Complex estimation of mitochondrial changes of immunocompetent blood cells in pregnant women with urgent and premature birth

Inflammation is among the factors promoting development of premature rupture of the membranes (PPROM). Upon the conditions of physiological immune imbalance in pregnancy, inflammation modifies its course and can even change the immune response. Appropriate indexes may be quantitative and functional. We used a marker of mitochondrial membrane potential (MPM, Ay) as an integral index of the functional state of immunocompetent blood cells (IBC) in 159 women who were examined at 8-14 weeks of gestation; they were observed up to 34-36 weeks. Of these cohort, 121 women were referred to a comparison group. The main group (n = 46) consisted of pregnant women with PPROM at the term of 28-33 weeks. The examination was carried out according to current medical standards, with informed consent, being approved by the Ethics committee at the Khabarovsk branch of Far Eastern Scientific Centre of Physiology and Pathology of Respiration — Research Institute of Maternity and Childhood Protection. Additionally, MPM and lymphocyte populations were determined by flow cytometry. The degree of disturbed energy supply in the IBC was based on the data of simultaneous determination of lymphocyte, granulocyte and monocyte numbers with reduced MPM values (application for invention No. 2020115963), thus revealing 3 degrees of energy deficiency: 1st degree, monovariant IBC composition with reduced MPM; 2nd degree, bivariant composition, 3rd degree, total changes. A relative and absolute decrease in CD3 (72% vs 78% and 1624 vs 1980), CD8 (28% vs 33% and 651 vs 851), an increase in CD19 (14% vs 9% and 304 vs 219) were revealed in pregnant women with PPROM. When assessing MPM values in the IBC populations, a decreased proportion of women without energy deficiency from the 1st to the 2nd trimester (from 41% to 30%), due to the 3rd degree of energy deficiency (from 17% to 26%) was detected. A shift of affected pools at the 2nd degree of energy deficiency in favor of lymphocytic-granulocytic association (from 7% to 25%) from lymphocytic-monocytic compartment (from 73% to 50%) was found. From the 2nd to 3rd trimester, we have detected redistribution of granulocyte pools at the 1st degree (0 to 8%) and from the lymphocytic-granulocytic association (25% and 5%) to monocytic-granulocytic (25% and 40%). In the group with PPROM, there was a decreased proportion of pregnant women without energy deficiency (13% and 27%), as well as with the 1st and 2nd degrees (17% vs 31% and 9% vs 17%), due to the 3rd degree of energy deficiency (61% and 26 %), relative to the comparison group. The IBC pools of in the main group were redistributed at the 1st degree in favor of granulocytes (25% and 8%), at the 2nd, in favor of the lymphocytic-monocytic association (100% and 55%) from the granulocytic-monocytic (0% and 40%). Such imbalance of bioenergetic processes in the IBC can be an important factor of pathologically ongoing inflammation. These changes could be caused by both higher incidence of infections in such patients and by alloimmune interactions between mother and fetus. However, they may also determine the pathological course of inflammation. Preterm birth, which is usually caused by PPROM, is a multifactorial pathological condition. However, independent on specific triggers, the changes in energy supply of IBC, at least, may serve as a significant biomarker of probability for this disorder

Features of mitochondrial membrane potential of immunocompetent blood cells in children with chronic nonspecific lung diseases accompanied by pneumofibrosis

