RESUMO A pandemia de Covid-19 reforçou a necessidade de esforços globais para garantir cobertura e acesso universal à saúde, impondo desafios na gestão da Atenção Primária à Saúde (APS). Este estudo objetivou desen- volver e aplicar um instrumento de avaliação da responsividade das Unidades Básicas de Saúde (UBS) diante da Covid-19, baseado na coprodução entre pesquisadores universitários e equipes técnicas da APS. O instrumento, dividido em dois módulos, incluiu identificação; horário de funcionamento; processo de trabalho; estrutura física, equipamentos, mobiliário, suprimentos e Equipamentos de Proteção Individual (EPI); atendimento, exames e acompanhamento de Usuários Sintomáticos Respiratórios (USR); vigilância, integração, comunicação e gestão. Todas as 165 UBS foram convidadas a completar o instrumento. Principais resultados: houve readequação da estrutura física (salas de espera, espaços internos/externos); fornecimento de EPI e de testes Covid-19, busca ativa de USR/suspeitos Covid-19 por telefone/visitas domiciliares, monitoramento de fluxos de transferência de pacientes e telessaúde. Concluindo, as UBS reorganizaram seus serviços para atender necessidades da pandemia. Fornecer informações sobre estrutura e capacidade de resposta das UBS pode subsidiar sistemas de saúde para planejamento e tomada de decisões, em diferentes níveis de gestão, crucial para determinar estratégias para reforçar a responsividade da APS em situações de pandemias e outras calamidades.

ABSTRACT The COVID-19 pandemic reinforced the need for global efforts to grant universal health coverage and access, which imposes management challenges for Primary Health Care (PHC). This study aimed to develop and apply an instrument to assess the PHC Units’ responsiveness to COVID-19, based on co-production efforts between university researchers and PHC technical teams. The instrument composed of two modules, included identification, operating hours, workforce, work process, structure, equipment, furniture, supplies, Personal Protection Equipment (PPE), Symptomatic Respiratory Patient (SRP) examinations and follow-up, information, surveillance, integration, communication, and management. All the 165 PHC Units in Brasília were invited to complete the instrument. Main results: there was physical structure adaptation (adequate configuration of waiting rooms, internal and external spaces allowing safe distance); provision of PPE and COVID-19 tests; active search for SRP/COVID-19 suspects by phone, mobile or home visits; monitoring flows of patient transfer and telehealth implementation. In conclusion, the PHC Units reorganized their services to meet the demands of the pandemic context. Providing information about structure and responsiveness of PHC Units may subside health systems for planning and decision-making at different levels of management, which is crucial to determine strategies to empower and reinforce PHC responsivity in situations of pandemics and other calamities.

RESUMO A pandemia de Covid-19 reforçou a necessidade de esforços globais para garantir cobertura e acesso universal à saúde, impondo desafios na gestão da Atenção Primária à Saúde (APS). Este estudo objetivou desen- volver e aplicar um instrumento de avaliação da responsividade das Unidades Básicas de Saúde (UBS) diante da Covid-19, baseado na coprodução entre pesquisadores universitários e equipes técnicas da APS. O instrumento, dividido em dois módulos, incluiu identificação; horário de funcionamento; processo de trabalho; estrutura física, equipamentos, mobiliário, suprimentos e Equipamentos de Proteção Individual (EPI); atendimento, exames e acompanhamento de Usuários Sintomáticos Respiratórios (USR); vigilância, integração, comunicação e gestão. Todas as 165 UBS foram convidadas a completar o instrumento. Principais resultados: houve readequação da estrutura física (salas de espera, espaços internos/externos); fornecimento de EPI e de testes Covid-19, busca ativa de USR/suspeitos Covid-19 por telefone/visitas domiciliares, monitoramento de fluxos de transferência de pacientes e telessaúde. Concluindo, as UBS reorganizaram seus serviços para atender necessidades da pandemia. Fornecer informações sobre estrutura e capacidade de resposta das UBS pode subsidiar sistemas de saúde para planejamento e tomada de decisões, em diferentes níveis de gestão, crucial para determinar estratégias para reforçar a responsividade da APS em situações de pandemias e outras calamidades.

