[Results of a randomized double-blind multicenter clinical trial of the efficacy and safety of riamilovir in the treatment of COVID-19].

AIM: To evaluate the efficacy and safety of riamilovir in the treatment of COVID-19 in adults. MATERIALS AND METHODS: The study included 180 patients with a laboratory-confirmed diagnosis of COVID-19 which fully meet the criteria for inclusion, non-inclusion and exclusion, signed a voluntary informed consent to participate in a clinical trial. RESULTS: The efficacy, good tolerability and safety of the drug riamilovir in the treatment of COVID-19 have been established. CONCLUSION: As a result of a multicenter randomized double-blind clinical trial, the effectiveness of the drug riamilovir for therapeutic use in patients with COVID-19 according to the 1250 mg/day scheme (250 mg capsules 5 times per day) for 10 days was established. The drug riamilovir in a daily dose of 1250 mg for 10 days does not differ in safety from placebo.

[Evaluation the effectiveness of immersive VR-assisted rehabilitation in a child with chemotherapy-induced neurological complication in acute lymphoblastic leukemia]. / Izuchenie vozmozhnosti reabilitatsii s pomoshch'yu virtual'noi real'nosti u rebenka s nevrologicheskim oslozhneniem, voznikshem na fone khimioterapii pri ostrom limfoblastnom leikoze.

Rehabilitation therapy is considered as an actual and complex system of knowledge, in which the main task is the development and implementation of new methods of rehabilitation. In present time, the most perspective rehabilitation program is utilizing virtual reality. A report was made with the utilization of rehabilitation therapy with virtual reality in a child with chemotherapy-induced neurological disorders in acute lymphoblastic leukemia. The child performed a set of exercises using fully immersive virtual reality. Over the course of rehabilitation positive dynamics was observed, namely increased muscle strength in the injured limb from 3 to 5 scores according to the Medical Research Council Weakness Scale. There was improved balance on the Berg Balance Scale from 35 to 42. In addition, there were increased range of active movements, partly restored biomechanics of gait with increased velocity by 2 times. According to the results of testing the psycho-emotional state using the Luscher color test and the graphic technique «Cactus¼ by M.A. Panfilova, self-esteem, the desire to succeed and independence were improved, the level of auto-aggression was decreased. The results show that rehabilitation using fully immersive virtual reality is probably a perspective tool in addition to traditional rehabilitation. It improves the neurological and psycho-emotional state, raises motivation of patients, which, in turn, helps to increase the effectiveness of rehabilitation therapy and speeds up the rehabilitation process.

Development of Drugs with Direct Antiviral Action Based on Azaheterocyclic Systems.

This article discusses the results of studies carried out in recent years by a team of scientists from the Postovskii Institute of Organic Synthesis, Ural Branch, Russian Academy of Sciences, in cooperation with the First President of Russia Boris Yeltsin Ural Federal University, Ural State Medical University, Volgograd State Medical University, and other scientific and production organizations of the country to create triazavirin (riamilovir) and other direct etiotropic antiviral drugs based on azaheterocyclic derivatives.

[A new approach to etiotropic therapy ARVI in children].

AIM: Confirmation of the efficacy and safety of the drug riamilovir (Triazavirin®), 100 mg capsules, in children aged 12-17 years with the diagnosis of acute viral respiratory infection (ARVI). MATERIALS AND METHODS: The multicenter study included 269 patients diagnosed with acute viral respiratory infection (ICD-10 code: J00, J02, J02.9, J04, J04.0, J04.1, J04.2, J06, J06.0, J06.9) in the presence of clinical manifestations and confirmation of the etiology of the disease by laboratory tests (PCR method). Patients were included in the study after one of the patient's parents/adoptive parents and the patient signed an informed consent to participate in the study. The interval between the appearance of the first symptoms of the disease and the inclusion of the patient in the study did not exceed 36 hours. RESULTS: As a result of a clinical study, the efficacy and safety of treatment with riamilovir (Triazavirin®) in sick children aged 12-17 years with a diagnosis of ARVI was shown. A decrease in the duration of the disease was shown when using the drug riamilovir (Triazavirin®) compared with the control group. No serious adverse events were detected during the study. CONCLUSION: As a result of the conducted clinical study, the high efficacy, safety and good tolerability of the drug riamilovir in the treatment of children aged 12-17 years with a diagnosis of ARVI was established. It is recommended to use the drug riamilovir in clinical practice as an etiotropic therapy in children aged 12-17 years with a diagnosis of ARVI due to its high efficacy and safety.

[Ontogenetic principles of accelerated aging and the prospects for its prevention and treatment.]

