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Inflammation plays a key role in the development and progression of type 2 diabetes (T2DM), a disease characterized by peripheral insulin resistance and systemic glucolipotoxicity. The main source of inflammation in the early stages of the disease is visceral adipose tissue (VT). Macrophages are innate immune cells that are present in all peripheral tissues, including VT. Violation of the response of VT (MT) macrophages to changes in the microenvironment underlies aberrant inflammation and the development of local and systemic insulin resistance. The inflammatory activation of macrophages is regulated at several levels: stimulation of cell surface receptors, intracellular signaling, transcription, and metabolic levels. Which are activated by the transformation of macrophages along the pro-inflammatory or anti-inflammatory pathways. Such polarization of macrophages in modern immunology is divided into classical anti-inflammatory M1 polarization and alternative anti-inflammatory M2 polarization of macrophages. The M1 / M2 ratio of macrophages in the process of inflammation ensures the resolution of inflammation at different stages of its development. The review considers the main mechanisms involved in VT inflammation and the development of insulin resistance in T2DM, supported with the participation of immunocompetent cells, M1 / M2, as well as growth factors and humoral immunity factors secreted during this process.

Introduction. The long-term event-free survival of patients with high-risk neuroblastoma (NB) receiving intensive complex therapy according to current russian standard do not exceed 40 %. Also, there is no standard tactics in patients with primary resistant and relapsed disease, most of them die due to disease progression. While, anti-GD2 immunotherapy (IT) proved to be effective in patients with high-risk NB, in Russian Federation this method is not generally available. There are currently two pilot studies ongoing in Raisa Gorbacheva Memorial Institute aimed to evaluate the effectiveness of anti-GD2 antibodies in high-risk NB patients.Aim of the study – describing a single-center experience of anti-GD2 IT in primary high-risk NB patients and patients with primary resistant and relapsed disease.Materials and methods. A total of 20 patients received anti-GD2 antibodies, 16 of them were included into pilot trials. The median age at IT initiation was 5 (3–17) years. In 13 cases the therapy was initiated in patients with high-risk disease after auto-HSCT, in 3 cases – in patients with 1st systemic relapse of primary resistant disease after 2nd-line therapy and haplo-HSCT, in 1 case – in patient with 2nd chemosensitive relapse after haplo-HSCT. Also, 3 patients with progressive chemoresistant disease received anti-GD2 antibodies as monotherapy (n = 1) or in combination with chemotherapy (n = 2) as salvage regimen.Results. Patients receiving anti-GD2 antibodies after auto-HSCT retain response to therapy in 11 of 13 cases with a median follow-up period of 15 (6–27) months, in 2 cases there was disease progression during or immediately after IT cessation. Both patients with disease progression responded well to salvage therapy. Two of 3 haplo-HSCT recipients with prior good response to 2nd-line therapy are currently in remission 16 and 36 months past haplo-HSCT, one patient progressed 55 months after transplantation. A patient with 2nd late relapse after haplo-HSCT currently maintains remission on IT. Both patients with chemorefractory progressive disease did not respond to IT and died due to disease progression. IT was characterized by acceptable toxicity. In most cases it was complicated by Gr 1–2 fever, rash or neuropathic pain effectively controlled by supportive therapy. However, three patients had signs of neurotoxicity requiring therapy termination in one case.Conclusion. Dinutuximab beta IT is characterized by acceptable toxicity. With a median follow-up of 18 (6–59) months the majority (14 of 17) patients receiving anti-GD2 antibodies as maintenance therapy after auto- or allogeneic HSCT retain response. However, we did not observe any response in patients with progressive chemorefractory disease.

