One Arctic - One Health

One Health takes a multidisciplinary approach to health risks and risk mitigation for humans, animals, plants and the environment, with the understanding that human health welfare is dependent on ecosystem health. The U.S. and Canada started the One Health project under the Sustainable Development Working Group (SDWG) of the Arctic Council in 2015, Finland joined the project as a colead in 2017. This report is a summary of the Finnish activities and achievements in the One Arctic - One Health project during the Finnish Chairmanship of the Arctic Council. The main actions included the One Arctic - One Health conference in Oulu, establishment of the TremArctic network, and two published Systematic Review papers and two manuscripts. There were also joint sessions and presentations in scientific conferences, seminars and workshops, and joint meetings and collaboration with the other Arctic Council Working Groups, the University of the Arctic, other organisations, and scientific projects. The report concludes with some updated proposals for further work, based on previous works and reflecting progress over the past two years. The Finnish One Arctic - One Health team consisted of scientists from the University of Oulu, National Institute for Health and Welfare (THL), University of Helsinki and the Finnish Food Authority. This work was supported by the grant of the Ministry for Foreign Affairs of Finland.Yhteisen terveyden (One Health) perusajatus on, että ihmisten, eläinten, kasvien ja ympäristön terveys on toisistaan riippuvaista, ainakin niin, että sairaassa ympäristössä ei ihminenkään voi olla hyvinvoiva. Yhdysvaltain johtaessa puhetta Arktisessa neuvostossa, USA ja Kanada aloittivat kestävän kehityksen työryhmän (SDWG) alaisuudessa One Health -hankkeen, jonka johtoon Suomi liittyi toimiessaan Arktisen neuvoston puheenjohtajana 2017-2019. Tämä raportti on yhteenveto Suomen toimista ja saavutuksista puheenjohtajakaudellaan. Tärkeimmät toimet olivat One Arctic - One Health -konferenssi Oulussa, TremArctic-verkoston toiminnan aloittaminen, kaksi julkaistua laajaa systemaattista katsausta ja kaksi käsikirjoitusta. Lisäksi Suomen työryhmä osallistui tieteellisiin konferensseihin, seminaareihin ja työpajoihin, sekä yhteisiin kokouksiin ja muuhun yhteistyöhön Arktisen neuvoston muiden työryhmien kanssa. Raportti sisältää myös päivitettyjä jatkotoimenpide-ehdotuksia, jotka perustuvat aikaisempaan työhön ja viimeisten kahden vuoden aikana tapahtuneeseen kehitykseen. Suomen Yksi Arktis – yhteinen terveys -työryhmä koostui asiantuntijoista Oulun yliopistosta, Terveyden ja hyvinvoinnin laitoksesta, Helsingin yliopistosta ja Ruokavirastosta. Hanketta rahoitti Suomen ulkoministeriö.Grundprincipen till One Health -tänkandet är att människohälsa, djurhälsa, planthälsa och ekosystemhälsa är nära besläktade. I alla fall så att människans välfärd kräver frisk natur. Under det amerikanska ordförandeskapet i Arktiska rådet inledde USA och Kanada One Health -projektet i regi av arbetsgruppen för hållbar utveckling (Sustainable Development Working Group, SDWG). Finland gick med i ledningen av projektet under Finland ordförandeskap 2017-2019. Denna rapport är en sammanfattning av finska åtgärder och resultat under Finlands ordförandeskap. De mest viktiga handlingarna var arrangerandet av One Arctic - One Health – konferensen i Uleåborg, startandet av TremArctic-nätverket, publiceringen av två systematiska litteraturöversikter och produceringen av två vetenskapliga manuskript. I tillägg deltog den finska arbetsgruppen i vetenskapliga konferenser, seminar och verkstäder med gemensamma sessioner och presentationer. Vidare hade man gemensamma möter samt annat samarbete med andra arbetsgrupper under Arktiska rådet. Rapporten innehåller också uppdaterade förslag till för ytterligare åtgärder baserade på tidigare arbeten och utvecklingen under Finland ordförandeskap. Finlands One Arctic – One Health - arbetsgrupp bestod av forskare från Uleåborgs universitet, Institutet för hälsa och välfärd, Helsingfors universitet, samt Livsmedelsverket. Projektet fick finansiering från det finska utrikesministeriet

2-Imidazole as a Substitute for the Electrophilic Group Gives Highly Potent Prolyl Oligopeptidase Inhibitors

Different five-membered nitrogen-containing heteroaromatics in the position of the typical electrophilic group in prolyl oligopeptidase (PREP) inhibitors were investigated and compared to tetrazole. The 2-imidazoles were highly potent inhibitors of the proteolytic activity. The binding mode for the basic imidazole was studied by molecular docking as it was expected to differ from the acidic tetrazole. A new putative noncovalent binding mode with an interaction to His680 was found for the 2-imidazoles. Inhibition of the proteolytic activity did not correlate with the modulating effect on protein-protein-interaction-derived functions of PREP (i.e., dimerization of alpha-synuclein and autophagy). Among the highly potent PREP inhibiting 2-imidazoles, only one was also a potent modulator of PREP-catalyzed alpha-synuclein dimerization, indicating that the linker length on the opposite side of the molecule from the five-membered heteroaromatic is critical for the disconnected structure-activity relationships

