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The article studies the evolution of the military-political course of the French Fifth Republic. The authors provide a comprehensive analysis of the four editions of the French White Paper, which are the conceptual foundations of the country’s defense and national security strategy. Particular attention is paid to the impact of the domestic political situation, international political and economic processes, as well as membership in the European Union and the North Atlantic Alliance on the formation of France’s defense policy. The methodological basis for the study of the French military policy evolution is a systematic approach: a comprehensive study of the Fifth Republic’s defense and national security strategy as parts of the global European security architecture, which consists of closely related components. In addition the authors use the concrete-historical method, as well as induction, deduction, content analysis and comparative analysis of the Fifth Republic’s regulatory and legal documentation in the field of national defense and security, which allowed identifying elements of the specifics and continuity of the military-political course of France. With the help of forecasting, as well as a statistical method based on official data from government departments and research centers, the authors assessed the state of the French Republic Armed Forces. The excessive involvement of the French armed forces in various external and internal military operations, accompanied by a reduction in the number of personnel and deterioration of their equipment, weakens of the combat potential of Paris.

Hepatitis C virus (HCV) is an oncogenic virus that causes chronic liver disease in more than 80% of patients. During the last decade, efficient direct-acting antivirals were introduced into clinical practice. However, clearance of the virus does not reduce the risk of end-stage liver diseases to the level observed in patients who have never been infected. So, investigation of HCV pathogenesis is still warranted. Virus-induced changes in cell metabolism contribute to the development of HCV-associated liver pathologies. Here, we studied the impact of the virus on the metabolism of polyamines and proline as well as on the urea cycle, which plays a crucial role in liver function. It was found that HCV strongly suppresses the expression of arginase, a key enzyme of the urea cycle, leading to the accumulation of arginine, and up-regulates proline oxidase with a concomitant decrease in proline concentrations. The addition of exogenous proline moderately suppressed viral replication. HCV up-regulated transcription but suppressed protein levels of polyamine-metabolizing enzymes. This resulted in a decrease in polyamine content in infected cells. Finally, compounds targeting polyamine metabolism demonstrated pronounced antiviral activity, pointing to spermine and spermidine as compounds affecting HCV replication. These data expand our understanding of HCV’s imprint on cell metabolism.

ABSTRACT Viral infections attract more and more attention, especially after the emergence of novel zoonotic coronaviruses and the monkeypox virus over the last 2 decades. Research on viruses is based to a great extent on mammalian cell lines that are permissive to the respective viruses. These cell lines are usually cultivated according to the protocols established in the 1950s to 1970s, although it is clear that classical media have a significant imprint on cell growth, phenotype, and especially metabolism. So, recently in the field of biochemistry and metabolomics novel culture media have been developed that resemble human blood plasma. As perturbations in metabolic and redox pathways during infection are considered significant factors of viral pathogenesis, these novel medium formulations should be adapted by the virology field. So far, there are only scarce data available on viral propagation efficiencies in cells cultivated in plasma-like media. But several groups have presented convincing data on the use of such media for cultivation of uninfected cells. The aim of the present review is to summarize the current state of research in the field of plasma-resembling culture media and to point out the influence of media on various cellular processes in uninfected cells that may play important roles in viral replication and pathogenesis in order to sensitize virology research to the use of such media.

Aim. To conduct comparative analysis of histological remission in patients with moderate and severe ulcerative colitis (UC), receiving biological therapy vedolizumab, mesenchymal stem cell (MSC) treatment and combined stem cells and vedolizumab therapy. Materials and methods. We studied biopsies of 75 patients with total or left-sided moderate and severe ulcerative colitis, divided into groups depending on treatment. The first group of UC patients (n=29) received stem cell therapy 2 mln per kg; the second group of UC patients (n=27) received vedolizumab and the third group (n=19) MSC and vedolizumab. The efficacy of treatment was assessed by C reactive protein (CRP), Mayo score (MS), fecal calprotectin (FC) and Geboes score (GS). Results. We determined medium correlation between basic FC and MS before treatment (r=0.6605, p0.05). After 12 weeks of treatment in the first group of UC patients (n=29) CRP was 7.82.1 mg/l, FC 409.344.85 g/g, medium GS 1.20.1 points. After 12 weeks of treatment in the second group of UC patients (n=27) CRP was 8.41.4 mg/l, FC 435.547.3 g/g, medium GS 1.350.15 points. After 12 weeks of treatment in the third group of UC patients (n=19) CRP was 6.41.1 mg/l, FC 290.617.5 g/g, medium GS 0.90.1 points. We proved strong direct relationship between FC and GS after 12 weeks of treatment in UC patients, receiving MSC (r=0.8392, p0.05). The statistically significant majority of patients, achieved histological remission, have less than 5-year duration of disease. Conclusion. Our study showed that clinical and endoscopic remission in UC patients does not always correlate with histological remission. Combined anti-cytokine and stem cells therapy contributes to achieve deep remission and decrease mucosa inflammation rather than single MSC or vedolizumab treatment. Deep remission could be achieved by earlier start of biological therapy. FC could be a predictor and marker of mucosa healing and histological remission

The biogenic polyamines, spermidine (Spd) and spermine (Spm), are present at millimolar concentrations in all eukaryotic cells, where they participate in the regulation of vitally important cellular functions. Polyamine analogs and derivatives are a traditional and important instrument for the investigation of the cellular functions of polyamines, enzymes of their metabolism, and the regulation of the biosynthesis of antizyme—a key downregulator of polyamine homeostasis. Here, we describe convenient gram-scale syntheses of a set of C-methylated analogs of Spd. The biochemical properties of these compounds and the possibility for the regulation of their activity by moving a methyl group along the polyamine backbone and by changing the stereochemistry of the chiral center(s) are discussed.

