70,504 research outputs found

    In vitro phenotypic screening of 7-chloro-4-amino(oxy)quinoline derivatives as putative anti-Trypanosoma cruzi agents

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    In this study, a series of 22 pre-synthesized 7-chloro-4-mino(oxy)quinoline derivatives was assayed in vitro as potential antichagasic agents. A primary screening against Trypanosoma cruzi epimastigotes and a non-specific cytotoxicity assay on murine fibroblasts were simultaneously performed, resulting quinolines 3, 7 and 12 with great selectivity (SI) on the extracellular parasite (SI7, SI3 , SI12 and SIBZ >9.44). Therefore, the activity of these derivatives was evaluated on intracellular amastigotes, achieving derivative 7 the best SI (SI = 12.73). These results, supported by the in silico prediction of a good oral bioavailability and a suitable risk profile, propose the 4-amino-7-chloroquinoline scaffold as a potential template for designing trypanocidal prototypes.Departamento Administrativo de Ciencia, Tecnolog铆a e Innovaci贸n [CO] Colciencias5507-543-31904Programa: Bioprospecci贸n y desarrollo de ingredientes naturales para las industrias cosm茅tica, farmac茅utica y de productos de aseo con base en la biodiversidad colombianan

    Indicators to monitor the status of the tree of life.

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    Following the failure to fully achieve any of the 20 Aichi biodiversity targets, the future of biodiversity rests in the balance. The Convention on Biological Diversity's Kunming鈥揗ontreal Global Biodiversity Framework (GBF) presents the opportunity to preserve nature's contributions to people (NCPs) for current and future generations by conserving biodiversity and averting extinctions. There is a need to safeguard the tree of life鈥攖he unique and shared evolutionary history of life on Earth鈥攖o maintain the benefits it bestows into the future. Two indicators have been adopted within the GBF to monitor progress toward safeguarding the tree of life: the phylogenetic diversity (PD) indicator and the evolutionarily distinct and globally endangered (EDGE) index. We applied both to the world's mammals, birds, and cycads to show their utility at the global and national scale. The PD indicator can be used to monitor the overall conservation status of large parts of the evolutionary tree of life, a measure of biodiversity's capacity to maintain NCPs for future generations. The EDGE index is used to monitor the performance of efforts to conserve the most distinctive species. The risk to PD of birds, cycads, and mammals increased, and mammals exhibited the greatest relative increase in threatened PD over time. These trends appeared robust to the choice of extinction risk weighting. EDGE species had predominantly worsening extinction risk. A greater proportion of EDGE mammals (12%) had increased extinction risk compared with threatened mammals in general (7%). By strengthening commitments to safeguarding the tree of life, biodiversity loss can be reduced and thus nature's capacity to provide benefits to humanity now and in the future can be preserved

    Exceptional multi-year prediction skill of the Kuroshio Extension in the CESM high-resolution decadal prediction system

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    Abstract The Kuroshio Extension (KE) has far-reaching influences on climate as well as on local marine ecosystems. Thus, skillful multi-year to decadal prediction of the KE state and understanding sources of skill are valuable. Retrospective forecasts using the high-resolution Community Earth System Model (CESM) show exceptional skill in predicting KE variability up to lead year 4, substantially higher than the skill found in a similarly configured low-resolution CESM. The higher skill is attained because the high-resolution system can more realistically simulate the westward Rossby wave propagation of initialized ocean anomalies in the central North Pacific and their expression within the sharp KE front, and does not suffer from spurious variability near Japan present in the low-resolution CESM that interferes with the incoming wave propagation. These results argue for the use of high-resolution models for future studies that aim to predict changes in western boundary current systems and associated biological fields

    SWHNMs Ecological Sounds of the Vietnamese Diaspora

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    A multi-voice poem by She Who Has No Master(s) containing "soundings" & "silences" from Vietnamese women & nonbinary writers in the US, Canada, and Viet Nam. dvan.org/she-who-has-no-masters/ (Poem coordinated by Diana Khoi Nguyen and Dao Strom, for AAAS Conference 2021 - "Unsettling Transpacific Ecologies")</p