A children’s health perspective on nano- and microplastics

BACKGROUND : Pregnancy, infancy, and childhood are sensitive windows for environmental exposures. Yet the health effects of exposure to nano- and microplastics (NMPs) remain largely uninvestigated or unknown. Although plastic chemicals are a well-established research topic, the impacts of plastic particles are unexplored, especially with regard to early life exposures. OBJECTIVES : This commentary aims to summarize the knowns and unknowns around child- and pregnancy-relevant exposures to NMPs via inhalation, placental transfer, ingestion and breastmilk, and dermal absorption. METHODS : A comprehensive literature search to map the state of the science on NMPs found 37 primary research articles on the health relevance of NMPs during early life and revealed major knowledge gaps in the field. We discuss opportunities and challenges for quantifying child-specific exposures (e.g., NMPs in breastmilk or infant formula) and health effects, in light of global inequalities in baby bottle use, consumption of packaged foods, air pollution, hazardous plastic disposal, and regulatory safeguards. We also summarize research needs for linking child health and NMP exposures and address the unknowns in the context of public health action. DISCUSSION : Few studies have addressed child-specific sources of exposure, and exposure estimates currently rely on generic assumptions rather than empirical measurements. Furthermore, toxicological research on NMPs has not specifically focused on child health, yet children’s immature defense mechanisms make them particularly vulnerable. Apart from few studies investigating the placental transfer of NMPs, the physicochemical properties (e.g., polymer, size, shape, charge) driving the absorption, biodistribution, and elimination in early life have yet to be benchmarked. Accordingly, the evidence base regarding the potential health impacts of NMPs in early life remains sparse. Based on the evidence to date, we provide recommendations to fill research gaps, stimulate policymakers and industry to address the safety of NMPs, and point to opportunities for families to reduce early life exposures to plastic.The European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant.https://ehp.niehs.nih.govdm2022School of Health Systems and Public Health (SHSPH

Global, regional, and national sex differences in the global burden of tuberculosis by HIV status, 1990–2019: results from the Global Burden of Disease Study 2019

Background Tuberculosis is a major contributor to the global burden of disease, causing more than a million deaths annually. Given an emphasis on equity in access to diagnosis and treatment of tuberculosis in global health targets, evaluations of differences in tuberculosis burden by sex are crucial. We aimed to assess the levels and trends of the global burden of tuberculosis, with an emphasis on investigating differences in sex by HIV status for 204 countries and territories from 1990 to 2019. Methods We used a Bayesian hierarchical Cause of Death Ensemble model (CODEm) platform to analyse 21 505 site-years of vital registration data, 705 site-years of verbal autopsy data, 825 site-years of sample-based vital registration data, and 680 site-years of mortality surveillance data to estimate mortality due to tuberculosis among HIV-negative individuals. We used a population attributable fraction approach to estimate mortality related to HIV and tuberculosis coinfection. A compartmental meta-regression tool (DisMod-MR 2.1) was then used to synthesise all available data sources, including prevalence surveys, annual case notifications, population-based tuberculin surveys, and tuberculosis cause-specific mortality, to produce estimates of incidence, prevalence, and mortality that were internally consistent. We further estimated the fraction of tuberculosis mortality that is attributable to independent effects of risk factors, including smoking, alcohol use, and diabetes, for HIV-negative individuals. For individuals with HIV and tuberculosis coinfection, we assessed mortality attributable to HIV risk factors including unsafe sex, intimate partner violence (only estimated among females), and injection drug use. We present 95% uncertainty intervals for all estimates. Findings Globally, in 2019, among HIV-negative individuals, there were 1.18 million (95% uncertainty interval 1.08-1.29) deaths due to tuberculosis and 8.50 million (7.45-9.73) incident cases of tuberculosis. Among HIV-positive individuals, there were 217 000 (153 000-279 000) deaths due to tuberculosis and 1.15 million (1.01-1.32) incident cases in 2019. More deaths and incident cases occurred in males than in females among HIV-negative individuals globally in 2019, with 342 000 (234 000-425 000) more deaths and 1.01 million (0.82-1.23) more incident cases in males than in females. Among HIV-positive individuals, 6250 (1820-11 400) more deaths and 81 100 (63 300-100 000) more incident cases occurred among females than among males in 2019. Age-standardised mortality rates among HIV-negative males were more than two times greater in 105 countries and age-standardised incidence rates were more than 1.5 times greater in 74 countries than among HIV-negative females in 2019. The fraction of global tuberculosis deaths among HIV-negative individuals attributable to alcohol use, smoking, and diabetes was 4.27 (3.69-5.02), 6.17 (5.48-7.02), and 1.17 (1.07-1.28) times higher, respectively, among males than among females in 2019. Among individuals with HIV and tuberculosis coinfection, the fraction of mortality attributable to injection drug use was 2.23 (2.03-2.44) times greater among males than females, whereas the fraction due to unsafe sex was 1.06 (1.05-1.08) times greater among females than males. Interpretation As countries refine national tuberculosis programmes and strategies to end the tuberculosis epidemic, the excess burden experienced by males is important. Interventions are needed to actively communicate, especially to men, the importance of early diagnosis and treatment. These interventions should occur in parallel with efforts to minimise excess HIV burden among women in the highest HIV burden countries that are contributing to excess HIV and tuberculosis coinfection burden for females. Placing a focus on tuberculosis burden among HIV-negative males and HIV and tuberculosis coinfection among females might help to diminish the overall burden of tuberculosis. This strategy will be crucial in reaching both equity and burden targets outlined by global health milestone