Hepatitis delta virus (HDV) is a viroid-like satellite that may co-infect individuals together with hepatitis B virus (HBV), as well as cause superinfection by infecting patients with chronic hepatitis B (CHB). Being a defective virus, HDV requires HBV structural proteins for virion production. Although the virus encodes just two forms of its single antigen, it enhances the progression of liver disease to cirrhosis in CHB patients and increases the incidence of hepatocellular carcinoma. HDV pathogenesis so far has been attributed to virus-induced humoral and cellular immune responses, while other factors have been neglected. Here, we evaluated the impact of the virus on the redox status of hepatocytes, as oxidative stress is believed to contribute to the pathogenesis of various viruses, including HBV and hepatitis C virus (HCV). We show that the overexpression of large HDV antigen (L-HDAg) or autonomous replication of the viral genome in cells leads to increased production of reactive oxygen species (ROS). It also leads to the upregulated expression of NADPH oxidases 1 and 4, cytochrome P450 2E1, and ER oxidoreductin 1α, which have previously been shown to mediate oxidative stress induced by HCV. Both HDV antigens also activated the Nrf2/ARE pathway, which controls the expression of a spectrum of antioxidant enzymes. Finally, HDV and its large antigen also induced endoplasmic reticulum (ER) stress and the concomitant unfolded protein response (UPR). In conclusion, HDV may enhance oxidative and ER stress induced by HBV, thus aggravating HBV-associated pathologies, including inflammation, liver fibrosis, and the development of cirrhosis and hepatocellular carcinoma.

Abstract Background Cisplatin, mitomycin C and anthracyclines demonstrate high activity in BRCA1-deficient tumors. This study aimed to evaluate the efficacy of the triplet combination of these drugs in BRCA1-driven high-grade serous ovarian carcinomas (HGSOCs). Methods Ten HGSOC patients with germ-line BRCA1 mutation received neoadjuvant chemotherapy (NACT) consisting of mitomycin C 10 mg/m2 (day 1), doxorubicin 30 mg/m2 (days 1 and 8) and cisplatin 80 mg/m2 (day 1), given every 4 weeks (MAP regimen). The comparator group included 16 women, who received standard NACT combination of paclitaxel 175 mg/m2 and carboplatin (6 AUC), given every 3 weeks (TCbP scheme). Results None of the patients treated by the MAP scheme demonstrated complete pathologic response in ovaries, while 4 women showed absence of tumor cells in surgically excised omental specimens. When chemotherapy response scores (CRS) were considered, poor responsiveness (CRS 1) was not observed in the MAP group, but was common for the TCbP regimen (6/16 (38 %) for ovaries and 5/16 (31 %) for omentum; p = 0.05 and 0.12, respectively). Median treatment-free interval (TFI) was not reached in women treated by the MAP, but was 9.5 months for the TCbP scheme (p = 0.1). The rate of the recurrence within 1 year after the completion of the treatment was 4/10 (40 %) for the MAP and 10/13 (77 %) for the TCbP (p = 0.1). Conclusions The attempt to intensify NACT by administering combination of 3 drugs did not result in high rate of complete pathologic responses. However, there was a trend towards higher efficacy of the MAP regimen versus conventional TCbP scheme with regard to CRS and clinical outcomes.

Introduction. Historically, France has always had an impact on the African continent. Despite the independence of most French colonies in Africa, France managed to maintain its position in the region. The system called “Françafrique” was created. The first element of this system is economic cooperation, namely the fact, that Africa provides an opportunity to use its natural resources. Another important element is the military one. The White paper of France has repeatedly emphasized the strategic importance of Africa for the Fifth Republic. In the 2010s, the situation in the region deteriorated. France’s assistance in overcoming internal crises in Mali, Chad, Libya can be considered an evidence of the increasing role of France in conflict resolution, and that is the thing which is analyzed by the author in this work. Methods and materials. While writing the article, both official documents of the French government and analytical works of famous French authors were used. Both general scientific methods (analysis, synthesis) and quantitative scientific methods (event analysis and content analysis) are used in the paper. Analysis. The article is devoted to the activities of France on the African continent in the period from 2011 to 2017. A Special attention is paid to the role of France in the conflict resolution of Africa. In particular, the paper considers France’s support for the adoption of the UN resolution in response to the civil war in Libya in 2011 and military intervention in the country; military operations of the Fifth Republic in the Sahel zone – Serval operation and in the Central African Republic – Sangaris operation, military presence of France in Djibouti. The paper emphasizes the key provisions of the French policy towards the African continent aimed at the preservation of French influence in the region. Results. In the article, the author comes to the following conclusions: France is not ready to abandon its military ambitions, it continues Barkhane operation, without stopping the fight against terrorism in the Sahel region; despite the competition from other countries (in particular, China and Japan), France’s military presence in Eastern Africa remains the same, France does not intend to leave the base in Djibouti.