The article presents a clinical case of a 25-year-old patient with progressive diffuse B-cell lymphoma with lesions of the S2 nerve root, accompanied by pain syndrome that is not relieved by systemic multimodal analgesia using opioids, antiepileptic and non-steroidal anti-inflammatory drugs. Polyneuropathy, secondary immunodeficiency, thrombocytopenia grade IV refractory to platelet concentrate transfusion, Guillain-Barre syndrome, impaired the somatic status and intensified the pain syndrome. Local anesthetics epidural port was successfully implanted to improve quality of analgesia. As a result of prolonged epidural infusion of 0.2% ropivacaine with titration rate from 4 to 7 ml/hour depending on the severity of the pain syndrome, that significantly improved patients quality of life was achieved by reducing the intensity of pain and increasing duration of night sleep. In the early postoperative and long-term follow-up periods (14 days), there were no hemorrhagic and infectious complications associated with the use of the epidural port.

Aim: the study was aimed to develop a reagent kit for the real-time RT-PCR diagnostics of virus causing COVID-19.Materials and Methods.Three target sites were chosen in the genome SARS-CoV-2. The testing included 220 samples, 48 artificially created positive samples (made from patients’ biomaterial) and 172 clinical samples (scrapes from nasal and pharyngeal cavities, bronchoalveolar lavage, expectoration, endotracheal/nasopharyngeal aspirate, feces, post-mortem material), obtained from two medical centers. Preliminary, the obtained biomaterial was analyzed with a reagent kit of comparison. The evaluation was performed with a confidential interval CI 95%. The calculation of CI for the sensitivity and specificity was made based on the distribution of χ2.Results.The authors developed a technology of novel coronavirus infection (COVID-19) real-time RT-PCR diagnostics for the application in practical healthcare and proposed the variants of testing at all the stages (preanalytical, analytical, and post-analytical, including automated results processing). The proposed reagent kit meets the requirements of the World Health Organization and the Ministry of Healthcare of the Russian Federation. The study results demonstrated high sensitivity and specificity. The sensitivity was 100% (95% CI) 95.6–100%; the specificity was 100% (95% CI) 96.7–100%.Conclusion.The proposed reagent kit was registered in the RF as a medical product; the registration certificate No. RZN 2020/9948 dated 01.04.2020. The application of the reagent kit in network laboratories will provide patients with access to testing for the virus causing COVID-19 and contribute to quick differential diagnostics, improvement of pandemic control, and accurate statistics on the spread of the virus.

For many years, interest in the issue of obesity has not faded, as obesity is now one of the most common pathologies in the world that directly affects quality of life and lifespan. Even a slight weight loss (5-10% of baseline values) in obese patients is known to improve metabolism and reduce the risk of a range of comorbidities. The article reflects the importance of comprehensive treatment of obesity, presents positive experience of using Reduxin (sibutramine in combination with microcrystalline cellulose) to reduce body weight and risk factors for cardiovascular disease in a specific clinical example in a patient with exogenous-constitutional obesity and eating disorders. The case of obesity in a young man of 24 years old is presented, when other components of the metabolic syndrome (except for arterial hypertension) were not formed. Thus, following the results of 24-week complex treatment, clinically significant reduction of body weight (by 21.7% of initial values) was observed in the patient. The data of psychological researches have shown that the patient has no increase of anxiety and depression level during treatment, but at the same time the indicators of quality of life according to the results of health questionnaire testing have improved. This clinical case corresponds to the results of the PrimaVera program and demonstrates that weight loss during sibutramine therapy in combination with microcrystalline cellulose has a positive impact on the overall health and emotional status of patients and leads to improved quality of life. Therefore, successful treatment of obesity and the maintenance of other outcomes are key to preventing cardiovascular disease.

The prevalence of T2D is steadily increasing annually, which resulted in an active search for a way to control the disease. The last decade has seen a rise in the number of new groups of glucose-lowering drugs, which not only proved effective in the management of hyperglycemia and safe against hypoglycemia, but also joined the ranks of the drugs of the first-line therapy. Among them is incretin-active agents - type 4 dipeptidyl peptidases inhibitors (IDPP-4, glyptines). Sitagliptin was the world's first approved IDPP-4, and began to be used successfully in Russia since 2007. The review presents data on the efficacy, safety (including cardiac safety) of sitagliptin use and accumulated experience of its use in the treatment of patients with type 2 diabetes.

