Insulin resistance in obesity: pathogenesis and effects

The prevalence of obesity in the world is described as the global epidepic. Being not only a chronic recurrent disease but also a serious risk factor, obesity leads to the development and aggravation of many non-communicable diseases. Excessive amount and adipose tissue dysfunction in obesity determines the risk of the development of type 2 diabetes, arterial hypertension, atherosclerosis, non-alcoholic fatty liver disease etc. Secondary insulin resistance often underlies the development of the above mentioned conditions. The mechanisms contributing to the development of insulin resistance in case of excessive adipose tissue accumulation are being intensively investigated over the last decades, however many questions yet remain unsolved. In this article we present the key mechanisms underlying insulin resistance in obesity and diagnostic approaches for insulin resistance as well as the current data in this topic. The authors review the close links between insulin resistance and obesity related diseases, namely disorders of carbohydrate metabolism, dyslipidemia, arterial hypertension, coronary artery disease and reproductive disorders

In Vitro and in Silico Liver Models: Current Trends, Challenges and Opportunities

Most common drug development failures originate from either bioavailability problems, or unexpected toxic effects. The culprit is often the liver, which is responsible for biotransformation of a majority of xenobiotics. Liver may be modeled using liver on a chip devices, which may include established cell lines, primary human cells, and stem cell-derived hepatocyte-like cells. The choice of biological material along with its processing and maintenance greatly influence both the device performance and the resultant toxicity predictions. Impediments to the development of liver on a chip technology include the problems with standardization of cells, limitations imposed by culturing and the necessity to develop more complicated fluidic contours. Fortunately, recent breakthroughs in the development of cell-based reporters, including ones with fluorescent label, permits monitoring of the behavior of the cells embed into the liver on a chip devices. Finally, a set of computational approaches has been developed to model both particular toxic response and the homeostasis of human liver as a whole; these approaches pave a way to enhance the in silico stage of assessment for a potential toxicity

Transcriptome of Extracellular Vesicles: State-of-the-Art

Exosomes and microvesicles are two major categories of extracellular vesicles (EVs) released by almost all cell types and are highly abundant in biological fluids. Both the molecular composition of EVs and their release are thought to be strictly regulated by external stimuli. Multiple studies have consistently demonstrated that EVs transfer proteins, lipids and RNA between various cell types, thus mediating intercellular communication, and signaling. Importantly, small non-coding RNAs within EVs are thought to be major contributors to the molecular events occurring in the recipient cell. Furthermore, RNA cargo in exosomes and microvesicles could hold tremendous potential as non-invasive biomarkers for multiple disorders, including pathologies of the immune system. This mini-review is aimed to provide the state-of-the-art in the EVs-associated RNA transcriptome field, as well as the comprehensive analysis of previous studies characterizing RNA content within EVs released by various cells using next-generation sequencing. Finally, we highlight the technical challenges associated with obtaining pure EVs and deep sequencing of the EV-associated RNAs

Adherence to antihypertensive medication in Russia: A scoping review of studies on levels, determinants and intervention strategies published between 2000 and 2017

Source at https://doi.org/10.1186/s13690-019-0366-9.Background - Arterial hypertension (HT) is common in the Russian adult population, with half of affected individuals inadequately controlled. Low adherence to medication seems likely to be a factor. We report a scoping review of studies on adherence to antihypertensive therapy (AHT) in Russia to determine the extent of research undertaken, the frequency of adherence among adults diagnosed with HT, methodologies used in the studies, and their ability to describe determinants of adherence. Methods - A scoping review of published studies that have assessed adherence to AHT in Russian HT patients searched the main Russian and international electronic databases eLIBRARY.ru, Russian Medicine, Embase, MEDLINE for full-text reports published in the Russian language between 2000 and 2017. The last search was on November 28, 2017. Among 520 reports identified, 31 were included in the review. Results - Eighteen studies assessed adherence using the 4-item Morisky Medication Adherence Scale (MMAS-4); others used bespoke questionnaires or pill counts. 25 studies assessed levels of adherence, 11 examined its determinants, and 18 examined intervention strategies. The proportion of “adherent” patients varied from 11 to 44% using the MMAS-4, from 23 to 74% when using bespoke questionnaires, and from 5 to 43% when using pill counts. Adherence was associated with sociodemographic factors, access to free drugs provided through the Medicine Assistance Scheme (MAS), use of home blood pressure (BP) monitoring, anxiety, and comorbidity. There was no evidence that adherence was associated with income or physical activity. Evidence of an association between MAS, grade of HT, or experience of hypertensive crisis was inconclusive. Various methods to improve adherence were studied including patient education (improved from 1.8 to 3.9 points, p = 0.0002 or 2.80 to 3.79 points, p < 0.0001 measured by the MMAS-4), telephone reminders (p < 0.0001), training in home BP monitoring (p < 0.05), and use of fixed-dose combinations (p < 0.05). Conclusions - The main determinants of adherence to AHT are sociodemographic characteristics, the severity of HT, and presence of comorbidity. Patient education and use of fixed-dose combinations of drugs were identified as most important for improving adherence. Most studies assessing adherence use self-reported methods so there is a need for greater use of objective methods

