Non-alcoholic fatty liver disease and type 2 diabetes mellitus: the problem of conjunction and phasing

The widespread prevalence of non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM), as well as their combination, determines the need for a targeted analysis of this pathology in order to optimize approaches to the diagnosis and treatment of patients with NAFLD and T2DM. As components of the metabolic syndrome, these two diseases have largely similar mechanisms of development and progression, simultaneously increasing the risk of adverse outcomes in comorbid patients. Despite the common pathophysiological mechanisms, the question of the development of NAFLD and T2DM remains significant.Upon conducting literature analysis, two main theories have been identified: alimentary and metabolic. According to the alimentary theory, the primary link in the pathogenesis is obesity and the associated excessive accumulation of free fatty acids and triglycerides in the liver, which subsequently leads to insulin resistance and the development of T2DM. In contrast, the metabolic theory considers diabetes-related insulin resistance as the first hit, which, regardless of obesity, creates preconditions for liver damage. In addition, the review focuses on the consideration of the new concept of Metabolic associated fatty liver disease (MAFLD) as a hepatic manifestation of the metabolic syndrome and considers the clinical phenotypes identified within this pathology. In conclusion, pathogenically based treatment goals in patients with NAFLD and T2DM are overcoming insulin resistance, correcting atherogenic dyslipidemia, and restoring the structures and functions of liver cells

Prediabetes. A new paradigm for early prevention of cardiovascular disease

This literature review focuses on the association of prediabetes with cardiovascular disease (CVD). Recently, much attention has been paid to the study of prediabetes due to its extremely high prevalence and strong association with a high risk of developing serious complications that worsen the quality of kife of patients. Prediabetes is not only a metabolic condition with a high risk of developing type 2 diabetes mellitus (T2DM), but also CVD and death from all causes. This association is true for both patients who do not yet have CVD and those with a history of CVD. Also during the COVID-19 pandemic, attention is drawn to the fact that people with prediabetes have a higher risk of a severe course of infection, complications and a worse prognosis of the disease. This is associated with hyperglycemia, the  presence of  chronic systemic inflammation of  a  low degree of  activity, impaired immune response mechanisms and a procoagulant state in patients with prediabetes, although these disorders are less developed than in patients with T2DM. Therefore, early screening of early disorders of normal metabolism. Since active early intervention at the stage of prediabetes helps to prevent the development of type 2 diabetes and CVD

Abnormal gut microbiota and impaired incretin effect as a cause of type 2 diabetes mellitus

It has now been established that the intestinal microbiota (CM) is one of the 11 links in the pathogenesis of type 2 diabetes mellitus (DM2). Th e fact is that when the composition of BM is disrupted and the concentration of its active metabolites changes, the processes of synthesis and secretion of incretin hormones are disrupted, the homeostasis of carbohydrates and fats in the body is disrupted, the processes of central regulation of appetite change, chronic infl ammation and insulin resistance of peripheral tissues develop. Th is review discusses possible ways of impairing the synthesis of incretin hormones and the incretin eff ect in patients with T2DM through the prism of BM and its active metabolites, and discusses possible ways of correcting the altered composition of BM with incretin drugs.A systematic literature search was carried out using the Scopus, PubMed, Web of Science databases

Clinical characteristics of patients with COVID-19 depending on the treatment received and the presence of type 2 diabetes mellitus

BACKGROUND. Type 2 diabetes mellitus (T2DM) is an independent risk factor for adverse clinical outcomes in patients with Covid-19. There is currently insufficient data evaluating the efficacy and safety of drugs for the treatment of COVID-19, especially in patients with T2DM.AIM. The aim of study was to identify an associative relationship between the drugs used and the clinical outcomes of patients with Covid-19 and T2DM.MATERIALS AND METHODS. A retrospective analysis of the clinical outcomes of 1753 patients with COVID-19 who were hospitalized to the redesignated departments of multidisciplinary city clinical hospital in the period from 23.03.2020 to 01.06.2020.RESULTS. The total number of patients is 1,753, of which 311 (17.7%) are patients with DM2. 92.6% of patients received treatment for COVID-19. At the same time, 91.4% of patients received antibiotics (a/b), 61.5% — bronchodilators, 56.6% — injectable anticoagulants (a/c), 45.2% — hydroxychloroquine, 6.3% — antiviral drugs, 5.4% — oral a/c, 4.6% — glucocorticosteroids (GCS), 1.9% — Tocilizumab.Decrease of risk of death among patients with COVID-19 was as the therapy of a/b (OR 0.07, 95% CI 0.05–0.11, p<0.05), bronchodilators (OR 0.12, 95% CI 0.08–0.18, p<0.05) and injection a/c (OR 0.47, 95% CI 0.34–0.67, p<0.05). At the same time, among patients with DM2, compared with patients without DM2, there was a more pronounced reduction in the risk of death during injectable a/c therapy: among patients with DM2, the risk of death decreased by 2.6 times (OR 0.39, 95% CI 0.21–0.73, p<0.05), among patients without DM2 — by 2.1 times (OR 0.47, 95% CI 0.31–0.71, p<0.05). Antiviral drugs was associated with an increased chance of death among patients without DM2 (OR 2.64, 95% CI 1.44–4.86, p<0.05) and among patients with DM2 (OR 4.98, 95% CI 2.11–11.75, p<0.05).CONCLUSION. A significant decrease of the risk of death among patients with COVID-19 was as the therapy of a/b, bronchodilators, and injectable a/c. An increase of the risk of death was observed during therapy with antiviral drugs

