[The National Consensus statement on the management of adult patients with non-alcoholic fatty liver disease and main comorbidities].

The National Consensus was prepared with the participation of the National Medical Association for the Study of the Multimorbidity, Russian Scientific Liver Society, Russian Association of Endocrinologists, Russian Association of Gerontologists and Geriatricians, National Society for Preventive Cardiology, Professional Foundation for the Promotion of Medicine Fund PROFMEDFORUM. The aim of the multidisciplinary consensus is a detailed analysis of the course of non-alcoholic fatty liver disease (NAFLD) and the main associated conditions. The definition of NAFLD is given, its prevalence is described, methods for diagnosing its components such as steatosis, inflammation and fibrosis are described. The association of NAFLD with a number of cardio-metabolic diseases (arterial hypertension, atherosclerosis, thrombotic complications, type 2 diabetes mellitus, obesity, dyslipidemia, etc.), chronic kidney disease and the risk of developing hepatocellular cancer were analyzed. The review of non-drug methods of treatment of NAFLD and modern opportunities of pharmacotherapy are presented. The possibilities of new molecules in the treatment of NAFLD are considered: agonists of nuclear receptors, antagonists of pro-inflammatory molecules, etc. The positive properties and disadvantages of currently used drugs (vitamin E, thiazolidinediones, etc.) are described. Special attention is paid to the multi-target ursodeoxycholic acid molecule in the complex treatment of NAFLD as a multifactorial disease. Its anti-inflammatory, anti-oxidant and cytoprotective properties, the ability to reduce steatosis an independent risk factor for the development of cardiovascular pathology, reduce inflammation and hepatic fibrosis through the modulation of autophagy are considered. The ability of ursodeoxycholic acid to influence glucose and lipid homeostasis and to have an anticarcinogenic effect has been demonstrated. The Consensus statement has advanced provisions for practitioners to optimize the diagnosis and treatment of NAFLD and related common pathogenetic links of cardio-metabolic diseases.

[The prospects for the creation of the National Center for Personalized Medicine of Endocrine Diseases].

The National Medical Research Center for Endocrinology (NMRCE) received the right to implement the development program of the World-class Research Centre "The National Center for personalized medicine of endocrine diseases" (NMCPMED). The objective of the NMCPMED will be not only the creation of a system of personalized treatment, but also the training of new specialists for medicine.  Fundamental researches, carried out on the basis of the already existing institutes and laboratories of the NMRCE will be expanded by creating new laboratories of the NCPMED created de novo in accordance with the approved project. This article introduces the reader to the most important laboratories that would be created in NCPMED. These are laboratories of general, molecular and population genetics, bioinformatics, pharmacogenomics, microbiota, genome editing, mathematical and digital technologies, non-invasive technologies for the diagnosis of endocrinopathies, cellular technologies, artificial intelligence and a fundamentally new laboratory of metabolic visualization and radioteranostics. The authors hope that readers of one of the main journals for endocrinologists in our country will actively participate in the  implementation of NMRCE, as both young and experienced talented researchers will have a chance to be a part of the Centre. To realize the ambitious implementation plans for the achievements of the Centre, it is necessary to radically change the worldview of the doctors in our country, to train them in a new way, and to expand the structure of the Center's team by increasing the number of specialists in medical genetics, transcriptomics, biostatistics and bioinformatics, working at the intersection of experimental and clinical endocrinology, and ensuring the transit of innovative technologies into clinical practice. New laboratories of the World-Class Research Center, will become the place of routine work of a new generation of doctors, who possess not only the basics of clinical work, but also the skills of fundamental researches that will allow them to significantly improve the methods of diagnosis and treatment.

[Resolution on the results of the first working meeting of the Scientific Advisory Board «Actual problems of glycemic variability as a new criterion of glycemic control and safety of diabetes therapy¼].

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 glycemia¼ (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 «minimum¼ 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).

[Urogenital tuberculosis in children].