Changes in metabolic pathways are often associated with the development of various pathologies including cancer, inflammatory diseases, obesity and metabolic syndrome. Identification of the particular metabolic events that are dysregulated may yield strategies for pharmacologic intervention. However, such studies are hampered by the use of classic cell media that do not reflect the metabolite composition that exists in blood plasma and which cause non-physiological adaptations in cultured cells. In recent years two groups presented media that aim to reflect the composition of human plasma, namely human plasma-like medium (HPLM) and Plasmax. Here we describe that, in four different mammalian cell lines, Plasmax enhances mitochondrial respiration. This is associated with the formation of vast mitochondrial networks and enhanced production of reactive oxygen species (ROS). Interestingly, cells cultivated in Plasmax displayed significantly less lysosomes than when any standard media were used. Finally, cells cultivated in Plasmax support replication of various RNA viruses, such as hepatitis C virus (HCV) influenza A virus (IAV), severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and several others, albeit at lower levels and with delayed kinetics. In conclusion, studies of metabolism in the context of viral infections, especially those concerning mitochondria, lysosomes, or redox systems, should be performed in Plasmax medium.

Since 1990s, the number of states conflicts decreased and they started saying that the classical wars disappeared but at the same time, the number of internal conflicts increased dramatically. The end of colonial regime in Africa didn’t bring peace to the region – the new wave of internal conflicts and civil wars overwhelmed the region. In the given article the authors analyze political and complicated socio-economic situation in the Tropical Africa, describe the conflicts in this zone, their typology, results and factors. The authors attempt to analyze internal and external causes of conflicts in the studied region, taking into account all elements of each conflict and their interdependence. The subject of the article is the conflict as the social element presenting the important part of international reality. It is noted that the crisis in the region influences every part of economic, social, and political spheres, so the solution is not possible without structural changes. In this connection, conflicts are the logical results of regional crisis as well as uncertain activity of international society. This situation provokes the large wave of migrants from the region and inside it. The countries the Tropical Africa can’t guarantee any suitable level of life for the citizens, and the situation can’t be resolved without active role of international community.

Enhanced production of reactive oxygen species (ROS) triggered by various stimuli, including viral infections, has attributed much attention in the past years. It has been shown that different viruses that cause acute or chronic diseases induce oxidative stress in infected cells and dysregulate antioxidant its antioxidant capacity. However, most studies focused on catalase and superoxide dismutases, whereas a family of peroxiredoxins (Prdx), the most effective peroxide scavengers, were given little or no attention. In the current review, we demonstrate that peroxiredoxins scavenge hydrogen and organic peroxides at their physiological concentrations at various cell compartments, unlike many other antioxidant enzymes, and discuss their recycling. We also provide data on the regulation of their expression by various transcription factors, as they can be compared with the imprint of viruses on transcriptional machinery. Next, we discuss the involvement of peroxiredoxins in transferring signals from ROS on specific proteins by promoting the oxidation of target cysteine groups, as well as briefly demonstrate evidence of nonenzymatic, chaperone, functions of Prdx. Finally, we give an account of the current state of research of peroxiredoxins for various viruses. These data clearly show that Prdx have not been given proper attention despite all the achievements in general redox biology.

Hepatitis C virus (HCV) infection is accompanied by the induction of oxidative stress, mediated by several virus proteins, the most prominent being the nucleocapsid protein (HCV core). Here, using the truncated forms of HCV core, we have delineated several mechanisms by which it induces the oxidative stress. The N-terminal 36 amino acids of HCV core induced TGF\(\upbeta\)1-dependent expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases 1 and 4, both of which independently contributed to the production of reactive oxygen species (ROS). The same fragment also induced the expression of cyclo-oxygenase 2, which, however, made no input into ROS production. Amino acids 37–191 of HCV core up-regulated the transcription of a ROS generating enzyme cytochrome P450 2E1. Furthermore, the same fragment induced the expression of endoplasmic reticulum oxidoreductin 1\(\upalpha\). The latter triggered efflux of Ca2+ from ER to mitochondria via mitochondrial Ca2+ uniporter, leading to generation of superoxide anions, and possibly also H2O2. Suppression of any of these pathways in cells expressing the full-length core protein led to a partial inhibition of ROS production. Thus, HCV core causes oxidative stress via several independent pathways, each mediated by a distinct region of the protein.

HCV core is an attractive HCV vaccine target, however, clinical or preclinical trials of core-based vaccines showed little success. We aimed to delineate what restricts its immunogenicity and improve immunogenic performance in mice. We designed plasmids encoding full-length HCV 1b core and its variants truncated after amino acids (aa) 60, 98, 152, 173, or up to aa 36 using virus-derived or synthetic polynucleotides (core191/60/98/152/173/36_191v or core152s DNA, respectively). We assessed their level of expression, route of degradation, ability to trigger the production of reactive oxygen species/ROS, and to activate the components of the Nrf2/ARE antioxidant defense pathway heme oxygenase 1/HO-1 and NAD(P)H: quinone oxidoreductase/Nqo-1. All core variants with the intact N-terminus induced production of ROS, and up-regulated expression of HO-1 and Nqo-1. The capacity of core variants to induce ROS and up-regulate HO-1 and Nqo-1 expression predetermined their immunogenicity in DNA-immunized BALB/c and C57BL/6 mice. The most immunogenic was core 152s, expressed at a modest level and inducing moderate oxidative stress and oxidative stress response. Thus, immunogenicity of HCV core is shaped by its ability to induce ROS and oxidative stress response. These considerations are important in understanding the mechanisms of viral suppression of cellular immune response and in HCV vaccine design.