ABSTRACT The COVID-19 pandemic reinforced the need for global efforts to grant universal health coverage and access, which imposes management challenges for Primary Health Care (PHC). This study aimed to develop and apply an instrument to assess the PHC Units’ responsiveness to COVID-19, based on co-production efforts between university researchers and PHC technical teams. The instrument composed of two modules, included identification, operating hours, workforce, work process, structure, equipment, furniture, supplies, Personal Protection Equipment (PPE), Symptomatic Respiratory Patient (SRP) examinations and follow-up, information, surveillance, integration, communication, and management. All the 165 PHC Units in Brasília were invited to complete the instrument. Main results: there was physical structure adaptation (adequate configuration of waiting rooms, internal and external spaces allowing safe distance); provision of PPE and COVID-19 tests; active search for SRP/COVID-19 suspects by phone, mobile or home visits; monitoring flows of patient transfer and telehealth implementation. In conclusion, the PHC Units reorganized their services to meet the demands of the pandemic context. Providing information about structure and responsiveness of PHC Units may subside health systems for planning and decision-making at different levels of management, which is crucial to determine strategies to empower and reinforce PHC responsivity in situations of pandemics and other calamities.

RESUMO Existe ampla evidência que a contenção da pandemia de Covid-19 requer vigilância sindrômica e isolamento de casos suspeitos/confirmados. É essencial a disponibilidade de testes diagnósticos no Sistema Único de Saúde, que poderia ser facilitada pela soberania nacional no desenvolvimento e produção, considerando-se a alta demanda/escassez no mercado internacional. Este estudo identificou as etapas da pesquisa translacional de testes diagnósticos para Covid-19 no Brasil, verificando sua distribuição geográfica, entre outros indicadores. Estudo transversal, exploratório, partindo de banco público com 789 projetos de Pesquisa, Desenvolvimento e Inovação (PD&I) em Covid-19, complementado com outras buscas, inclusive no CVLattes dos pesquisadores. No banco, havia 89 projetos de testes diagnósticos. Em 45 casos, foi possível obter informações complementares para classificá-los conforme as etapas da pesquisa translacional. Identificaram-se 15 inovações que atingiram o estágio T3, ou seja, tiveram seus produtos incorporados em protocolos clínicos na atenção à saúde, mesmo considerando-se as profundas restrições orçamentárias em PD&I. O Brasil possui potencial de desenvolvimento e implementação de produtos tecnológicos na área de testes de diagnóstico para Sars-CoV-2. Políticas públicas de PD&I em saúde necessitam ser priorizadas para ampliação de cooperações nacionais e internacionais, a fim de promover efetiva autonomia nacional na vigilância sindrômica e à saúde da população.

ABSTRACT There is much evidence suggesting that mitigating the COVID-19 pandemic requires syndromic surveillance and isolation of suspected/confirmed cases. The availability of diagnostic tests in the Brazilian Unified Health System (SUS) is essential, which could be facilitated by national sovereignty in development and production, considering the high demand/lack of supply in the international market. This study identified the stages of translational research into diagnostic tests for COVID-19 in Brazil, verifying their geographic distribution, among other indicators. A cross-sectional, exploratory study based on a public database with 789 Research, Development, and Innovation (RD&I) projects regarding COVID-19, complemented by other searches, including the researchers’ curricula (CVLattes). There were 89 diagnostic test projects in the database. In 45 cases, it was possible to obtain additional information to classify them according to the translational research stages. Fifteen innovations that reached the T3 stage were identified, with their products incorporated into clinical protocols in healthcare, even considering the deep budget restrictions in RD&I. Brazil has the potential to develop and implement technological products in the field of diagnostic tests for SARS-CoV-2. Public health RD&I policies need to be prioritized to expand national and international cooperation to promote effective national autonomy in syndromic surveillance and population health.

