristics of patients with DLBCL, excessive expression of the BCL2 and c-Myc oncoproteins, as well as with low rates of overall and progressive survival. Overexpression of pAKT1 is an independent prognostic factor and statistically significantly affects the risk of an adverse outcome in DLBCL.
Conclusion. The degree of pAKT1 expression is an informative criterion that allows to predict the course of diffuse large B-cell lymphoma. It is advisable to use the indicated marker when stratifying patients into risk groups.

Aim. To study the effects of lithium salts on production of cytokines by immunocompetent cells in the whole-blood culture of patients with alcohol dependence and affective disorders.
Materials and methods. The study materials were blood samples from 25 patients with alcohol dependence (AD) and 12 patients with bipolar disorder (BD). Blood diluted 1:1 with complete RPMI-1640 medium (Gibco, UK) was added to the wells of the culture plate, then new lithium salts (succinate, fumarate, pyruvate, ascorbate) and a reference salt – lithium carbonate at a final concentration of 1.2 mmol / l per lithium ion – were added. In parallel, control samples without lithium salts were tested; the samples were incubated for a day. The concentration of cytokines (interferon (IFN) γ, interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17A, tumor necrosis factor (TNF) α) was determined in the culture supernatants on the MAGPIX multiplex analyzer (Luminex, USA) (Center for Collective Use “Medical Genomics”, Tomsk NRMC) using the Human Cytokine / Chemokine Magnetic Bead Panel (Merck, Germany).
Results. All lithium salts had a unidirectional effect on the production of cytokines by immunocompetent cells (ICC), except for lithium ascorbate and IL-8. The concentrations of cytokines in the supernatants of loaded and control samples (spontaneous production) were comparable, which indicates an absence of stimulating or suppressing effects of salts on the functional activity of ICC under the experimental conditions. The effect of lithium ascorbate as an IL-8 inducer was detected: the production of IL-8 induced by lithium ascorbate was 2.3–2.5 times higher than its spontaneous production.
Conclusion. The obtained results, as well as the previously revealed antioxidant and cytoprotective properties of new lithium salts, confirmed that they are promising for development of pharmacological agents with combined action.

Aim. To assess the hemodynamic status by transpulmonary thermodilution (TPTD) in patients with ischemic heart disease (IHD) with different comorbidities before and after coronary artery bypass grafting (CABG).
Materials and methods. 66 patients with IHD (40 men and 26 women) aged 53 to 77 years who were admitted for planned CABG were examined. The patients were divided into three groups according to the comorbidity: cardiovascular, respiratory, and metabolic. The first comorbidity was represented by a combination of IHD and multifocal atherosclerosis, the second – by IHD and chronic obstructive pulmonary disease (COPD), and the third – by IHD and metabolic syndrome (MS). All patients underwent CABG with the use of cardiopulmonary bypass. Hemodynamic parameters were recorded by the TPTD method using the Pulsion Picco Plus module (Germany) at 3 stages: after the start of mechanical ventilation (stage I), after the completion of cardiopulmonary bypass (stage II), and 24 hours after CABG (stage III).
Results. The patients with IHD with different comorbidities differed in characteristic signs of hemodynamic changes. In IHD with comorbid COPD, after withdrawal from the cardiopulmonary bypass and 24 hours after CABG, the highest index of systemic vascular resistance, the minimum values of the global ejection fraction, and a decrease in the global end-diastolic volume and pulmonary blood volume less noticeable compared with other groups of patients were noted. With comorbid respiratory and metabolic disorders, the maximum values for the indices of extravascular lung water and pulmonary vascular permeability were recorded. In the patients with a comorbid cardiovascular disease, hemodynamic and volume status violations in the dynamic follow-up were less pronounced.
Conclusion. The use of the TPTD method in patients with IHD before and after CABG makes it possible to specify the functional state of the circulatory system in different comorbidities, which increases the effectiveness of risk stratification and the accuracy of predicting possible complications.