AIM: To analyze the clinical spectrum of urogenital tuberculosis (TB) in children from 1993-1997 to 2013-2017, who were treated at the FSCU "Kiritsy". MATERIALS AND METHODS: Clinical forms of urogenital tuberculosis were diagnosed in 195 children (stage 1) and 158 children (stage 2). Conventional methods of TB diagnosis, including clinical, laboratory, imaging studies, tuberculin skin test and urine culture for BCG were used. In all cases, standard treatment for TB in combination with physiotherapy were performed. RESULTS: When comparing the clinical spectrum of urogenital tuberculosis in children in 1993-1997 yy. (stage 1) and 2013 and 2017 yy. (stage 2), who were treated at the children's tuberculosis clinic "Kiritsy", the authors concluded that during the last 5 years the number of children with urogenital tuberculosis had decreased by 1.5 times (195 children in 1 stage, 158 in 2 stage) and proportion of children with a destructive form of urogenital tuberculosis decreased by 4 times (15 children in stage 1, 4 in stage 2). The contemporary diagnostic methods (urine culture, Diaskintest, ultrasound, instrumental methods) contributed to improved diagnosis of urogenital tuberculosis. Novel powerful antituberculous antibiotics allowed to significantly improve treatment outcomes. RESULTS: 1) The incidence of urogenital tuberculosis in children over the past 5 years has decreased by 1.5 times compared with 90th years of the the last century. 2) At the current stage, the use of urine culture, Diaskintest, ultrasound, x-ray and instrumental methods contributes to the diagnosis of urogenital tuberculosis in children. 3) Multidisciplinary team consisted of pediatricians, pediatric urologists, phthisiopediatric as well as sanitary and educational work in the foci of infection allow to identify the urogenital tuberculosis in children.

[Diabetes mellitus and chronic liver diseases. Literature review (part 2): treatment features].

Diabetes mellitus (DM) and chronic liver disease (CLD) are pathological conditions associated with each other and reaching epidemic proportions. There is a strong pathogenetic relationship of carbohydrate metabolism disorders and a number of CLD. Common mechanisms that provoke metabolic and autoimmune disorders in the development of various CLD, leading to steatosis, insulin resistance (IR), impaired glucose tolerance and the development of DM are described. Effective glycemic control can have a beneficial effect on the treatment of these patients, and, conversely, there is evidence of a positive effect of CLD therapy on carbohydrate metabolism. This review discusses the correction of carbohydrate metabolism in patients with CLD, the main groups of modern hypoglycemic drugs, mechanisms of their action, the impact on the physiology of the liver, the possibility of using each of these pharmacological groups in patients with impaired liver function. The modern approaches and possibilities of drug effects on the process of fibrogenesis in CLD, the effect of these drugs on carbohydrate metabolism are listed.

[Diabetes mellitus and chronic liver diseases. Part 1: general mechanisms of etiology and pathogenesis].

In recent years there has been an active discussion about the relationship between diabetes mellitus (DM) and chronic liver diseases (CLD). On the one hand, patients with diabetes have an increased risk of developing CLD. On the other hand, patients with CLD very often identify abnormal glucose metabolism which ultimately leads to impaired glucose tolerance and the development of diabetes. This review outlines potential causal relationships between some CLD and DM. Common mechanisms that provoke metabolic and autoimmune disorders in the development of various nosologies of the CKD group, leading to steatosis, insulin resistance, impaired glucose tolerance and the development of diabetes are described. Certain features of the assessment of carbohydrate metabolism compensation in patients with hepatic dysfunction, anemia and protein metabolism disorders are described.

[Intermittent hypoxia due to sleep apnea syndrome in patients with type 2 diabetes mellitus]. / Periodicheskaia gipoksiia na fone sindroma apnoé vo sne u bol'nykh sakharnym diabetom 2-go tipa.

