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Amiodarone is an antiarrhythmic drug that is widely used in clinical practice to control various types of arrhythmias. One of the most significant side effects of amiodarone therapy is thyroid dysfunction, which is observed in about 15–20% of patients. This article presents a clinical case of a 55-year-old patient with a paroxysmal form of atrial fibrillation, for which amiodarone therapy was performed with the development of manifest amiodarone-induced thyrotoxicosis, refractory to drug therapy with glucocorticosteroids and thyrostatics. Due to the ineffectiveness of drug therapy, a total thyroidectomy was performed, which led to a rapid resolution of thyrotoxicosis and normalization of the heart rhythm.

The benign monomelic amyotrophy of the lower limb is a slowly progressive disease that is clinically manifested by muscle atrophy in only one lower limb. This disease is quite rare, while it is most common in Asian countries (about 80 cases have been described). According to the literature a total of 16 cases of benign monomelic amyotrophy of the lower limb were described in Europe by 2000. Etiology and pathogenesis have not been reliably studied now. The article presents a clinical case of the development of this disease in a 42-year-old patient. The patient was admitted with complaints of weakness in the right leg and its decrease in volume. During the period of hospitalization, diff erential diagnosis was carried out with amyotrophic lateral sclerosis, progressive muscle atrophy, Hirayama disease, vascular and paraneoplastic processes. According to the results of a comprehensive laboratory and instrumental examination, the diagnosis was fi rst established: benign monomelic amyotrophy of the lower limb. The father of a patient who had atrophy of the muscles of the left lower limb would also be examined. According to the data of hereditary anamnesis, an assumption was made about the presence of the phenomenon of anticipation in the inheritance of benign monomelic amyotrophy of the lower limb. This article describes for the fi rst time a case of benign monomelic amyotrophy of the lower limb in the domestic literature, as well as a familial case of this disease all over the world.

Статья посвящена проблеме развития речи детей среднего дошкольного возраста. Авторами описаны формы и методы работы по формирования мелкой моторики и речи воспитанников.

A dangerous viral disease COVID-19, caused by a new RNA coronavirus SARS-COV-2, has been actively spreading in the world since December 2019. The main manifestations of this disease are bilateral pneumonia, often accompanied by the development of acute respiratory syndrome and respiratory failure. Patients with diabetes mellitus (DM) are at high risk of infection with the SARS-COV-2 virus, severe illness and death.Maintaining of target glycemic levels is the most important factor in a favorable outcome of COVID-19 in both type 1 and type 2 DM. The choice of antihyperglycemic therapy in a patient with DM in the acute period of COVID-19 depends on the initial therapy, the severity of hyperglycemia, the severity of the viral infection and the patient’s clinical condition.The article presents the recommendations of the board of experts of the Russian Association of Endocrinologists on glycemic control and the choice of antihyperglycemic therapy in patients with type 2 DM and COVID-19, and also on the use of glucocorticosteroids used in the treatment of COVID-19 in patients with type 2 DM.

BACKGROUND: The poor outcomes of chronic hepatitis C (CHC) and type 2 diabetes determine the socio-economic significance of the combined pathology since they lead to premature death. The proportion of patients with type 2 diabetes with markers of viral hepatitis (VH) in the Russian Federation is not known, which does not allow us to estimate the burden for the state of this medical problem.OBJECTIVE: Assessment of the prevalence of concomitant pathology, HCV infection and type 2 diabetes, as well as the proportion of severe liver damage in its structure, according to the analysis of the primary medical records of four Moscow hospitals.MATERIALS AND METHODS: A retrospective analysis of the medical records of patients with HCV infection and diabetes mellitus, who admitted at different periods to four hospitals in Moscow, was carried out, as well as a total examination for the presence of anti-HCV in the blood of all patients with diabetes who were admitted within a certain period to the endocrinology department of a multidisciplinary hospital. Additionally, to determine the proportion of patients with liver cirrhosis (LC), an additional examination of patients with this combined pathology was carried out in accordance with the standards for the diagnosis of hepatitis C.RESULTS: In total, according to data from 4 hospitals in Moscow, over a certain period, 2% (105/5298) of diabetes patients with anti-HCV in their blood were identified. Sex ratio for men: women = 54 (51%): 51 (49%). Patients aged 50–69 years prevailed — 70% (74/105). Seroprevalence of HCV in cohorts of patients with type 2 diabetes according to the analysis in 3 health facilities: 0.9% (20/2196), 1.9% (8/432), 1.9% (28/1500). A significant drawback was revealed that did not allow assessing the true seroprevalence of HCV: not all patients were hospitalized with the results of a VH test, and not all of them were assigned an examination for VH markers if it was not performed before hospitalization. The proportion of type 2 diabetes patients with anti-HCV in the blood according to the results of total screening (3.7%; 16/432) became comparable to the proportion of type 2 diabetes patients among patients with CHC admitted to an infectious hospital (4.2%; 49 / 1170). The proportion of patients with LC according to the analysis of the medical records of the infectious hospital is 65% (32/49), in the group of endocrinological patients with additional examination it is 18% (13/71).CONCLUSION: For the first time in the Russian Federation, data were obtained on the prevalence of HCV infection in combination with type 2 diabetes. The results of the study indicate the need to develop effective screening programs to detect active HCV infection in the group of patients with diabetes, as well as patients among them with severe hepatic fibrosis for the timely conduct of highly effective antiviral therapy, which will prevent poor outcomes in a separate perspective.

