92 research outputs found
Intersectoral collaboration in the COVID-19 response in Latin America and the Caribbean
World Health Organization (WHO) / Pan American Health Organization (PAHO) encouraged the utilization of whole-of-society and whole-of-government strategic approaches to increase countries’ resilience towards mitigating the impact of the COVID-19 pandemic. Strategies included the implementation of multi-sectoral, multi-partner and multi-stakeholder planning, coordination, consultation, and action. We reviewed the experiences of three Latin American and Caribbean countries, related to the implementation of collaborative strategies in tackling COVID-19, specifically the nature of the collaboration, the dynamics and the stakeholders involved. A systematic literature review identified relevant publications and content analysis was conducted to determine the collaborative strategies. Colombia, Costa Rica, and Trinidad and Tobago were selected as case studies since they were from different LAC subregions and because of the accessibility of relevant literature. In the three countries, the pandemic response was coordinated by a national executive committee, led by the Ministry of Health. Intersectoral collaboration was evident in each, with the key stakeholders being public sector agencies, the private/corporate sector, private/non-profit, academic institutions, and international agencies. It was used primarily to facilitate data-driven, evidenced-informed decision-making and guidelines; to expand clinical care capacity and strengthen the national medical response; and to provide support for the most vulnerable populations. While the institutionalization of intersectoral collaboration can be recommended for the health sector beyond the pandemic, research is needed to evaluate the impact of specific collaborative strategies as well as barriers and facilitators
Convergent Sets of Data from In Vivo and In Vitro Methods Point to an Active Role of Hsp60 in Chronic Obstructive Pulmonary Disease Pathogenesis
BACKGROUND: It is increasingly clear that some heat shock proteins (Hsps) play a role in inflammation. Here, we report results showing participation of Hsp60 in the pathogenesis of chronic obstructive pulmonary diseases (COPD), as indicated by data from both in vivo and in vitro analyses.
METHODS AND RESULTS: Bronchial biopsies from patients with stable COPD, smoker controls with normal lung function, and non-smoker controls were studied. We quantified by immunohistochemistry levels of Hsp10, Hsp27, Hsp40, Hsp60, Hsp70, Hsp90, and HSF-1, along with levels of inflammatory markers. Hsp10, Hsp40, and Hsp60 were increased during progression of disease. We found also a positive correlation between the number of neutrophils and Hsp60 levels. Double-immunostaining showed that Hsp60-positive neutrophils were significantly increased in COPD patients. We then investigated in vitro the effect on Hsp60 expression in bronchial epithelial cells (16HBE) caused by oxidative stress, a hallmark of COPD mucosa, which we induced with H\u2082O\u2082. This stressor determined increased levels of Hsp60 through a gene up-regulation mechanism involving NFkB-p65. Release of Hsp60 in the extracellular medium by the bronchial epithelial cells was also increased after H\u2082O\u2082 treatment in the absence of cell death.
CONCLUSIONS: This is the first report clearly pointing to participation of Hsps, particularly Hsp60, in COPD pathogenesis. Hsp60 induction by NFkB-p65 and its release by epithelial cells after oxidative stress can have a role in maintaining inflammation, e.g., by stimulating neutrophils activity. The data open new scenarios that might help in designing efficacious anti-inflammatory therapies centered on Hsp60 and applicable to COP
A Mycobacterium leprae Hsp65 Mutant as a Candidate for Mitigating Lupus Aggravation in Mice
Hsp60 is an abundant and highly conserved family of intracellular molecules. Increased levels of this family of proteins have been observed in the extracellular compartment in chronic inflammation. Administration of M. leprae Hsp65 [WT] in [NZBxNZW]F1 mice accelerates the Systemic Lupus Erythematosus [SLE] progression whereas the point mutated K409A Hsp65 protein delays the disease. Here, the biological effects of M. leprae Hsp65 Leader pep and K409A pep synthetic peptides, which cover residues 352–371, are presented. Peptides had immunomodulatory effects similar to that observed with their respective proteins on survival and the combined administration of K409A+Leader pep or K409A pep+WT showed that the mutant forms were able to inhibit the deleterious effect of WT on mortality, indicating the