    Small babies, big risks: global estimates of prevalence and mortality for vulnerable newborns to accelerate change and improve counting

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    Small newborns are vulnerable to mortality and lifelong loss of human capital. Measures of vulnerability previously focused on liveborn low-birthweight (LBW) babies, yet LBW reduction targets are off-track. There are two pathways to LBW, preterm birth and fetal growth restriction (FGR), with the FGR pathway resulting in the baby being small for gestational age (SGA). Data on LBW babies are available from 158 (81%) of 194 WHO member states and the occupied Palestinian territory, including east Jerusalem, with 113 (58%) having national administrative data, whereas data on preterm births are available from 103 (53%) of 195 countries and areas, with only 64 (33%) providing national administrative data. National administrative data on SGA are available for only eight countries. Global estimates for 2020 suggest 13路4 million livebirths were preterm, with rates over the past decade remaining static, and 23路4 million were SGA. In this Series paper, we estimated prevalence in 2020 for three mutually exclusive types of small vulnerable newborns (SVNs; preterm non-SGA, term SGA, and preterm SGA) using individual-level data (2010-20) from 23 national datasets (鈭110 million livebirths) and 31 studies in 18 countries (鈭0路4 million livebirths). We found 11路9 million (50% credible interval [Crl] 9路1-12路2 million; 8路8%, 50% Crl 6路8-9路0%) of global livebirths were preterm non-SGA, 21路9 million (50% Crl 20路1-25路5 million; 16路3%, 14路9-18路9%) were term SGA, and 1路5 million (50% Crl 1路2-4路2 million; 1路1%, 50% Crl 0路9-3路1%) were preterm SGA. Over half (55路3%) of the 2路4 million neonatal deaths worldwide in 2020 were attributed to one of the SVN types, of which 73路4% were preterm and the remainder were term SGA. Analyses from 12 of the 23 countries with national data (0路6 million stillbirths at 鈮22 weeks gestation) showed around 74% of stillbirths were preterm, including 16路0% preterm SGA and approximately one-fifth of term stillbirths were SGA. There are an estimated 1路9 million stillbirths per year associated with similar vulnerability pathways; hence integrating stillbirths to burden assessments and relevant indicators is crucial. Data can be improved by counting, weighing, and assessing the gestational age of every newborn, whether liveborn or stillborn, and classifying small newborns by the three vulnerability types. The use of these more specific types could accelerate prevention and help target care for the most vulnerable babies

    Results from the second WHO external quality assessment for the molecular detection of respiratory syncytial virus, 2019-2020

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    BACKGROUND: External quality assessments (EQAs) for the molecular detection of human respiratory syncytial virus (RSV) are necessary to ensure the standardisation of reliable results. The Phase II, 2019-2020 World Health Organization (WHO) RSV EQA included 28 laboratories in 26 countries. The EQA panel evaluated performance in the molecular detection and subtyping of RSV-A and RSV-B. This manuscript describes the preparation, distribution, and analysis of the 2019-2020 WHO RSV EQA. METHODS: Panel isolates underwent whole genome sequencing and in silico primer matching. The final panel included nine contemporary, one historical virus and two negative controls. The EQA panel was manufactured and distributed by the UK National External Quality Assessment Service (UK NEQAS). National laboratories used WHO reference assays developed by the United States Centers for Disease Control and Prevention, an RSV subtyping assay developed by the Victorian Infectious Diseases Reference Laboratory (Australia), or other in-house or commercial assays already in use at their laboratories. RESULTS: An in silico analysis of isolates showed a good match to assay primer/probes. The panel was distributed to 28 laboratories. Isolates were correctly identified in 98% of samples for detection and 99.6% for subtyping. CONCLUSIONS: The WHO RSV EQA 2019-2020 showed that laboratories performed at high standards. Updating the composition of RSV molecular EQAs with contemporary strains to ensure representation of circulating strains, and ensuring primer matching with EQA panel viruses, is advantageous in assessing diagnostic competencies of laboratories. Ongoing EQAs are recommended because of continued evolution of mismatches between current circulating strains and existing primer sets