Idiopathic facial nerve neuropathy (FNN), or Bell's palsy, is characterized by a manifest neurological defect and a pronounced decrease in the quality of life of patients.Objective: to evaluate the efficacy and safety of ipidacrine in patients with FNN in an open-label observational study.Patients and methods. The study included 35 patients with FNN, who were divided into two groups. Treatment in the main group (n=20) included the basic regimen (glucocorticoids, B vitamins, pentoxifylline, glycine, a complex of non-pharmacological therapies), as well as the anticholinesterase drug ipidacrine (Ipigrix). Treatment of patients in the control group (n=15) was limited to the basic regimen. The followup was six months. The treatment effectiveness was assessed with the House-Brackmann scale, FaCE (Facial Clinimetric Evaluation), SAQ (The Synkinesis Assessment Questionnaire), electroneuromyography (ENMG), and determining the number of patients with indications for botulinum therapy.Results and discussion. After six months of treatment, more significant restoration of facial nerve function was observed in the main group, according to the House-Brackmann scale (1.4±0.5), FaCE (90±9.8), and ENMG results, compared to the control group (HouseBrackmann – 1.9±0.7 points, FaCE – 78±11.8 points; p75 mm on the visual analog scale, poor recovery of facial nerve function in the first month of treatment (3 and 4 points on the House–Brackmann scale).Conclusion. The use of ipidacrine in the complex treatment of patients with FNN improves the efficiency of restoration of the function of the facial nerve after 6 months without increasing the risk of pathological synkinesis.

Disclaimer. The EAC Guidelines represent the views of the EAC, and were produced after careful consideration of the scientific and medical knowledge, and the evidence available at the time of their publication. The EAC is not responsible in the event of any contradiction, discrepancy, and/or ambiguity between the EAC Guidelines and any other official recommendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies. Health professionals are encouraged to take the EAC Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic, or therapeutic medical strategies; however, the EAC Guide-lines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient’s health condition and in consultation with that patient and, where appropriate and/or necessary, the patient’s caregiver. Nor do the EAC Guidelines exempt health professionals from taking into full and careful consideration the relevant official updated recommendations or guidelines issued by the competent public health authorities, in order to manage each patient’s case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations. It is also the health professional’s responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription.

BACKGRAUND: There is evidence of a multifactorial effect of SARS-CoV2 on carbohydrate metabolism with the development of hyperglycemia and the weighting of COVID19 even in people without DM.AIMS: Assess the prevalence of disorders carbohydrate metabolism (DCM) in hospitalized patients with a new coronavirus infection without a history of DM.MATERIALS AND METHODS: Patients with PCR-confirmed diagnosis of COVID19 aged 18-75 years (n=72) without a history of diabetes were examined. Observation was carried out from the moment of hospitalization to discharge. Patients were collected anamnesis data, laboratory and instrumental studies, HbA1c, fasting plasma glucose (FPG), postprandial glycemia.RESULTS: The prevalence of DCM (HbA1c≥6%) in 72 patients with COVID19 without a history of diabetes admitted to the hospital was 41,7%, while HbA1c ≥6,5% had 8,3%. The median HbA1c in the moderate-flow group was 5,7% [5,3–6,0], and in the severe-flow group it was 6,0% [5,8–6,2] (p=0,008). Participants were divided into groups according to the level of HbA1c≥6% and < 6%. The examined patients showed a high prevalence of risk factors for developing DM: age over 45 years — 83,3%, cardiovascular diseases — 46,3%, obesity — 50%. The study groups didn’t differ statistically in terms of risk factors for DM. In the group with HbA1c≥6%, FPG≥6,1 mmol / l on the second day and postprandial glycemia ≥7,8 mmol/l were observed in more cases than in the group with HbA1c1c was higher than in FPG (41,7% vs 29,2%, p=0,006). On the seventh day, the number of patients with FPG ≥ 6,1 mmol / l in the first group decreased from 39,1% to 4,4% (p=0,01), and in the second group-from 12,9% to 9,7% (p=1,0). There was a direct correlation between the level of HbA1c and C-reactive protein (r=0,271; p=0,048), and an inverse correlation with the content of lymphocytes in the blood (r=-0,25; p=0,068).CONCLUSIONS: In patients with a new coronavirus infection without a history of DM, a high prevalence of DCM was detected — 41,7%. Against the background of comparability of the studied groups by risk factors for DM, an increase in HbA1c, FPG and postprandial glycemia is a manifestation of transient hyperglycemia. Given the high prevalence of DCM, it can be assumed that SARS-CoV2 has diabetogenic properties.