OBJECTIVES: To evaluate the possible association between intermittent hypoxia (IH) and HbA1c in patients with insufficient control type of 2 diabetes mellitus (T2DM). MATERIAL AND METHODS: In this cross-sectional study 183 patients with HbAc1≥7% underwent three-channel overnight monitoring (ApneaLink) and completed Berlin Questionnaire, Epworth Sleepiness Scale and Pittsburgh Sleep Quality Index. Patients were divided in two groups, based on the cut-off value of oxygen desaturation index≥15. RESULTS AND CONCLUSION: There were 79 (43%) patients with intermittent hypoxia, which was associated with poorer glycaemic control, defined as HbA1c>8.7% (sample median) in the univariate analysis and after adjustment for body mass index OR 2,40 (CI 1.21-4.95, p=0.021). Neither of three questionnaires yielded satisfactory results as a screening method in patients with T2DM. There is a need to implement instrumental screening of sleep-disordered breathing in this population and to study the effects of CPAP-therapy on glycaemic control and carbohydrate metabolism.

Time Dependence of the Electron and Positron Components of the Cosmic Radiation Measured by the PAMELA Experiment between July 2006 and December 2015.

Cosmic-ray electrons and positrons are a unique probe of the propagation of cosmic rays as well as of the nature and distribution of particle sources in our Galaxy. Recent measurements of these particles are challenging our basic understanding of the mechanisms of production, acceleration, and propagation of cosmic rays. Particularly striking are the differences between the low energy results collected by the space-borne PAMELA and AMS-02 experiments and older measurements pointing to sign-charge dependence of the solar modulation of cosmic-ray spectra. The PAMELA experiment has been measuring the time variation of the positron and electron intensity at Earth from July 2006 to December 2015 covering the period for the minimum of solar cycle 23 (2006-2009) until the middle of the maximum of solar cycle 24, through the polarity reversal of the heliospheric magnetic field which took place between 2013 and 2014. The positron to electron ratio measured in this time period clearly shows a sign-charge dependence of the solar modulation introduced by particle drifts. These results provide the first clear and continuous observation of how drift effects on solar modulation have unfolded with time from solar minimum to solar maximum and their dependence on the particle rigidity and the cyclic polarity of the solar magnetic field.

New upper limit on strange quark matter abundance in cosmic rays with the PAMELA space experiment.

In this work we present results of a direct search for strange quark matter (SQM) in cosmic rays with the PAMELA space spectrometer. If this state of matter exists it may be present in cosmic rays as particles, called strangelets, having a high density and an anomalously high mass-to-charge (A/Z) ratio. A direct search in space is complementary to those from ground-based spectrometers. Furthermore, it has the advantage of being potentially capable of directly identifying these particles, without any assumption on their interaction model with Earth's atmosphere and the long-term stability in terrestrial and lunar rocks. In the rigidity range from 1.0 to ∼1.0×10^{3} GV, no such particles were found in the data collected by PAMELA between 2006 and 2009. An upper limit on the strangelet flux in cosmic rays was therefore set for particles with charge 1≤Z≤8 and mass 4≤A≤1.2×10^{5}. This limit as a function of mass and as a function of magnetic rigidity allows us to constrain models of SQM production and propagation in the Galaxy.

[Mathematical Modeling of the Blood Glucose Regulation System in Diabetes Mellitus Patients].

Interest in the mathematical modeling of the carbohydrate metabolism regulation system increases in recent years. This is associated with a "closed loop" insulin pump development (it controls an insulin infusion depending on the blood glucose level). To create an algorithm for the automatic control of insulin (and other hormones) infusion using an insulin pump it is necessary to accurately predict glycaemia level. So, the primary objective of mathematical modeling is to predict the blood glucose level changes, caused by the wide range of external factors. This review discusses the main mathematical models of blood glucose level control physiological system (simplified insulin-glucose system). The two major classes of models--empirical and theoretical--are described in detail. The ideal mathematical model of carbohydrate metabolism regulatory system is absent. However, the success in the field of blood glucose level control modeling and simulating is essentialfor the further development of diabetes prevention and treatment technologies, and creating an artificial pancreas in particular.

Thymus in experimental carcinogenesis of the prostate gland.