Hepatitis C virus (HCV) is the etiological agent accounting for chronic liver disease in approximately 2–3% of the population worldwide. HCV infection often leads to liver fibrosis and cirrhosis, various metabolic alterations including steatosis, insulin and interferon resistance or iron overload, and development of hepatocellular carcinoma or non-Hodgkin lymphoma. Multiple molecular mechanisms that trigger the emergence and development of each of these pathogenic processes have been identified so far. One of these involves marked induction of a reactive oxygen species (ROS) in infected cells leading to oxidative stress. To date, markers of oxidative stress were observed both in chronic hepatitis C patients and in various in vitro systems, including replicons or stable cell lines expressing viral proteins. The search for ROS sources in HCV-infected cells revealed several mechanisms of ROS production and thus a number of cellular proteins have become targets for future studies. Furthermore, during last several years it has been shown that HCV modifies antioxidant defense mechanisms. The aim of this review is to summarize the present state of art in the field and to try to predict directions for future studies.

Dear Colleagues!We are glad to present the 10th Edition (revised) of the Standards of Specialized Diabetes Care. These evidence-based guidelines were designed to standardize and facilitate diabetes care in all regions of the Russian Federation.The Standards are updated on the regular basis to incorporate new data and relevant recommendations from national and international clinical societies, including World Health Organization Guidelines (WHO, 2011, 2013), International Diabetes Federation (IDF, 2011, 2012, 2013), European Association for the Study of Diabetes (EASD 2018, 2019), American Diabetes Association (ADA, 2018, 2019, 2021), American Association of Clinical Endocrinologists (AACE, 2020, 2021), International Society for Pediatric and Adolescent Diabetes (ISPAD, 2018) and Russian Association of Endocrinologists (RAE, 2019). Current edition of the “Standards” also integrates results of completed randomized clinical trials (ADVANCE, ACCORD, VADT, UKPDS, SAVOR, TECOS, LEADER, EXAMINE, ELIXA, SUSTAIN, DEVOTE, EMPA-REG OUTCOME, CANVAS, DECLARE, CARMELINA, REWIND, CREDENCE, CAROLINA, DAPA-CKD, DAPA-HF, EMPEROR-Reduced trial, VERIFY, VERTIS CV, PIONEER, etc.), as well as findings from the national studies of diabetes mellitus (DM), conducted in close partnership with a number of Russian hospitals.Latest data indicates that prevalence of DM in the world increased during the last decade more than two-fold, reaching some 537 million patients by the end of 2021. According to the current estimation by the International Diabetes Federation, 643 million patients will be suffering from DM by 2030 and 784 million by 2045.Like many other countries, Russian Federation experiences a sharp rise in the prevalence of DM. According to Russian Federal Diabetes Register, there are at least 4 871 863 patients with DM in this country on 01.01.2021 (3,34% of population) with 92,3% (4 498 826)–Type 2 DM, 5,6% (271 468)–Type 1 DM and 2,1% (101 569)–other types of DM, including 9 729 women with gestational DM. However, these results underestimates real quantity of patients, because they consider only registered cases. Results of Russian epidemiological study (NATION) confirmed that only 54% of Type 2 DM are diagnosed. So real number of patients with DM in Russia is 10 million patients (about 7% of population). This is a great long-term problem, because a lot of patients are not diagnosed, so they don’t receive any treatment and have high risk of vascular complications.Severe consequences of the global pandemic of DM include its vascular complications: nephropathy, retinopathy, coronary, cerebral and peripheral vascular disease. These conditions are responsible for the majority of cases of diabetes-related disability and death.In сurrent edition of the “Standards”:New goals of glycemic control for continuous glucose monitoring (time in range, below range and above range, glucose variability) are given.It also features updated guidelines on stratification of treatment in newly diagnosed Type 2 diabetes.In the recommendations for the personalization of the choice of antidiabetic agents, it is taken into account that in certain clinical situations (the presence of atherosclerotic cardiovascular diseases and their risk factors, chronic heart failure, chronic kidney disease, obesity, the risk of hypoglycemia) certain classes of hypoglycemic agents (or individual drugs) have proven advantages.Indications for the use of antidiabetic agents in chronic kidney disease are expanded.Information about insulin pump therapy is added.Recommendations on vaccination are added.An algorithm for replacing some insulin preparations with others is given.This text represents a consensus by the absolute majority of national experts, achieved through a number of fruitful discussions held at national meetings and forums. These guidelines are intended for endocrinologists, primary care physicians, pediatricians and other medical professionals involved in the treatment of DM.Compared with previous edition of the Standards of Specialized Diabetes Care edited by Dedov I.I., Shestakova M.V., ­Mayorov A.Yu., 10th edition, Moscow, 2021 (signed for printing on 10.09.2021) a number of changes have been made.On behalf of the Working Group

