Evaluation of the bibliometric scenario of the Delphi method with Brazilian affiliations

The Delphi method is a technique used to reach consensus among specialists in an area who will be able to predict demands or analyze conjunctures about strategic themes. Within this context, the present work consisted of a bibliometric evaluation performed in the Scopus database with the aid of VOSviewer software, prioritizing journals with an affiliation of Brazilian institutions and that made use of the Delphi method for the development of their research. Data collection went through validation stages, and the results obtained showed that this tool was used in several areas of knowledge, with great emphasis on health, more specifically in Medicine, Nursing, and Public health. Together, these three areas accounted for more than 60% of publications made available

The Work Disability Prevention CIHR Strategic Training Program: Program Performance After 5 Years of Implementation

Introduction The Work Disability Prevention (WDP) Canadian Institutes of Health Research (CIHR) Strategic Training Program was developed in 2001 and is a unique program in the world. The main objective of this program is to help future researchers develop transdisciplinary knowledge, skills and attitudes regarding WDP. The purpose of this paper is to present a descriptive portrait of the program's performance over the past 5 years, as well as the trainees' and alumni's perspectives on the WDP CIHR Training Program. Methods Data on the program's performance were collected from documents in the program records. The trainees' opinions on the WDP training program were obtained through focus groups and telephone interviews. The data collected were compiled and divided into themes to summarize the qualitative findings pertaining to each question. Results From 2003 to 2007, five successive summer sessions have been offered, involving 44 high-caliber applicants from nine countries, 34 mentors and collaborators, 29 guest speakers and 15 stakeholders. Overall, trainees appreciated the networking, the opportunity to interact with people from different disciplines and countries, the openness, and the international perspective and uniqueness of the program. The least appreciated aspects concerned mainly the e-learning course, evaluations and information on optional courses. The coordination and logistics were judged appropriate and several topics were suggested to improve the program quality. Conclusion In general, the program implementation went well, with good participation from mentors, speakers and stakeholders; the program was appreciated by the trainees and alumni. This paper underscores the importance of the international perspective, the transdisciplinarity and the scientific networking established through the progra

Biodistributions, Myelosuppression and Toxicities in Mice Treated with an Anti-CD45 Antibody Labeled with the α-Emitting Radionuclides Bismuth-213 or Astatine-211

We previously investigated the potential of targeted radiotherapy using a bismuth-213- labeled anti-CD45 antibody to replace total body irradiation as conditioning for hematopoietic cell transplantation in a canine model. While this approach allowed sustained marrow engraftment, limited availability, high cost and short half-life of bismuth-213 induced us to investigate an alternative α-emitting radionuclide, astatine-211, for the same application. Biodistribution and toxicity studies were conducted with conjugates of the anti-murine CD45 antibody 30F11 with either bismuth-213 or astatine-211. Mice were injected with 2-50 μCi on 10 μg or 20 μCi on 2 or 40 μg 30F11 conjugate. Biodistribution studies showed that the spleen contained the highest concentration of radioactivity, ranging from 167±23 to 417±109 % injected dose/gram (%ID/g) after injection of the astatine-211 conjugate and 45±9 to 166±11 %ID/g after injection of the bismuth-213 conjugate. The higher concentrations observed for astatine-211- labeled 30F11 were due to its longer half-life, which permitted better localization of isotope to the spleen before decay. Astatine-211 was more effective at producing myelosuppression for the same quantity of injected radioactivity. All mice injected with 20 or 50 μCi astatine-211 but none with the same quantities of bismuth-213 had lethal myeloablation. Severe reversible acute hepatic toxicity occurred with 50 μCi bismuth-213, but not with lower doses of bismuth-213 or with any dose of astatine-211. No renal toxicity occurred with either radionuclide. The data suggest that smaller quantities of astatine-211-labeled anti-CD45 antibody are sufficient to achieve myelosuppression and myeloablation with less non-hematological toxicity compared with bismuth-213-labeled antibody

Desigualdades sociais em saúde e o câncer de colo do útero no Brasil: uma análise da realidade brasileira

A detecção precoce do câncer de colo do útero, além de outros fatores, está intimamente relacionada com a prevenção e tratamento da infecção pelo papiloma vírus humano (HPV). Todavia, vários elementos contribuem para a detecção tardia e dificuldade de acesso aos tratamentos adequados. Por isso, objetivamos realizar um debate sobre os principais fatores condicionantes para a detecção tardia do câncer de colo do útero na Política Pública de Saúde do Brasil. Como método de construção deste trabalho realizamos uma abordagem qualitativa através de pesquisa de bibliografias relacionadas à temática. Percebemos com base nas bibliografias que, na população brasileira, os fatores de risco para o desenvolvimento de câncer de colo do útero estão intrinsecamente relacionados com o baixo nível socioeconômico e as grandes dificuldades de acesso à rede de atenção básica.Facultad de Trabajo Socia