neutralizing potential of the mutant molecules in SLE progression. Molecular modeling showed that replacing Lysine by Alanine affects the electrostatic potential of the 352–371 region. The number of interactions observed for WT is much higher than for Hsp65 K409A and mouse Hsp60. The immunomodulatory effects of the point-mutated protein and peptide occurred regardless of the catalytic activity. These findings may be related to the lack of effect on survival when F1 mice were inoculated with Hsp60 or K409A pep. Our findings indicate the use of point-mutated Hsp65 molecules, such as the K409A protein and its corresponding peptide, that may minimize or delay the onset of SLE, representing a new approach to the treatment of autoimmune diseases
Administration of M. leprae Hsp65 Interferes with the Murine Lupus Progression
The heat shock protein [Hsp] family guides several steps during protein synthesis, are abundant in prokaryotic and eukaryotic cells, and are highly conserved during evolution. The Hsp60 family is involved in assembly and transport of proteins, and is expressed at very high levels during autoimmunity or autoinflammatory phenomena. Here, the pathophysiological role of the wild type [WT] and the point mutated K409A recombinant Hsp65 of M. leprae in an animal model of Systemic Lupus Erythematosus [SLE] was evaluated in vivo using the genetically homogeneous [NZBxNZW]F1 mice. Anti-DNA and anti-Hsp65 antibodies responsiveness was individually measured during the animal's life span, and the mean survival time [MST] was determined. The treatment with WT abbreviates the MST in 46%, when compared to non-treated mice [p<0.001]. An increase in the IgG2a/IgG1 anti-DNA antibodies ratio was also observed in animals injected with the WT Hsp65. Incubation of BALB/c macrophages with F1 serum from WT treated mice resulted in acute cell necrosis; treatment of these cells with serum from K409A treated mice did not cause any toxic effect. Moreover, the involvement of WT correlates with age and is dose-dependent. Our data suggest that Hsp65 may be a central molecule intervening in the progression of the SLE, and that the point mutated K409A recombinant immunogenic molecule, that counteracts the deleterious effect of WT, may act mitigating and delaying the development of SLE in treated mice. This study gives new insights into the general biological role of Hsp and the significant impact of environmental factors during the pathogenesis of this autoimmune process
A Possible Alignment between the Orbits of Planetary Systems and their Visual Binary Companions
Astronomers do not have a complete picture of the effects of wide-binary companions (semimajor axes greater than 100 au) on the formation and evolution of exoplanets. We investigate these effects using new data from Gaia Early Data Release 3 and the Transiting Exoplanet Survey Satellite mission to characterize wide-binary systems with transiting exoplanets. We identify a sample of 67 systems of transiting exoplanet candidates (with well-determined, edge-on orbital inclinations) that reside in wide visual binary systems. We derive limits on orbital parameters for the wide-binary systems and measure the minimum difference in orbital inclination between the binary and planet orbits. We determine that there is statistically significant difference in the inclination distribution of wide-binary systems with transiting planets compared to a control sample, with the probability that the two distributions are the same being 0.0037. This implies that there is an overabundance of planets in binary systems whose orbits are aligned with those of the binary. The overabundance of aligned systems appears to primarily have semimajor axes less than 700 au. We investigate some effects that could cause the alignment and conclude that a torque caused by a misaligned binary companion on the protoplanetary disk is the most promising explanation. © 2022. The Author(s). Published by the American Astronomical Society.AB022006; ANR-15-IDEX-01; 80NSSC19K1727; National Science Foundation, NSF; National Aeronautics and Space Administration, NASA: 18-2XRP18_2-0136; New York Community Trust, NYCT; Australian Research Council, ARC; National Research Foundation, NRF; Japan Society for the Promotion of Science, KAKEN: 15H02063, 18H05442, 20K14521, 22000005, JP17H04574, JP18H05439, JP20J21872, JP20K14518, JP21K13955; Ministry of Education, Culture, Sports, Science and Technology, MEXT; Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, SNF; Fonds De La Recherche Scientifique - FNRS, FNRS: FRFC 2.5.594.09; Ministry of Science, ICT and Future Planning, MSIP; Nagoya University, NU: 10147207, 