RESUMO Existe ampla evidência que a contenção da pandemia de Covid-19 requer vigilância sindrômica e isolamento de casos suspeitos/confirmados. É essencial a disponibilidade de testes diagnósticos no Sistema Único de Saúde, que poderia ser facilitada pela soberania nacional no desenvolvimento e produção, considerando-se a alta demanda/escassez no mercado internacional. Este estudo identificou as etapas da pesquisa translacional de testes diagnósticos para Covid-19 no Brasil, verificando sua distribuição geográfica, entre outros indicadores. Estudo transversal, exploratório, partindo de banco público com 789 projetos de Pesquisa, Desenvolvimento e Inovação (PD&I) em Covid-19, complementado com outras buscas, inclusive no CVLattes dos pesquisadores. No banco, havia 89 projetos de testes diagnósticos. Em 45 casos, foi possível obter informações complementares para classificá-los conforme as etapas da pesquisa translacional. Identificaram-se 15 inovações que atingiram o estágio T3, ou seja, tiveram seus produtos incorporados em protocolos clínicos na atenção à saúde, mesmo considerando-se as profundas restrições orçamentárias em PD&I. O Brasil possui potencial de desenvolvimento e implementação de produtos tecnológicos na área de testes de diagnóstico para Sars-CoV-2. Políticas públicas de PD&I em saúde necessitam ser priorizadas para ampliação de cooperações nacionais e internacionais, a fim de promover efetiva autonomia nacional na vigilância sindrômica e à saúde da população.

ABSTRACT There is much evidence suggesting that mitigating the COVID-19 pandemic requires syndromic surveillance and isolation of suspected/confirmed cases. The availability of diagnostic tests in the Brazilian Unified Health System (SUS) is essential, which could be facilitated by national sovereignty in development and production, considering the high demand/lack of supply in the international market. This study identified the stages of translational research into diagnostic tests for COVID-19 in Brazil, verifying their geographic distribution, among other indicators. A cross-sectional, exploratory study based on a public database with 789 Research, Development, and Innovation (RD&I) projects regarding COVID-19, complemented by other searches, including the researchers’ curricula (CVLattes). There were 89 diagnostic test projects in the database. In 45 cases, it was possible to obtain additional information to classify them according to the translational research stages. Fifteen innovations that reached the T3 stage were identified, with their products incorporated into clinical protocols in healthcare, even considering the deep budget restrictions in RD&I. Brazil has the potential to develop and implement technological products in the field of diagnostic tests for SARS-CoV-2. Public health RD&I policies need to be prioritized to expand national and international cooperation to promote effective national autonomy in syndromic surveillance and population health.

The aim of this study is to support health management, with recent and reliable information, during the COVID-19 pandemic.  Notified and confirmed cases and deaths by COVID-19 were evaluated from three public databases. 1)  Data from the Coronavirus Panel of the Ministry of Health, updated daily, show the existence of two epidemic waves. 2)  The Civil Registry Transparency Portal, also with recent data, points to high mortality rates of COVID-19, especially in older age groups. 3)  The cases, reported by the Information System of the Epidemiological Surveillance of Influenza (Sivep-gripe), confirmed mainly by laboratory test, show predominance of men, high age groups, white race/color, residence in urban areas, presence of comorbidities, higher occurrence of hospitalization and lower use of intensive care unit. This last database, in addition to the first wave, records only the first eight epidemiological weeks of the second wave.  The vertiginous rate of increase in cases and deaths in the second wave points to the need for more drastic measures of social distancing, in addition to the expansion of vaccination against COVID-19. The combination of the three banks expands information that can support timely decision-making.

O objetivo deste estudo é apoiar a gestão em saúde, com informações recentes e confiáveis, durante a pandemia de COVID-19. Casos notificados e confirmados e óbitos por COVID-19 foram avaliados a partir de três bancos de dados públicos.1) Dados do Painel Coronavírus do Ministério da Saúde, atualizados diariamente, mostram a existência de duas ondas epidêmicas. 2) O Portal da Transparência do Registro Civil, também com dados recentes, aponta altas taxas de mortalidade do COVID-19, especialmente nas faixas etárias mais velhas. 3) Os casos notificados pelo Sistema de Informação da Vigilância Epidemiológica da Influenza (Sivep-gripe), confirmados principalmente por exame laboratorial, mostram predominância de homens, faixas etárias elevadas, raça/cor branca, residência em áreas urbanas, presença de comorbidades, maior ocorrência de internação e menor uso de unidade de terapia intensiva. Esta última base de dados, além da primeira onda, registra apenas as primeiras oito semanas epidemiológicas da segunda onda. A vertiginosa taxa de aumento de casos e óbitos na segunda onda aponta para a necessidade de medidas mais drásticas de distanciamento social, além da expansão da vacinação contra o COVID-19. A combinação dos três bancos expande as informações, que podem apoiar a tomada de decisões em tempo oportuno.