    findings from the World Mental Health Surveys

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    Funding Information: The Argentina survey 鈭 Estudio Argentino de Epidemiolog铆a en Salud Mental (EASM)鈥夆垝鈥墂as supported by a grant from the Argentinian Ministry of Health (Ministerio de Salud de la Naci贸n)鈥夆垝鈥(Grant Number 2002鈥17270/13鈥5). The S茫o Paulo Megacity Mental Health Survey is supported by the State of S茫o Paulo Research Foundation (FAPESP) Thematic Project Grant 03/00204鈥3. The Colombian National Study of Mental Health (NSMH) is supported by the Ministry of Social Protection. The Mental Health Study Medell铆n 鈥 Colombia was carried out and supported jointly by the Center for Excellence on Research in Mental Health (CES University) and the Secretary of Health of Medell铆n. The ESEMeD project is funded by the European Commission (Contracts QLG5鈥1999-01042; SANCO 2004123, and EAHC 20081308), the Piedmont Region (Italy)), Fondo de Investigaci贸n Sanitaria, Instituto de Salud Carlos III, Spain (FIS 00/0028), Ministerio de Ciencia y Tecnolog铆a, Spain (SAF 2000鈥158-CE), Generalitat de Catalunya (2017 SGR 452; 2014 SGR 748), Instituto de Salud Carlos III (CIBER CB06/02/0046, RETICS RD06/0011 REM-TAP), and other local agencies and by an unrestricted educational grant from GlaxoSmithKline. The Lebanese Evaluation of the Burden of Ailments and Needs of the Nation (L.E.B.A.N.O.N.) is supported by the Lebanese Ministry of Public Health, the WHO (Lebanon), National Institute of Health / Fogarty International Center (R03 TW006481鈥01), anonymous private donations to IDRAAC, Lebanon, and unrestricted grants from, Algorithm, AstraZeneca, Benta, Bella Pharma, Eli Lilly, Glaxo Smith Kline, Lundbeck, Novartis, OmniPharma, Pfizer, Phenicia, Servier, UPO. The Mexican National Comorbidity Survey (MNCS) is supported by The National Institute of Psychiatry Ramon de la Fuente (INPRFMDIES 4280) and by the National Council on Science and Technology (CONACyT-G30544- H), with supplemental support from the Pan American Health Organization (PAHO). The Nigerian Survey of Mental Health and Wellbeing (NSMHW) is supported by the WHO (Geneva), the WHO (Nigeria), and the Federal Ministry of Health, Abuja, Nigeria. The Portuguese Mental Health Study was carried out by the Department of Mental Health, Faculty of Medical Sciences, NOVA University of Lisbon, with collaboration of the Portuguese Catholic University, and was funded by Champalimaud Foundation, Gulbenkian Foundation, Foundation for Science and Technology (FCT) and Ministry of Health. The Romania WMH study projects 鈥淧olicies in Mental Health Area鈥 and 鈥淣ational Study regarding Mental Health and Services Use鈥 were carried out by National School of Public Health & Health Services Management (former National Institute for Research & Development in Health), with technical support of Metro Media Transilvania, the National Institute of Statistics-National Centre for Training in Statistics, SC Cheyenne Services SRL, Statistics Netherlands and were funded by Ministry of Public Health (former Ministry of Health) with supplemental support of Eli Lilly Romania SRL. The Psychiatric Enquiry to General Population in Southeast Spain 鈥 Murcia (PEGASUS-Murcia) Project has been financed by the Regional Health Authorities of Murcia (Servicio Murciano de Salud and Consejer铆a de Sanidad y Pol铆tica Social) and Fundaci贸n para la Formaci贸n e Investigaci贸n Sanitarias (FFIS) of Murcia. The US National Comorbidity Survey Replication (NCS-R) is supported by the National Institute of Mental Health (NIMH; U01-MH60220) with supplemental support from the National Institute of Drug Abuse (NIDA), the Substance Abuse and Mental Health Services Administration (SAMHSA), the Robert Wood Johnson Foundation (RWJF; Grant 044708), and the John W. Alden Trust. Dr. Stein is supported by the Medical Research Council of South Africa (MRC). Publisher Copyright: 漏 2023, The Author(s).Background: Posttraumatic stress disorder (PTSD) is associated with significant morbidity, but efficacious pharmacotherapy and psychotherapy are available. Data from the World Mental Health Surveys were used to investigate extent and predictors of treatment coverage for PTSD in high-income countries (HICs) as well as in low- and middle-income countries (LMICs). Methods: Seventeen surveys were conducted across 15 countries (9 HICs, 6 LMICs) by the World Health Organization (WHO) World Mental Health Surveys. Of 35,012 respondents, 914 met DSM-IV criteria for 12-month PTSD. Components of treatment coverage analyzed were: (a) any mental health service utilization; (b) adequate pharmacotherapy; (c) adequate psychotherapy; and (d) effective treatment coverage. Regression models investigated predictors of treatment coverage. Results: 12-month PTSD prevalence in trauma exposed individuals was 1.49 (S.E., 0.08). A total of 43.0% (S.E., 2.2) received any mental health services, with fewer receiving adequate pharmacotherapy (13.5%), adequate psychotherapy (17.2%), or effective treatment coverage (14.4%), and with聽all components of treatment coverage lower in LMICs than HICs. In a multivariable model having insurance (OR = 2.31, 95 CI 1.17, 4.57) and severity of symptoms (OR =.35, 95% CI 0.18, 0.70) were predictive of effective treatment coverage. Conclusion: There is a clear need to improve pharmacotherapy and psychotherapy coverage for PTSD, particularly in those with mild symptoms, and especially in LMICs. Universal health care insurance can be expected to increase effective treatment coverage and therefore improve outcomes.publishersversionpublishe

