Application of non-HDL cholesterol for population-based cardiovascular risk stratification: results from the Multinational Cardiovascular Risk Consortium.

BACKGROUND: The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment. METHODS: In this risk-evaluation and risk-modelling study, we used Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America. Individuals without prevalent cardiovascular disease at baseline and with robust available data on cardiovascular disease outcomes were included. The primary composite endpoint of atherosclerotic cardiovascular disease was defined as the occurrence of the coronary heart disease event or ischaemic stroke. Sex-specific multivariable analyses were computed using non-HDL cholesterol categories according to the European guideline thresholds, adjusted for age, sex, cohort, and classical modifiable cardiovascular risk factors. In a derivation and validation design, we created a tool to estimate the probabilities of a cardiovascular disease event by the age of 75 years, dependent on age, sex, and risk factors, and the associated modelled risk reduction, assuming a 50% reduction of non-HDL cholesterol. FINDINGS: Of the 524 444 individuals in the 44 cohorts in the Consortium database, we identified 398 846 individuals belonging to 38 cohorts (184 055 [48·7%] women; median age 51·0 years [IQR 40·7-59·7]). 199 415 individuals were included in the derivation cohort (91 786 [48·4%] women) and 199 431 (92 269 [49·1%] women) in the validation cohort. During a maximum follow-up of 43·6 years (median 13·5 years, IQR 7·0-20·1), 54 542 cardiovascular endpoints occurred. Incidence curve analyses showed progressively higher 30-year cardiovascular disease event-rates for increasing non-HDL cholesterol categories (from 7·7% for non-HDL cholesterol <2·6 mmol/L to 33·7% for ≥5·7 mmol/L in women and from 12·8% to 43·6% in men; p<0·0001). Multivariable adjusted Cox models with non-HDL cholesterol lower than 2·6 mmol/L as reference showed an increase in the association between non-HDL cholesterol concentration and cardiovascular disease for both sexes (from hazard ratio 1·1, 95% CI 1·0-1·3 for non-HDL cholesterol 2·6 to <3·7 mmol/L to 1·9, 1·6-2·2 for ≥5·7 mmol/L in women and from 1·1, 1·0-1·3 to 2·3, 2·0-2·5 in men). The derived tool allowed the estimation of cardiovascular disease event probabilities specific for non-HDL cholesterol with high comparability between the derivation and validation cohorts as reflected by smooth calibration curves analyses and a root mean square error lower than 1% for the estimated probabilities of cardiovascular disease. A 50% reduction of non-HDL cholesterol concentrations was associated with reduced risk of a cardiovascular disease event by the age of 75 years, and this risk reduction was greater the earlier cholesterol concentrations were reduced. INTERPRETATION: Non-HDL cholesterol concentrations in blood are strongly associated with long-term risk of atherosclerotic cardiovascular disease. We provide a simple tool for individual long-term risk assessment and the potential benefit of early lipid-lowering intervention. These data could be useful for physician-patient communication about primary prevention strategies. FUNDING: EU Framework Programme, UK Medical Research Council, and German Centre for Cardiovascular Research

Gendered self-views across 62 countries: a test of competing models

Social role theory posits that binary gender gaps in agency and communion should be larger in less egalitarian countries, reflecting these countries’ more pronounced sex-based power divisions. Conversely, evolutionary and self-construal theorists suggest that gender gaps in agency and communion should be larger in more egalitarian countries, reflecting the greater autonomy support and flexible self-construction processes present in these countries. Using data from 62 countries (N = 28,640), we examine binary gender gaps in agentic and communal self-views as a function of country-level objective gender equality (the Global Gender Gap Index) and subjective distributions of social power (the Power Distance Index). Findings show that in more egalitarian countries, gender gaps in agency are smaller and gender gaps in communality are larger. These patterns are driven primarily by cross-country differences in men’s self-views and by the Power Distance Index (PDI) more robustly than the Global Gender Gap Index (GGGI). We consider possible causes and implications of these findings

Social and philosophic foundations of youth nonconformity in contemporary Russia

The purpose of this article is to consider and analyse various approaches to understand nonconformity in general and in the youth environment in particular in order to synthesize and learn from the data and knowledge obtained, and develop a more general and integrated perspective on its essence, determinacy and manifestation specifics. The results discussed in the paper deal with the social-and-philosophical point of view on the various approaches to understanding nonconformity both in a historical retrospect and in modern science. The study revealed that in recent decades the concept of nonconformity has lost its negative connotation. Different conceptual approaches used in studying the phenomenon indicate its significance in the society and personality development, its innovative potential to create and develop new social values, patterns of behaviour and moral standards in the dynamically changing world. Various forms of nonconformity manifestation specify the particularities of contemporary youth subcultures and their socializing potential. The materials of the paper may be of theoretical and practical value to develop programs and teaching materials on social philosophy, sociology and social psychology, as well as the programs connected with prevention of destructive forms of nonconformity in order to bring the processes of young people‘s social adaptation and socialization into compliance. © 2018, Ecozone, OAIMDD. All rights reserved

Molecular genetic prognostic factors for metastatic regional lymph node involvement in breast cancer patients

