Association of C3435T (rs1045642) polymorphism of the MDR1 gene with the increased risk of colorectal cancer in russian females from Central Russia

The objective of this study was to examine associations of single nucleotide polymorphisms, rs1045642 within the MDR1 gene and rs1799930 within the NAT2 gene, with the risk of colorectal cancer (CRC) in the population of Central Russi

DICER and DROSHA gene expression in peripheral mononuclear blood cells from rheumatoid arthritis patients under methotrexate therapy

The aim of this research was studying the level of DROSHA and DICER genes expression in peripheral mononuclear blood cells (PBMC) in rheumatoid arthritis (RA) patients under methotrexate therapy. Materials and methods. 82 people (from 45 to 70 years) enrolled in this study were divided into 3 groups (the first one - healthy donors (n=33 median age 49.93±1.87); the second group - rheumatoid arthritis patients without any therapy (n=15; median age 57.28±15.18) and the third group (n=34; median age 60.88±9.02) - rheumatoid arthritis patients who treated at least 4 weeks with methotrexate therapy (10-20 mg/week). The DICER and DROSHA genes expression level was determined by real-time PCR. Results. The number of DICER gene transcripts in PBMC in rheumatoid arthritis patients without therapy as in RA patients treated with methotrexate was reduced in comparison with the healthy donors (p0.05 respectively). The level of DROSHA gene expression in PBMC was not significantly different in all groups enrolled in this study (p>0.05). Conclusion. Our findings suggest that that the DICER gene expression level in perifheral mononuclear blood cells decreased with the development of rheumatoid arthritis. Methotrexate doesn’t influence on the mRNA level of this gene

Multi-site genetic analysis of diffusion images and voxelwise heritability analysis : a pilot project of the ENIGMA–DTI working group

The ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium was set up to analyze brain measures and genotypes from multiple sites across the world to improve the power to detect genetic variants that influence the brain. Diffusion tensor imaging (DTI) yields quantitative measures sensitive to brain development and degeneration, and some common genetic variants may be associated with white matter integrity or connectivity. DTI measures, such as the fractional anisotropy (FA) of water diffusion, may be useful for identifying genetic variants that influence brain microstructure. However, genome-wide association studies (GWAS) require large populations to obtain sufficient power to detect and replicate significant effects, motivating a multi-site consortium effort. As part of an ENIGMA–DTI working group, we analyzed high-resolution FA images from multiple imaging sites across North America, Australia, and Europe, to address the challenge of harmonizing imaging data collected at multiple sites. Four hundred images of healthy adults aged 18–85 from four sites were used to create a template and corresponding skeletonized FA image as a common reference space. Using twin and pedigree samples of different ethnicities, we used our common template to evaluate the heritability of tract-derived FA measures. We show that our template is reliable for integrating multiple datasets by combining results through meta-analysis and unifying the data through exploratory mega-analyses. Our results may help prioritize regions of the FA map that are consistently influenced by additive genetic factors for future genetic discovery studies. Protocols and templates are publicly available at (http://enigma.loni.ucla.edu/ongoing/dti-working-group/)

Innovative Technics of Managing Engineers' Global Competencies

Higher education modernization in the CIS countries takes place under the conditions of dynamic changes in economy and society. These changes are determined by the social and economic development of the country and the world globalization processes - cross-border intercultural communication, knowledge transparency, and the establishment of information society. Educational globalization is a continuous process of creating a unified global educational system, in which the distinctions between its member educational systems are being blended

Glycemia control and choice of antihyperglycemic therapy in patients with type 2 diabetes mellitus and COVID-19: a consensus decision of the board of experts of the Russian association of endocrinologists

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

Heritability of fractional anisotropy in human white matter: a comparison of Human Connectome Project and ENIGMA-DTI data

The degree to which genetic factors influence brain connectivity is beginning to be understood. Large-scale efforts are underway to map the profile of genetic effects in various brain regions. The NIH-funded Human Connectome Project (HCP) is providing data valuable for analyzing the degree of genetic influence underlying brain connectivity revealed by state-of-the-art neuroimaging methods. We calculated the heritability of the fractional anisotropy (FA) measure derived from diffusion tensor imaging (DTI) reconstruction in 481 HCP subjects (194/287 M/F) consisting of 57/60 pairs of mono- and dizygotic twins, and 246 siblings. FA measurements were derived using (Enhancing NeuroImaging Genetics through Meta-Analysis) ENIGMA DTI protocols and heritability estimates were calculated using the SOLAR-Eclipse imaging genetic analysis package. We compared heritability estimates derived from HCP data to those publicly available through the ENIGMA-DTI consortium, which were pooled together from five-family based studies across the US, Europe, and Australia. FA measurements from the HCP cohort for eleven major white matter tracts were highly heritable (h2 = 0.53–0.90, p < 10− 5), and were significantly correlated with the joint-analytical estimates from the ENIGMA cohort on the tract and voxel-wise levels. The similarity in regional heritability suggests that the additive genetic contribution to white matter microstructure is consistent across populations and imaging acquisition parameters. It also suggests that the overarching genetic influence provides an opportunity to define a common genetic search space for future gene-discovery studies. Uniquely, the measurements of additive genetic contribution performed in this study can be repeated using online genetic analysis tools provided by the HCP ConnectomeDB web application

Effect of SGLT2 inhibitors on stroke and atrial fibrillation in diabetic kidney disease: Results from the CREDENCE trial and meta-analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-Analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-Analysis. RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: Total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]). CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Диагностическая эффективность перфузионной компьютерной томографии миокарда с чреспищеводной электрокардиостимуляцией у больных с исходным диагнозом «острый коронарный синдром»

