BMI1 regulates PRC1 architecture and activity through homo- and hetero-oligomerization.

BMI1 is a core component of the polycomb repressive complex 1 (PRC1) and emerging data support a role of BMI1 in cancer. The central domain of BMI1 is involved in protein-protein interactions and is essential for its oncogenic activity. Here, we present the structure of BMI1 bound to the polyhomeotic protein PHC2 illustrating that the central domain of BMI1 adopts an ubiquitin-like (UBL) fold and binds PHC2 in a beta-hairpin conformation. Unexpectedly, we find that the UBL domain is involved in homo-oligomerization of BMI1. We demonstrate that both the interaction of BMI1 with polyhomeotic proteins and homo-oligomerization via UBL domain are necessary for H2A ubiquitination activity of PRC1 and for clonogenic potential of U2OS cells. Here, we also emphasize need for joint application of NMR spectroscopy and X-ray crystallography to determine the overall structure of the BMI1-PHC2 complex

Impact of the COVID-19 Pandemic on Myocardial Revascularization in Patients with Acute Coronary Syndrome in the Russian Federation

Aim. To compare and analyze the results of myocardial revascularization in the Russian Federation (RF) with acute coronary syndrome (ACS) before the onset (2018-2019) and during the novel coronavirus infection (COVID-19) pandemic (2020-2021).Material and methods. The analysis included the number of cases of ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation acute coronary syndrome (NSTE-ACS), the number of cases of myocardial revascularization in the above forms of ACS, the number of deaths depending on the form of ACS and the method performed revascularization. The period of time before the start of the coronavirus pandemic corresponded to the annual data received in the Russian Federation for 2018-2019. The period of the coronavirus disease pandemic corresponded to the annual data received in the country for 2020-2021. Absolute, relative, estimated values of patient hospitalization, myocardial revascularization procedures, and mortality in ACS were compared between time periods before and during the COVID-19 pandemic. The data for analysis were obtained from the monitoring of the Ministry of Health of Russia.Results. In 2018 and 2019 in the RF, 531,019 and 501,238 patients were hospitalized with a diagnosis of ACS, and during the pandemic (2020-2021) - 403,931 and 397,930 patients, respectively. Reduction in the number of patients diagnosed with ACS admitted to hospitals in Russia by 22.32% in 2020-2021 years was mainly due to a significant decrease in hospitalizations of patients with a diagnosis of NSTE-ACS (by 29.03%). At the same time, admission to clinics of patients with STEMI decreased only by 6.02%. During the COVID-19 pandemic, mortality increased significantly in PPCI (by 9.6%) and in the general STEMI group (by 12.3%); significantly increased mortality both in the general group (by 48%) and during PCI in patients with NSTE-ACS (by 28.6%); there was an increase in the average annual number of PPCI (by 12.6%), which was accompanied by an increased average annual number of PPCI per 1 million of population (up to 451 per 1 million of population); a slight increase in the average time "symptom-balloon" (by 2 minutes) was recorded; there was an absolute slight decrease and a relative increase in the number of PCIs in NSTE-ACS (by 2.7% and 37.1%, respectively). In 2021, in the Russian Federation, primary PCI was performed in 50.2%, thrombolytic therapy - in 23.1%, and 26.7% of patients remained without reperfusion. Pharmacoinphasive strategy was applied in 60%, and isolated thrombolysis - in 40% of patients.Conclusion. During the COVID-19 pandemic, revascularization in patients with ACS in Russia corresponded to the following trends recorded in the literature: increased hospital mortality in PPCI and in the general STEMI group; hospital mortality both in the general group and during PCI in patients with NSTE-ACS. The indicators of myocardial revascularization in ACS in the RF during the pandemic were fundamentally different from the data of Western countries: there was an increase in the average annual number of PPCI and the average annual number of PPCI per 1 million population; a slight increase in the average symptom-balloon time was recorded; revealed an absolute slight decrease and a relative increase in the number of PCIs in NSTE-ACS

What is changing in the treatment of acute coronary syndrome in the Russian Federation?