Pneumofibrosis is a pathological outcome of pulmonary tissue inflammation. It can complicate any lung and bronchial disorder. The mitochondrial membrane potential reflects functional state of immunocompetent blood cells that influence progression of a chronic inflammatory process. The aim of this work was to study the features of mitochondrial membrane potential (MMP) of immunocompetent blood cells in children with chronic nonspecific lung diseases (CNPD), accompanied by pneumofibrosis. We have examined 79 children with CNPD manifesting with symptoms of focal pneumofibrosis. The group of patients included children with congenital lung malformations (43%), consequences of bronchopulmonary dysplasia (41%), chronic bronchitis (10%), post-pneumonic pulmonary fibrosis (6%). The average age of children was 6.5±1.2 years, including 43 boys (54%) and 36 girls (46%). The comparison group included 46 children with COPD without signs of pulmonary fibrosis, the control group consisted of 30 apparently healthy children. The contents of cells with reduced MMP among lymphocytes, monocytes, and granulocytes in peripheral blood was determined with JC-1 dye, using the BD FACSCalibur instrument and Cell Quest Pro software (Becton Dickinson, USA). The proportion of lymphocytes with reduced MMP in patients with COPD was similar in the children of the main and comparison group, exceeding the indexes of the control group by 1.7 times (p < 0.001). Decreased MMP of granulocytes in children with pneumofibrosis was detected 1.9 times more often than in children with fibrosis-free CNPD cases (p < 0.05), and 3.4 times more common than in children from the control group (p < 0.001). Monocytes with reduced MMM in children with pulmonary fibrosis were detected 2 times more often than in children with COPD without fibrosis (p < 0.05), and 7.3 times more frequent than in the control group (p < 0.001). The changes were more expressed in children during exacerbation of the disease. The revealed features suggest a decreased level of metabolic activity of blood cells, thus, probably, presenting an immunopathogenetic basis for development of pneumofibrosis

Comparative effectiveness and safety of non-vitamin K antagonists for atrial fibrillation in clinical practice: GLORIA-AF Registry

Background and purpose: Prospectively collected data comparing the safety and effectiveness of individual non-vitamin K antagonists (NOACs) are lacking. Our objective was to directly compare the effectiveness and safety of NOACs in patients with newly diagnosed atrial fibrillation (AF). Methods: In GLORIA-AF, a large, prospective, global registry program, consecutive patients with newly diagnosed AF were followed for 3 years. The comparative analyses for (1) dabigatran vs rivaroxaban or apixaban and (2) rivaroxaban vs apixaban were performed on propensity score (PS)-matched patient sets. Proportional hazards regression was used to estimate hazard ratios (HRs) for outcomes of interest. Results: The GLORIA-AF Phase III registry enrolled 21,300 patients between January 2014 and December 2016. Of these, 3839 were prescribed dabigatran, 4015 rivaroxaban and 4505 apixaban, with median ages of 71.0, 71.0, and 73.0 years, respectively. In the PS-matched set, the adjusted HRs and 95% confidence intervals (CIs) for dabigatran vs rivaroxaban were, for stroke: 1.27 (0.79–2.03), major bleeding 0.59 (0.40–0.88), myocardial infarction 0.68 (0.40–1.16), and all-cause death 0.86 (0.67–1.10). For the comparison of dabigatran vs apixaban, in the PS-matched set, the adjusted HRs were, for stroke 1.16 (0.76–1.78), myocardial infarction 0.84 (0.48–1.46), major bleeding 0.98 (0.63–1.52) and all-cause death 1.01 (0.79–1.29). For the comparison of rivaroxaban vs apixaban, in the PS-matched set, the adjusted HRs were, for stroke 0.78 (0.52–1.19), myocardial infarction 0.96 (0.63–1.45), major bleeding 1.54 (1.14–2.08), and all-cause death 0.97 (0.80–1.19). Conclusions: Patients treated with dabigatran had a 41% lower risk of major bleeding compared with rivaroxaban, but similar risks of stroke, MI, and death. Relative to apixaban, patients treated with dabigatran had similar risks of stroke, major bleeding, MI, and death. Rivaroxaban relative to apixaban had increased risk for major bleeding, but similar risks for stroke, MI, and death. Registration: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01468701, NCT01671007. Date of registration: September 2013

Anticoagulant selection in relation to the SAMe-TT2R2 score in patients with atrial fibrillation. the GLORIA-AF registry