Aim. To assess the relationship between changes in serum brain-derived neurotrophic factor (BDNF) level, regression of motor deficiency, and restoration of functional activity in patients with ischemic stroke after stage II of medical rehabilitation.
Materials and methods. The study included 49 patients with ischemic stroke in the middle cerebral artery after stage I of medical rehabilitation. Group I (n = 32) went through stage II of rehabilitation in the early recovery period, group II (n = 17) was discharged for outpatient monitoring at the place of residence. Observation points: day 14 and day 90. Evaluation scales: National Institute of Health Stroke Scale (NIHSS), Fugle – Meyer Scale (FMA), Modified Rankin Scale (mRS). Serum BDNF levels were determined using a MAGPIX multiplex analyzer (Luminex, USA).
Results. A comparative analysis of the studied population showed that patients who underwent motor rehabilitation in the early recovery period had greater regression of neurologic deficit according to the ΔNIHSS scale (pgr.I–II = 0.043), a more pronounced increase in the functional activity on the ΔmRS scale (pgr.I–II = 0.047), and positive dynamics according to the FMA scale (pday14–90 = 0.003) in comparison with patients who received outpatient follow-up. The concentration of BDNF was significantly reduced by the end of the early recovery in the group II (pday14–90_gr.II = 0.002). On the contrary, there was no decrease in the level of the BDNF (pday14–90_gr.I = 0.613) in the group of patients undergoing rehabilitation.
Conclusion. The results of the study demonstrated the clinical effectiveness of stage II of the comprehensive rehabilitation of patients in the early period of stroke recovery. We can suggest that the success of neurorehabilitation is closely associated with an increase of the BDNF level against the background of its performance. This makes BDNF a potential marker of evaluating the effectiveness of ongoing rehabilitation treatment.

Aim. To study the Bcl-2 level in mitochondria of various organs in female mice with standard and stimulated growth of an experimental B16/F10 melanoma.
Materials and methods. The study included С57ВL/6 female mice (n = 168). The experimental animals were divided into the following groups: an intact group (n = 21), a group with modelled chronic neuropathic pain (CNP) (n = 21), an M group with B16/F10 melanoma (n = 63), and a CNP + M group (n = 63). The Bcl-2 concentration (ng / mg protein) in mitochondrial samples was determined by ELISA (Thermo Fisher Scientific, Austria). Statistical analysis of the results was carried out using Statistica 10.0.
Results. Compared to the Bcl-2 levels in the intact animals, CNP decreased this parameter in the cardiac mitochondria by 1.3 times, while increasing it by 5.9 times in the skin mitochondria. In the dynamics of standard melanoma growth, the Bcl-2 content changed compared with the corresponding intact values in the mitochondria of the brain, heart, and skin, but did not change in the liver and kidneys. In the mitochondria in melanoma, the Bcl-2 levels were high throughout the entire period of standard tumor growth in comparison with the intact skin. The stimulated melanoma growth in CNP was involving more organs into the pathological process as the tumor was growing. Thus, in comparison with the values in the CNP group, the mitochondrial Bcl-2 levels changed in the heart at week 1; in the heart and skin – at week 2; in the heart, skin, and brain – at week 3. The Bcl-2 levels did not change in the liver and kidney mitochondria. In the mitochondria in the CNP-stimulated melanoma, the Bcl-2 levels were lower than in the skin mitochondria in CNP throughout the entire tumor growth period.
Conclusion. The liver and kidney mitochondria are somewhat Bcl-2 stable in both standard and stimulated tumor growth. It is assumed that different Bcl-2 dynamics in the mitochondria in melanoma depending on the variant of tumor development reflects the modulating effect of CNP and the ability to change the Bcl-2 levels according to the growth phase.

Aim. To perform quantitative evaluation of the degree of white matter tract abnormalities in children with spastic cerebral palsy by magnetic resonance tractography to determine severity of the disease, as well as to carry out a dynamic assessment of treatment effectiveness.
Materials and methods. The study included 46 children (32 males, 14 females; average age 5.4 ± 1.1 years). The participants were divided into two groups. The experimental group consisted of 23 children with spastic cerebral palsy. The control group included 23 children without any neurological disorder. Examination of the brain was performed on the Siemens Essenza 1,5 Т system (Siemens, Germany) and included magnetic resonance tractography to reconstruct the major white matter tracts. The number of fibers, average fractional anisotropy value, apparent diffusion coefficient, and coefficient of myelination of major white matter tracts in the brain were calculated and analyzed.
Results. We found a significant difference in the above-stated parameters between the groups. The experimental group showed a decrease in the absolute number of fibers at the central and posterior segments of the corpus callosum, corticospinal tracts, and left inferior longitudinal fasciculus. Besides, we detected a decrease in fractional anisotropy at 2–5 segments of the corpus callosum and right lateral corticospinal tract, an increase in the apparent diffusion coefficient at 2, 4, and 5 segments of the corpus callosum and left lateral corticospinal tract, and a decrease in the myelination coefficient in all the examined tracts, except for superior longitudinal fasciculus. We revealed a positive correlation between the intensity of the motor disturbance and the coefficient of myelination at the anterior corpus callosum and inferior longitudinal fasciculus.
Conclusion. Magnetic resonance tractography is an informative technique for unbiased evaluation of white matter tract anatomy, as well the level and degree of motor tract damage. The most useful characteristics of white matter tract anatomy are the absolute number of fibers in the tract, fractional anisotropy, and coefficient of myelination. Some of them correlated with the intensity of motor disturbance, so they can be regarded as potential predictors of rehabilitation potential.