Objective: To investigate the flows of hospitalizations for COVID-19 in the 450 regions and 117 Brazilian health macro-regions between March and October 2020. Method: Descriptive study, comprising all hospitalizations due to COVID-19 registered in the Flu Epidemiological Surveillance Information System (SIVEP-Gripe) between the 8th and 44th epidemiological weeks of 2020. The proportion of hospitalizations for COVID-19 occurred within same health region of residency was calculated, stratified according to periods of greater and lesser demand for health care, according to the population size of health regions. The indicator of migratory efficacy was calculated, which takes into account the evasion and invasion of patients, by crossing the data of origin of the patients (health region of residence) with the data of the place of hospitalization (health region of attendance). Results: 397,830 admissions were identified for COVID-19 in the period. Evasion was 11.9% of residents in health regions and 6.8% in macro-regions, pattern that was maintained during the peak period of hospitalizations for COVID-19. There was an average of 17.6% of evasion of residents of health regions in the Northeast and of 8.8% in health regions of the South. Evasion was more accentuated in health regions with up to 100 thousand / inhabitants (36.9%), which was 7 times greater than that observed in health regions with more than 2 million / inhabitants (5.2%). The negative migratory efficacy indicator (-0.39) indicated a predominance of evasion. Of the 450 Brazilian health regions, 117 (39.3%) had a coefficient of migratory efficacy between -1 and -0.75 and 113 (25.1%) between -0.75 and -0.25. Conclusion: The results indicate that the regionalization of the health system proved to be adequate in the organization of care in the territory, however the long distances traveled are still worrying.

Objetivo: Investigar os fluxos de internações por COVID-19 nas 450 regiões e 117 macrorregiões de saúde brasileiras no período de março a outubro de 2020. Método: Estudo descritivo, compreendendo todas as internações por COVID-19 registradas no Sistema de Informação de Vigilância Epidemiológica da Gripe (SIVEP-Gripe) entre a 8ª e a 44ª semanas epidemiológicas de 2020. Foi calculada a proporção das internações por COVID-19 realizadas pelos residentes que ocorreram dentro da sua respectiva região de saúde, estratificado segundo períodos de maior e menor demanda de internações e segundo o porte populacional das regiões de saúde. Foi calculado o indicador de eficácia migratória, que leva em consideração a evasão e invasão de pacientes, por meio do cruzamento dos dados de origem dos pacientes (região de saúde de residência) com os dados do local da realização das internações (região de saúde de atendimento). Resultados: Foram identificadas 397.830 internações por COVID-19 no Brasil. A evasão foi de 11,9% dos residentes nas regiões de saúde e de 6,8% nas macrorregiões; o padrão que se manteve também no período de pico das internações por COVID-19. Houve em média 17,6% de evasão dos residentes das regiões de saúde do Nordeste e de 8,8% nas regiões de saúde do Sul. A evasão foi mais acentuada nas regiões de saúde com até 100 mil/hab. (36,9%), a qual foi 7 vezes maior que a verificada nas regiões de saúde com mais de 2 milhões/habitantes (5,2%). O indicador de eficácia migratória negativo (-0,39) indicou predomínio da evasão. Das 450 regiões de saúde brasileiras, 117 (39,3%) apresentaram coeficiente de eficácia migratória entre -1 e -0,75 e 113 (25,1%) entre -0,75 e -0,25. Conclusão: Os resultados indicam que a regionalização do sistema de saúde mostrou-se adequada na organização do atendimento no território, porém as longas distâncias percorridas ainda são preocupantes