The review focuses on the new WHO classification published in 2019. Unlike the previous classification, this classification does not recognize subtypes of T1DM and T2DM and offers new types of diabetes: “hybrid types of diabetes” and “unclassified diabetes”. This classification provides practical guidance to clinicians for assigning a type of diabetes to individuals and choose appropriate treatment (whether or not to start treatment with insulin), particularly at the time of diagnosis. This review presents the variety of forms of diabetes, the features of their clinical picture, and also emphasizes the importance of molecular genetic and immunological studies to identify types of diabetes and determine personalized therapy. The selection of “hybrid forms” of diabetes is due to the fact that the treatment of these types of diabetes has its own characteristics associated with the specific pathogenesis of diseases. However, it is obvious that further studies should relate to the study of the mechanisms of damage and decrease in the function of в-cells. Perhaps future classification systems and, as a consequence, personalized treatment will focus on various mechanisms of damage to β-cells.

Type 2 diabetes mellitus (T2DM) is a multifactorial metabolic disease, the development of which is mediated by both genetic disorders and various intracellular and extracellular molecular processes. One of the main pathogenetic mechanisms for the development of T2DM is a progressive decrease in the mass and functional reserve of β-cells, which largely determines the course of T2DM. The mechanisms of action of most sugar-lowering drugs are associated with increased secretion of insulin, so it is obvious that the effectiveness of the therapy will also largely depend on the functional state of β-cells. All this explains the great interest in studying the mechanisms of damage of β-cells in T2DM and factors that can accelerate this process, leading to their death and the development of a relative and then absolute insulin deficiency. The mechanisms of dysfunction β-cells in T2DM have not been studied much. This article provides an overview of the data of domestic and foreign literature of recent years on the molecular, intracellular features of various mechanisms of damage and death of β-cells in type 2 diabetes. The results of studies aimed at studying the possible factors and processes leading to their launch are presented.

Dear Colleagues! We are glad to present the 9th Edition (revised) of Standards of Diabetes Care. These evidence-based guidelines were designed to standardize and facilitate diabetes care in all regions of the Russian Federation. The Standards are updated on the regular basis to incorporate new data and relevant recommendations from national and international clinical societies, including World Health Organization Guidelines (WHO, 2011, 2013), International Diabetes Federation (IDF, 2011, 2012, 2013), American Diabetes Association (ADA, 2018, 2019), American Association of Clinical Endocrinologists (AACE, 2019), International Society for Pediatric and Adolescent Diabetes (ISPAD, 2014, 2018) and Russian Association of Endocrinologists (RAE, 2011, 2012, 2015). Current edition of the “Standards” also integrates results of completed randomized clinical trials (ADVANCE, ACCORD, VADT, UKPDS, SAVOR, TECOS, LEADER, EXAMINE, ELIXA, SUSTAIN, DEVOTE, EMPA-REG OUTCOME, CANVAS, DECLARE, CARMELINA, REWIND, etc.), as well as findings from the national studies of diabetes mellitus (DM), conducted in close partnership with a number of Russian hospitals. Latest data indicates that prevalence of DM in the world increased during the last decade more than two-fold, reaching some 463 million patients by the end of 2019. According to the current estimation by the International Diabetes Federation, 578 million patients will be suffering from diabetes mellitus by by 2030 and 700 million by 2045. Like many other countries, Russian Federation experiences a sharp rise in the prevalence of DM. According to Russian Federal Diabetes Register, there are at least 4 584 575 patients with DM in this country by the end of 2018 (3,1% of population) with 92% (4 238 503) – Type 2 DM, 6% (256 202) – Type 1 DM and 2% (89 870) – other types of DM, including 8 006 women with gestational DM. However, these results underestimates real quantity of patients, because they consider only registered cases. Results of Russian epidemiological study (NATION) con- firmed that only 54% of Type 2 DM are diagnosed. So real number of patients with DM in Russia is 9 million patients (about 6% of population). This is a great long-term problem, because a lot of patients are not diagnosed, so they don’t receive any treatment ant have high risk of vascular complications. Severe consequences of the global pandemics of DM include its vascular complications: nephropathy, retinopathy, coronary, cerebral, coronary and peripheral vascular disease. These conditions are responsible for the majority of cases of diabetes-related disability and death. In сurrent edition of the “Standards”: New goals of glycemic control for the elderly, based on the presence of functional dependence, as well as for pregnant women, children and adolescents, are given. Added a snippet that describes the continuous glucose monitoring. Only low-density lipoprotein cholesterol level is used as a target for lipid metabolism. Proposes more stringent target levels of blood pressure. It also features updated guidelines on stratification of treatment in newly diagnosed Type 2 diabetes: the excess of the initial level of HbA1c over the target level was used as a criterion. In the recommendations for the personalization of the choice of antidiabetic agents, it is taken into account that in certain clinical situations (the presence of atherosclerotic cardiovascular diseases and their risk factors, chronic heart failure, chronic kidney disease, obesity, the risk of hypoglycemia) certain classes of hypoglycemic agents (or individual drugs) have proven advantages. Recommendations for psychosocial support are added. The position of metabolic surgery as a method of treatment of DM with morbid obesity is updated. Recommendations for diagnostic and treatment of hypogonadism syndrome in men with DM are added. For the first time, evidence levels of confidence and credibility levels of recommendations for diagnostic, therapeutic, rehabilitative and preventive interventions based on a systematic review of the literature are given in accordance with the recommendations of the Center for Healthcare Quality Assessment and Control of the Ministry of Health of the Russian Federation. This text represents a consensus by the absolute majority of national experts, achieved through a number of fruitful discus- sions held at national meetings and forums. These guidelines are intended for endocrinologists, primary care physicians and other medical professionals involved in the treatment of DM. On behalf of the Working Group