The findings of large-scale cardiovascular outcome trials have been demonstrated that sodium-glucose cotransporter 2 ­inhibitors (iSGLT-2) have shown beneficial cardiovascular effects. In this review proposed mechanisms underlying iSGLT-2-associated cardiovascular benefits have been discussed: haemodynamic and intracellular effects, including metabolic effects and electrolyte changes; and also, the effect on markers of cardiovascular disease (CVD). The hemodynamic effects of SGLT-2 are characterized by reduction of cardiac preload and afterload as a result of osmotic diuresis, a decrease in blood pressure and arterial stiffness. The metabolic effects of this medicine are accompanied by an increase the production of ketone bodies, followed by improving ATP production and myocardial energetics. Also, iSGLT-2 modulate ion transporters (NHE1 and NHE3). A reduction of cytoplasmic sodium and calcium levels and increasing mitochondrial calcium levels in the cardiomyocytes enhances the synthesis of ATP and increases cell viability. Effect of iSGLT-2 on CVD markers showed a decrease in the levels of the N-terminal pro-B-type natriuretic peptide and highly sensitive troponin I in elderly patients with type 2 diabetes mellitus (T2DM). Thus, this class of agents has a multifactorial effect on the functioning of cardiovascular system. Further studies will help to explain the all possible cardioprotective effects of iSGLT-2 in individuals with and without T2DM.

The aim of this study was to determine the optimal harvest time to achieve maximum milled rice yield and quality of white rice in some newly introduced Italian rice varieties grown under agro-ecological conditions in the region of Kocani town, Republic of North Macedonia. During the 2014 and 2015, fourteen rice varieties were cultivated to estimate the milled rice yield and broken kernels from three different harvest times. From each rice variety, samples with moisture content between 20-22% (I variant), 18-20% (II variant) and 16-18% (III variant) were taken. From the third harvest variant the highest percentage of milled rice yield (65.23%) was obtained but also the highest rate of broken kernels (12.79%). From the remaining two harvests, almost identical milled rice yields were received (64.19% from the first variant and 64.33% from the second variant), but in terms of broken kernels, there were significant differences. The optimum moisture content during the harvest in order to obtain maximum yield and quality of milled rice ranged from 18% to 20%. The varieties Arsenal, Sprint and Mirko had the most favorable values for milled rice yield and broken kernels.

BACKGROUND: Patients with Type 2 Diabetes (T2DM) and patients on maintenance hemodialysis (MHD) are at a high risk of adverse clinical course of COVID-19. To date, the causes of high mortality in these groups are not fully understood. Data about peculiarity of clinical course and Tocilizumab (TCZ) administration in patients with T2DM receiving MHD due to outcome of diabetic kidney disease (DKD) are not yet highlighted in current publications.AIMS: Identification of risk factors (RF) of adverse COVID-19 outcome and evaluation of TCZ administration in patients with T2DM receiving MHD due to DKD.MATERIALS AND METHODS: The patients treated in Moscow City Hospital No52 were included in retrospective observational study. The observation period was from 04.15 to 07.30 2020. The study endpoints were the outcomes of hospitalization — discharge or lethal outcome. Data were collected from electronic medical database. The following independent variables were analysed: gender, age, body mass index, time from the onset of symptoms to hospital admission, cardiovascular and general comorbidity (Charlson Index, CCI), cardiovascular event (CVE) during hospitalization, treatment in ICU, mechanical ventilation (MV), degree of lung damage according to CT data, level of prandial glycemia at admission, MHDassociated parameters (vintage, type of vascular access, frequency of complications). The autopsy reports were evaluated for the purpose of lethal structure investigation. In a subgroup treated TCZ the time from symptoms onset to TCZ administration and number of laboratory indicators were evaluated.RESULTS: 53 patients were included, mean age 68 ±9 y, males — 49%. General mortality in observation cohort was 45%, mortality in ICU — 81%, mortality on MV — 95%. High cardiovascular and general comorbidity was revealed (mean CCI — 8,3 ±1,5 points). The causes of outcomes according to autopsy reports data: CVE 37,5% (among them — acute myocardial infarction during hospitalization), severe respiratory failure — 62,5%. The independent predictors of lethal outcome were: MV (OR 106; 95% CI 11,5–984; р CONCLUSIONS: The number of RF of adverse COVID-19 outcome in patients with T2DM receiving MHD due to DKD are identified. CVE is one of the leading causes of mortality in study cohort. According to our experience the preventive (instead of rescue) strategy of TCZ administration should be used.

Recent studies on nuclear-encoded mitochondrial genes (N-mt genes) in Drosophila melanogaster have shown a unique pattern of expression for newly duplicated N-mt genes, with many duplicates having a testis-biased expression and playing an essential role in spermatogenesis. In this study, we investigated a newly duplicated N-mt gene—i.e., Cytochrome c oxidase 4-like (COX4L)—in order to understand its function and, consequently, the reason behind its retention in the D. melanogaster genome. The COX4L gene is a duplicate of the Cytochrome c oxidase 4 (COX4) gene of OXPHOS complex IV. While the parental COX4 gene has been found in all eukaryotes, including single-cell eukaryotes such as yeast, we show that COX4L is only present in the Brachycera suborder of Diptera; thus, both genes are present in all Drosophila species, but have significantly different patterns of expression: COX4 is highly expressed in all tissues, while COX4L has a testis-specific expression. To understand the function of this new gene, we first knocked down its expression in the D. melanogaster germline using two different RNAi lines driven by the bam-Gal4 driver; second, we created a knockout strain for this gene using CRISPR-Cas9 technology. Our results showed that knockdown and knockout lines of COX4L produce partial sterility and complete sterility in males, respectively, where a lack of sperm individualization was observed in both cases. Male infertility was prevented by driving COX4L-HA in the germline, but not when driving COX4-HA. In addition, ectopic expression of COX4L in the soma caused embryonic lethality, while overexpression in the germline led to a reduction in male fertility. COX4L-KO mitochondria show reduced membrane potential, providing a plausible explanation for the male sterility observed in these flies. This prominent loss-of-function phenotype, along with its testis-biased expression and its presence in the Drosophila sperm proteome, suggests that COX4L is a paralogous, specialized gene that is assembled in OXPHOS complex IV of male germline cells and/or sperm mitochondria.