Desigualdades sociais em saúde e o câncer de colo do útero no Brasil: uma análise da realidade brasileira

A detecção precoce do câncer de colo do útero, além de outros fatores, está intimamente relacionada com a prevenção e tratamento da infecção pelo papiloma vírus humano (HPV). Todavia, vários elementos contribuem para a detecção tardia e dificuldade de acesso aos tratamentos adequados. Por isso, objetivamos realizar um debate sobre os principais fatores condicionantes para a detecção tardia do câncer de colo do útero na Política Pública de Saúde do Brasil. Como método de construção deste trabalho realizamos uma abordagem qualitativa através de pesquisa de bibliografias relacionadas à temática. Percebemos com base nas bibliografias que, na população brasileira, os fatores de risco para o desenvolvimento de câncer de colo do útero estão intrinsecamente relacionados com o baixo nível socioeconômico e as grandes dificuldades de acesso à rede de atenção básica.Facultad de Trabajo Socia

A functional genomics approach reveals suggestive quantitative trait loci associated with combined TLR4 and BCP crystal-induced inflammation and osteoarthritis

Objective: Basic calcium phosphate (BCP) crystals can activate the NLRP3 inflammasome and are potentially involved in the pathogenesis of osteoarthritis (OA). In order to elucidate relevant inflammatory mechanisms in OA, we used a functional genomics approach to assess genetic variation influencing BCP crystal-induced cytokine production. Method: Peripheral blood mononuclear cells (PBMCs) were isolated from healthy volunteers who were previously genotyped and stimulated with BCP crystals and/or lipopolysaccharide (LPS) after which cytokines release was assessed. Cytokine quantitative trait locus (cQTL) mapping was performed. For in vitro validation of the cQTL located in anoctamin 3 (ANO3), PBMCs were incubated with Tamoxifen and Benzbromarone prior to stimulation. Additionally, we performed co-localisation analysis of our top cQTLs with the most recent OA meta-analysis of genome-wide association studies (GWAS). Results: We observed that BCP crystals and LPS synergistically induce IL-1β in human PBMCs. cQTL analysis revealed several suggestive loci influencing cytokine release upon stimulation, among which are quantitative trait locus annotated to ANO3 and GLIS3. As functional validation, anoctamin inhibitors reduced IL-1β release in PBMCs after stimulation. Co-localisation analysis showed that the GLIS3 locus was shared between LPS/BCP crystal-induced IL-1β and genetic association with Knee OA. Conclusions: We identified and functionally validated a new locus, ANO3, associated with LPS/BCP crystal-induced inflammation in PBMCs. Moreover, the cQTL in the GLIS3 locus co-localises with the previously found locus associated with Knee OA, suggesting that this Knee OA locus might be explained through an inflammatory mechanism. These results form a basis for further exploration of inflammatory mechanisms in OA.</p

Exosomes secreted by cardiomyocytes subjected to ischaemia promote cardiac angiogenesis

Funding Information: This work was supported by European Regional Development Fund (FEDER) through the Operational Program for Competitiveness Factors (COMPETE) [HealthyAging2020 CENTRO-01-0145-FEDER-000012-N2323, POCI-01-0145-FEDER-016385, POCI-01-0145-FEDER-007440 to CNC.IBILI, POCI-01-0145-FEDER-007274 to i3S/INEB and NORTE-01-0145-FEDER-000012 to T.L.L.]; national funds through the Portuguese Foundation for Science and Technology (FCT) [PTDC/SAU-ORG/119296/2010, PTDC/ NEU-OSD/0312/2012, PESTC/ SAU/UI3282/2013-2014, MITP-TB/ECE/0013/ 2013, FCT-UID/NEU/04539/2013], PD/BD/52294/2013 to T.M.R.R., SFRH/ BD/85556/2012 (co-financed by QREN) to V.C.S]; Lisboa Portugal Regional Operational Programme (LISBOA 2020) and Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement; and by INFARMED Autoridade Nacional do Medicamento e Produtos de Saúde, I.P. [FIS-FIS-2015-01_CCV_20150630-157]. Publisher Copyright: © 2017 The Author.Aims Myocardial infarction (MI) is the leading cause of morbidity and mortality worldwide and results from an obstruction in the blood supply to a region of the heart. In an attempt to replenish oxygen and nutrients to the deprived area, affected cells release signals to promote the development of new vessels and confer protection against MI. However, the mechanisms underlying the growth of new vessels in an ischaemic scenario remain poorly understood. Here, we show that cardiomyocytes subjected to ischaemia release exosomes that elicit an angiogenic response of endothelial cells (ECs). Methods and results Exosomes secreted by H9c2 myocardial cells and primary cardiomyocytes, cultured either in control or ischaemic conditions were isolated and added to ECs. We show that ischaemic exosomes, in comparison with control exosomes, confer protection against oxidative-induced lesion, promote proliferation, and sprouting of ECs, stimulate the formation of capillary-like structures and strengthen adhesion complexes and barrier properties. Moreover, ischaemic exosomes display higher levels of metalloproteases (MMP) and promote the secretion of MMP by ECs. We demonstrate that miR-222 and miR-143, the relatively most abundant miRs in ischaemic exosomes, partially recapitulate the angiogenic effect of exosomes. Additionally, we show that ischaemic exosomes stimulate the formation of new functional vessels in vivo using in ovo and Matrigel plug assays. Finally, we demonstrate that intramyocardial delivery of ischaemic exosomes improves neovascularization following MI. Conclusions This study establishes that exosomes secreted by cardiomyocytes under ischaemic conditions promote heart angiogenesis, which may pave the way towards the development of add-on therapies to enhance myocardial blood supply.publishersversionpublishe