Study design

info:eu-repo/semantics/publishedVersio

Seroprevalence of SARS-Cov-2 Antibodies in Adults, Arkhangelsk, Russia.

Population-based data on coronavirus disease in Russia and on the immunogenicity of the Sputnik V vaccine are sparse. In a survey of 1,080 residents of Arkhangelsk 40-75 years of age, 65% were seropositive for IgG. Fifteen percent of participants had been vaccinated; of those, 97% were seropositive

Identification of Novel Candidate Markers of Type 2 Diabetes and Obesity in Russia by Exome Sequencing with a Limited Sample Size

Type 2 diabetes (T2D) and obesity are common chronic disorders with multifactorial etiology. In our study, we performed an exome sequencing analysis of 110 patients of Russian ethnicity together with a multi-perspective approach based on biologically meaningful filtering criteria to detect novel candidate variants and loci for T2D and obesity. We have identified several known single nucleotide polymorphisms (SNPs) as markers for obesity (rs11960429), T2D (rs9379084, rs1126930), and body mass index (BMI) (rs11553746, rs1956549 and rs7195386) (p &lt; 0.05). We show that a method based on scoring of case-specific variants together with selection of protein-altering variants can allow for the interrogation of novel and known candidate markers of T2D and obesity in small samples. Using this method, we identified rs328 in LPL (p = 0.023), rs11863726 in HBQ1 (p = 8 &times; 10&minus;5), rs112984085 in VAV3 (p = 4.8 &times; 10&minus;4) for T2D and obesity, rs6271 in DBH (p = 0.043), rs62618693 in QSER1 (p = 0.021), rs61758785 in RAD51B (p = 1.7 &times; 10&minus;4), rs34042554 in PCDHA1 (p = 1 &times; 10&minus;4), and rs144183813 in PLEKHA5 (p = 1.7 &times; 10&minus;4) for obesity; and rs9379084 in RREB1 (p = 0.042), rs2233984 in C6orf15 (p = 0.030), rs61737764 in ITGB6 (p = 0.035), rs17801742 in COL2A1 (p = 8.5 &times; 10&minus;5), and rs685523 in ADAMTS13 (p = 1 &times; 10&minus;6) for T2D as important susceptibility loci in Russian population. Our results demonstrate the effectiveness of whole exome sequencing (WES) technologies for searching for novel markers of multifactorial diseases in cohorts of limited size in poorly studied populations

Genetic landscape in Russian patients with familial left ventricular noncompaction

BackgroundLeft ventricular noncompaction (LVNC) cardiomyopathy is a disorder that can be complicated by heart failure, arrhythmias, thromboembolism, and sudden cardiac death. The aim of this study is to clarify the genetic landscape of LVNC in a large cohort of well-phenotyped Russian patients with LVNC, including 48 families (n=214).MethodsAll index patients underwent clinical examination and genetic analysis, as well as family members who agreed to participate in the clinical study and/or in the genetic testing. The genetic testing included next generation sequencing and genetic classification according to ACMG guidelines.ResultsA total of 55 alleles of 54 pathogenic and likely pathogenic variants in 24 genes were identified, with the largest number in the MYH7 and TTN genes. A significant proportion of variants −8 of 54 (14.8%) −have not been described earlier in other populations and may be specific to LVNC patients in Russia. In LVNC patients, the presence of each subsequent variant is associated with increased odds of having more severe LVNC subtypes than isolated LVNC with preserved ejection fraction. The corresponding odds ratio is 2.77 (1.37 −7.37; p &lt;0.001) per variant after adjustment for sex, age, and family.ConclusionOverall, the genetic analysis of LVNC patients, accompanied by cardiomyopathy-related family history analysis, resulted in a high diagnostic yield of 89.6%. These results suggest that genetic screening should be applied to the diagnosis and prognosis of LVNC patients

