Sports complex TRP as a motivational factor for active physical exercises for young students

The issue of preserving the health of students today is very serious. In this regard, it is important to create positive motivation in youth sports, development and improvement of physical qualities. Thus, the question arises, how to introduce students to physical education and sport through engaging them in the delivery of standards "TRP"Вопрос сохранения здоровья учащейся молодежи на сегодняшний день стоит очень остро. В связи с этим, важно создать положительную мотивацию у молодежи для занятий спортом, развития и совершенствования физических качеств. Таким образом, возникает вопрос, каким образом можно приобщить студентов к физкультуре и спорту через привлечение их к сдаче норм «ГТО

Comparative analysis of the vaccination rate of preschool children

The purpose of the study is to conduct a comparative analysis of the level of vaccination of preschool children.Цель исследования – провести сравнительный анализ уровня привитости детей дошкольного возраста

2020 Clinical practice guidelines for Hypertrophic cardiomyopathy

Russian Society of Cardiology (RSC)With the participation: Russian Association of Cardiovascular SurgeonsEndorsed by: Research and Practical Council of the Ministry of Health of the Russian Federation Task Force: Gabrusenko S.A. (Chairman), Gudkova A.Ya.* (Chairman), Koziolova N.A. (Chairman), Alexandrova S.A., Berseneva M.I., Gordeev M.L., Dzemeshkevich S.L., Zaklyazminskaya E.V., Irtyuga O.B., Kaplunova V.Yu., Kostareva A.A., Krutikov A.N., Malenkov D.A., Novikova T.N., Saidova M.A., Sanakoev M.K., Stukalova O.V

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease

JUVENILE ARTHRITIS IN PEDIATRIC AND ADULT RHEUMATOLOGY SERVICE: THE PROBLEM OF CONTINUITY IN THE MANAGEMENT OF PATIENTS

The undeniable progress made over the last decade in the treatment of patients with severe juvenile arthritis has ranked in the order of priorities for the provision of efficient and reliable continuity in the management tactics for patients after their transition from their follow-up by a pediatrician to adult rheumatology service. A number of objective difficulties in organizing such continuity are associated primarily with the heterogeneity of the juvenile arthritis group in its clinical manifestations and nosological outcomes. The features of physiological processes of a growing organism cause significant differences in the nature of the course, manifestations of certain clinically significant syndromes (for example, delayed axial skeleton involvement after the onset in juvenile spondyloarthritis), radiological pattern and immunological markers in juvenile-onset rheumatic diseases. Timely active therapy with increasingly available innovative technologies, biological agents in particular, provides a successful disease-modifying effect, so when a patient with juvenile arthritis is transferred from his/her follow-up by a pediatrician to adult rheumatology service, there may be a wrong opinion about the performed redundant therapy and the expediency of its cancellation or correction, which sometimes leads to irreparable negative consequences. The used indices and other tools to assess the activity and functional status are fundamentally different in children and adults with joint inflammatory diseases. The paper presents a brief review of the current state of the problem and international experience with continuity in the follow-up of patients with juvenile arthritis between pediatric and adult rheumatology service

Optimization of systemic juvenile arthritis treatment regimens with correction of tocilizumab intravenous administration according to data of observational retrospective study