We studied structural changes in the prostate gland, thymus, and lymph nodes in CBA mice after transplantation of Ehrlich ascites tumor cells into the prostate gland. On experimental day 5, the number of blood and lymph vessels decreased in the gland; the percentage of connective tissue elements and glandular tissue and the number of immunoblasts in the thymus increased. On day 18, the number of blood vessels in the tumor decreased; the width of the cortex and glandular tissue increased in the thymus, while the number of immunoblasts was reduced. On day 28, tumor infiltration and increased number of lymphatic vessels in its stroma were observed; parenchyma was reduced, and the area of the connective tissue increased in the thymus. These structural changes indicated the development of accidental involution of the thymus during carcinogenesis of the prostate.

Cosmic-ray positron energy spectrum measured by PAMELA.

Precision measurements of the positron component in the cosmic radiation provide important information about the propagation of cosmic rays and the nature of particle sources in our Galaxy. The satellite-borne experiment PAMELA has been used to make a new measurement of the cosmic-ray positron flux and fraction that extends previously published measurements up to 300 GeV in kinetic energy. The combined measurements of the cosmic-ray positron energy spectrum and fraction provide a unique tool to constrain interpretation models. During the recent solar minimum activity period from July 2006 to December 2009, approximately 24,500 positrons were observed. The results cannot be easily reconciled with purely secondary production, and additional sources of either astrophysical or exotic origin may be required.

Cloning of Dirac fermions in graphene superlattices.

Superlattices have attracted great interest because their use may make it possible to modify the spectra of two-dimensional electron systems and, ultimately, create materials with tailored electronic properties. In previous studies (see, for example, refs 1-8), it proved difficult to realize superlattices with short periodicities and weak disorder, and most of their observed features could be explained in terms of cyclotron orbits commensurate with the superlattice. Evidence for the formation of superlattice minibands (forming a fractal spectrum known as Hofstadter's butterfly) has been limited to the observation of new low-field oscillations and an internal structure within Landau levels. Here we report transport properties of graphene placed on a boron nitride substrate and accurately aligned along its crystallographic directions. The substrate's moiré potential acts as a superlattice and leads to profound changes in the graphene's electronic spectrum. Second-generation Dirac points appear as pronounced peaks in resistivity, accompanied by reversal of the Hall effect. The latter indicates that the effective sign of the charge carriers changes within graphene's conduction and valence bands. Strong magnetic fields lead to Zak-type cloning of the third generation of Dirac points, which are observed as numerous neutrality points in fields where a unit fraction of the flux quantum pierces the superlattice unit cell. Graphene superlattices such as this one provide a way of studying the rich physics expected in incommensurable quantum systems and illustrate the possibility of controllably modifying the electronic spectra of two-dimensional atomic crystals by varying their crystallographic alignment within van der Waals heterostuctures.

Diabetes Attitudes, Wishes and Needs second study (DAWN2™): cross-national comparisons on barriers and resources for optimal care--healthcare professional perspective.

AIMS: The second Diabetes Attitudes, Wishes and Needs (DAWN2) study sought cross-national comparisons of perceptions on healthcare provision for benchmarking and sharing of clinical practices to improve diabetes care. METHODS: In total, 4785 healthcare professionals caring for people with diabetes across 17 countries participated in an online survey designed to assess diabetes healthcare provision, self-management and training. RESULTS: Between 61.4 and 92.9% of healthcare professionals felt that people with diabetes needed to improve various self-management activities; glucose monitoring (range, 29.3-92.1%) had the biggest country difference, with a between-country variance of 20%. The need for a major improvement in diabetes self-management education was reported by 60% (26.4-81.4%) of healthcare professionals, with a 12% between-country variance. Provision of diabetes services differed among countries, with many healthcare professionals indicating that major improvements were needed across a range of areas, including healthcare organization [30.6% (7.4-67.1%)], resources for diabetes prevention [78.8% (60.4-90.5%)], earlier diagnosis and treatment [67.9% (45.0-85.5%)], communication between team members and people with diabetes [56.1% (22.3-85.4%)], specialist nurse availability [63.8% (27.9-90.7%)] and psychological support [62.7% (40.6-79.6%)]. In some countries, up to one third of healthcare professionals reported not having received any formal diabetes training. Societal discrimination against people with diabetes was reported by 32.8% (11.4-79.6%) of participants. CONCLUSIONS: This survey has highlighted concerns of healthcare professionals relating to diabetes healthcare provision, self-management and training. Identifying between-country differences in several areas will allow benchmarking and sharing of clinical practices.