Aim: The SAMe-TT2R2 score helps identify patients with atrial fibrillation (AF) likely to have poor anticoagulation control during anticoagulation with vitamin K antagonists (VKA) and those with scores >2 might be better managed with a target-specific oral anticoagulant (NOAC). We hypothesized that in clinical practice, VKAs may be prescribed less frequently to patients with AF and SAMe-TT2R2 scores >2 than to patients with lower scores. Methods and results: We analyzed the Phase III dataset of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), a large, global, prospective global registry of patients with newly diagnosed AF and ≥1 stroke risk factor. We compared baseline clinical characteristics and antithrombotic prescriptions to determine the probability of the VKA prescription among anticoagulated patients with the baseline SAMe-TT2R2 score >2 and ≤ 2. Among 17,465 anticoagulated patients with AF, 4,828 (27.6%) patients were prescribed VKA and 12,637 (72.4%) patients an NOAC: 11,884 (68.0%) patients had SAMe-TT2R2 scores 0-2 and 5,581 (32.0%) patients had scores >2. The proportion of patients prescribed VKA was 28.0% among patients with SAMe-TT2R2 scores >2 and 27.5% in those with scores ≤2. Conclusions: The lack of a clear association between the SAMe-TT2R2 score and anticoagulant selection may be attributed to the relative efficacy and safety profiles between NOACs and VKAs as well as to the absence of trial evidence that an SAMe-TT2R2-guided strategy for the selection of the type of anticoagulation in NVAF patients has an impact on clinical outcomes of efficacy and safety. The latter hypothesis is currently being tested in a randomized controlled trial. Clinical trial registration: URL: https://www.clinicaltrials.gov//Unique identifier: NCT01937377, NCT01468701, and NCT01671007

Genomic analyses inform on migration events during the peopling of Eurasia.

High-coverage whole-genome sequence studies have so far focused on a limited number of geographically restricted populations, or been targeted at specific diseases, such as cancer. Nevertheless, the availability of high-resolution genomic data has led to the development of new methodologies for inferring population history and refuelled the debate on the mutation rate in humans. Here we present the Estonian Biocentre Human Genome Diversity Panel (EGDP), a dataset of 483 high-coverage human genomes from 148 populations worldwide, including 379 new genomes from 125 populations, which we group into diversity and selection sets. We analyse this dataset to refine estimates of continent-wide patterns of heterozygosity, long- and short-distance gene flow, archaic admixture, and changes in effective population size through time as well as for signals of positive or balancing selection. We find a genetic signature in present-day Papuans that suggests that at least 2% of their genome originates from an early and largely extinct expansion of anatomically modern humans (AMHs) out of Africa. Together with evidence from the western Asian fossil record, and admixture between AMHs and Neanderthals predating the main Eurasian expansion, our results contribute to the mounting evidence for the presence of AMHs out of Africa earlier than 75,000 years ago.Support was provided by: Estonian Research Infrastructure Roadmap grant no 3.2.0304.11-0312; Australian Research Council Discovery grants (DP110102635 and DP140101405) (D.M.L., M.W. and E.W.); Danish National Research Foundation; the Lundbeck Foundation and KU2016 (E.W.); ERC Starting Investigator grant (FP7 - 261213) (T.K.); Estonian Research Council grant PUT766 (G.C. and M.K.); EU European Regional Development Fund through the Centre of Excellence in Genomics to Estonian Biocentre (R.V.; M.Me. and A.Me.), and Centre of Excellence for Genomics and Translational Medicine Project No. 2014-2020.4.01.15-0012 to EGC of UT (A.Me.) and EBC (M.Me.); Estonian Institutional Research grant IUT24-1 (L.S., M.J., A.K., B.Y., K.T., C.B.M., Le.S., H.Sa., S.L., D.M.B., E.M., R.V., G.H., M.K., G.C., T.K. and M.Me.) and IUT20-60 (A.Me.); French Ministry of Foreign and European Affairs and French ANR grant number ANR-14-CE31-0013-01 (F.-X.R.); Gates Cambridge Trust Funding (E.J.); ICG SB RAS (No. VI.58.1.1) (D.V.L.); Leverhulme Programme grant no. RP2011-R-045 (A.B.M., P.G. and M.G.T.); Ministry of Education and Science of Russia; Project 6.656.2014/K (S.A.F.); NEFREX grant funded by the European Union (People Marie Curie Actions; International Research Staff Exchange Scheme; call FP7-PEOPLE-2012-IRSES-number 318979) (M.Me., G.H. and M.K.); NIH grants 5DP1ES022577 05, 1R01DK104339-01, and 1R01GM113657-01 (S.Tis.); Russian Foundation for Basic Research (grant N 14-06-00180a) (M.G.); Russian Foundation for Basic Research; grant 16-04-00890 (O.B. and E.B); Russian Science Foundation grant 14-14-00827 (O.B.); The Russian Foundation for Basic Research (14-04-00725-a), The Russian Humanitarian Scientific Foundation (13-11-02014) and the Program of the Basic Research of the RAS Presidium “Biological diversity” (E.K.K.); Wellcome Trust and Royal Society grant WT104125AIA & the Bristol Advanced Computing Research Centre (http://www.bris.ac.uk/acrc/) (D.J.L.); Wellcome Trust grant 098051 (Q.A.; C.T.-S. and Y.X.); Wellcome Trust Senior Research Fellowship grant 100719/Z/12/Z (M.G.T.); Young Explorers Grant from the National Geographic Society (8900-11) (C.A.E.); ERC Consolidator Grant 647787 ‘LocalAdaptatio’ (A.Ma.); Program of the RAS Presidium “Basic research for the development of the Russian Arctic” (B.M.); Russian Foundation for Basic Research grant 16-06-00303 (E.B.); a Rutherford Fellowship (RDF-10-MAU-001) from the Royal Society of New Zealand (M.P.C.)