Background. The pathogenesis of nonalcoholic fatty liver disease (NAFLD), which develops in obesity and type 2 diabetes mellitus (T2DM), is associated with the effects of inflammatory factors on the liver parenchyma and liver mitochondrial dysfunction.
Aim. To determine the role of sTNFSF14 in the regulation of liver mitochondrial biogenesis in obese patients with and without T2DM.
Materials and methods. The study included 263 obese patients with and without T2DM and 42 apparently healthy donors. Quantitative determination of cytokines in the blood plasma was performed by fluorescence flow cytometry. The level of relative gene expression in the liver biopsy samples was investigated by real-time PCR. Semi-quantitative determination of proteins in the liver biopsy samples was studied by western blotting.
Results. The study showed that the levels of sTNFSF14, interleukin (IL)-10, gp130 / sIL-6Rb, and sIL-6Ra in the blood plasma of the obese patients without T2DM significantly exceeded the similar values in the control patients and obese patients with T2DM. In the liver biopsy samples of the obese patients with T2DM and a body mass index (BMI) > 40 kg / m2, the expression level of the dynamin-1-like protein (DRP1 / DNM1L) gene was lower than in the control group, and the expression level of the mitofusin 2 (MFN2) gene tended to be higher. Compared with the control group, an increase in the expression level of the NADH-ubiquinone oxidoreductase chain 4 (MT-ND4) gene was recorded in the liver of all the obese patients. The patients with obesity showed a decrease in the amount of mitochondrial DNA (mtDNA) compared with the control group.
Conclusion. Thus, sTNFSF14, interacting with IL-10 and gp130 / sIL-6Rb in the circulation, positively effects the liver in the obese patients without T2DM. A low level of sTNFSF14 in the blood plasma of the obese patients with T2DM results in decreased mitochondrial division and increased cellular respiration.

Background. Diabetic nephropathy (DN) in patients with type 2 diabetes mellitus (T2DM) is associated with a risk of developing chronic heart failure (CHF). The degree of albuminuria is a marker of DN and is associated with an increased risk of chronic heart failure (CHF).
Aim. To evaluate fibrosis biomarkers and echocardiographic parameters in patients with T2DM without CHF, depending on urinary albumin excretion.
Materials and methods. The study included 42 patients with T2DM without verified CHF. The patients were divided into two groups: 1) a group with normoalbuminuria and 2) a group with a moderate increase in albuminuria (albumin / creatinine ratio of 30–300 mg / g). Echocardiography was performed and galectin-3, ST-2, PIСP, MMP-9, and TIMP-1 concentrations were measured.
Results. The groups did not differ by age, sex, body mass index (BMI), glycated hemoglobin (HbA1c), and glomerular filtration rate (GFR). Galectin-3 concentrations were significantly higher in the group with a moderate increase in albuminuria than in the group of patients without albuminuria – 13.6 (11.2; 15.1) ng / ml and 7.4 (6.7; 7.9) ng / ml, respectively, p = 0.002. The groups also did not differ in the values of biomarkers, such as P1CP, TIMP-1, and MMP-9. Besides, the group with normoalbuminuria had lower E/e’ values than the group with a moderate increase in albuminuria – 8 (7; 9) and 10 (9; 12.5), p = 0.02.
Conclusion. The patients with type 2 diabetes and a moderate increase in albuminuria have higher values of galectin-3 and a more pronounced diastolic dysfunction. The identified changes may reflect a higher risk of chronic heart failure in this group of patients.