Climate Change, Human Health, and Resilience in the Holocene

Climate change is an indisputable threat to human health, especially for societies already confronted with rising social inequality, political and economic uncertainty, and a cascade of concurrent environmental challenges. Archaeological data about past climate and environment provide an important source of evidence about the potential challenges humans face and the long-term outcomes of alternative short-term adaptive strategies. Evidence from well-dated archaeological human skeletons and mummified remains speaks directly to patterns of human health over time through changing circumstances. Here, we describe variation in human epidemiological patterns in the context of past rapid climate change (RCC) events and other periods of past environmental change. Case studies confirm that human communities responded to environmental changes in diverse ways depending on historical, sociocultural, and biological contingencies. Certain factors, such as social inequality and disproportionate access to resources in large, complex societies may influence the probability of major sociopolitical disruptions and reorganizations—commonly known as “collapse.” This survey of Holocene human–environmental relations demonstrates how flexibility, variation, and maintenance of Indigenous knowledge can be mitigating factors in the face of environmental challenges. Although contemporary climate change is more rapid and of greater magnitude than the RCC events and other environmental changes we discuss here, these lessons from the past provide clarity about potential priorities for equitable, sustainable development and the constraints of modernity we must address

Climate change, human health, and resilience in the Holocene

Climate change is an indisputable threat to human health, especially for societies already confronted with rising social inequality, political and economic uncertainty, and a cascade of concurrent environmental challenges. Archaeological data about past climate and environment provide an important source of evidence about the potential challenges humans face and the long-term outcomes of alternative short-term adaptive strategies. Evidence from well-dated archaeological human skeletons and mummified remains speaks directly to patterns of human health over time through changing circumstances. Here, we describe variation in human epidemiological patterns in the context of past rapid climate change (RCC) events and other periods of past environmental change. Case studies confirm that human communities responded to environmental changes in diverse ways depending on historical, sociocultural, and biological contingencies. Certain factors, such as social inequality and disproportionate access to resources in large, complex societies may influence the probability of major sociopolitical disruptions and reorganizations—commonly known as “collapse.” This survey of Holocene human–environmental relations demonstrates how flexibility, variation, and maintenance of Indigenous knowledge can be mitigating factors in the face of environmental challenges. Although contemporary climate change is more rapid and of greater magnitude than the RCC events and other environmental changes we discuss here, these lessons from the past provide clarity about potential priorities for equitable, sustainable development and the constraints of modernity we must address

Power efficiency of outer hair cell somatic electromotility

© 2009 Rabbitt et al. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS Computational Biology 5 (2009): e1000444, doi:10.1371/journal.pcbi.1000444.Cochlear outer hair cells (OHCs) are fast biological motors that serve to enhance the vibration of the organ of Corti and increase the sensitivity of the inner ear to sound. Exactly how OHCs produce useful mechanical power at auditory frequencies, given their intrinsic biophysical properties, has been a subject of considerable debate. To address this we formulated a mathematical model of the OHC based on first principles and analyzed the power conversion efficiency in the frequency domain. The model includes a mixture-composite constitutive model of the active lateral wall and spatially distributed electro-mechanical fields. The analysis predicts that: 1) the peak power efficiency is likely to be tuned to a specific frequency, dependent upon OHC length, and this tuning may contribute to the place principle and frequency selectivity in the cochlea; 2) the OHC power output can be detuned and attenuated by increasing the basal conductance of the cell, a parameter likely controlled by the brain via the efferent system; and 3) power output efficiency is limited by mechanical properties of the load, thus suggesting that impedance of the organ of Corti may be matched regionally to the OHC. The high power efficiency, tuning, and efferent control of outer hair cells are the direct result of biophysical properties of the cells, thus providing the physical basis for the remarkable sensitivity and selectivity of hearing.This work was supported by NIDCD R01 DC04928 (Rabbitt), NIDCD R01 DC00384 (Brownell) and NASA Ames GSRA56000135 (Breneman)