BACKGROUND: There is an interaction between cell-mediated pathway of the vessel calcification and atherosclerosis processes. In some studies the relation beeen circulating osteogenic progenitor cells and cardiovascular diseases was shown. Though its role in the development of cerebrovascular diseases (CVD) in Type 2 diabetes mellitus (T2DM) remains unknown. AIM: To study the level of circulating endothelial (CD34 + VEGFR2 +) and osteogenic (CD34 + OCN +) progenitor cells in patients with CVD and T2DM. METHODS: We observed patients with CVD (coronary artery disease and / or chronic limb threatening ischemia) with T2DM and without T2DM. Patients with CVD and T2DM were included in group 1 patients with CVD and without T2D were included in group 2. The level of CD34 + VEGFR2 cells and CD34 + OCN+ cells was determined by flow cytometry.There were no differences in the age, gender, lipid profile, body mass index, creatinine clearance, myocardial revascularization and lower limb revascularization between the 2 groups.The level of CD34 + VEGFR2 cells and CD34 + OCN+ cells was determined by flow cytometry. The number of cells was determined by a percentage of the number of CD34+ cells. RESULTS: We observed 71 patients (38 women, mean age 67 years [62, 74]). Forty six patients were included in group 1 (28 women, mean age 68 years [63;75], 25 patients (10 women, 66 years [55;72]) were included in group 2. We found that in patients with CVD and T2DM demonstrated higher amounts of CD34+OCN+ cells than CD34+VEGFR2+ cells. (29.7% [26.2;36.1] and 11.8% [9.57;17.2], p

One of the leading and unresolved problems in medicine is gastric cancer. The risk of developing RJ in H. pylori-infected patients is 2–4 times higher than in uninfected patients. The role of the cells of the immune system in the transformation of chronic atrophic gastritis in the Russian pancreas is undeniable, while the first cells that respond to a foreign antigen are neutrophilic granulocytes (NG). The aim of our work was to study the chemiluminescent activity of neutrophilic granulocytes in Helicobacter pylori, associated gastric cancer. A survey of 50 patients with chronic atrophic gastritis (CAH) and 50 patients with gastric cancer (RG) was performed. The control group consisted of 85 healthy donors. Evaluation of spontaneous and induced chemiluminescence (CL) was carried out for 90 minutes on a 36-channel chemiluminescent analyzer “CL 3606” (Russia). The following indicators were determined: the time the curve reached the maximum CL intensity, the maximum value of the CL intensity, the area under the CL curve. As an amplifier used luminol. The respiratory burst inducer was the opsonized zymosan. The enhancement of CL induced by opsonized zymosan was evaluated by the ratio of the area induced to the area of spontaneous CL and indicated by the activation index. Statistical data processing was carried out using Statistica for Windows 8.0 application software packages. The critical level of significance in testing statistical hypotheses was taken to be p

Aim: To study the predominant serum responses (antibodies IgG, IgA, IgE) against H. pylori in relation to the indicators of the system “lipid peroxidation–antioxidant system” in various pathogenetic variants of chronic gastritis (CG). Materials and Methods: Sixty patients with CG, 33 patients with chronic atrophic gastritis (CAG) and 31 patients with chronic allergic gastritis (CALG) were examined. The values of the system of lipid peroxidation and antioxidant protection in plasma were determined in the serum of patients using a spectrophotometric method. Statistical data processing was carried out using the Statistica 7.0 software package (StatSoft, Tulsa, OK, USA). Results: With serum responses “antibodies IgG > IgA” and “high concentrations of IgE antibodies”, we found unidirectional changes in the form of an increase in the amount of diene conjugates, malondialdehyde and an increase in the activity of all enzymes: superoxide dismutase, catalase, glutathione-S-transferase and glutathione peroxidase. With a serum response with low concentrations of IgG, IgA antibodies, multidirectional changes were found in the form of an increase in the amount of diene conjugates, malondialdehyde and a decrease in the activity of all enzymes: superoxide dismutase, catalase, glutathione-S-transferase and glutathione peroxidase relative to the control group. Conclusions: The obtained data testify to the balance of lipid peroxidation and antioxidant system processes and depend on the characteristics of the immune response to H. pylori infection.

Gastric cancer is a global health problem. The pathogenesis of this disease remains unclear. This study included 198 H. pylori (+) men aged 45 to 60 years old. Group A included 63 practically healthy men, group B included 45 men with severe atrophic body gastritis, group C included 37 men with epithelial gastric cancer stages I–II according to TNM, and group D included 54 men with epithelial gastric cancer stages III–IV according to the TNM scale. The content of malondialdehyde (MDA), diene conjugates (DCs), superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), and glutathione peroxidase (GPO) was detected using an enzyme immunoassay (ELISA) or spectrophotometric methods in the blood plasma. The concentrations of MDA and DC were increased in the patients of group B compared with group A, and in patients of groups C and D compared with groups A and B. The ratio of MDA/SOD and MDA/CAT was decreased in the patients in group D compared with the patients in group C, and was significantly higher compared with group A. The ratios of MDA/GPO and MDA/GST increased linearly and were at a maximum in groups C and D. Our work determined that indicators of oxidative stress may be the biochemical substrate, which brings together the various stages of the Correa cascade, and may explain disease progression. The dynamics of changes in the content of SOD and CAT in the plasma in patients with gastric cancer may be a target of future investigations.