This article examines the phenomenon of «intrauterine programming¼, which largely determines the further life cycle and the likelihood of developing a number of age-associated pathological processes. The possibility of the formation of pathological (accelerated) aging at various stages of ontogenesis is discussed with the use of large literary material from the standpoint of modern science. The reasons, mechanisms and phenotypic manifestations of accelerated aging and the possibilities of the earliest one, its diagnosis starting from the perinatal period, and prediction of age-associated pathologies are discussed in close interrelation.

[A pilot study of cytokine profile in cerebrospinal fluid of children with acute lymphocytic leukemia and neurotoxic side effects of chemotherapy]. / Issledovanie tsitokinovogo profilia likvora pri neirotoksicheskikh oslozhneniiakh khimioterapii ostrogo limfoblastnogo leikoza u detei.

In some cases standard chemotherapy of acute lymphocytic leukemia (ALL) leads to neurotoxicity; its mechanisms, methods of prognosis, and prevention are being actively studied. The aim of this study was to assess the cytokine profile in cerebrospinal fluid (CSF) of children with ALL and neurotoxic side effects of chemotherapy. This prospective study included 24 children with ALL aged from 3 to 17 years. Patients were further subdivided into ALL patients with (main group) and without neurological complications (comparison group). The level of cytokines in CSF was measured by Xmap technology (Luminex) using Invitrogen test systems (eBioscience) and the Luminex 200 system. The comparative analysis of the cytokine profile in the group of children with chemotherapy-induced neurotoxic complications revealed elevated levels of chemokine CXCL12 (SDF-1α) and stem cell factor (SCF). Increased level of these cytokines in CSF was characterized by a relatively risk for development of toxic peripheral neuropathy.

[The serum biomarkers in diagnostic of hypoxic ischemic affection of central nervous system in children.]

The diagnostic of hypoxic ischemic encephalopathy of newborns continues to be an actual problem of neonatology. In the course of study healthy children and children with hypoxic ischemic damage of central nervous system were examined. The level of neurotrophic factors in blood was determined using enzyme-linked immunosorbent assay technique. The study established increasing of activity of neuro-specific enolase (NSE), decreasing of content of brain derived neurotrophic growth factor (BDNF) in serum of children of early age. These laboratory parameters are characterized by multi-directional shifts under the given pathology. The receiver operating characteristic analysis permitted to establish diagnostic sensitivity and diagnostic specificity for NSE - 56% and 85% correspondingly and for BDNF - 91% and 46% correspondingly. The level of brain derived neurotrophic growth factor had no significant diagnostic effectiveness. The correlation analysis established no relationships between state of newborn under delivery on Apgar score and level of neurotrophic factors (r<0.3, p>0.05).

Maternal and newborn infants amino acid concentrations in obese women born themselves with normal and small for gestational age birth weight.

This study was undertaken to compare amino acid concentrations in maternal and newborn infants' serum in normal pregnancy and two groups of obese women who were born themselves with normal and small for gestational age (SGA) birth weight. Maternal cholesterol, lipoproteins concentrations and maternal and infants amino acid concentrations were evaluated at the time of delivery in 28 normal pregnancies, 46 obese pregnant women with normal birth weight (Ob-AGA group) and 44 obese pregnant women born themselves SGA (Ob-SGA group). Mean birth weight of newborn infants in Ob-SGA group was significantly less than in normal and Ob-AGA groups. Cholesterol and lipoproteins were significantly elevated in obese women (more prominent in Ob-SGA group). Most amino acid concentrations and fetal-maternal amino acid gradients were significantly lower in Ob-SGA group. These data suggest significant changes in placental amino acid transport/synthetic function in obese women who were born themselves SGA.

[Open, non-comparative phase III clinical study to evaluate the efficacy and safety of sapropterin in patients with phenylketonuria and hyperphenylalaninemia].

BACKGROUND: Phenylketonuria (PKU) is an autosomal recessive inherited disease associated with impaired metabolism of the amino acids phenylalanine (Phe) and tyrosine. The main criterion for diagnosis of PKU is high blood Phe level determined during neonatal screening. In case where PKU patient is responsive to tetrahydrobiopterin treatment, sapropterin restores the impaired activity of the enzyme phenylalanine hydroxylase, resulting in the stimulation of normal Phe metabolism and thereby enhancing patient tolerance to natural products. AIM: The present open, non-comparative clinical study was initiated to assess the degree and frequency of response after 8-day sapropterin administration and assess the safety of 6-week sapropterin treatment in patients with PKU and hyperphenylalaninemia. PATIENTS AND METHODS: The study enrolled 90 patients with PKU. The criterion of response to 8-day sapropterin therapy was the reduction of Phe blood levels ≥ 30% compared with the baseline value. RESULTS: Positive response to treatment was observed in 30 (33.3%) patients (95% CI 23.7-44.1). The mean percentage change in Phe blood levels after the 8-day response test period compared to Phe levels prior to dosing was 14.1 ± 28.4% in the overall subject population (95% CI 8.2-20.1) and 44.3 ± 15.1% in the subpopulation of patients with a positive response (95% CI 38.6-49.9). During the study, adverse events were reported in 24 (26.7%) patients in the overall population in 16 (53.3%) patients in the subpopulation who had a response. CONCLUSION: The study results confirmed the efficacy and safety of sapropterin therapy in patients with PKU, which is consistent with international clinical trials data.