Objective: to assess the possibility of using varying interval between intravenous infusions of tocilizumab (TCZ) as a tool for choosing the optimal treatment regimen in systemic juvenile arthritis (SJA).Subjects and methods. The observational retrospective study included 72 patients (29 boys and 43 girls) with a SJA fulfilled ILAR criteria, who received TCZ ≥12 months, in which previous therapy with various anti-rheumatic drugs was ineffective. We studied the changes of the main clinical and laboratory parameters of the SJA activity after correction of the interval between infusions.Results and discussion. In the studied group median age of onset was 3.8 [2.1; 5.9] years, duration of disease before the appointment of TCZ – 26.5 [9.25; 62.25] months. Therapy is continued by 70 patients, the median duration of therapy is 5.0 [2.75; 6.38] years. The initial interval between TCZ infusions was 2 weeks in 49 (group 1) and 4 weeks in 23 patients (group 2). After 6 months of therapy in group 2, the interval was reduced to 2 weeks in 15 (65.2%) patients due to decreased effectiveness. Prolongation of the period between the introduction of TCZ in patients of group 1 who did not reach the inactive status of the disease in the 1st year of the disease resulted in a significant increase of erythrocyte sedimentation rate, C-reactive protein level and exacerbation of systemic manifestations of SJA (p<0.01) in the absence of statistically significant changes of joint status parameters (p>0.05). 40% of these patients had involvement of «new» joints, including hip joints. «Harbingers» of exacerbation in the period of increasing intervals between infusions were: arthralgia (88%), myalgia (65%), sore throat (30%), dysphoria (50%, more often in preschool children), increase of ferritin level and number of leukocytes. In 90.3% of patients who have reached the inactive status of the disease, it was possible to gradually increase the interval between infusions. In 6 patients, TCZ was canceled by gradually increasing the intervals, in 4 of them, therapy was resumed at an initial interval of 2 weeks after 3, 6, 21 and 22 months, respectively, in two patients, a drug-free remission was maintained during 23 and 20 months. Reduction of intervals to the initial 2 weeks was performed in 13 (18.1%) patients. The development of exacerbations with the need to reduce the interval to the initial one was most often observed at 24–35 months of therapy, which chronologically coincided with the period of active growth. Currently, 15 patients receiving TCZ with an interval of 5–6 weeks, and 40 – with an interval of 4 weeks, 9 patients – 3 weeks, in 6 patients attempt to increase the interval to more than 2–2,5 weeks was unsuccessful.Conclusion. Experience suggests the need to comply with a two-week interval between infusions of TCZ at the initial stage of therapy in most patients with SJA until the inactive stage of the disease, followed by a smooth individual increase in the interval to 4 weeks (2–3 days under careful medical supervision). Appearance of initial signs of exacerbation, requires to reduce the interval to 2 weeks. Before deciding on the complete withdrawal of TCZ, it is advisable to increase the interval between infusions to 5–6 weeks under careful clinical and laboratory control

MODERN VIEWS ON THE GENE NOTCH1 MUTATIONS ROLE FOR AORTIC COARCTATION

Aim. By the observation of aortic coarctation victims families, to reveal factors predisposing to the disease development, and to evaluate the prevalence of NOTCH1 genes mutation/replacements in patients with this kind of defect. Material and methods. Totally 68 patients included with aortic coarctation. All patients underwent echocardiographic investigation, direct and indirect manometry, multispiral computed aortography and intraoperational revision of coarctation zone. 51 patient underwent screening of 10 from 34 exones of NOTCH1 gene. Control group consisted 200 patients without IHD.Results. In more than a half of the cases coarctation coexisted with bicuspid aortic valve and in circa a hlaf of the cases there was combination of coarctation with arc or descending hypoplasia. Totally 29 NOTCH1 gene types were found. Four from those led to aminoacids exchange, of those only one, R1279H, was revealed in patients group and control group either. This type was much more prevalent in patients with aortic coarctation comparing to control group (p<0,05).Conclusion. The most important factors in coarctation development are heredity (33,8%) and complicated pregnancy (57,4%). The exchange of R1279H in gene NOTCH1 was much more prevalent in patients with the defect studied and might be an associated with the disease allele

Pregnancy outcomes in patients with rheumatoid arthritis and systemic lupus erythematosus. Part II. Neonatal outcomes

Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are the most common autoimmune rheumatic diseases (RD) that occur mostly in women of childbearing age, and the occurrence of pregnancy is an expected fact. Due to the ongoing disputes over the ethics of maintaining birth rates among an unhealthy population, modern researchers focus attention on studies of the mutual impact of RD and pregnancy, on the safety of pharmacotherapy during conception and gestation, and on the health of the offspring born to female patients with RD.Objective: to evaluate the neonatal outcomes of pregnancy in patients with RA and SLE.Subjects and methods. An investigation was conducted to study the health status of 73 babies born to 72 female patients with RD (76 cases of pregnancy), of whom 29 patients with RA (32 cases of pregnancy) and 43 with SLE (44 cases of pregnancy) were followed up prospectively at the V.A. Nasonova Research Institute of Rheumatology and the Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology. The health status of the babies was evaluated in the first year of their life. Supervising neonatologists and pediatricians recorded abnormalities in the newborns and subsequently analyzed using their medical records (extracts from maternity hospitals, children's hospitals, and outpatient cards).Results and discussion. Of the 76 supervised pregnancies, 72 (94.7%) resulted in 73 live births (one twin pregnancy in a patient with SLE). There were three (6.8%) cases of pregnancy loss in the second trimester in patients with SLE having antiphospholipid syndrome (APS) and one (3.1%) case of perinatal death (a boy and a girl from a monochorionic diamniotic twin with reversed arterial perfusion) in a patient with seropositive RA. The height and body weight of all the newborns conformed to gestational age. Patients with RA and SLE compared to the population more often gave birth to low birthweight babies (9.7 and 21.4% versus 60.9 per 1,000 live births in the Russian population). In the groups of mothers with RA and SLE, their infants had a high Apgar score of 8–9 at one and five minutes. Various abnormalities were detected in 5 (16.1%) and 15 (35.7%) babies born to mothers with RA and to those with SLE, respectively. Among the neonatal congenital anomalies (malformations), there was patent foramen ovale, patent ductus arteriosus, and hip joint dysplasia, which were more common in the babies born to mothers with SLE having APS and exceeded the population-based incidence of these anomalies. The babies were more commonly diagnosed with congenital pneumonia than those in the population; there were single cases of umbilical hernia, hemangioma, thrombocytopenia, hemorrhagic disease of the newborn, perinatal encephalopathy, and congenital hearing loss.Conclusion. The mothers with RA and SLE more often gave birth to low birthweight babies than did those in the population. The infants born to mothers with RA and SLE had significantly more frequently congenital heart defects (patent foramen ovale, patent ductus arteriosus) and congenital pneumonia. The detected abnormalities were more common in the newborns born to mothers with SLE having APS. Maternal RA and SLE activities and/or performed therapy were not found to have a negative impact on the incidence of abnormalities in babies