Chloro-s-triazines-toxicokinetic, toxicodynamic, human exposure, and regulatory considerations

Abstract Chloro-s-triazines-atrazine, cyanazine, propazine, simazine, and terbuthylazine-are structurally similar herbicides, differing only in specific s-triazine4-and 6-N alkyl substituents. It is generally regarded that their toxicokinetics, such as, metabolic pathways, biological effects and toxicities, also share more similar features than the differences. Consequently, it is useful to compare their characteristics to potentially find useful structure-activity relationships or other similarities or differences regarding different active compounds, their metabolites, and biological effects including toxic outcomes. The ultimate goal of these exercises is to apply the summarized knowledge-as far as it is possible regarding a patchy and often inadequate database-to cross the in vitro-in vivo and animal-human borders and integrate the available data to enhance toxicological risk assessment for the benefit of humans and ecosystems

Temporal trends of contaminants in Arctic human populations

Abstract The first Arctic Monitoring and Assessment Programme (AMAP) report was published in 1998 and followed by three assessment reports of human health (AMAP 2003, 2009 and 2015). The focus area of the AMAP reports was to monitor levels of environmental contaminants in the Arctic and to assess the health effects connected with detected levels in Arctic countries. This review gives an overview of temporal trends of contaminants and their health effects in humans of the Arctic based on data published by AMAP, as well as Russian scientific literature. Several time series of 31 contaminants in humans of the Arctic from different cohorts are reported. The lengths of time series and periods covered differ from each other. International restrictions have decreased the levels of most persistent organic pollutants in humans and food webs. Percentage changes for contaminants in human biological matrices (blood samples from children, mothers and males and breast milk samples) for the period of sampling showed declining trends in most of the monitored Arctic locations, with the exception of oxychlordane, hexachlorobenzene (HCB), 2,2′,4,4′,5,5′-hexabromodiphenyl ether (PBDE153) and perfluorinated compounds (PFCs)

2-Imidazole as a Substitute for the Electrophilic Group Gives Highly Potent Prolyl Oligopeptidase Inhibitors

Different five-membered nitrogen-containing heteroaromatics in the position of the typical electrophilic group in prolyl oligopeptidase (PREP) inhibitors were investigated and compared to tetrazole. The 2-imidazoles were highly potent inhibitors of the proteolytic activity. The binding mode for the basic imidazole was studied by molecular docking as it was expected to differ from the acidic tetrazole. A new putative noncovalent binding mode with an interaction to His680 was found for the 2-imidazoles. Inhibition of the proteolytic activity did not correlate with the modulating effect on protein-protein-interaction-derived functions of PREP (i.e., dimerization of alpha-synuclein and autophagy). Among the highly potent PREP inhibiting 2-imidazoles, only one was also a potent modulator of PREP-catalyzed alpha-synuclein dimerization, indicating that the linker length on the opposite side of the molecule from the five-membered heteroaromatic is critical for the disconnected structure-activity relationships.Peer reviewe

Human infectious diseases and the changing climate in the Arctic

Abstract Climatic factors, especially temperature, precipitation, and humidity play an important role in disease transmission. As the Arctic changes at an unprecedented rate due to climate change, understanding how climatic factors and climate change affect infectious disease rates is important for minimizing human and economic costs. The purpose of this systematic review was to compile recent studies in the field and compare the results to a previously published review. English language searches were conducted in PubMed, ScienceDirect, Scopus, and PLOS One. Russian language searches were conducted in the Scientific Electronic Library “eLibrary.ru”. This systematic review yielded 22 articles (51%) published in English and 21 articles (49%) published in Russian since 2012. Articles about zoonotic and vector-borne diseases accounted for 67% (n = 29) of the review. Tick-borne diseases, tularemia, anthrax, and vibriosis were the most researched diseases likely to be impacted by climatic factors in the Arctic. Increased temperature and precipitation are predicted to have the greatest impact on infectious diseases in the Arctic