Objective. To identify molecular genetic prognostic factors for metastatic regional lymph node involvement in breast cancer (BC) on the basis of the gene-expression profiling analysis of primary tumors. Subjects and methods. The investigation enrolled 200 patients with morphologically verified unicentric invasive BC (T1-4N0-3M0,) who had been treated at the Ulyanovsk Regional Clinical Oncology Dispensary in 2012 to 2015. A tumor tissue molecular genetic study was performed using reverse transcription-polymerase chain reaction (RT-PCR) assay; a diagnostic panel consisted of 28 functional genes. Results. In the metastatic regional lymph node involvement group, the primary breast tumor was characterized by enhanced proliferative activity in terms of the expression of the Ki-67 gene (p = 0.028) and by the higher mRNA levels of the NAT (p = 0.039) and CD68 (p &lt;0.001) genes with a reduction in PTEN expression (p &lt;0.001) and with decreased ESR1 gene expression (p = 0.043). A discriminant analysis showed that the accuracy in predicting the presence or absence of metastatic regional lymph node involvement on the basis of a primary tumor molecular genetic study using a 7-gene expression panel was 91.9 and 78.8%, respectively. Conclusion. The primary breast tumor tissue molecular genetic study involving a set of 7 genes (PTEN, CD68, CCNB1, MGB1, MYC, BCL2, and ESR1) can become an additional diagnostic tool for assessing the presence of metastatic lymph node involvement when planning the volume of axillary lymph node dissection in BC patients. © 2020, Bionika Media Ltd.. All rights reserved

Orthodoxy and modernity their contact facets in russian society

The manifestation of globalization, the crisis of national cultures, the decline of morality, reassessment of moral values, spiritual impoverishment, pop culture invasion throughout the civilized world are the factors that have affected the current socio-cultural situation. In the attempts to cope with the situation and get it under control, Russia has always had high hopes to revive the spiritual culture of nations inhabiting the country and appreciate the contribution they had made to the national culture treasury and Russian civilization. The purpose of the paper is to prove that, despite the crisis in culture and moral decline in the modern Russian society, Orthodox values are one of the important elements of the axiological base in the development of modern Russia. The study carried out made it possible to come to the conclusion that preservation of Orthodox Christianity as a socio-cultural matrix of Russian society depends on the ability of Orthodoxy to respond in a timely manner to the challenges of our time. The authors also emphasize the idea that the Orthodox ethics has not only formed and consolidated, but is still successfully supporting functioning of the distinctive features in the Russian national character which include spirituality as a super-individuality, patriotism as love and devotion to a homeland and one's own people, great power status as a trust in a strong state, the desire for freedom and independence from external circumstances. The study allowed predicting the growth of socio-and-cultural tensions in „religious ― secular‟ direction (including scientific). © 2019, Ecozone, OAIMDD. All rights reserved

CATALYTIC PROPERTIES OF THE EUKARYOTIC EXOSOME

The eukaryotic exosome complex is built around the backbone of a 9‑subunit ring similar to phosporolytic ribonucleases such as RNase PH and polynucleotide phosphorylase (PNPase). Unlike those enzymes, the ring is devoid of any detectable catalytic activities, with the possible exception of the plant version of the complex. Instead, the essential RNA decay capability is supplied by associated hydrolytic ribonucleases belonging to the Dis3 and Rrp6 families. Dis3 proteins are endowed with two different activities: the long known processive 3′‑5′ exonucleolytic one and the recently discovered endonucleolytic one. Rrp6 proteins are distributive exonucleases. This chapter will review the current knowledge about the catalytic properties of theses nucleases and their interplay within the exosome holocomplex

Detection and Attribution of Wildfire Pollution in the Arctic

The Arctic experiences poor air quality due to transport of pollutants from mid-latitudes, with wildfires providing an episodic source of trace gases and particulates. We present a multi-year time series of the total columns of CO, HCN, and C2H6 measured using Fourier transform infrared spectrometers at ten sites affiliated with the Network for Detection of Atmospheric Composition Change (NDACC). Six are high-latitude sites: Eureka, Ny Alesund, Thule, Kiruna, Poker Flat, and St. Petersburg, and four are mid-latitude sites: Zugspitze, Jungfraujoch, Toronto, and Rikubetsu. For each site, the inter-annual trends and seasonal variabilities of the CO total column time series are accounted for, allowing ambient concentrations to be determined. Enhancements above ambient levels are then used to identify possible wildfire pollution events. Since the abundance of each trace gas emitted in a wildfire event is specific to the type of vegetation burned and the burning phase, correlations of CO to the long-lived wildfire tracers HCN and C2H6 allow for further confirmation of the detection of wildfire pollution, while complementary measurements of aerosol optical depth from nearby AERONET sites confirms the presence of wildfire smoke. GEOS-Chem tagged CO simulations with Global Fire Assimilation System (GFAS) biomass burning emissions were used to determine the source attribution of CO concentrations at each site from 2003-2017. The influence of the various wildfire sources is found to differ between sites; however, North American and Eurasian boreal wildfires fires are found to be the greatest contributors to episodic CO enhancements in the summertime at all sites

Detection of wildfire pollution in the Arctic using a network of FTIR spectrometers and GEOS-Chem

Ground-based FTIR instruments provide simultaneous measurements of CO, HCN and C2H6 at high-latitudes. Detection of CO enhancements and strong correlations with HCN and C2H6 are indicative of wildfire pollution events. The GEOS-Chem tagged CO simulation provides attribution of CO sources to FTIR measurements from 2003-2017. At all FTIR sites, wildfire pollution events are detected annually and attributed to Boreal wildfires in North America and Asia