Проблеми продовження експлуатації та реконструкція великопанельних п’ятиповерхових будівель 50 – 60-х років хх ст.

Raising of the problem. In many regions is utilised housing, that age is more than half a century. According to the research materials of the analytical center of Ukrainian Cities Association there are 25,5 thousand houses built by first mass series project of large, block and brick buildings with a total area of 72 million M2 today in the state, rather those, that require reconstruction and modernization. In general, most of the housing stock of Ukraine is in a poor technical condition due to its deficient funding; it keeps the tendency of premature aging of the housing stock.One of the major problems of modern construction industry is the continuation of housing exploitation, in particular is it the building era of mass construction of 50-60-ies of XX century, called "Khrushchevki". According to the State Statistics Service of Ukraine the deterioration of residential buildings in Ukraine amounts to 47.2%, which makes us think of the immediate actions to occure this situation. The most acceptable way, at first viewe, seems the reconstruction of "Khrushchvki". However, the reconstruction is a complex problem that requires the construction industry solution due to the economic component, the social factor, the views of residents of these homes to create a technological and economical viable result.Analysis of publications. The problem of the "Khrushchevki" reconstruction is the subject of continual researches of leading builders of Ukraine. In the researchers' attention just as the technological problems [1 - 3], so economic components [4 - 6], in general, give an idea of the work scale required to overcome the impending crisis.The purpose of the article. Defining the main problems of exploatation of panel five- story buildings of 50 - 60-ies twentieth century and their residents thoughts about existing inconvenience, as well as associated economic, technological and legal problems in the implementation of buildings reconstruction.Conclusions. Thus, the continued exploatation of large five-storey buildings today is a big problem that requires a consistent scientific basis and achievements of mechanisms to solve it. On the construction industry lie the tasks of different nature: technological (development projects and successful design solutions for reconstruction, heat and sound insulation of residential buildings, a significant decrease in the heat capacity of the wall surfaces of concrete panels), economic (creation and selection of economic viable options of reconstruction, reducing the cost of the work), social and legal (housing quality improvement in compliance with regulatory requirements and legislative support). In the aspect of these tasks is an interesting study of foreign experience (eg, Germany, Poland, Czech Republic), the reconstruction of five-story building. On these and other questions will be directed our further research.Постановка проблемы. Во многих регионах эксплуатируется жилье, возраст которого составляет более полувека. По материалам исследований аналитического центра Ассоциации городов Украины, сегодня в государстве насчитывается 25 500 крупнопанельных, блочных и кирпичных домов построенных по проектам первых массовых серий, общей площадью 72 млн м2, то есть требующих восстановления путем реконструкции и модернизации. Вообще большая часть жилого фонда Украины находится в неудовлетворительном техническом состоянии из-за недостаточного финансирования мер по его содержанию; сохраняется тенденция преждевременного старения жилого фонда.Одной из важнейших проблем для современной строительной отрасли остается продолжение эксплуатации жилищного фонда страны, в частности - зданий времен массовой застройки 50-60-х годов ХХ века, так называемых "хрущевок". По данным Государственной службы статистики Украины изношенность жилых домов составляет 47,2 %, что заставляет задуматься над немедленными мерами по решению этой ситуации. Наиболее приемлемым способом на первый взгляд кажется реконструкция "хрущевок". Однако реконструкция представляет собой комплексную проблему, которая требует решения строительной отраслью с учетом экономической составляющей, социального фактора, мнения жителей этих домов - для создания технологически и экономически целесообразного результата.