Interaction-driven spectrum reconstruction in bilayer graphene.

The nematic phase transition in electronic liquids, driven by Coulomb interactions, represents a new class of strongly correlated electronic ground states. We studied suspended samples of bilayer graphene, annealed so that it achieves very high quasiparticle mobilities (greater than 10(6) square centimers per volt-second). Bilayer graphene is a truly two-dimensional material with complex chiral electronic spectra, and the high quality of our samples allowed us to observe strong spectrum reconstructions and electron topological transitions that can be attributed to a nematic phase transition and a decrease in rotational symmetry. These results are especially surprising because no interaction effects have been observed so far in bilayer graphene in the absence of an applied magnetic field.

Cosmic-ray electron flux measured by the PAMELA experiment between 1 and 625 GeV.

Precision measurements of the electron component in the cosmic radiation provide important information about the origin and propagation of cosmic rays in the Galaxy. Here we present new results regarding negatively charged electrons between 1 and 625 GeV performed by the satellite-borne experiment PAMELA. This is the first time that cosmic-ray e⁻ have been identified above 50 GeV. The electron spectrum can be described with a single power-law energy dependence with spectral index -3.18 ± 0.05 above the energy region influenced by the solar wind (> 30 GeV). No significant spectral features are observed and the data can be interpreted in terms of conventional diffusive propagation models. However, the data are also consistent with models including new cosmic-ray sources that could explain the rise in the positron fraction.

Giant nonlocality near the Dirac point in graphene.

Transport measurements have been a powerful tool for discovering electronic phenomena in graphene. We report nonlocal measurements performed in the Hall bar geometry with voltage probes far away from the classical path of charge flow. We observed a large nonlocal response near the Dirac point in fields as low as 0.1 tesla, which persisted up to room temperature. The nonlocality is consistent with the long-range flavor currents induced by the lifting of spin/valley degeneracy. The effect is expected to contribute strongly to all magnetotransport phenomena near the neutrality point.

PAMELA measurements of cosmic-ray proton and helium spectra.

Protons and helium nuclei are the most abundant components of the cosmic radiation. Precise measurements of their fluxes are needed to understand the acceleration and subsequent propagation of cosmic rays in our Galaxy. We report precision measurements of the proton and helium spectra in the rigidity range 1 gigavolt to 1.2 teravolts performed by the satellite-borne experiment PAMELA (payload for antimatter matter exploration and light-nuclei astrophysics). We find that the spectral shapes of these two species are different and cannot be described well by a single power law. These data challenge the current paradigm of cosmic-ray acceleration in supernova remnants followed by diffusive propagation in the Galaxy. More complex processes of acceleration and propagation of cosmic rays are required to explain the spectral structures observed in our data.

PAMELA results on the cosmic-ray antiproton flux from 60 MeV to 180 GeV in kinetic energy.

The satellite-borne experiment PAMELA has been used to make a new measurement of the cosmic-ray antiproton flux and the antiproton-to-proton flux ratio which extends previously published measurements down to 60 MeV and up to 180 GeV in kinetic energy. During 850 days of data acquisition approximately 1500 antiprotons were observed. The measurements are consistent with purely secondary production of antiprotons in the Galaxy. More precise secondary production models are required for a complete interpretation of the results.

Density of states and zero Landau Level probed through capacitance of graphene.

We report capacitors in which a finite electronic compressibility of graphene dominates the electrostatics, resulting in pronounced changes in capacitance as a function of magnetic field and carrier concentration. The capacitance measurements have allowed us to accurately map the density of states D, and compare it against theoretical predictions. Landau oscillations in D are robust and zero Landau level (LL) can easily be seen at room temperature in moderate fields. The broadening of LLs is strongly affected by charge inhomogeneity that leads to zero LL being broader than other levels.