The relevance of the problem under study is due to the formation of knowledge, skills, and abilities of future teachers in the process of their professional training; the essence of pedagogical practice as an integral process is considered. The article is aimed at theoretical and practical justification, actualization of the importance of professional practice in the course of professional training and training of teachers, which should be considered as one of the priority goals and important prerequisites for the socio-economic and spiritual progress of a multicultural society. It is pedagogical practice that is an important means of preparing a future teacher for innovative activities and in the professional formation and development of a future specialist. The leading approach to the study of this problem is a systematic approach that allows you to identify, justify and group the scientific, theoretical and practical prerequisites for students ' readiness for professional activity in the multicultural educational space of the school. The study showed that pedagogical practice provides students with training not only for practical work with students, but also for an innovative style of their professional activity. The materials of the article can be useful for specialists in the field of improving the quality of professional education.

The first case of COVID-19 was diagnosed in St. Petersburg on March 2, 2020; the period of increase in the incidence lasted for 10 weeks, the maximum rates were recorded in mid-May, and subsequently there was a statistically significant decrease in the incidence.Objective: to determine the level and structure of community immunity to SARS-CoV-2 among the population of St. Petersburg during the period of intensive spread of COVID-19.Materials and methods. Selection of volunteers for the study was carried out through interviewing and randomization. The exclusion criterion was active COVID-19 infection at the time of the survey. 2713 people aged 1 to 70 years and above were examined for the presence of specific antibodies to SARS-CoV-2. Antibodies were detected by enzyme immunoassay.Results and discussion. Studies have shown that in St. Petersburg, in the active phase of COVID-19 epidemic, there was a moderate seroprevalence to SARS-CoV-2, which amounted to 26 %, against the background of a high frequency (84.5 %) of asymptomatic infection in seropositive individuals who did not have a history of COVID-19 disease, positive PCR result and ARI symptoms on the day of examination. The maximum indicators of herd immunity were established in children 1–6 years old (31.1 %), 7–13 years old (37.7 %) and people over 70 years old (30.4 %). Differences in the level of seroprevalence in the age groups of 18–49 years are statistically significant. The highest level of seroprevalence was found among the unemployed (29.7 %), healthcare workers (27.1 %), education sector (26.4 %) and business sector personnel (25 %). In convalescents, COVID-19 antibodies are produced in 75 % of cases. In individuals with positive result of PCR analysis carried out earlier, antibodies are detected in 70 % of the cases. The results of the study of herd immunity to SARS-CoV-2 are essential to forecast the development of the epidemiological situation, as well as to plan measures for specific and non-specific prevention of COVID-19.

According to accumulated clinical data, one of the causes of severe damage to lung epithelial cells associated with SARS-CoV-2 (2019-nCoV) is an acute, timely underestimated "cytokine storm" (cytokine cascade, hypercytokinaemia) with characteristic signs of an expressed hyper-inflammatory syndrome with subsequent polyorganic failure. The study presents the results of the analysis of the effectiveness of tocilizumab therapy (TCZ) in patients (n = 181) of different age groups with developed pneumonia caused by SARS-CoV-2. The aim of the study was to evaluate the effectiveness of TCZ therapy in patients of different age groups with developed pneumonia in the frame of COVID-19. Methods. Patients (n = 181) with community-acquired pneumonia caused by coronavirus SARS-CoV-2 are included in a one-center, non-randomized, prospective study to evaluate the effectiveness of TCZ therapy conducted at the State Public Health Institution "City Clinical Hospital No.52" of the Moscow City Health Department. Patients were divided into 3 age subgroups – up to 50 years, 50–70 years and over 70 years. Patients with community-acquired SARS-CoV-2-induced pneumonia receiving non-invasive oxygen support and patients who had artificial lung ventilation (ALV) were given a single dose of 400 mg of TCZ in addition to basic therapy. Results. There are no significant differences between age groups in the severity of pneumonia according to the data of the computed tomography (CT), however, a more severe condition and a higher mortality rate (p < 0.001) were reliably observed in patients over 70 age compared to the other age groups. After TCZ treatment in patients of each age group, the severity of the condition assessed on the National Early Warning Score (NEWS2) has been significantly reduced compared to the baseline. Conclusion. According to the data of the pilot study the efficacy and safety of TCZ in patients of all presented age groups with COVID-associated pulmonary tissue lesion and signs of "cytokine storm" was demonstrated. At the same time, patients up to 50 years after the therapy of TCZ managed to achieve greater clinical efficiency compared to patients in other groups. According to the severity of the state and laboratory criteria, the lowest clinical efficacy of TCZ therapy was observed in patients over 70 years of age; as a consequence, the highest mortality rate was observed in the same group. At the same time, the TCZ therapy has not had a positive impact on the change of laboratory values and the severity of the disease in case of unfavorable outcome.