[Perinantal programming of arterial hypertension in child].

There is a growing number of evidence linking fetal intrauterine malnutrition, other adverse events or exposures and arterial hypertension during the following life. After important epidemiological studiesfrom many countries, research now focuses on mechanisms of organ dysfunction and on refining the understanding of the interaction between common elements ofadverse perinatal conditions and normal development. This review focused on advances in comprehension of the influence of intrauterine malnutrition on developmental programming of hypertension. Significant decrease in nephrons number was demonstrated as a result of fetal asymmetrical growth restriction syndrome both in human and experimental animal model. The role of malnutrition and dexametasone induced rennin-angiotensin system inhibition in fetal and newborn nephrogenesis is discussed. Recent studies have revealed important mechanisms of altered vascular function and structure as well as sympathetic regulation of the cardiovascular system in perinatal hypertension models. Some of adverse effects on nephrogenesis and blood pressure regulation could be reversed by special diet and treatment during first two years of life. While the complexity of the interactions between antenatal and postnatal influences on blood pressure is increasingly recognized, the importance of early postnatal life in modulating developmental programming offers the hope of a critical 1000 days window of opportunity to reverse programming and prevent or reduce child hypertension.

[Gene-determined hemocoagulation disease as a cause of ischemic stroke in children].

History of thrombosis and polymorphisms of genes of hemocoagulation system were studied in 27 children with ischemic stroke. The distribution of allelic variants in the Russian population was compared to that in other world populations. Each patient had 4 and more allelic variants of hemocoagulation's genes. The most frequent were polymorphisms G-455A FGB, C807T ITGA2 and 675 4G4G PAI-1. Thrombotic episodes and vascular events under the age of 50 were noted in the family history of 81.5% patients. The modern data on frequencies of hemocoagulation gene polymorphisms in clinical and non-clinical populations of children and their phenotypic features are analyzed.

[Clinical and hematologic abnormalities in children health, caused by exposure to lead].

The article deals with clinical results of medical examination and treatment of children residents of industrial districts in Sverdlovsk area, with various methods of analysis determining relationships between heavy metals, metalloids and marker anamnestic data and hematologic abnormalities (changes in RBC, platelets and reticulocytes counts).

[Organization of medical care for patients with cardiovascular diseases].

Morbidity with cardiovascular diseases in Sverdlovsk region has increased nearly twice over 10 years. Cardiovascular diseases are main causes of disablement and death, taking over a half of the total population losses over recent years. The article was aimed to specify approaches to manage risks of population losses with cardiovascular diseases. Structuring main blocks in organization of medical care for cardiovascular patients was attempted.

[The intrauterine programming of adult and children's disesases].

The intrauterine programming hypothesis proposed that cardiovascular and metabolic disease originate through developmental plasticity and fetal adaptation arising from failure of the materno-placental supply of nutrients. The hypothesis is supported by experimental data in animals indicating that maternal nutrition can program long term effects on the offspring. The intrauterine conditions in which the fetus develops have an important role in regulating the function of its physiological systems later in life. Intrauterine programming of physiological systems occurs at the gene, cell, tissue, organ, and system levels and causes permanent structural and functional changes, which can lead to overt disease, particularly with increasing age. The physiological prevention of disease programming is discussing.

[Rehabilitation of the population living in poor environmental areas in the Sverdlovsk Region].

Medical rehabilitation of the population living in poor environmental areas has been realized since 1999 and is the basis for environmental safety policy in the Sverdlovsk Region, along with the prevention and reduction of environmental pollution, the rational use, conservation, and replenishment of natural complexes. Medical rehabilitation activities for the population's health are aimed at managing the risks associated with human environmental factors, managing address medical prophylactic services, individual behavioral factors, habits, and awareness of the population. Interaction of the participants of the medical rehabilitation system provides for tackling the set health promotion tasks in the Sverdlovsk Region.

[Rehabilitation for dwellers of ecologically unfavorable territories of Sverdlovsk region]. / Reabilitatsiia zdorov'ia naseleniia na ékologicheski neblagopoluchnykh territoriiakh Sverdlovskoi oblasti.

The article covers organizational and methodic aspects associated with creation of rehabilitation system for dwellers of ecologically unfavorable territories of Sverdlovsk region.