Aim. To study the structure of mood fluctuations at the preclinical stage based on the findings of screening methods.
Materials and methods. A total of 129 students participated in the study. The average age was 18.95 ± 0.08 years. We used the clinical and psychopathological method, the Mini-International Neuropsychiatric Interview (MINI), and screening methods, such as the diagnostic questionnaire for bipolar disorder (Hypomania Checklist-32 (HCL-32)), and Hamilton Depression Scale (HAMD-17).
Results. Upon a clinical and psychopathological examination according to ICD-10 criteria, class V, mental and behavioral disorders (F00-F99), including affective pathology, were not detected. According to the findings of the HCL-32 screening technique, 61.2% (n = 79) of respondents had a cumulative score above the threshold. Analysis of individual items on the HCL-32 scale across the entire sample revealed that the majority of examinees positively assessed the impact of mood elevations on the family sphere (63.57%; n = 82), social activities (68.99%; n = 89), work (75.19%; n = 91), and recreational sphere (82.17%; n = 106). Positive (36.43%; n = 47; 95% confidence interval (CI) 28.13–44.74) and neutral (37.21%; n = 48; 95% CI 33.35–50.37) assessments of mood elevations were also detected by the respondents’ immediate circle, which, in general, significantly complicates recognition of hypomania symptoms and delays seeking specialized care. In the structure of mood elevation episodes irritability (r = –0.684), conflict (r = –0.665), risk-taking behavior (r = –0.550), increased sexual desire (r = 0.527), increased energy and activity (r = 0.431), distractibility (r = –0.467), stimulant use (r = –0.467), and decreased need for sleep (r = 0.408) dominated. These signs are very similar to the clinical manifestations of a hypomanic episode in bipolar II disorder.
Signs of mild depression revealed according to the HAMD-17 scale in 34.8% (n = 45) of respondents included sleep disorders (r = 0.693), decreased ability to work (r = 0.520), depressive mood (r = 0.579), hypochondria (r = 0.466), general somatic symptoms (r = –0.508), and gastrointestinal disorders (r = 0.513). These signs did not result in chief complaints and were not the reason for seeking specialized care.
Conclusion. In the non-clinical sample, in the structure of mood swings, mood elevations dominated, which were not subjectively identified as illness symptoms and did not appear as complaints in clinical and psychopathological examinations. Low mood was accompanied by general somatic symptoms, which may indicate subsequent formation of comorbid pathology. The identified subsyndromal signs of hypomania and depression in the nonclinical sample in the absence of complaints and psychiatric care-seeking are of clinical significance as predictors of a bipolar affective disorder and require further clinical and dynamic monitoring.

Aim. To identify the role of the autonomic nervous system in stress cardiomyopathy in an experimental model of Takotsubo syndrome.
Materials and methods. The study was carried out on 120 female Wistar rats. Stress modeling was performed by immobilizing animals on the back for 24 hours. Intact rats were used as controls. The rats were decapitated after termination of immobilization under general anesthesia with ether. Stress cardiomyopathy (SCM) was quantified by accumulation of 99mTc pyrophosphate radiopharmaceutical (99mTc PP) in the myocardium. The pharmacological agents used included the ganglionic blocker hexamethonium, administered five times at a dose of 20 mg / kg; guanethidine (50 mg / kg) administered subcutaneously once a day for three days, the last injection was performed 24 hours before immobilization; the muscarinic receptor antagonist atropine methyl nitrate (1 mg / kg); the α1-AR (adrenergic receptor) antagonist prazosin (2 mg / kg); the α2-AR antagonist yohimbine, administered at a dose of 2 mg / kg; the β1-AR antagonist nebivolol (1.2 mg / kg); the β2-AR antagonist ICI 118,551 (0.3 mg / kg); and the β3-AR antagonist L-748337 (0.1 mg / kg).
Results. Three-day administration of guanethidine caused a decrease in the degree of 99mTc-PP accumulation in the heart by 35.9%. Hexamethonium did not affect the degree of SCM. The blockade of the muscarinic receptor caused an increase in accumulation of 99mTc-PP by 26.5%. Inhibition of α1-AR did not affect SCM. The blockade of α2-AR caused a 2.2-fold increase in the accumulation compared with stress control. The blockade of β1-AR reduced 99mTc-PP accumulation by 2.5 times. The blockade of β2-AR by ICI 118,551 increased the degree of 99mTcPP accumulation by 34.6%. Inhibition of β3-AR had no effect on SCM.
Conclusion. The adrenergic system and β1-adrenergic receptor play an important role in the development of SCM. The parasympathetic nervous system ensures resistance of the heart to stress.