RESUMO Objetivou-se investigar os fluxos de internações por Covid-19 nas 450 regiões e 117 macrorregiões de saúde brasileiras, de março a outubro de 2020. Realizou-se estudo descritivo, compreendendo todas as internações por Covid-19 registradas no Sistema de Informação de Vigilância Epidemiológica da Gripe entre a 8ª e a 44ª semanas epidemiológicas de 2020. Identificaram-se 397.830 internações por Covid-19 no Brasil. A evasão foi de 11,9% dos residentes nas regiões de saúde e de 6,8% nas macrorregiões; padrão que se manteve no período de pico das internações por Covid-19. Houve, em média, 17,6% de evasão dos residentes das regiões de saúde do Nordeste e de 8,8% das do Sul. A evasão foi mais acentuada nas regiões de saúde com até 100 mil/hab. (36,9%), a qual foi 7 vezes maior que a verificada naquelas com mais de 2 milhões/habitantes (5,2%). O indicador de eficácia migratória negativo (-0,39) indicou predomínio da evasão. Das 450 regiões de saúde brasileiras, 117 (39,3%) apresentaram coeficiente de eficácia migratória entre-1 e-0,75; e 113 (25,1%), entre-0,75 e-0,25. Os resultados indicam que a regionalização do sistema de saúde mostrou-se adequada na organização do atendimento no território, porém, as longas distâncias percorridas ainda são preocupantes.

ABSTRACT The study aims to investigate the flows of Covid-19 hospitalizations in the 450 Brazilian health regions and 117 health macro-regions between March and October 2020. This descriptive study includes all Covid-19 hospitalizations registered in the Influenza Epidemiological Surveillance Information System between the eighth and forty-fourth epidemiological weeks of 2020. In Brazil, 397,830 admissions were identified for Covid-19. Emigration was 11.9% for residents in health regions and 6.8% in macro-regions; this pattern was also maintained during the peak period of Covid-19 hospitalizations. The average evasion for residents of health regions was 17.6% in the Northeast and 8.8% in the South. Evasion was more accentuated in health regions with up to 100 thousand inhabitants(36.9%), which was 7 times greater than that observed in health regions with more than 2 million inhabitants (5.2%). The negative migratory efficacy indicator (-0.39) revealed a predominance of evasion. Of the 450 Brazilian health regions, 117 (39.3%) had a coefficient of migratory efficacy between-1 and-0.75, and 113 (25.1%) between-0.75 and-0.25. Results indicate that the regionalization of the health system exhibited adequate organization of healthcare in the territory; however, the long distances traveled are still worrisome.

RESUMO Objetivou-se investigar os fluxos de internações por Covid-19 nas 450 regiões e 117 macrorregiões de saúde brasileiras, de março a outubro de 2020. Realizou-se estudo descritivo, compreendendo todas as internações por Covid-19 registradas no Sistema de Informação de Vigilância Epidemiológica da Gripe entre a 8ª e a 44ª semanas epidemiológicas de 2020. Identificaram-se 397.830 internações por Covid-19 no Brasil. A evasão foi de 11,9% dos residentes nas regiões de saúde e de 6,8% nas macrorregiões; padrão que se manteve no período de pico das internações por Covid-19. Houve, em média, 17,6% de evasão dos residentes das regiões de saúde do Nordeste e de 8,8% das do Sul. A evasão foi mais acentuada nas regiões de saúde com até 100 mil/hab. (36,9%), a qual foi 7 vezes maior que a verificada naquelas com mais de 2 milhões/habitantes (5,2%). O indicador de eficácia migratória negativo (-0,39) indicou predomínio da evasão. Das 450 regiões de saúde brasileiras, 117 (39,3%) apresentaram coeficiente de eficácia migratória entre-1 e-0,75; e 113 (25,1%), entre-0,75 e-0,25. Os resultados indicam que a regionalização do sistema de saúde mostrou-se adequada na organização do atendimento no território, porém, as longas distâncias percorridas ainda são preocupantes.