Purpose: the main objective of preparation of article consists in formation of conceptual reasons for the new approach to administrative-territorial division of the Russian Federation corresponding to the relevant calls facing the country in the modern economic conditions. For achievement of this purpose in article the following research tasks are delivered and successfully solved: 1) to create new approach to administrative-territorial division of the Russian Federation on the basis of stability of her subjects; 2) to develop conceptual model of acceptance of the administrative decision on enlargement of regions by use of the modern methods of the quantitative and qualitative analysis of nature of regional development and a status of an economic security of the territory; 3) to define composition and structure of regional clusters, to give their characteristic in specific parametric space; 4) to develop recommendations about formation of administrative decisions on enlargement of regions taking into account specifics of development of the territories in a section of each cluster. Methods: by preparation of article general scientific methods of researches, such as systematization, generalization, cause-effect analysis and also receptions of the quantitative are used (hierarchical and iterative methods, statistic analysis) and qualitative (methods of the spatial analysis, theory of image identification) analysis. The new conceptual model based on synthesis of qualitative and quantitative methods of assessment of effectiveness of association of territories is developed for achievement of the goal of a research. According to the offered model making decision on association of the region is carried out in four steps. At the first stage justification of expediency of integration of territories is carried out and the general concept of association of regions is formed; at the second stage – holding a procedure of the cluster analysis and registration of results of a clustering by definition of uniform groups of regions on the basis of identification of similarity of the quantitative values characterizing stability of development of regions and a condition of indicators of their economic security; at the third stage – diagnostics of proximity of objects in a cluster on the basis of the principle of territorial contiguity and formation of the list and structure of regions concerning which the procedure of integration can be recommended; at the fourth stage – development of recommendations of integration of regions for stability of territorial subjects of the Russian Federation and ensuring economic security of the Russian Federation. Results: the new approach to administrative-territorial division of the Russian Federation on the basis of stability of subjects assuming that in case of making decision on combining of regions the requirement of increase in level of stability of development of the territories and their economic security shall act as the purpose and the expected result of process is developed. The conceptual model of making decision on enlargement of regions concretizing logic and content of process which application in practice of public administration by regional development will allow to provide framing of adequate approaches to administrative-territorial division of the Russian Federation is created. The recommendations concerning making decisions on combining of regions allowing to consider adequately specifics of social and economic development and level of an economic security of the territories are provided. Conclusions and Relevance: the researches conducted in article represent development of scientific ideas of the modern approaches to administrative-territorial division of the Russian Federation. Practical application of the received results will allow to enhance procedures of acceptance of administrative decisions concerning enlargement of regions taking into account the current trends in development of the country and on this basis to ensure steady positive social and economic dynamics and an economic security of the Russian Federation.

Purpose: investigation of the possibility of applying special regimes of economic activity on the territory of the Arctic zone of the Russian Federation.Methods: the research methodology is based on methods of generalization, analogy, comparative and system analysis; the rules for assessing the effectiveness of the operation of special economic zones were used.Results: the expediency of applying special regimes of economic activity in the Arctic zone of Russia is considered. Mechanisms for establishing and operating such special economic regimes as special economic zones, territorial development zones, territories for outpacing socio-economic development, industrial parks, technoparks and clusters have been studied. The possibility of linking the supposed support zones of development in the Arctic with special modes of economic activity is considered.Conclusions and Relevance: the current trends in the social and economic development of the Arctic zone of the Russian Federation, the need to diversify the region's economy and attract investment determine the appropriateness of using such economic regimes that will contribute to the achievement of the objectives of state policy in the Arctic, taking into account specific conditions for managing the macroregion.The study allows us to conclude that at present there is no clear separation between the indicated regimes. Their effectiveness and effectiveness is not directly dependent on the number of benefits provided.At the present time, any of the existing special regimes in our country can be established on the territory of the Arctic zone of Russia. The adoption of such a decision should be based on a strategic vision for the development of the whole circumpolar region and its individual territories, and also be accompanied by an assessment of the falling incomes, planned tax revenues and the volume of benefits provided within a particular regime of economic activity., Moscow, Russian Federation

Cargo safety in transportation is the main responsibility of the carrier. The increasing of the cargo safety level during of transportation is directly related to the necessity of considering the factors are influence on the cargo safety, which have a complex and invariant impact. Identification of the most important factors (dominant) in the process of the transportation contributes to rational conduct of and technological actions from the point of view of cargo safety during transportation.