Aim. To evaluate potential associations between quantitative features of visceral and subcutaneous adipose tissue (AT) and anthropometric characteristics of obesity, metabolic disorders, and the state of the abdominal aorta in patients with chronic coronary artery disease (CAD).
Materials and methods. The study included 55 patients (average age 61.2 ± 7.2 years) with chronic CAD. Magnetic resonance imaging (MRI) was performed on a 1.5 T MRI scanner using T2-weighted spin-echo modes. The area and volume of abdominal subcutaneous (SAT) and visceral adipose tissue (VAT) were calculated at the L4–L5 level; the total volumes of abdominal SAT and VAT were determined. Parameters of lipid and carbohydrate metabolism, as well as adipokine profile were studied in the blood serum.
Results. In the course of a multiple linear regression analysis, we detected the independent determinants, which described 95% of the total VAT volume variability and were represented by waist circumference (WC) and serum levels of high-density lipoprotein (HDL) cholesterol and adiponectin. The model was characterized by the significance level p < 0.000001, the residuals of the model were normal. We calculated the coefficients in the model: 1.39 for WC, –0.26 for HDL cholesterol, and –0.19 for adiponectin. We detected a positive correlation between the abdominal aorta (AA) diameter and SAT area at the L4–L5 level (rs = 0.48; p = 0.0014), which does not depend on gender, and reverse correlations between the aorta diameter and glycated hemoglobin (HbA1c) level (rs = –0.40; p = 0.0359) and postprandial glycemia (rs = –0.40; p = 0.0273). The patients with a dilated aorta (group 2), when compared with the patients with a normal aorta diameter (group 1), did not differ in the AT accumulation, but demonstrated decreased levels of HbA1c and postprandial glycemia, which resulted in a smaller number of patients with type 2 diabetes mellitus.
Conclusion. We identified independent determinants of an increase in the total volume of abdominal visceral AT, such as an increase in WC and a decrease in serum adiponectin and HDL cholesterol levels. Results of the study indicate the presence of a link between the AA remodeling, accumulation of subcutaneous AT, and impaired glucose metabolism.

Aim. To study the content of cytokines in the blood serum of patients with obstructive jaundice of gallstone origin before and after surgical treatment, depending on the development of postoperative complications.
Materials and methods. The treatment group consisted of 70 patients with the diagnosis of obstructive jaundice of gallstone origin, verified following a comprehensive clinical and instrumental examination. In 54 patients, the postoperative period was uncomplicated, and in 16 patients, various infectious complications in the postoperative period were revealed. The control group consisted of 125 healthy volunteers. The concentration of six cytokines (interleukin (IL)-2, IL-4, IL-18, IL-10, tumor necrosis factor alpha (TNFα), and interferon gamma (INF γ)) was determined using reagent kits manufactured by Vector-Best LLC (Novosibirsk, Russian Federation) by enzyme-linked immunosorbent assay on the Thermo Scientific analyzer (BioMerieux, France).
Results. We identified significantly high concentrations of proinflammatory cytokines in the blood serum of patients with obstructive jaundice of gallstone origin upon admission, compared with the data obtained in the study of blood serum in the control group and in patients with obstructive jaundice after surgery. In the postoperative period in patients with obstructive jaundice without complications, the proinflammatory cytokines are significantly reduced and IL-4 is increased, whereas with the development of infectious complications, the level of proinflammatory cytokines is significantly elevated.
Conclusion. In the pathogenesis of obstructive jaundice, a local inflammatory process plays an essential role. This is confirmed by statistically significant changes in the studied cytokines. The established increase in the concentration of IL-4, which has anti-inflammatory activity, indicates its importance in the mechanisms underlying the absence of infectious complications in the postoperative period of obstructive jaundice of gallstone origin. The revealed increase in the levels of IL-18, TNFα, and INFγ in the blood serum of patients suggests their role in the pathogenesis of infectious complications in the postoperative period of obstructive jaundice of gallstone origin.