Анализ публикаций. Проблема реконструкции "хрущевок" является предметом постоянных исследований ведущих строителей Украины. В поле внимания исследователей находятся как технологические проблемы [1 - 3], так и экономические составляющие [4 - 6], которые в целом дают представление о масштабе необходимой работы для преодоления неминуемого кризиса.Цель статьи - выяснение основных проблем эксплуатации панельных пятиэтажных зданий 50 - 60-х гг. ХХ в. и мнения их жителей относительно существующих неудобств, а также сопутствующих экономических, технологических и правовых проблем при осуществлении реконструкции таких зданий.Выводы. Продолжение эксплуатации крупнопанельных пятиэтажных домов на сегодня является большой разновекторной проблемой, требующей последовательного научного обоснования и наработки механизмов ее решения. Перед строительной отраслью стоят задачи разного характера: технологические (разработка проектов и удачных конструктивных решений реконструкции, тепло- и звукоизоляция жилых помещений, существенное уменьшение теплоемкости стеновых поверхностей бетонных панелей), экономические (создание и выбор экономически целесообразного варианта реконструкции, уменьшение себестоимости работ) и социально - правовые (повышение качества жилья с соблюдением нормативных требований и законодательного обеспечения). В аспекте указанных задач интересным является изучение зарубежного опыта (например, Германии, Польши, Чехии) реконструкции пятиэтажек. На эти и другие вопросы будут направлены наши дальнейшие исследования.Постановка проблеми. У багатьох регіонах експлуатується житло, вік якого становить понад півстоліття. За матеріалами досліджень аналітичного центру Асоціації міст України, сьогодні в державі налічується 25 500 великопанельних, блочних і цегляних будинків зведених за проектами перших масових серій, загальною площею 72 млн м2, тобто тих, що потребують відновлення шляхом реконструкції і модернізації. Взагалі більша частина житлового фонду України перебуває в незадовільному технічному стані через недостатнє фінансування заходів щодо його утримання; зберігається тенденція передчасного старіння житлового фонду.Однією з найважливіших проблем для сучасної будівельної галузі залишається продовження експлуатації житлового фонду країни, зокрема, – будинків часів масової забудови 50-60-х років ХХ ст., так званих “хрущовок”. За даними Державної служби статистики України, зношеність житлових будинків складає 47,2 %, що змушує замислитись над негайними заходами щодо вирішення цієї ситуації. Найбільш прийнятним способом, на перший погляд, здається реконструкція “хрущовок”. Проте реконструкція становить комплексну проблему, яка потребує вирішення будівельною галуззю із врахуванням економічної складової, соціального чинника, думки мешканців цих будинків для створення технологічно й економічно доцільного результату.Аналіз публікацій. Проблема реконструкції “хрущовок” - предмет постійних досліджень провідних будівельників України. У полі уваги дослідників як технологічні проблеми [1 – 3], так і економічні складові [4 – 6], що в цілому дають уявлення про масштаб необхідної роботи для подолання неминучої кризи.Мета статті – висвітлення основних проблем експлуатації панельних п’ятиповерхових будівель 50 – 60-х рр. ХХ ст. та думки їх мешканців щодо існуючих незручностей, а також супутніх економічних, технологічних і правових проблем у здійсненні реконструкції таких будівель.Висновки. Продовження експлуатації великопанельних п’ятиповерхових будинків наразі є великою різновекторною проблемою, яка потребує послідовного наукового обґрунтування та напрацювання механізмів її вирішення. Перед будівельною галуззю постають завдання різного характеру: технологічні (розроблення проектів і вдалих конструктивних рішень реконструкції, тепло- і звукоізоляція житлових приміщень, істотне зменшення теплоємності стінових поверхонь бетонних панелей), економічні (створення й обрання економічно доцільного варіанта реконструкції, зменшення собівартості робіт) та соціально-правові (підвищення якості житла з дотриманням нормативних вимог та законодавчого забезпечення). В аспекті означених завдань цікавим є вивчення зарубіжного досвіду (наприклад, Німеччини, Польщі, Чехії) реконструкції п’ятиповерхівок. На ці та інші питання будуть спрямовані наші подальші дослідження