The work of the national network of vascular centers of the Russian Federation (RF), based on the Clinical recommendations of the Russian Society of Cardiology and the procedure for providing medical care to patients with cardiovascular diseases, has led to significant positive results in the treatment of patients with acute coronary syndrome (ACS) in the country, although a number of targets have not yet been reached. The purpose of the publication is to demonstrate the trend in therapeutic approaches to the management of patients with ACS in 2020-2022. in Russia and analysis of their effectiveness. Quantitative and qualitative indicators of the treatment of patients with ACS for the presented analysis were obtained on the basis of monitoring data from the Russian Ministry of Health for 2018-2021. presented: Monitoring of measures to reduce mortality from coronary heart disease, letters of the Ministry of Health of Russia dated March 13, 2015 No. 17-6 / 10 / 1-177 and dated July 24, 2015 No. 17-9 / 10 / 2-4128, within which data collection carried out monthly, on the portal of the Federal State Budgetary Institution "TsNIIOIZ" of the Ministry of Health of Russia - Automated system for monitoring medical statistics and the register REGION-IM (Russian Register of Acute Myocardial Infarction) - a multicenter prospective observational cohort study for 2020-2022, organized by the Federal State Budgetary Institution "National Medical Research Center of Cardiology named after Academician E.I. Chazov" of the Ministry of Health of Russia. In Russia with a diagnosis of ACS in 2020 and 2021 403,931 and 397,930 patients were hospitalized, respectively. The decrease in the number of patients diagnosed with ACS admitted to Russian hospitals by 22.32% was mainly due to a significant decrease in hospital admissions of patients diagnosed with non-ST elevation ACS (non-STE-ACS) (by 29.03%). At the same time, the admission of patients with ST elevation myocardial infarction (STEMI) decreased only by 6.02%. Compared to 2018-2019, in 2020-2022. increased mortality in primary percutaneous coronary intervention (PCI) (by 9.6%) and in the general STEMI group (by 12.3%); significantly increased mortality both in the general group of NSTE-ACS (by 48%) and during PCI for patients with non-STE-ACS (by 28.6%); there was an increase in the average annual number of primary PCI (by 12.6%); an absolute and relative increase in the number of PCI in non-STE-ACS was revealed (by 2.7 and 37.1%, respectively). In the country's hospitals, by the time of discharge, 95% of patients receive statins, beta-blockers – 87%, ACE inhibitors – 80%, acetylsalicylic acid – 82%, P2Y12 inhibitors – 98% of patients, regardless of the type of ACS. In Russia in 2020-2022 unfavorable tendencies in the provision of care to patients with ACS include: increased mortality in primary PCI and in the general STEMI group; increased mortality both in the general group of non-STE-ACS and during PCI for patients with non-STE-ACS. The positive results of the work of the national network of vascular centers include: absolute, relative and estimated increase in the number of primary PCI; absolute and relative increase in the number of PCI in non-STE-ACS; a high level of prescribing drugs with a proven positive effect on the prognosis

Russian guidelines for sudden cardiac death risk assessment and prevention (second edition) – 2018. Pocket version

cardiovascular diseases, sudden cardiac death, risk, treatment, preventionCardiovascular mortality in Russia is one of the highest in the world reaching 614 deaths per 100,000 annually. The main causes of death from cardiovascular diseases are the progression of congestive heart failure (about half of all cases) and sudden cardiac death (the other half). Thus, we can assume that the incidence of sudden cardiac death in 2016 was no less than 300,000. In the abbreviated version of the National Recommendations in English, the principles of decision-making algorithms in various clinical situations are used

Improvement of cardiovascular risk assessment using machine learning methods

The increase in the prevalence of cardiovascular diseases (CVDs) specifies the importance of their prediction, the need for accurate risk stratification, preventive and treatment interventions. Large medical databases and technologies for their processing in the form of machine learning algorithms that have appeared in recent years have the potential to improve predictive accuracy and personalize treatment approaches to CVDs. The review examines the application of machine learning in predicting and identifying cardiovascular events. The role of this technology both in the calculation of total cardiovascular risk and in the prediction of individual diseases and events is discussed. We compared the predictive accuracy of current risk scores and various machine learning algorithms. The conditions for using machine learning and developing personalized tactics for managing patients with CVDs are analyzed

Perspectives on the Use of Transthoracic Echocardiography Results for the Prediction of Ventricular Tachyarrhythmias in Patients with Non-ischemic Cardiomyopathy

Aim. To perform a comparative analysis of indicators of transthoracic echocardiography (TE), to establish echocardiographic predictors and their predictive role in the occurrence of stable ventricular tachyarrhythmia (VT) paroxysms in patients with nonischemic chronic heart failure (HF) and cardioverter-defibrillator (ICD) implanted for primary prevention of sudden cardiac death.Material and Methods. A prospective study was carried out, which included 166 patients with nonischemic HF at the age of 54 (49; 59) years with the left ventricle ejection fraction (LV EF) ≤35% and an ICD implanted. The observation time was 24 months. The primary endpoint was the first-ever stable paroxysm of VT (lasting for ≥30 seconds), detected in the «monitor» zone of VT, or paroxysm of VT, which required ICD therapy.  A total of 34 TE indicators were evaluated. Chi-square, Fischer, Manna-Whitney, single-factor logistic regression (LR), and multi-factor LR were used for data processing and analysis and for predictive modelling. Model accuracy was estimated using 4 metrics: ROC curve area (AUC), sensitivity, specificity and diagnostic efficiency.Results. During the two-year observation, 32 patients (19.3%) had a primary endpoint. The average time of occurrence of a stable VT episode was 21.6±0.6 months (95% confidence interval [CI] 20.5-22.8 months). The value of LV end-systolic dimension was the only parameter independently associated with VT (odds ratio 2.8 per unit increase, 95% CI 1.04-7.5; p=0.042). The complex analysis of echocardiographic indicators made it possible to identify 5 factors with the greatest predictive potential, which are linearly and nonlinearly related to occurrence of VT. These included the LV end-diastolic and end-systolic volumes, LV mass, index of relative LV wall thickness, upper-lower size of the right atrium. The metrics of the best predictive model were: AUC – 0.71 0.069 with 95% CI 0.574-0.843; specificity 50%, sensitivity 90.9%; diagnostic efficiency 57.1%.Conclusion. The study made it possible to evaluate the possibilities of the results of TE in predicting the probability of VT occurrence in patients with nonischemic HF and reduced LV EF. Predictive indicators have been identified that can be used to stratify the arrhythmic risk in the exposed cohort of patients