Aim. To study the incidence rate, clinical features, and prognosis of seasonal affective disorder (SAD) in senior (6th-year) medical students.
Materials and methods. SAD screening using the Seasonal Pattern Assessment Questionnaire (SPAQ, 1987) included 119 undergraduate medical students. 78 students were females (65.5%) and 41 – males (34.5%) (p = 0.001). The average age of women was 23 (22; 23) years, the average age of men – 23 (22; 24) years. Statistical processing was performed using the Mann – Whitney U-test, Pearson’s χ2 test, and Spearman’s rank correlation coefficient (rs).
Results. The data on the prevalence of affective disorders with a seasonal pattern in medical students were obtained: SAD – 9.2%, sub-SAD – 13.5%, psychological undulation of season perception (PUSP) – 16.8%. The number of students who did not exhibit seasonal undulation of the six main characteristics recorded by the SPAQ was 72 (60.5%) (p = 0.001). There were statistically significant differences in the higher median Global Seasonality Score of the SPAQ for SAD compared with PUSP, both with and without account of the gender factor (p = 0.001). The use of a binary logistic regression model made it possible to identify groups of students with or without SAD according to the SPAQ. The data obtained determined the contribution of the following factors: gender, seasonality, body weight, and the number of sleep hours per day in spring.
Conclusion. The study made it possible to obtain a logistic regression model that allowed to predict the greatest likelihood of developing SAD.

Inflammatory bowel disease (IBD) is a common pathology that reduces the quality and duration of a patient’s life. The cornerstone of treatment of IBD patients is polypharmacotherapy based on the use of salicylates, antibiotics, immunomodulatory and biological drugs, and topical dosage forms. Multicomponent treatment has shown to reduce the quality of life and negatively affect adherence to drug therapy in IBD patients.
One of the leading causes of treatment failure is low treatment adherence, which leads to disease progression, disability, and increased financial costs. Currently, there are many factors that affect adherence to therapy, some of them are modifiable, which creates opportunities to improve the effectiveness of existing medical interventions. However, the available data on the level of adherence in IBD patients are not numerous and homogeneous, so a low level of adherence to drug therapy in IBD patients is registered in 7–72% of cases.
An important issue in understanding adherence in IBD patients is a lack of research on the level of adherence to counselling and lifestyle modification. However, the course of IBD, treatment features related to the duration of therapy and necessary lifestyle modifications (nutrition), as well as regular monitoring of laboratory and instrumental parameters determine the need to assess adherence to lifestyle modification and counselling along with adherence to drug therapy.

 The use of molecular genetic approaches to identification of tissues and biological fluids of the body, which often provide important information for reconstruction of a potential crime, is relevant for forensic studies. MicroRNAs (miRNAs) are short, single-stranded noncoding RNAs (containing on average 18–22 nucleotides) that regulate gene expression at the post-transcriptional level by binding to the 3’-untranslated region (3’-UTR) of specific mRNA targets, which results in a decrease in protein expression by blocking translation and / or promotes degradation of
target mRNAs. MiRNAs are involved in virtually all biological processes, including cell proliferation, apoptosis, and differentiation. By acting on target genes, miRNAs are involved in regulation of many pathological processes.
In addition, numerous miRNAs called circulating miRNAs were found in  many biological fluids of the human body, for example, in blood. Molecular genetic approaches undoubtedly outperform histological and  immunological tests in tissue characterization, and miRNAs, due to their characteristic tissue specificity and stability in biological fluids, have potential for application in forensic practice and are of great interest for experts. 

 Impairment of extracellular and intracellular calcium homeostasis can have a damaging effect on the functioning of both individual organs and systems and the whole organism. In the cardiovascular system, disorders of
calcium metabolism trigger a cascade of auto-inflammatory responses, leading to persistent morphological and functional disturbances. In this review, impaired calcium homeostasis is defined as a predictor of the development of hypersensitivity in cardiovascular diseases. We analyzed the development of a cardiovascular pathology (atherosclerosis, aortic valve calcification, and essential hypertension) with impaired calcium metabolism and pathological mechanisms that cause the disturbances. Calcium sensors, polymorphic variants of genes, and hormones involved in calcium metabolism can reveal the features of calcium metabolism and contribute to a personalized approach to treatment of cardiovascular diseases. 