The thickness of the epicardial fat is the "visit card" of metabolic syndrome

Aims. On the basis of echocardiography to evaluate the thickness of epicardial fat (TEF) in patients with metabolic syndrome (MS) and to establish a connection with the main indicators of laboratory and instrumental methods of research. Materials and methods. The study included 76 patients, 43 patients with MS and 33 without MS. The average age of patients in the MS group at the time of inclusion in the study was 62.7&plusmn;10.3 years in the control group (without MS) &ndash; 60&plusmn;14.7 years. All patients underwent a comprehensive examination that included the collection of complaints, study of history, physical examination, anthropometric measurements, laboratory (including the study of the levels of caspase &ndash; 8, leptin in blood plasma enzyme-linked immunosorbent assay using kits &laquo;Platinum ELISA&raquo;) and instrumental examination (echocardiography, ultrasound examination of organs of small pelvis). TEF was determined using transthoracic echocardiography on the machine Acuson Sequoia 512. Results. According transthoracic echocardiography was significantly higher in the group of patients with MS and was 4.67&plusmn;1.7 mm, as compared to 2.66&plusmn;1.15 mm in the control group (p&lt;0.001). Identified moderate and strong correlation between TEF and weight of the patients, waist circumference, ratio of waist circumference to hip circumference, body mass index, glucose levels in the blood plasma, the presence of diabetes mellitus type 2, ultrasonic signs of steatosis of the liver and pancreas, increased aminotransferases, the level of caspase-8 concentration in plasma leptin. Patients the MS group with increased TEF increases the risk of developing hypertension, ischemic heart disease, left ventricular hypertrophy, diastolic dysfunction of the left ventricle type 2, level of caspase-8 and concentration in plasma leptin. Conclusion. Based on the obtained data, the measurement of TEF is justified in patients with MS in everyday clinical practice. The correlations between the TEF and the clinical and metabolic parameters of the CVD and MS make it possible to consider the TEF as a new marker of the risk of developing MS and cardiovascular diseases

What can motivate smokers to quit? Results from Russian Tobacco Control Policy Evaluation Survey

Introduction The Russian State Tobacco Control policy aims at decreasing the prevalence of smokers by means of preventing taking up smoking and motivating smokers to quit. The aim of this study is to analyse the quitting intentions of smokers under the Russian tobacco control law and factors that could motivate them to quit. Methods Cross-sectional data from Russian Tobacco Control Law Evaluation Survey (2017-2018) are analysed, based on multistage random national representative sample of 11625 adult respondents, stratified by smoking status: 6569 smokers, 2377 former smokers, 2679 never smokers, in 10 Russian Federal subjects, interviewed with questionnaire comparable with the one of ITC Project. Data are compared with the results of ‘EURESTPLUS ITC Europe Surveys’. Results Significant majority of smokers (56.6%) had signs of high tobacco dependence and 81.4% of smokers considered themselves dependent on tobacco. 50,9% of the smokers were convinced that quitting smoking is difficult or very difficult, only 14.0% had clear intentions to quit, 51.9% - were somewhat willing and 34.1% - had no willingness to quit. Accordingly, only 7.3% were planning to quit within one month, and 13.9% - within 6 months, which was lower than in England and the same/lower than in the Netherlands, but higher than in other 6 countries. 32.4% of smokers had planned to quit sometime beyond six months, and 46.4% - had no quitting plans at all. Similarly, this was higher than in England and the Netherlands, the same as in Romania, and lower than in the rest of the countries. The most powerful potential stimuli for quitting smoking were the concern for personal health (for 52.4% somewhat and 36.3% very much important) and being told of having a smoking related illness: (39.6% and 42.2% respectively). Those were followed by reasons for family values, like the influence of family and friends (49% and 25.2%), setting an example for children (45.2% and 28.4%), planning or expecting a child (33.5% and 36.3%) and concerns about the health of the others (51.6% and 17.4%). From the legislative measures most of all could motivate smokers to quit prices of cigarettes (41.5% somewhat and 22.4% very much). Doctor’s advice to quit could motivate about 52% of the smokers, possible availability of medication as well as restrictions at work and societal disapproval – about 48% of smokers. The least number smokers would be impressed by availability of quitlines and warning labels on cigarette packages (32.1% and 35.9% respectively). Conclusions General intention to quit among smokers in Russia is still low, and for the majority of smokers having smoking related diseases is the most powerful motivational factor to quit. Data should be used to better shape Russian Tobacco control policy interventions