Aim. To study the quantity of endothelial progenitor cells (EPCs) and levels of vascular endothelial growth factor A (VEGF-A) in patients with type 2 diabetes mellitus (T2DM) after endovascular interventions on coronary and peripheral arteries. Materials and methods. We observed 68 patients with stable angina pectoris and critical limb ischaemia, admitted for elective percutaneous coronary intervention and endovascular revascularisation of the lower extremity. The number of CD34+VEGFR2+CD45- and CD34+CD133+CD45- cells and levels of VEGF-A were determined before endovascular intervention and 2–4 days after the surgery. Results. We found that in patients without diabetes, the levels of EPCs increased significantly after endovascular interventions (CD34+VEGFR2+CD45-cells, p < 0.0001; CD34+ CD133+CD45-cells p = 0.041). The levels of EPCs in the peripheral blood of patients with T2DM before and after endovascular interventions did not significantly differ. The analysis of VEGF-A showed a statistically significant increase after intervention in both groups. In addition, in patients with an HbA1c level of 10 years, the levels of EPCs before and after endovascular interventions did not significantly differ. Conclusions. Patients with diabetes exhibited impaired EPC mobilisation after endovascular interventions. Poor glycaemic control and a long duration of diabetes are among the risk factors of EPC mobilisation.

Dear Colleagues! We are glad to present the 8th Edition of Standards of Diabetes Care. These evidence-based guidelines were designed to standardize and facilitate diabetes care in all regions of the Russian Federation. The Standards are updated on the regular basis to incorporate new data and relevant recommendations from national and international clinical societies, including World Health Organization Guidelines (WHO, 2011, 2013), International Diabetes Federation (IDF, 2011, 2012, 2013), American Diabetes Association (ADA, 2012, 2017), American Association of Clinical Endocrinologists (AACE, 2017), International Society for Pediatric and Adolescent Diabetes (ISPAD, 2014) and Russian Association of Endocrinologists (RAE, 2011, 2012, 2015). Current edition of the “Standards” also integrates results of completed randomized clinical trials (ADVANCE, ACCORD, VADT, UKPDS, SAVOR, TECOS, LEADER, EMPA-REG OUTCOME, etc.), as well as findings from the national studies of diabetes mellitus (DM), conducted in close partnership with a number of Russian hospitals. Latest data indicates that prevalence of DM in the world increased during the last decade more than two-fold, reaching some 415 million patients by the end of 2015. According to the current estimation by the International Diabetes Federation, 642 million patients will be suffering from DM by 2040. These observations resulted in the UN Resolution on Diabetes 61/225 passed on 20.12.2006, and in 2011 - UN Political Declaration, addressed to national health systems, calling for the establishment of multidisciplinary strategy in the prevention and control of non-communicable diseases, where special attention is drawn to the problem of diabetes as one of the leading causes of disability and mortality. Like many other countries, Russian Federation experiences a sharp rise in the prevalence of DM. According to Russian Federal Diabetes Register, there are at least 4.35 million patients with DM in this country by the end of 2016 (3% of population) with 92% (4 million) – Type 2 DM, 6% (255 th) – Type 1 DM and 2% (75 th) – other types of DM. However, these results underestimates real quantity of patients, because they consider only registered cases. Results of Russian epidemiological study (NATION) confirmed that only 50% of Type 2 DM are diagnosed. So real prevalence of patients with DM in Russia is no less than 8-9 million patients (about 6% of population). This is a great long-term problem, because a lot of patients are not diagnosed, so they don’t receive any treatment ant have high risk of vascular complications. Severe consequences of the global pandemics of DM include its vascular complications: nephropathy, retinopathy, coronary, cerebral, coronary and peripheral vascular disease. These conditions are responsible for the majority of cases of diabetes-related disability and death. Current edition of the “Standards” emphasizes the patient-oriented approach in making decisions on therapeutic goals, such as levels of glycaemia and blood pressure. It also features updated guidelines on the management of Type 2 DM and its vascular complications, added information about bariatric surgery as a method of treatment of DM with morbide obesity. This text represents a consensus by the absolute majority of national experts, achieved through a number of fruitful discussions held at national meetings and forums. These guidelines are intended for endocrinologists and diabetologists, primary care physicians, cardiologists and other medical professionals involved in prevention and treatment of DM. On behalf of the Working Group

The article describes a variety of severe clinical manifestations of diabetic autonomic neuropathy in patients with type 2 diabetes mellitus and coronary heart disease. The peculiarity of this case is the simultaneous onset of autonomic neuropathy and lesions of the cardiovascular system, complications of untreated diabetes, without acute decompensation in carbohydrate metabolism.

At a meeting of the Council of legislators dedicated to addressing the priorities, including designated in the Message of the President of the Federal Assembly December 13, 2012 Russian President Vladimir Putin on the issue of integration of Russian regions he noted that "coarsen" should be "based on the need to better address the social-economic problems combined into larger entities. " April 27, 2016 Speaker of the Federation Council V. Matviyenko said that "it is necessary to enlarge the regions, and not just on someone's will, but having by this economic, investment and other studies." However, today, against the background of political decisions on enlargement areas necessary methodological study of issues of their eff ectiveness, the formation of methodological tools allowing to carry out a preliminary assessment and to give reasonable suggestions to relevant federal authorities on the issue of integration of regions. The article presents the historical experience of integration of regions and methodological approaches that have been put in its basis SOPS. The authors also put forward the aspects on which we must focus in continuing the policy of integration of regions at the present stage of economic development and regional policy in Russia.