Background. Immune responses and inflammation play an important role in the pathogenesis of ischemic stroke.
Aim. To analyze the involvement of neutrophils in the pathogenesis of ischemic stroke.
Results. Data on the contribution of neutrophil granulocytes to the development of local sterile inflammation and secondary brain injury in acute ischemic stroke were summarized. Mechanisms of neutrophil influence on thrombosis, neutrophil extracellular trap formation (NETosis), protease release, and direct interaction with platelets with subsequent formation of platelet-leukocyte aggregates were discussed. Available information on the effectiveness of reperfusion therapy and an association of changes in neutrophil activity with development of infectious complications of stroke were presented. In addition, research data were presented on the contribution of neutrophils to atherogenesis, which is one of the most important etiological factors in ischemic stroke. The review showed that the contribution of neutrophils to the pathogenesis of ischemic stroke is associated with implementation of their secretory, regulatory, and phagocytic functions, as well as with NETosis.
Conclusion. It was shown that neutrophils are involved in the pathogenesis of ischemic stroke and modulate a response to treatment.

Local allergic rhinitis is a new atopic disease recognized in modern allergy and rhinology. Its clinical symptoms are currently well described and compared with conventional allergic rhinitis, however, diagnostic and therapeutic protocols, including antigen-specific immunotherapy (ASIT), should be specified.

Therefore, local allergic rhinitis often remains underdiagnosed and by mistake is referred to non-allergic rhinitis. Yet, the pathogenesis and mechanisms of allergen tolerance breakdown in this endotype of allergic rhinitis remain understudied. Researchers continue to study the network of tolerogenic cells and biomolecules, such as regulatory T cells, tolerogenic dendritic cells, interleukin (IL)-10, IL-35, transforming growth factor-β (TGF-b), vegetative innervation of the nose, and neurotransmitters.

 The review focuses on diagnostic markers of local allergic rhinitis. 

 This review addresses the use of vascular catheterization in small laboratory animals in biomedical research with an emphasis on the technological aspects of the method. The use of vascular catheters for blood sampling, drug delivery or biomonitoring improves the quality of the study (reliability and reproducibility of results) and promotes compliance with modern bioethical standards. The key factors that determine the success of the surgery and the entire study are considered with an up-to-date approach. In particular, recommendations are given on the choice of the vessel and the type and size of the catheter, depending on the characteristics of the animal and the study objectives. Catheterization of the external jugular vein of a rat is described in detail, and the fundamental stages of the procedure are the same for all major vessels of rodents. Much attention is paid to potential complications of vascular catheterization, care for catheterized animals in the postoperative period, as well as measures for maintaining the patency of the catheter and its proper functioning. The main limitations for the widespread use of catheterization in research are insufficient qualification of the surgeon and the need to use surgical equipment and microsurgical instruments. 

Radioresistance of prostate cancer is a complex therapeutic problem. Biochemical recurrence after radiation therapy occurs in 22–69% of patients with prostate cancer. Nearly half of these patients progress to a clinical relapse within 15 years, and a third progress to castration-resistant prostate cancer. This review analyzes literature data on radioresistance mechanisms in prostate cancer cells. We searched for literature published in eLibrary, PubMed, and Scopus databases by key words: prostate cancer, radioresistance, markers. In total, 568 foreign and 178 national articles published between 1975 and 2020 were found. Of these publications, 77 articles were selected (published in 2001–2020), which reveal the molecular basis of tumor radioresistance.
Modern understanding of the origin of radioresistant cancer cells focuses on processes leading to enhanced DNA repair, activation of anti-apoptotic signaling pathways, and a decrease in the level of endogenous and exogenous reactive oxygen species. The state of a tumor microenvironment, autophagy, and epithelial-mesenchymal transition also play an important role in radioresistance. Currently, the mechanisms of resistance to radiation therapy are explained by the existence of tumor stem cells, which provide genetic heterogeneity and activation of carcinogenesis signaling pathways. The tumor can also be protected from radiation by a hypoxic microenvironment. Since cancer stem cells can acquire plasticity in response to radiation therapy, search for markers of radioresistance for screening and identification of radioresistant prostate cancer is relevant.