Guidelines on treatment of patients with arterial hypertension comorbid with metabolic disorders and diabetes mellitus type 2

Based on the material of short prose by I. S. Turgenev (“The Dream”, “The Song of Triumphant Love”, “Klara Milich”) and V. O. Pelevin (“Go to Sleep”, “The Blue Lantern”, “The Contemplator of the Shadow”), the article deals with the problem of transformation of conception and the ways of implementation of dream states. It also analyzes the change in the function of sleep and dreams in classical and post-classical literature. In classical literature, oneiric text is defined as a verbal presentation of a dream of a character or the author in a work of fiction. In mystery short stories and novellas by Turgenev, we are dealing with the verbal recreation of sleep as a borderline state of the character, as an experience of a different kind of existence, and as a way of immersion in the irrational region of the human psyche. Turgenev’s oneiropoetics and science fiction are aimed at discovering the unknown in the human psyche and are associated with the eternal problems of love and death, search for the truth, and the achievement of integrity of the artistic-philosophical world. In the postmodern era, dreams become one of the most common ways of text constructing and serve to convey the idea of total virtualization of reality. The modern author does not set the task to describe dreams; they create a text according to the logic of the dream. Meanwhile, the same eternal questions as in classical literature are subject to artistic reflection in Pelevin’s stories: the truth and lies, the good and the evil, the search for the meaning of life, freedom, and belief in God. The dialogue between the postmodern writer and the classic is based on the idea of inseparability of the sensuous and the supersensuous, the contradictions between which can be removed in an act of artistic study of the secrets of the human psyche. The writer of the epoch-making era speaks with contemporaries about the human consciousness that has fallen into the trap, because there are no practical methods for “lifting the shackles of the mind”, but the chances for transcendence and self-realization in consciousness-created worlds still remain. Pelevin’s dreams often become a manifestation of esoteric consciousness and mystical revelation.

According to key diabetic studies, the early use of metformin glucose lowering therapy is associated with a reduced risk of developing micro- and, in the long term, 10-year follow-up, macrovascular complications and cardiovascular mortality. Short-term studies results on combined glucose lowering therapy with metformin suggests that combination therapy can have several advantages on the one side from the effectiveness of glycemic control and on another side from positive effect on the development of complications of type 2 diabetes. The question of the start time of combined hypoglycemic therapy remains open. According to the results of recent large-scale studies, real world evidence data, careful glycemic control during the first year from the moment of diagnosis of type 2 diabetes is crucial for further management of the disease and slow the progression of complications. However, due to the fact that the clinical benefits of early combination therapy were not demonstrated in randomized clinical trials, this approach, despite the theoretical background, was not recommended for widespread use in international guidelines for the treatment diabetes patients. Russian algorithms on the treatment diabetes patients recommend combined glucose lowering therapy at the start of treatment at a HbA1c level of 1% higher than the target. A 5-year VERIFY study results were demonstrated long-term sustained glycemic control in combination with vildagliptin + metformin prescribed for native diabetes patients with relatively low HbA1c values, as well as the advantages of this approach in comparison with the standard strategy for phased intensification of monotherapy. The results of the VERIFY study provided a wealth of information to discuss early treatment intensification, the clinical benefits of this approach and a possible review of the treatment strategy for native diabetes patients.

The peculiarity of natural conditions of Yakutia plays an important role in the formation of economic activities of its population. A significant number of rivers and lakes are a favorable condition for the development and preservation of traditional fishing. Currently, more than 89% of the commercial fish catch is produced in the lower reaches of the large northern rivers and lakes in the Arctic and subarctic zones of Yakutia. The main part of this catch is whitefish species, which are valued for their fat content, protein content, culinary, and taste qualities. Fish is a valuable food product for the population of Yakutia. This article presents the results of the study on the nutritional value and the content of heavy metals in the Arctic cisco meat. The high content of fat and protein in the studied samples shows that the Arctic cisco meat belongs to high-protein and high-calorie products and has a high biological value. It was found that on average, the level of toxic metals in the Arctic cisco meat does not exceed the norms accepted in Russia for fish products. The data obtained suggest that the content of heavy metals in fish is due to the peculiarities of living conditions and environmental pollution. Over the past decades, the volume of fish production in Yakutia has been declining due to the socioeconomic and climatic factors. Due to the anthropogenic pollution of water in rivers and lakes by oil products and effluents and waste from various sectors of the economy, especially the mining industry, there is a reduction in the fish resources and there is a need to monitor the environmental condition of the fishing reservoirs and the fish food quality.