Oncological diseases are the main causes of death in the world. Modern treatment of cancer patients contributes to an increase in survival rate due to strong chemotherapeutic drugs, the use of which is accompanied by toxic effects on cardiomyocytes. The main manifestations of cardiotoxicity are left ventricular dysfunction, myocardial ischemia, thromboembolic complications, chronic heart failure. As a result, the risk of cardiovascular mortality may be higher than the risk of death from the tumor process. An important task of oncologists and cardiologists is the early diagnosis of cardiotoxic complications in order to start treatment in time and reduce mortality from cardiovascular pathology in cancer patients.

The article is devoted to the role of self-monitoring of the level of glycemia in achieving the goals of treatment in patients with diabetes mellitus. The dependence between the compensation of carbohydrate metabolism and the level of motivation of the trained patient for the control of glycemia is shown, the necessity of regular self-monitoring of glycemia by the patient is grounded. The main methods and means used for self-monitoring of glycemia are given and their characteristics are given. The importance of teaching patients to self-control methods as a measure of preventing the occurrence of complications of diabetes mellitus is substantiated. Comparative data on the prevalence of complications in patients, both not using self-monitoring, and conducting it, are given. Teaching patients proper glycemic control with portable glucometers is an important and indispensable component of diabetes therapy.

Type 2 diabetes is a chronic progressive disease the prevalence of which is increasing. The development of new strategies for the treatment of diabetes, among which drugs that modulate the “incretin effect” are worth noting, continues. Dipeptidyl peptidase-4 inhibitors (DPP-4, gliptins) are a group of oral antidiabetic incretin drugs that enhance the glucose-induced activity of β-cells and suppress excessive glucagon secretion by pancreatic α-cells. This group of antidiabetic drugs is widespread due to a number of relevant benefits, such as neutral effect on body weight, low risk of hypoglycaemia, convenient administration scheme and good adherence to treatment. Efficacy and safety of treatment demonstrated by global multicenter trials allow for a wide use of gliptins in clinical practice.

Diabetes mellitus implies the need for self-monitoring under the supervision of the attending physician. In the conditions of increasing prevalence of diabetes, the physician’s key task is to properly educate the patient in applying the main principles of self-monitoring. Learning the principles of glycemic control with a portable glucometer is an essential component of diabetes treatment.

Modern representation of self-monitoring blood glucose can be characterised by new technologies introduced in recent years, including tools to identify trends and patterns of glycaemia (PatternAlert ). These technologies simplify self-monitoring and help avoid errors in the interpretation of blood glucose levels in patients. This study examines the primary trends in the management and control of diabetes, as well as the strengths and weaknesses of the control of glycated haemoglobin (HbA1c). In addition, this study raises broader questions on self-control in patients with diabetes mellitus, which are beyond the issues of the normalisation of blood glucose levels.

The article investigates the value of canagliflozin in the management of type 2 diabetes mellitus from the perspective of a clinically-based patient-centred approach. It focusses on the outcomes of a 52-week double-blind, active-controlled study. The results of this clinical trial demonstrate that canagliflozin, which provides significant weight loss ability, improves the quality of life and satisfaction with physical and emotional health in patients with diabetes compared with sitagliptin.

A relationship between thermal effects and relaxation of the high-frequency shear modulus upon heat treatment of bulk Zr48(Cu5/6Ag1/6)44Al8 metallic glass is found. This relationship is attributed to the relaxation of a interstitial-type defect system frozen-in from the melt upon glass production. Calorimetric data show that thermal effects occurring on heating include heat release below the glass transition temperature, heat absorption above it and heat release caused by crystallization. The equation derived within the Interstitialcy theory can be used to calculate the shear modulus relaxation using the calorimetric data. The obtained results are used to trace the defect concentration as functions of temperature and thermal prehistory.