To analyze results of the studies covering modern scientific views on the genetics of familial amyotrophic lateral sclerosis (FALS).
We searched for full-text publications containing the key words “amyotrophic lateral sclerosis”, “FALS”, and “genetics” in the literature for the past 10 years in both Russian and English in eLibrary, PubMed, Web of Science, and OMIM databases. In addition, the review includes earlier publications of historical interest.
This review summarizes all existing information on four most widespread genes associated with FALS: SOD1, TARDBP, FUS, and C9ORF72. The review also describes the functions of these genes and possible pathogenetic mechanisms of motor neuron death in amyotrophic lateral sclerosis (ALS), such as mitochondrial dysfunction, oxidative stress, glutamate excitotoxicity, damage to axonal transport components, and pathological neurofilament aggregation.
As modern methods of molecular genetic diagnostics evolve, our knowledge about multifactorial FALS genetics expands. This information should be taken into consideration in clinical practice of neurologists. Information about the genes associated with ALS and understanding of particular pathogenetic mechanisms of the disease play a key role in the development of effective therapeutic strategies.

The aim of the study was to analyze medical literature on the role of microRNA in the pathophysiology of atrial fibrillation and the possibilities of using microRNAs as biomarkers.
The analysis of modern medical literature was carried out using the PubMed – NCBI database.

Atrial fibrillation (AF) is a common and serious cardiovascular disease. The pathophysiological mechanisms underlying the development of atrial fibrillation are not entirely clear. In addition, there are no optimal biomarkers for early detection and assessment of the prognosis for patients with atrial fibrillation. Recently, the attention of researchers has been directed to the molecules of microRNA. There is a lot of evidence that they are involved in the pathogenesis of neurological, oncological, and cardiovascular diseases. This review examines the role of microRNAs in the pathophysiology of atrial fibrillation. The possibility of using microRNA as a biomarker for the diagnosis and prediction of atrial fibrillation is also discussed.
MicroRNAs play a crucial role in the pathophysiology of atrial fibrillation, regulating the mechanisms of atrial remodeling, such as electrical remodeling, structural remodeling, remodeling of the autonomic nervous system, and impaired regulation of calcium levels. The stability of microRNAs and the possibility to study them in various biological fluids and tissues, including blood, make these molecules a promising diagnostic biomarker for various cardiovascular diseases. The presented data clearly indicate that AF is associated with changes in the expression level of various microRNAs, which can be quantified using a polymerase chain reaction. Further research is required to assess the role of microRNAs as biomarkers for atrial fibrillation, in particular to establish precise reference limits.

 A clinical case of treatment for ventricular arrhythmia from the right ventricular outflow tract using non-invasive real-time electrophysiological mapping and the “Astrocard” navigation system (“Meditek”, Russia) is presented. This clinical case demonstrates the accuracy of non-invasive real-time mapping for the diagnosis and treatment of ventricular arrhythmias. 

 The article presents a case of granulomatosis with polyangiitis, which is difficult for clinical diagnosis. Recently, the incidence of systemic vasculitis has increased, and given the similarity of clinical symptoms with other pathologies, a doctor of any specialty should carry out differential diagnosis. Granulomatosis with polyangiitis is characterized mainly by damage to the upper respiratory tract, lungs, and kidneys. The main method for diagnosing granulomatosis with polyangiitis is biopsy with histological examination,  which allows to detect inflammation in the affected tissues. A feature of granulomatosis with polyangiitis is detection of antineutrophil cytoplasmic antibodies in the blood serum. However, these antibodies are recorded only in 80% of patients and are not detected in the remission phase, which makes diagnosis much more difficult. 

Idiopathic pulmonary fibrosis (IPF) is one of the most common diseases in the group of interstitial lung diseases, which is characterized by persistent progression and poor prognosis. Over the past decade, experts have made significant progress in developing a diagnostic algorithm for IPF patients. This algorithm includes analysis of clinical, laboratory, and instrumental data, primarily the results of high-resolution computed tomography (HRCT). Precise adherence to the diagnostic algorithm and correct interpretation of HRCT data are prerequisites for IPF diagnosis.
Specialists of the Tomsk region have developed routing of patients with suspected IPF. The presented clinical case is a successful example of adhering to this algorithm. Wide implementation of modern diagnostic algorithms into diagnosis and treatment of IPF and quality improvement of imaging methods, primarily HRCT, carried out as a part of the differential diagnosis, open up prospects for early diagnosis of this pathology. A timely prescribed antifibrotic therapy (nintedanib, pirfenidone) in IPF allows to slow down pathological progression and improves the prognosis.