Material and methods An open-labeled, randomized, active-controlled multicenter trial of favipiravir in out- and hospitalized patients with mild to moderate COVID-19 was conducted Eligible patients were aged 18-60 years and had laboratory confirmed by PCR test infection of SARS-CoV-2 Patients were randomly assigned in a 2:1 ratio to receive either favipiravir (1800 mg BID on day 1, followed by 800 mg BID for 9 days), or standard of care (SOC) treatment (umifenovir + intranasal interferon alpha-2b, or hydroxychloroquine for up to 10 days) In needed, patients received concomitant symptomatic medication The co-primary outcomes were the time to clinical improvement and the time to viral clearance Results and discussion It was found that the median time to clinical improvement was 6 0 [interquartile range (IQR) 4 0;9 3] days in favipiravir group and 10 0 (IQR 5 0;21 0) days in SOC group;the median difference was 4 days [hazard ratio (HR) 1 63;95% confidence interval (CI) 1 14-2 34, p=0 007] The rate of clinical improvement in the favipiravir group on day 7 was 1 5-fold higher compared to SOC: 52 7% vs 35 7% [risk ratio (RR) 1 50;95% CI 1 02-2 22;p=0 020] Despite an absence of statistically significant difference between the median time to viral elimination, the rates of viral elimination on day 3 and day 5 were significantly higher in favipiravir group: on the day 3 viral elimination was observed for in 71 4% of patients, who received favipiravir vs 57 1% in SOC group (RR 1 27;95% CI 0 99-1 64;p=0 030), on the day 5 81 2 vs 67 9%, respectively (RR 1 22;95% CI 1 00-1 48;р=0 022) Favipiravir was well tolerated: most of the adverse events (AE) were mild The most common AEs were asymptomatic hyperuricemia, transient elevation of ALT & AST, and gastrointestinal disorders (diarrhea, nausea, abdominal pain) Цель исследования - оценка эффективности и безопасности фавипиравира для лечения новой коронавирусной инфекции (COVID-19) легкого и среднетяжелого течения Материал и методы Проведено открытое рандомизированное многоцентровое клиническое исследование с активным контролем у амбулаторных и госпитализированных пациентов с COVID-19 легкого и среднетяжелого течения В исследовании приняли участие 168 пациентов в возрасте 18-60 лет с подтвержденной инфекцией SARS-CoV-2 (методом полимеразной цепной реакции мазков из рото- и носоглотки) Пациенты были рандомизированы в соотношении 2:1 в группы терапии фавипиравиром (по 1800 мг 2 раза в 1-й день, по 800 мг 2 раза в день - со 2-го по 10-й дни) либо стандартной терапии (умифеновир + интраназальный интерферон альфа-2b или гидроксихлорохин, длительность - до 10 дней) Пациенты также получали необходимую сопутствующую симптоматическую терапию Комбинированная первичная конечная точка включала оценку медиан времени до улучшения клинического статуса и элиминации вируса Результаты и обсуждение Установлено, что в группе фавипиравира клиническое улучшение наступало на 4 дня быстрее, чем в группе стандартной терапии: медианы времени до клинического улучшения составили 6,0 [межквартильный диапазон (МКД) 4,0;9,3] дня и 10,0 (МКД 5,0;21,0) дней соответственно [hazard ratio (HR) 1,63;95% доверительный интервал (ДИ) 1,14-2,34, р=0,007] Частота клинического улучшения на 7-й день в группе фавипиравира была в 1,5 раза выше по сравнению с группой стандартной терапии: 52,7 против 35,7% [risk ratio (RR) 1,50;95% ДИ 1,02-2,22;р=0,020] Достоверной разницы медиан времени до элиминации вируса не наблюдалось Однако частота элиминации вируса на 3-й и 5-й день в группе фавипиравира была значимо выше: на 3-й день она наблюдалась у 71,4% пациентов в группе фавипиравира против 57,1% в группе стандартной терапии (RR 1,27;95% ДИ 0,99-1,64;р=0,030), а на 5-й день у 81,2 против 67,9% соответственно (RR 1,22;95% ДИ 1,00-1,48;р=0,022) Фавипиравир хорошо переносился пациентами, а большинство нежелательных явлений имели легкую степень тяжести Среди наиболее частых нежелательных явлений отмечали бессимптомную гиперурикемию, транзиторное повышение уровней аланин- и аспартат-аминотрансферазы и желудочно-кишечные нарушения (диарея, тошнота, боль в животе) Полученные результаты подтверждают преимущество фавипиравира по сравнению со стандартной этиотропной терапией при применении у пациентов с COVID-19 легкого и среднетяжелого течения

Background The nuclear transport machinery is involved in a well-known male meiotic drive system in Drosophila. Fast gene evolution and gene duplications have been major underlying mechanisms in the evolution of meiotic drive systems, and this might include some nuclear transport genes in Drosophila. So, using a comprehensive, detailed phylogenomic study, we examined 51 insect genomes for the duplication of the same nuclear transport genes. Results We find that most of the nuclear transport duplications in Drosophila are of a few classes of nuclear transport genes, RNA mediated and fast evolving. We also retrieve many pseudogenes for the Ran gene. Some of the duplicates are relatively young and likely contributing to the turnover expected for genes under strong but changing selective pressures. These duplications are potentially revealing what features of nuclear transport are under selection. Unlike in flies, we find only a few duplications when we study the Drosophila duplicated nuclear transport genes in dipteran species outside of Drosophila, and none in other insects. Conclusions These findings strengthen the hypothesis that nuclear transport gene duplicates in Drosophila evolve either as drivers or suppressors of meiotic drive systems or as other male-specific adaptations circumscribed to flies and involving a handful of nuclear transport functions.