Aim. To study the changes of the left (LV) and right (RV) ventricles diastolic function, the segmental LV diastolic function in patients with anemic cardiomyopathy after the iron and selenium drugs therapy.Material and methods. Patients (n=54) with severe chronic post-hemorrhagic iron deficiency anemia, complicated by cardiomyopathy were treated with iron sulfate and sele- nium. Segmental LV diastolic function was evaluated with pulsed tissue Doppler, and global diastolic function of the LV and RV – with Doppler echocardiography, before and af- ter treatment. Control group contained 16 healthy individualsResults. Disorders of segmental LV diastolic function, and both ventricles global diastolic function were found in anemic patients with cardiomyopathy. Flow rate rapid filling re- duced by 27.1% compared with this in control (pConclusion. Echocardiography and myocardial tissue Doppler provide early finding of segmental LV diastolic function disorders in anemic cardiomyopathy. Iron and selenium ther- apy leads to improvement of myocardial diastolic function in these patients.

Aim. To study the effect of antiviral therapy (AVT) on some cardiac hemodynamic parameters in patients with chronic viral hepatitis (CVH).Material and methods. Segmental systolic and diastolic functions of the ventricles as well as global diastolic function were evaluated in 25 patients with CVH by pulsed tissue Doppler mapping and by the method of Doppler echocardiography, respectively. The blood flow speed and diameter of blood vessels in liver were determined by ultrasound Doppler. Cardiac hemodynamics was examined in all patients before and after AVT with interferon in combination with ribavirin with formation of persistent virological response. Healthy people (n=19) were included into control group.Results. Reduction in atrial and ventricular sizes, decrease in left ventricular mass, improvement of systolic function of both ventricles, as well as diastolic function of the left ventricle were found in patients with CVH after specific treatment. Reduction in hepatic arterial and portal blood flow speed and a total number of heart rhythm disorders were also observed. Therefore AVT in patients with CVH shows a positive impact on cardiac hemodynamics. Medium-strength correlation (r=0.31; pConclusion. Patients with CVH that do not receive AVT have worse prognosis and indicators of cardiac hemodynamics in comparison with patients who receive specific AVT.

We consider an optimal control problem for a hybrid dynamic system, where jumps of a trajectory may occur only at the moments of hitting a given closed subset of an extended phase space. A time reparameterization technique is developed to reduce the original problem to the one with bounded controls. We show that the reparameterized problem is equivalent to optimization in a class of generalized solutions to the hybrid system.

An optimal impulsive control problem is considered under constraint on the total impulse of control. In the problem there are conventional bounded controls and vector-valued measures (impulsive control). Based on a needle-shaped variation procedure an algorithm for optimal control of impulsive dynamic systems is elaborated. A discontinuous time reparameterization technique is applied. Control improvement property is established. Convergence analysis is provided.

Optimal control problem for logic-dynamic systems is considered. Based on sufficient optimality conditions, similar to Krotov's conditions, a method for successive control improvement is developed. First- and second-order computational algorithms are constructed.

Iodine deficiency disorders are one of the most common problems in thyroidology and endocrinology. Due to the vulnerability to reduced consumption of iodine, a special interest in the study of the effects of iodine deficiency and its prevention are pregnant and lactating women, patients of reproductive age and children is shown.

Explicit asymptotic formulas for reachable sets of linear dynamic systems with two types of control bounds, geometric constraints and constraints on the total impulse of the control action, are compared. A detailed proof of asymptotic formulas for the case of geometric constraints was first given. It was shown that, despite the similarity of the problem statement and methods to study the asymptotics of reachable sets for the considered types of constraints, the results obtained are essentially different. For example, for the impulsive case in the space of shapes of reachable sets, a multidimensional attractor may arise, while, in the case of geometric constraints, the corresponding attractor is reduced to a single point.