On the Complexity of Query Result Diversification

Query result diversification is a bi-criteria optimization problem for ranking query results. Given a database D, a query Q and a positive integer k, it is to find a set of k tuples from Q(D) such that the tuples are as relevant as possible to the query, and at the same time, as diverse as possible to each other. Subsets of Q(D) are ranked by an objective function defined in terms of relevance and diversity. Query result diversification has found a variety of applications in databases, information retrieval and operations research. This paper studies the complexity of result diversification for relational queries. We identify three problems in connection with query result diversification, to determine whether there exists a set of k tuples that is ranked above a bound with respect to relevance and diversity, to assess the rank of a given k-element set, and to count how many k-element sets are ranked above a given bound. We study these problems for a variety of query languages and for three objective functions. We establish the upper and lower bounds of these problems, all matching, for both combined complexity and data complexity. We also investigate several special settings of these problems, identifying tractable cases. 1

Possibilities of application a fixed combination of alogliptin and pioglitazone for type 2 diabetes mellitus treatment

Hyperglycemia in T2DM is based on three main mechanisms: insulin resistance, progressive β-cell dysfunction, and excess glucose production by the liver.The onset of T2DM is usually preceded by a long period of insulin resistance. Prescribing sugar drugs that affect different links of pathogenesis, reducing a steady decrease in glycemia. To date, in clinical practice, various combinations of hypoglycemic drugs are used, the choice of which is determined by the characteristics of the course of diabetes in the patient, the presence of concomitant diseases and complications of diabetes, as well as the dominant clinical problem. This resolution provides an expert council opinion on the feasibility of using a combination of alogliptin and pioglitazone in patients with type 2 diabetes

Evaluation of the impact of unhealthy nutrition on the intestinal microbiota, mitochondrial function and the formation of multiple organ metabolic syndrome, ways of correction

BACKGROUND: The problem of metabolic syndrome is considered a demographic catastrophe. According to WHO experts,«by 2025, the prevalence of metabolic syndrome (MS) in the world will amount to more than 300 million people, and in the next 25 years it is expected to increase by 50%.» The pathophysiological mechanisms of MS formation and the role of unhealthy diet on the development of intestinal dysbiosis, mitochondrial insufficiency remain unclear.AIM: To study the effect of unhealthy diet on the state of the intestinal microbiota and the development of metabolicmitochondrial insufficiency in the formation of a multi-organ metabolic syndrome, evaluation of ways of correction.MATERIALS AND METHODS: Clinical picture assessment, anthropometric data (body mass index), laboratory results (glucose, cholesterol and fractions) were carried out in patients with MS, triglycerides, aspartate aminotransferase, alanine aminotransferase, C-reactive protein, lipid peroxidation indicators: malondialdehyde, diene conjugates, schiff bases, hydroperoxides, catalase, superoxide dismutase, succinate dehydrogenase (ASDH), α-glycerophosphate dehydrogenase (α-AGFDH). Hemorheological parameters were evaluated by the apparent viscosity of blood, the yield strength, the aggregation coefficient of erythrocytes and platelets. The microbiota and microbiome of the intestine were evaluated by species, strain composition and the level of metabolites-propionic, butyric, acetic acid, lipopolysaccharides, peptidoglycans. A questionnaire was conducted to study the nature of nutrition.RESULTS: The study included 128 patients with MS and 25 healthy individuals. According to medical outpatient records from anamnesis, questioning of each patient, complaints and clinical picture, 26.2% of patients had type 2 diabetes, 3.74% of men had erectile dysfunction, 7.5% of women had polycystic ovaries, 15.1% had night apnea syndrome, 8.7% hyperuricemic syndrome, 96.5% of patients had metabolic fatty liver steatosis. According to the results of the survey, it was revealed that 99.8% of patients adhered to an unhealthy and unbalanced, high-calorie diet, 46.4% of patients had a low level of physical activity, 48.7% had an average. The revealed disorders of lipid, carbohydrate metabolism, microbiota and intestinal microbiome were associated with increased lipid peroxidation, decreased levels of antioxidant defense enzymes, indicators reflecting mitochondrial function against the background of hemorheological disorders.CONCLUSION: In multi-organ MS, unhealthy diet can be considered as a targeted risk factor triggering pathophysiological mechanisms at the level of the intestinal microbiota, followed by a cascade of metabolic disorders in the form of activation of lipid peroxidation with inhibition of antioxidant defense enzymes, the development of multi-organ mitochondrial insufficiency and the development of latent hemorheological syndrome. The revealed metabolic complex obviously constitutes a multiorgan morphological cluster underlying the development of multi-organ metabolic syndrome. Based on the identified disorders, pathogenetically justified correction of MS should include a balanced diet with mitochondrial protective therapy