10147214; Université de Liège, ULg; Universidad Católica de la Santísima Concepción, UCSC: DI-FIAI 03/2021; National Astronomical Observatory of Japan, NAOJ; Precursory Research for Embryonic Science and Technology, PRESTO: JPMJPR1775; Instituto de Astrofísica de Andalucía, IAA: SEV-2017-0709This paper includes data collected by the TESS mission, which are publicly available from the Mikulski Archive for Space Telescopes (MAST). Funding for the TESS mission is provided by NASA’s Science Mission directorate.K.K.M. acknowledges support from the New York Community Trust's Fund for Astrophysical Research.The research leading to these results has received funding from the ARC grant for Concerted Research Actions, financed by the Wallonia-Brussels Federation. TRAPPIST is funded by the Belgian Fund for Scientific Research (Fond National de la Recherche Scientifique, FNRS) under the grant FRFC 2.5.594.09.F. TRAPPIST-North is a project funded by the University of Liège (Belgium), in collaboration with Cadi Ayyad University of Marrakech (Morocco).This work is partly supported by JSPS KAKENHI grant No. JP20K14518, and by Astrobiology Center SATELLITE Research project AB022006.This work is partly supported by JSPS KAKENHI grant No. JP21K13955.This work is partly supported by JSPS KAKENHI grant No. 20K14521.This paper is based on observations made with the MuSCAT3 instrument, developed by the Astrobiology Center and under financial supports by JSPS KAKENHI (JP18H05439) and JST PRESTO (JPMJPR1775), at Faulkes Telescope North on Maui, HI, operated by the Las Cumbres Observatory.The IRSF project is a collaboration between Nagoya University and the South African Astronomical Observatory (SAAO) supported by the Grants-in-Aid for Scientific Research on Priority Areas (A) (grant Nos. 10147207 and 10147214) and Optical & Near-Infrared Astronomy Inter-University Cooperation Program, from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan and the National Research Foundation (NRF) of South Africa.C.R.-L. acknowledges financial support from the State Agency for Research of the Spanish MCIU through the Center of Excellence Severo Ochoa award for the Instituto de Astrofísica de Andalucía (SEV-2017-0709).M.T. is supported by MEXT/JSPS KAKENHI grant Nos. 18H05442, 15H02063, and 22000005.This work is partly supported by JSPS KAKENHI grant No. JP18H05439, and JST PRESTO grant No. JPMJPR1775, and a University Research Support Grant from the National Astronomical Observatory of Japan (NAOJ).P.J.A. acknowledges support from grant AYA2016-79425-C3-3-P of the Spanish Ministry of Economy and Competitiveness (MINECO) and the Centre of Excellence “Severo Ochoa” award to the Instituto de Astrofísica de Andalucía (SEV-2017-0709)
A Possible Alignment Between the Orbits of Planetary Systems and their Visual Binary Companions
Astronomers do not have a complete picture of the effects of wide-binary companions (semimajor axes greater than 100 au) on the formation and evolution of exoplanets. We investigate these effects using new data from Gaia Early Data Release 3 and the Transiting Exoplanet Survey Satellite mission to characterize wide-binary systems with transiting exoplanets. We identify a sample of 67 systems of transiting exoplanet candidates (with well-determined, edge-on orbital inclinations) that reside in wide visual binary systems. We derive limits on orbital parameters for the wide-binary systems and measure the minimum difference in orbital inclination between the binary and planet orbits. We determine that there is statistically significant difference in the inclination distribution of wide-binary systems with transiting planets compared to a control sample, with the probability that the two distributions are the same being 0.0037. This implies that there is an overabundance of planets in binary systems whose orbits are aligned with those of the binary. The overabundance of aligned systems appears to primarily have semimajor axes less than 700 au. We investigate some effects that could cause the alignment and conclude that a torque caused by a misaligned binary companion on the protoplanetary disk is the most promising explanation
Mirada a las Políticas de Aseguramiento Universal en Salud en el Perú
Midori de Habich, Gerente de IAGes. Evento realizado el 19 de junio de 2018 en el Campus San Isidro de la Universidad Peruana de Ciencias Aplicadas (UPC).¿Qué es una reforma de salud? En esta charla, Midori de Habich describirá la tendencia de la reforma de salud en los últimos quince años en el Perú, las tensiones recurrentes entorno a esta reforma y reflexiones para mirar el futuro
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