THE PHENOMENON OF NEUTROPENIA DURING TOCILIZUMAB THERAPY IN PATIENTS WITH JUVENILE IDIOPATHIC ARTHRITIS

Tocilizumab (TCZ) is one of the biological agents that are most commonly used in the treatment of juvenile idiopathic arthritis (JIA), especially its systemic variant. The development of neutropenia, which is associated with the use of TCZ and its mechanism of action, requires a detailed study. Based on the analysis of their own results and comparison of the latter with the data available in the literature, the authors analyze the aspects of development of neutropenia during TCZ therapy. Objective: to analyze all cases of neutropenia with the use of TCZ in polyarticular (pJIA) and systemic (sJIA) variants of the disease. Subjects and methods. The open-label prospective study enrolled 27 patients with pJIA and 83 patients with sJIA, who were resistant to prior standard therapy. The treatment duration was 4 to 84 months (median, 22 months for pJIA; 34 months for sJIA). The frequency and timing of neutropenia and the relationship to infection and concomitant/previous therapy were examined. Results and discussion. 22 and 62 patients with pJIA and sJIA, respectively, continued treatment; its median duration was 27.4 [9; 72] months. 7 patients with pJIA and 21 with sJIA, discontinued TCZ due to severe adverse events (n=2 and n=11, respectively) and organizational reasons (n=5 and n=7); in sJIA, therapy was discontinued for sustained remission in two patients and for secondary inefficiency in one patient. At least one episode of neutropenia was observed in 63% of patients with pJIA and in 48.2% of those with sJIA; among them, there was grade 1 neutropenia in 5 and 15 patients, respectively; grade 2 in 6 and 15, grade 3 in 4 and 10, and grade 4 in two patients with pJIA. Neutropenia was more frequently observed in the first months of therapy for pJIA; that was seen in patients with sJIA when the latter reached its inactive status. In 5 patients with sJIA, neutropenia was recorded as a manifestation of macrophage activation syndrome (MAS); no correlation with TCZ infusions was found. Neutropenia was not associated with an increased rate of infections. The use of methotrexate was not significantly related to the low level of neutrophils, whereas the earlier age was associated with the degree and frequency of neutropenia. All cases of neutropenia were recorded in patients with a therapeutic response rate of >50% according to the American College of Rheumatology Pediatric (ACR Pedi) criteria. The findings suggest that there are different mechanisms and periods of neutropenia during TCZ therapy for JIA: 1) benign, transient neutropenia, a predictor of the high efficiency of therapy, develops primarily in the first few days after infusion; 2) neutropenia as a phenomenon of «redundancy» of therapy (more resistant) develops more often in the inactive phase of the disease; 3) neutropenia as a component of MAS, which is associated with its other markers. No relationship was found between neutropenia and an increased risk of infections. TCZ-treated patients need careful clinical and laboratory monitoring, including consideration of a risk for neutropenia and subsequent individual treatment when this condition is identified

The research of ammonium hexafluorosilicate desublimation

The authors have studied the laws of ammonium hexafluorosilicate desublimation on a pilot production unit. The proposed explanation of desublimation was proved by a set of investigations of physical and mechanical properties of desublimate samples. The paper introduces the construction of the improved desublimator, cyclone type advective desublimator