The Large Enriched Germanium Experiment for Neutrinoless Double Beta Decay (LEGEND)

The observation of neutrinoless double-beta decay (0${\nu}{\beta}{\beta}$) would show that lepton number is violated, reveal that neutrinos are Majorana particles, and provide information on neutrino mass. A discovery-capable experiment covering the inverted ordering region, with effective Majorana neutrino masses of 15 - 50 meV, will require a tonne-scale experiment with excellent energy resolution and extremely low backgrounds, at the level of $\sim$0.1 count /(FWHM$\cdot$t$\cdot$yr) in the region of the signal. The current generation $^{76}$Ge experiments GERDA and the MAJORANA DEMONSTRATOR utilizing high purity Germanium detectors with an intrinsic energy resolution of 0.12%, have achieved the lowest backgrounds by over an order of magnitude in the 0${\nu}{\beta}{\beta}$ signal region of all 0${\nu}{\beta}{\beta}$ experiments. Building on this success, the LEGEND collaboration has been formed to pursue a tonne-scale $^{76}$Ge experiment. The collaboration aims to develop a phased 0${\nu}{\beta}{\beta}$ experimental program with discovery potential at a half-life approaching or at $10^{28}$ years, using existing resources as appropriate to expedite physics results.Comment: Proceedings of the MEDEX'17 meeting (Prague, May 29 - June 2, 2017

2νββ2\nu\beta\beta decay of 76^{76}Ge into excited states with GERDA Phase I

Two neutrino double beta decay of $^{76}$Ge to excited states of $^{76}$Se has been studied using data from Phase I of the GERDA experiment. An array composed of up to 14 germanium detectors including detectors that have been isotopically enriched in $^{76}$Ge was deployed in liquid argon. The analysis of various possible transitions to excited final states is based on coincidence events between pairs of detectors where a de-excitation $\gamma$ ray is detected in one detector and the two electrons in the other. No signal has been observed and an event counting profile likelihood analysis has been used to determine Frequentist 90\,\% C.L. bounds for three transitions: ${0^+_{\rm g.s.}-2^+_1}$: $T^{2\nu}_{1/2}>$1.6$\cdot10^{23}$ yr, ${0^+_{\rm g.s.}-0^+_1}$: $T^{2\nu}_{1/2}>$3.7$\cdot10^{23}$ yr and ${0^+_{\rm g.s.}-2^+_2}$: $T^{2\nu}_{1/2}>$2.3$\cdot10^{23}$ yr. These bounds are more than two orders of magnitude larger than those reported previously. Bayesian 90\,\% credibility bounds were extracted and used to exclude several models for the ${0^+_{\rm g.s.}-0^+_1}$ transition

Characterization of 30 76^{76}Ge enriched Broad Energy Ge detectors for GERDA Phase II

The GERmanium Detector Array (GERDA) is a low background experiment located at the Laboratori Nazionali del Gran Sasso in Italy, which searches for neutrinoless double beta decay of $^{76}$Ge into $^{76}$Se+2e$^-$. GERDA has been conceived in two phases. Phase II, which started in December 2015, features several novelties including 30 new Ge detectors. These were manufactured according to the Broad Energy Germanium (BEGe) detector design that has a better background discrimination capability and energy resolution compared to formerly widely-used types. Prior to their installation, the new BEGe detectors were mounted in vacuum cryostats and characterized in detail in the HADES underground laboratory in Belgium. This paper describes the properties and the overall performance of these detectors during operation in vacuum. The characterization campaign provided not only direct input for GERDA Phase II data collection and analyses, but also allowed to study detector phenomena, detector correlations as well as to test the strength of pulse shape simulation codes.Comment: 29 pages, 18 figure