The ILE462VAL polymorphism of the cytochrome P450 CYP1A1 gene among Tundra Nenets in Yamalo-Nenets Autonomous Okrug, Nganasans in the Taimyr Peninsula and Russians in Siberia

The work concerns a polymorphism of the cytochrome Р450 CYP1A1 gene, the CYP1A1*2C variant (Ile462Val, rs1048943). This substitution results in a two- fold increase in enzyme activity, which leads to accumulation of active intermediates and increases the risk of DNA mutations and chemically induced carcinogenesis. It has been demonstrated that the 462Val allele may be a risk factor in some oncological and other multifactorial diseases. This study was performed on Tundra Nenets in Yamalo-Nenets Autonomous Okrug (N = 271), Nganasans in the Taimyr Peninsula (N = 186) and Russians in North Siberia (N = 267). The cohorts did not include descendants of mixed marriages. Genotyping was performed using Real-Time PCR with competitive TaqMan allele-specific probes. The frequency of the 462Val allele in the Tundra Nenets cohort was 23.8 % (95 % CI 20.4–27.6 %), which corresponds to the frequency range found in East Asian populations and is higher than the values typical of European populations. The 462Val allele frequency in the Russian cohort was 5.8 % (95 % CI 4.1–8.1 %), which corresponds to the frequency range of European populations. The 462Val allele frequency in the Nganasans cohort was 39.0 % (95 % CI 34.2–44.0 %), which is higher than the frequencies found in European, Asian and African populations. Frequencies of the  462Val variant close to that in Nganasans have been observed in Greenland Inuits, native Americans as a whole and the Southern Chinese. A high-frequency occurrence of the 462Val allele among Tundra Nenets and Nganasans may be indicative of a populationwide risk of diseases influenced by this genetic polymorphism, especially when traditional mainstays are gone or previously unknown ecotoxicants appear in the areas

Застосування антиоксидантів з вмістом міді хворим при лікуванні флегмон щелепно-лицевої локалізації

Для прискорення перебігу І фази нами запропоновано в рану введення разом з маззю «Левоміколь» церулоплазміну. Мідь має один поліпептидний ланцюг, але декілька лізоформ, завдяки чому проходить вклинювання активних центрів препарата в пошкоджені системи антиоксидантного захисту. Він легко сполучається з іншими активними формами, захищаючи клітину від ушкоджень зовні від вільних радикалів. Церулоплазмін нормалізує рівень заліза в тканинах знижуючи тим самим кількість N0. Виявлено, що при введені церулоплазміну в гнійну рану, у хворих вже на другий день відбувається зниження температури, в рані відбуваються процеси очищення від некротичних мас вже на 3 день. Нами припущено, що церулоплазмін діє як антиоксидант та частково, як антибактеріальний препарат і стимулює регенеративні процеси в рані; For acceleration of the course of phase І we are proposed in the wound of introduction together with the ointment "Levomikol" ceruloplasmin. Copper has a single polypeptide chain, but several lysoforms, which results in the inclusion of active drug centers in damaged antioxidant defense systems. It is easily interconnected with other active forms, protecting the cell against damage from the outside of free radicals. Ceruloplasmin normalizes the level of iron in the tissues thereby reducing the number of N0. It was revealed that when ceruloplasmin is administered in purulent wound, patients are already on the second day a decrease in temperature, in the wound there are processes of clearing from necrotic masses for 3 days. We assume that ceruloplasmin acts as an antioxidant and partly as an antibacterial drug and stimulates regenerative processes in the wound; C Для ускорения течения и фазы нами предложено в рану введение вместе с мазью «Левомиколь» церулоплазмина. Медь имеет один полипептидная цепь, но несколько лизоформ, благодаря чему проходит вклинивание активных центров препарата в поврежденные системы антиоксидантной защиты. Он легко сочетается с другими активными формами, защищая клетку от повреждений снаружи от свободных радикалов. Церулоплазмин нормализует уровень железа в тканях снижая тем самым количество N0. Обнаружено, что при введении церулоплазмина в гнойную рану, у больных уже на второй день происходит снижение температуры, в ране происходят процессы очистки от некротических масс уже на 3 день. Нами предположено, что церулоплазмин действует как антиоксидант и частично, как антибактериальный препарат и стимулирует регенеративные процессы в ране

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.)

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries