Institution
Oswaldo Cruz Foundation
Facility•Rio de Janeiro, Brazil•
About: Oswaldo Cruz Foundation is a facility organization based out in Rio de Janeiro, Brazil. It is known for research contribution in the topics: Population & Trypanosoma cruzi. The organization has 18673 authors who have published 36752 publications receiving 802378 citations. The organization is also known as: Fundação Oswaldo Cruz & FIOCRUZ.
Topics: Population, Trypanosoma cruzi, Immune system, Leishmania, Health care
Papers published on a yearly basis
Papers
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TL;DR: The economic burden associated with d Dengue in Brazil is substantial with large variations in reported cases and consequently costs reflecting the dynamic of dengue transmission.
Abstract: Dengue is an increasing public health concern in Brazil. There is a need for an updated evaluation of the economic impact of dengue within the country. We undertook this multicenter study to evaluate the economic burden of dengue in Brazil.
132 citations
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TL;DR: NLRP12/NLRP3-dependent activation of caspase-1 is likely to be a key event in mediating systemic production of IL-1β and hypersensitivity to secondary bacterial infection during malaria.
Abstract: Cyclic paroxysm and high fever are hallmarks of malaria and are associated with high levels of pyrogenic cytokines, including IL-1β. In this report, we describe a signature for the expression of inflammasome-related genes and caspase-1 activation in malaria. Indeed, when we infected mice, Plasmodium infection was sufficient to promote MyD88-mediated caspase-1 activation, dependent on IFN-γ-priming and the expression of inflammasome components ASC, P2X7R, NLRP3 and/or NLRP12. Pro-IL-1β expression required a second stimulation with LPS and was also dependent on IFN-γ-priming and functional TNFR1. As a consequence of Plasmodium-induced caspase-1 activation, mice produced extremely high levels of IL-1β upon a second microbial stimulus, and became hypersensitive to septic shock. Therapeutic intervention with IL-1 receptor antagonist prevented bacterial-induced lethality in rodents. Similar to mice, we observed a significantly increased frequency of circulating CD14+CD16−Caspase-1+ and CD14dimCD16+Caspase-1+ monocytes in peripheral blood mononuclear cells from febrile malaria patients. These cells readily produced large amounts of IL-1β after stimulation with LPS. Furthermore, we observed the presence of inflammasome complexes in monocytes from malaria patients containing either NLRP3 or NLRP12 pyroptosomes. We conclude that NLRP12/NLRP3-dependent activation of caspase-1 is likely to be a key event in mediating systemic production of IL-1β and hypersensitivity to secondary bacterial infection during malaria.
132 citations
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Harvard University1, Centers for Disease Control and Prevention2, Johns Hopkins University Applied Physics Laboratory3, Columbia University4, Cooperative Research Centre5, Carnegie Mellon University6, Johns Hopkins University7, University of Massachusetts Amherst8, University of Florida9, University of Notre Dame10, University of Oxford11, University of London12, University of Exeter13, Oswaldo Cruz Foundation14, Indian Statistical Institute15, Mount Holyoke College16, RAND Corporation17, Miami University18, University of California, San Francisco19, Hokkaido University20, University of Minnesota21, University of São Paulo22, University of Miami23, Virginia Tech24, University of South Florida25, Stanford University26, University of Georgia27, University of KwaZulu-Natal28, State University of New York Upstate Medical University29, University of Michigan30, West Virginia University31, University of Maryland, College Park32, Puerto Rico Department of Health33, University of Nebraska Medical Center34, National Oceanic and Atmospheric Administration35, United States Department of Health and Human Services36, United States Department of Energy Office of Science37, Defense Intelligence Agency38
TL;DR: An open collaborative forecasting challenge to assess probabilistic forecasts for seasonal epidemics of dengue, a major global public health problem, revealed that average forecast skill was lower for models including biologically meaningful data and mechanisms and that both multimodel and multiteam ensemble forecasts consistently outperformed individual model forecasts.
Abstract: A wide range of research has promised new tools for forecasting infectious disease dynamics, but little of that research is currently being applied in practice, because tools do not address key public health needs, do not produce probabilistic forecasts, have not been evaluated on external data, or do not provide sufficient forecast skill to be useful. We developed an open collaborative forecasting challenge to assess probabilistic forecasts for seasonal epidemics of dengue, a major global public health problem. Sixteen teams used a variety of methods and data to generate forecasts for 3 epidemiological targets (peak incidence, the week of the peak, and total incidence) over 8 dengue seasons in Iquitos, Peru and San Juan, Puerto Rico. Forecast skill was highly variable across teams and targets. While numerous forecasts showed high skill for midseason situational awareness, early season skill was low, and skill was generally lowest for high incidence seasons, those for which forecasts would be most valuable. A comparison of modeling approaches revealed that average forecast skill was lower for models including biologically meaningful data and mechanisms and that both multimodel and multiteam ensemble forecasts consistently outperformed individual model forecasts. Leveraging these insights, data, and the forecasting framework will be critical to improve forecast skill and the application of forecasts in real time for epidemic preparedness and response. Moreover, key components of this project-integration with public health needs, a common forecasting framework, shared and standardized data, and open participation-can help advance infectious disease forecasting beyond dengue.
132 citations
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University of Pittsburgh1, University of Iowa2, University of Puerto Rico3, Oswaldo Cruz Foundation4, University of Southern Denmark5, University of Colorado Denver6, University of British Columbia7, Federal University of Rio de Janeiro8, University of the Philippines Manila9, Johns Hopkins University10
TL;DR: The results support the highly heterogeneous nature of OFCs and illustrate the utility of meta-analysis for discovering new genetic risk factors.
Abstract: Nonsyndromic orofacial clefts (OFCs) are a heterogeneous group of common craniofacial birth defects with complex etiologies that include genetic and environmental risk factors. OFCs are commonly categorized as cleft lip with or without cleft palate (CL/P) and cleft palate alone (CP), which have historically been analyzed as distinct entities. Genes for both CL/P and CP have been identified via multiple genome-wide linkage and association studies (GWAS); however, altogether, known variants account for a minority of the estimated heritability in risk to these craniofacial birth defects. We performed genome-wide meta-analyses of CL/P, CP, and all OFCs across two large, multiethnic studies. We then performed population-specific meta-analyses in sub-samples of Asian and European ancestry. In addition to observing associations with known variants, we identified a novel genome-wide significant association between SNPs located in an intronic TP63 enhancer and CL/P (p = 1.16 × 10−8). Several novel loci with compelling candidate genes approached genome-wide significance on 4q21.1 (SHROOM3), 12q13.13 (KRT18), and 8p21 (NRG1). In the analysis of all OFCs combined, SNPs near FOXE1 reached genome-wide significance (p = 1.33 × 10−9). Our results support the highly heterogeneous nature of OFCs and illustrate the utility of meta-analysis for discovering new genetic risk factors.
132 citations
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TL;DR: A direct correlation between LD formation and PGE2 production was observed, indicating that ML‐induced LDs constitute intracellular sites for eicosanoid synthesis and that foamy cells may be critical regulators in subverting the immune response in leprosy.
Abstract: A hallmark of LL is the accumulation of Virchow's foamy macrophages. However, the origin and nature of these lipids, as well as their function and contribution to leprosy disease, remain unclear. We herein show that macrophages present in LL dermal lesions are highly positive for ADRP, suggesting that their foamy aspect is at least in part derived from LD (also known as lipid bodies) accumulation induced during ML infection. Indeed, the capacity of ML to induce LD formation was confirmed in vivo via an experimental model of mouse pleurisy and in in vitro studies with human peripheral monocytes and murine peritoneal macrophages. Furthermore, infected cells were shown to propagate LD induction to uninfected, neighboring cells by generating a paracrine signal, for which TLR2 and TLR6 were demonstrated to be essential. However, TLR2 and TLR6 deletions affected LD formation in bacterium-bearing cells only partially, suggesting the involvement of alternative receptors of the innate immune response besides TLR2/6 for ML recognition by macrophages. Finally, a direct correlation between LD formation and PGE(2) production was observed, indicating that ML-induced LDs constitute intracellular sites for eicosanoid synthesis and that foamy cells may be critical regulators in subverting the immune response in leprosy.
132 citations
Authors
Showing all 18833 results
Name | H-index | Papers | Citations |
---|---|---|---|
Douglas T. Golenbock | 123 | 317 | 61267 |
Guy A. Zimmerman | 109 | 328 | 39740 |
David Brown | 105 | 1257 | 46827 |
Liam Smeeth | 104 | 753 | 53433 |
Ann M. Dvorak | 99 | 437 | 41073 |
David C. Spray | 95 | 400 | 28732 |
Theodore A. Slotkin | 89 | 575 | 30070 |
Fernando Q. Cunha | 88 | 682 | 31501 |
Mauro M. Teixeira | 86 | 713 | 31301 |
Ricardo T. Gazzinelli | 86 | 340 | 28233 |
Peter F. Weller | 85 | 331 | 22005 |
João B. Calixto | 81 | 460 | 23029 |
Frederic J. Seidler | 80 | 372 | 19564 |
João Santana da Silva | 80 | 399 | 19060 |
Deborah Carvalho Malta | 77 | 706 | 61000 |