The paper studies the matter related to the use of an interactive computer simulator in Mathematics course when using blended learning technology in the current university education. As an example, the authors describe the original computer software Integral Test 1.0, designed to practice the antiderivative skills and academic performance rating when studying the topic Function Integration of one real variable. A special feature of this software, which distinguishes it from standard diagnostic programs favourably, is that a student is not asked to choose the correct answer from several suggested options. He needs to enter the answer on his own in the field intended for this purpose. The antiderivative is typed from the keyboard as a string according to the customary rules, and the software visualizes the answer in the traditional form and verifies it. Using such a simulator allows one to actualize a component of the interactive mode of blended learning technology. Students have an opportunity to work out their computing skills without a teacher’s supervision. The authors present the results of an experiment that was conducted among first-year students majored in Engineering for two years. The experiment confirmed the effectiveness of using an interactive computer simulator in blended mathematics study. In particular, the quality of academic performance in the experimental group increased by 8.7%.

June 19, 2018 the meeting of the Scientific Advisory Board took place in Moscow, chaired by Professor G.R. Galstyan, (co-chair - A.V. Zilov) devoted to the discussion of the possibilities of improving the results of treatment of diabetes mellitus (DM) by consideration of «variability of glycemia» (VG) as an additional criterion of the glycemic control effectiveness (especially of insulin therapy) as well as one of the goals of treatment in patients with unstable glycemia. The purpose of the working meeting was to develop a strategy for the introduction of VG as a predictor and an additional criterion in assessing the effectiveness and safety of hypoglycemic therapy to improve the pharmacotherapy of diabetes and reduce cardiovascular and total mortality. Aims: - to conduct a comprehensive data analysis of the relationship between VG and adverse DM outcomes, such as hypoglycemia, micro-and macrovascular complications, cardiovascular and total mortality; - to accumulate and analyze published data and the experience of decrease of VG and improving outcomes of diabetes on the background of different versions of insulin therapy; - to compare existing methods of glycaemia monitoring and VG assessment, their validity and availability in real practice in the context of limited budget; - to analyze the informativeness, clinical and prognostic significance of various parameters of VG assessment and determine their reasonable «minimum» for a comprehensive assessment of VG as a criterion for evaluating the effectiveness of treatment of DM and predictors of negative diabetes outcomes. The following reports were heard during the discussion: Glycemic variability: clinical and prognostic value. Types of glycemic variability. (Alexey V. Zilov, MD, PhD in Medicine, Assistant Professor). Methods of assessment of variability of glycemia in clinical trials and routine practice (Tatiana N. Markova, MD, PhD in Medicine, Professor). Current international and national recommendations on glycemic monitoring (Gagik R. Galstyan, MD, PhD in Medicine, Professor). Peculiarities of glycemic variability and its evaluation among children and adolescents (Alisa V. Vitebskaya, MD, PhD in Medicine).19 июня 2018 г. в Москве состоялось заседание Научно-консультативного совета под председательством д.м.н., профессора Г.Р. Галстяна и к.м.н., доцента А.В. Зилова, посвященное обсуждению возможностей улучшения результатов лечения сахарного диабета (СД) путем использования вариабельности гликемии (ВГ) в качестве дополнительного критерия эффективности контроля гликемии (в первую очередь, на фоне инсулинотерапии), а также одной из целей лечения у пациентов с нестабильной гликемией. Целью рабочей встречи была выработка стратегии внедрения ВГ в качестве предиктора и дополнительного критерия при оценке эффективности и безопасности сахароснижающей терапии с целью совершенствования фармакотерапии СД и снижения общей и сердечно-сосудистой смертности при этом заболевании. Задачи: – провести комплексный анализ данных о взаимосвязи между ВГ и неблагоприятными исходами СД, такими как гипогликемия, микро- и макрососудистые осложнения СД, сердечно-сосудистая и общая смертность; – аккумулировать и проанализировать опубликованные данные и имеющийся опыт снижения ВГ и улучшения исходов СД на фоне различных вариантов инсулинотерапии; – сравнить существующие методики мониторинга гликемии и оценки ВГ, их валидность и доступность в реальной практике в условиях ограниченных ресурсов здравоохранения; – проанализировать информативность, клиническую и прогностическую значимость различных параметров оценки ВГ и определить их обоснованный «минимум» для комплексной оценки ВГ в качестве критерия оценки эффективности лечения СД и предикторов негативных исходов СД. В рамках дискуссии были заслушаны следующие доклады: – Вариабельность гликемии: Клиническое и прогностическое значение. Виды вариабельности гликемии. (к.м.н., доцент Зилов А.В.). – Методы оценки вариабельности гликемии в клинических исследованиях и рутинной практике (д.м.н., профессор Маркова Т.Н.). – Действующие международные и национальные рекомендации по мониторингу гликемии (д.м.н., профессор Галстян Г.Р.). – Особенности вариабельности гликемии и ее оценки у детей и подростков (к.м.н. Витебская А.В.).