    Seasonal and inter-seasonal RSV activity in the European Region during the COVID-19 pandemic from autumn 2020 to summer 2022.

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    BACKGROUND: The emergence of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in early 2020 and subsequent implementation of public health and social measures (PHSM) disrupted the epidemiology of respiratory viruses. This work describes the epidemiology of respiratory syncytial virus (RSV) observed during two winter seasons (weeks 40-20) and inter-seasonal periods (weeks 21-39) during the pandemic between October 2020 and September&nbsp;2022. METHODS: Using data submitted to The European Surveillance System (TESSy) by countries or territories in the World Health Organization (WHO) European Region between weeks 40/2020 and 39/2022, we aggregated country-specific weekly RSV counts of sentinel, non-sentinel and Severe Acute Respiratory Infection (SARI) surveillance specimens and calculated percentage positivity. Results for both 2020/21 and 202&frac12;2 seasons and inter-seasons were compared with pre-pandemic 2016/17 to 2019/20 seasons and&nbsp;inter-seasons. RESULTS: Although more specimens were tested than in pre-COVID-19 pandemic seasons, very few RSV detections were reported during the 2020/21 season in all surveillance systems. During the 2021 inter-season, a gradual increase in detections was observed in all systems. In 202&frac12;2, all systems saw early peaks of RSV infection, and during the 2022 inter-seasonal period, patterns of detections were closer to those seen before the COVID-19&nbsp;pandemic. CONCLUSION: RSV surveillance continued throughout the COVID-19 pandemic, with an initial reduction in transmission, followed by very high and out-of-season RSV circulation (summer 2021) and then an early start of the 202&frac12;2 season. As of the 2022/23 season, RSV circulation had not yet&nbsp;normalised.</p
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