Accurate and Fast Retrieval for Complex Non-metric Data via Neighborhood Graphs

We demonstrate that a graph-based search algorithm-relying on the construction of an approximate neighborhood graph-can directly work with challenging non-metric and/or non-symmetric distances without resorting to metric-space mapping and/or distance symmetrization, which, in turn, lead to substantial performance degradation. Although the straightforward metrization and symmetrization is usually ineffective, we find that constructing an index using a modified, e.g., symmetrized, distance can improve performance. This observation paves a way to a new line of research of designing index-specific graph-construction distance functions

THE STUDY OF ANAMNESTIC FACTORS AND THEIR ROLE IN ESTIMATION OF SHORT-TERM (IN-HOSPITAL) PROGNOSIS IN PATIENTS UNDERWENT BRAIN STROKE OR TRANSIENT ISCHEMIC ATTACK, BY THE DATA FROM LIS-2 REGISTRY

Aim. To assess the role of anamnestic factors in estimation of the shortest-term (in-hospital) prognosis in patients after stroke. Material and methods. We included all patients during the period 01.01.2009 to 31.12.2011 (n=960), who were diagnosed the stroke ot TIA inMHILyubertsyDistrictHospital№2.Results. Into the registry LIS-2 included 960 patients. During hospitalization 207 patients died, in-hospital mortality was 21,6%. Mortality increased with the age, and the age became an independent death risk factor in hospital (p=0,037). Hemoorhagic stroke increased the risk of death 6,95 times, and consciousness disorders — 2-5 times (depending on the level of disorder), CHF signs— by 3,14 times, and AF— 1,86 times. These values were evaluated as independent anamnestic risk factors of the in-hospital death.Conclusion. The data from LIS-2 registry demonstrates analogy with the data from other stroke registries in RF. In-hospital mortality in LIS-2 was 2-3 times higher comparing to the registries of other countries. Factors influenced in-hospital mortality were age, type of the stroke, level of consciousness at admission, CHF and cardiac rhythm disorders as AF

Possibilities for predicting ventricular tachyarrhythmias in patients with heart failure with reduced ejection fraction based on surface electrocardiography. First results from a single-center prospective study

According to current clinical guidelines, the risk of life-threatening ventricular tachyarrhythmias (VTAs) in patients with heart failure (HF) is determined by left ventricular ejection fraction (LVEF). The available clinical and experimental data indicate the imperfection of this one-factor approach, which specifies the need to search for new predictors of VTAs. In this prospective study, we performed a comparative analysis of surface electrocardiographic parameters in HF patients with LVEF ≤35% without syncope or sustained ventricular arrhythmias in history, who were implanted with cardioverter defibrillator as a primary prevention of sudden cardiac death. During the two-year follow-up, the primary endpoint (new-onset persistent VTA episode, or VTA/ventricular fibrillation that required electrotherapy) was recorded in 42 patients (25,5%). The secondary endpoint (an increase in LVEF by 5% or more of the initial level against the background of cardiac resynchronization therapy) was more often recorded in the group of patients without VTAs (41 (33%) vs 4 (9,5%), p=0,005). The studied cohort of patients was characterized by a left axis deviation (72%), LV hypertrophy signs (84%), impaired intra-atrial (P wave duration of 120 (101-120) ms) and intraventricular conduction (QRS duration of 140 (110-180) ms), ventricular electrical systole prolongation (QTcor — 465 (438-504) ms). Differences between the groups divided depending on reaching the primary endpoint in terms of the Cornell product, Cornell voltage index and ICEB, as well as the detection rate of complete left bundle branch block morphology had levels of significance close to critical (p=0,09; p=0,05; p=0,1; p=0,09, respectively). The multivariate predictive model included following factors: Cornell product, Tp-Te/ QRS, P wave duration (diagnostic efficiency of the model was 60%: sensitivity, 61,1%, specificity, 59,6%; p=0,007)