The Scientific Advisory Board, chaired by Professor G. R. Galstyan (cochair - A.V. Zilov), met in Moscow on 19 June 2018 to discuss the possibilities of improving the results of diabetes mellitus (DM) treatment by considering glycaemic variability (GV) as an additional criterion for effective glycaemic control (especially in patients receiving insulin therapy) and as one of the goals of treatment in patients with unstable glycaemia. The purpose of the working meeting was to develop a strategy for the introduction of GV as a predictor and as an additional criterion for assessing the effectiveness and safety of hypoglycaemic therapy to improve the pharmacotherapy of diabetes and reduce cardiovascular and total mortality. The aims of the working meeting were to conduct a comprehensive data analysis of the relationship between GV and hypoglycaemia; to gather and analyse published data and the experience of decrease in GV and improved outcomes of diabetes against the background of different types of insulin therapy; to compare existing methods of glycaemia monitoring and GV assessment and examine their validity and availability in real practice in the context of limited budget and to analyse the informativeness and clinical and prognostic significance of various parameters of GV assessment and to determine their reasonable ‘minimum’ for a comprehensive assessment of GV as a criterion for evaluating the effectiveness of DM treatment and the predictors of negative diabetes outcomes. The following reports were presented during the discussion: ‘Glycemic variability: clinical and prognostic value. Types of glycemic variability’ (Candidate of Medical Sciences, assistant Professor Zilov A.V.); ‘Methods of assessment of variability of glycemia in clinical trials and routine practice’ (PhD, Professor Markova T. N.); ‘Current international and national recommendations on glycemic monitoring’ (PhD, Professor Galstyan G. R.) and ‘Peculiarities of glycemic variability and its evaluation among children and adolescents’ (Candidate of Medical Sciences Vitebskaya A.V.).

In 2008 the Food and Drug Administration has revised approval process for new antidiabetic agents and introduced a requirement to demonstrate the cardiovascular safety in an international multicenter trial. Currently cardiovascular outcome trials of dipeptidyl peptidase-4 (DPP-4) inhibitors (SAVOR-TIMI53, EXAMINE and TECOS), sodium-glucose cotransporter 2 inhibitors (EMPAREG, CANVAS), glucagon-like peptide-1 receptor agonists (ELIXA, EXSCEL LEADER and SUSTAIN-6), ultralong-acting and insulin (DEVOTE) have been completed. The trials confirmed cardiovascular safety of these glucose-lowering medications, and in addition, EMPA-REG OUTCOME (empagliflozin), CANVAS (canagliflozin) and LEADER (liraglutide) have also demonstrated cardioprotective effect of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists. These data led to the changes of clinical guidelines for the management of type 2 diabetes.

Variants of artistic reconstruction of the events of the Great Patriotic War in modern mass literature are considered. The material is multi-genre texts of the 2000s: an alternative version of the history of the Great Patriotic War, free-thinking fantasies in a mystical spirit, a postmodern historical melodrama, a fantasy novel, a military-fantasy action movie. Particular attention is paid to the national bestsellers of the 2000s: novels by A. Turgenev (V. Kuritsyn) “Sleep and Believe: Blockade novel” and I. Boyashov “Tanker, or “The White Tiger.” It is shown that A. Turgenev in his work combines the legends of the besieged time with the cliches of a spy novel and love melodrama, I. Boyashov is the author of the story of the duel of a Russian tanker and a German miracle tank in the form of modern fantasy. The article affirms the idea that with the leave of the generation of front-line soldiers, the war moves from living memory into a repository of plots and images for literature and art, and becomes fertile material for constructing a different reality. It is hypothesized that mass literature, reconstructing the facts and events of the recent past, is involved in modeling and rethinking the ideological and value orientations of society and the formation of a new identity.

Currently, an urgent task for food enterprises of the Russian Federation is to improve the quality and safety of their products through the introduction of a system for analyzing critical control points (HACCP). This is important not only for the health of the population, but also for enhancing the advantages of products. The article presents materials concerning implementation of the principles of HASSP on the enterprise JSC «MOROZKO». Theoretical aspects of system of HASSP are given, problems are analyzed and recommendations about their minimization in the conditions of implementation of technical regulations of the Customs union 021/2011 «About safety of food products» are developed. Data of sanitary and microbiological control at veterinary and sanitary examination of the cooled and frozen meat of different software suppliers are provided to the normalized indicators in compliance with normative requirements of meat and meat products. Need of carrying out monitoring of microbiological indicators for critical control points is proved. On the basis of monitoring of microbiological indicators of raw materials, water, air, the equipment, overalls, hands of workers the assessment of risk of microbial contamination of finished goods by pathogenic microorganisms and microorganisms - activators of damage of raw materials and products is carried out. The quantitative composition of microflora was determined during air monitoring in the workshops of the enterprise. Comparative analysis of the influence of disinfection of different types of the equipment on its sanitary states by washout method from the equipment is carried out.

The variety of tissue cells express receptors of vitamin D. The possible causative connection between lack of vitamin D and a number of inflammatory diseases such as bronchial asthma has stimulated interest in the potentially positive effects of vitamin D in the theraputic schemes. Conflicting data was demonstrated by numerous studies concerning the relationship of vitamin D and development of asthma . Most of them stress attention on the lack of studies with targeting population excluding subclasters and phenotypes of bronchial asthma, especially groups associated with low levels of vitamin D obesity, COPD and asthma, atopic patients. The question of prescribing of vitamin D in asthma, in the case of laboratory-proven deficiency or lack of vitamin D can be an option in therapy.