Introduction. Computed tomography angiography (CTA) is widely used to detect atherosclerotic changes in coronary arteries (CA). However, the method is limited by the impossibility to perform functional assessment of detected stenoses. Perfusion computed tomography of the myocardium (PCT) can be used for this purpose.Aim of the study. To assess diagnostic accuracy of PCT of the myocardium with transesophageal electrocardiostimulation (TEES) and stress-echocardiography (stress-echoCG) with veloergometry (VEM) in detection of transient ischemia in patients with initial diagnosis of “acute coronary syndrome” (ACS) with borderline stenoses (50–75%) in CA in relation to measurements of fractional flow reserve (FFR).Materials and Methods. The study included 30 patients with the initial diagnosis of ACS with borderline (50–75%) stenoses in CA according to CTA or coronary angiography (CAG). Subsequently, they underwent myocardial PCT with 320-row detector with TEES, as well as stress-echoCG with VEM. Invasive FFR measurement was used as a reference method. FFR value &lt; 0.8 indicated hemodynamic significance of stenosis. Myocardial perfusion was assessed visually. Regional myocardial contractility of the left ventricle was assessed by stress-echoCG.Results. All patients were examined according to the stated protocol. PCT with TEES revealed FFR-significant stenoses with sensitivity, specificity, prognostic value of positive result and prognostic value of negative result 56, 93, 90, 65% respectively, stress-echoCG with VEM 62, 93, 91, 68% respectively.Conclusion. Myocardial PCT with TEES enables to detect perfusion defects associated with transient ischemia, and the diagnostic accuracy of the method in comparison with FFR is comparable with the already well-proven stress-echoCG. The use of PCT with TEES in combination with CTA can be considered as a promising diagnostic tool in patients without known coronary anatomy and with suspected ACS.Введение. Компьютерная томографическая ангиография (КТА) широко используется для выявления атеросклеротических изменений в коронарных артериях (КА). Однако метод ограничен невозможностью проведения функциональной оценки выявленных стенозов. С этой целью может использоваться перфузионная компьютерная томография миокарда (ПКТ).Цель исследования. Оценить диагностическую точность методов ПКТ миокарда с чреспищеводной электрокардиостимуляцией (ЧПЭС) и стресс-эхокардиографии (стресс-ЭхоКГ) с велоэргометрией (ВЭМ) в выявлении преходящей ишемии у больных с исходным диагнозом «острый коронарный синдром» (ОКС) с пограничными стенозами (50–75%) в КА по отношению к измерениям фракционного резерва кровотока (ФРК).Материалы и методы. В исследование были включены 30 больных с исходным диагнозом ОКС с пограничными (50–75%) стенозами в КА по данным КТА или коронарной ангиографии (КАГ). Впоследствии им были выполнены ПКТ миокарда на томографе с 320-рядным детектором с ЧПЭС, а также стресс-ЭхоКГ с ВЭМ. В качестве референтного метода использовалось инвазивное измерение ФРК. Значение показателя ФРК &lt; 0,8 указывало на гемодинамическую значимость стеноза. Перфузия миокарда оценивалась визуально. При проведении стресс-ЭхоКГ оценивалась региональная сократимость миокарда левого желудочка.Результаты. Все больные обследованы согласно заявленному протоколу. ПКТ с ЧПЭС выявила ФРК-значимые стенозы с чувствительностью, специфичностью, прогностической ценностью положительного результата и прогностической ценностью отрицательного результата 56, 93, 90, 65% соответственно, стресс-ЭхоКГ с ВЭМ 62, 93, 91, 68% соответственно.Выводы. ПКТ миокарда с ЧПЭС позволяет выявить дефекты перфузии, ассоциированные с преходящей ишемией, а диагностическая точность метода при сравнении с ФРК сопоставима с уже хорошо зарекомендовавшей себя стресс-ЭхоКГ. Использование ПКТ с ЧПЭС в комбинации с КТА можно рассматривать как перспективный диагностический инструмент у больных без известной коронарной анатомии и с подозрением на ОКС

Multi-site study of additive genetic effects on fractional anisotropy of cerebral white matter:Comparing meta and megaanalytical approaches for data pooling

Combining datasets across independent studies can boost statistical power by increasing the numbers of observations and can achieve more accurate estimates of effect sizes. This is especially important for genetic studies where a large number of observations are required to obtain sufficient power to detect and replicate genetic effects. There is a need to develop and evaluate methods for joint-analytical analyses of rich datasets collected in imaging genetics studies. The ENIGMA-DTI consortium is developing and evaluating approaches for obtaining pooled estimates of heritability through meta-and mega-genetic analytical approaches, to estimate the general additive genetic contributions to the intersubject variance in fractional anisotropy (FA) measured from diffusion tensor imaging (DTI). We used the ENIGMA-DTI data harmonization protocol for uniform processing of DTI data from multiple sites. We evaluated this protocol in five family-based cohorts providing data from a total of 2248 children and adults (ages: 9-85) collected with various imaging protocols. We used the imaging genetics analysis tool, SOLAR-Eclipse, to combine twin and family data from Dutch, Australian and Mexican-American cohorts into one large "mega-family". We showed that heritability estimates may vary from one cohort to another. We used two meta-analytical (the sample-size and standard-error weighted) approaches and a mega-genetic analysis to calculate heritability estimates across-population. We performed leave-one-out analysis of the joint estimates of heritability, removing a different cohort each time to understand the estimate variability. Overall, meta- and mega-genetic analyses of heritability produced robust estimates of heritability