ABSTRACT The study aims to investigate the flows of Covid-19 hospitalizations in the 450 Brazilian health regions and 117 health macro-regions between March and October 2020. This descriptive study includes all Covid-19 hospitalizations registered in the Influenza Epidemiological Surveillance Information System between the eighth and forty-fourth epidemiological weeks of 2020. In Brazil, 397,830 admissions were identified for Covid-19. Emigration was 11.9% for residents in health regions and 6.8% in macro-regions; this pattern was also maintained during the peak period of Covid-19 hospitalizations. The average evasion for residents of health regions was 17.6% in the Northeast and 8.8% in the South. Evasion was more accentuated in health regions with up to 100 thousand inhabitants(36.9%), which was 7 times greater than that observed in health regions with more than 2 million inhabitants (5.2%). The negative migratory efficacy indicator (-0.39) revealed a predominance of evasion. Of the 450 Brazilian health regions, 117 (39.3%) had a coefficient of migratory efficacy between-1 and-0.75, and 113 (25.1%) between-0.75 and-0.25. Results indicate that the regionalization of the health system exhibited adequate organization of healthcare in the territory; however, the long distances traveled are still worrisome.

Resumo Este trabalho compara a resposta superovulatória de éguas doadoras de embriões das raças Quarto de Milha (QM) e Crioula, utilizando um protocolo com baixa dose de extrato de pituitária equina (EPE). Oito éguas QM e seis éguas Crioulas foram acompanhadas durante 3 ciclos estrais consecutivos, sendo que cada ciclo corresponde a um grupo. Grupo Controle – monitoramento do crescimento folicular até a ovulação; Grupo EPE – monitoramento ultrassonográfico até que os folículos atingissem cerca de 20 mm de diâmetro e, posteriormente, administração de 7 mg de EPE, duas vezes ao dia, até a indução da ovulação com 2500UI de hCG; Grupo Pós-EPE – idem ao grupo controle. Os dados foram submetidos à análise de variância, utilizando o procedimento GLM do pacote estatístico SAS, sendo previamente testadas para normalidade dos resíduos, e as médias comparadas pelo teste de Tukey ao nível de 5%. Nas éguas Crioulas tratadas com EPE houve um aumento no número de ovulações (p=0,0534), com média de 3,33±2,06 quando comparadas aos grupos controle e pós-EPE e às éguas da raça QM (2,00±0,53). O tratamento com EPE na dose preconizada permitiu uma melhor resposta superovulatória e produção embrionária nas éguas Crioulas, quando comparadas com as éguas Quarto de Milha.

Abstract This study compared the superovulatory response of embryos donor mares of Quarter Horse (QH) and Crioula using a protocol with low dose of equine pituitary extract (EPE). Eight QH mares and six Crioula mares were monitored during 3 consecutive estrous cycles, with each cycle corresponds to a group. Control Group - monitoring of follicle growth up to the ovulation; EPE group - when the follicles reached 20 mm in diameter were administered 7 mg EPE twice daily. When the follicles achieved a diameter 35 mm, the ovulation was induced with 2500UI hCG; Post-EPE Group - idem to the control group. Data were analyzed using GLM procedure of the SAS statistical package. The variables were submitted to the Tukey’s test and least square means adjusted for multiple comparisons using the Tukey-Kramer’s test, with significance level of 5%. Values are presented as mean ± SD. In the Crioula mares treated with EPE, there was an increase in the number of ovulations (p =0.0534) with a mean of 3.33 ± 2.06 ovulations when compared to the control and post-EPE groups, and mares QM. (2.00±0.53). Treatment with EPE in the recommended dose allowed better superovulatory response and rate of embryo recovery in Crioula mares when compared to the QM mares

Abstract Background: In recent decades, snake venom disintegrins have received special attention due to their potential use in anticancer therapy. Disintegrins are small and cysteine-rich proteins present in snake venoms and can interact with specific integrins to inhibit their activities in cell-cell and cell-ECM interactions. These molecules, known to inhibit platelet aggregation, are also capable of interacting with certain cancer-related integrins, and may interfere in important processes involved in carcinogenesis. Therefore, disintegrin from Crotalus durissus collilineatus venom was isolated, structurally characterized and evaluated for its toxicity and ability to interfere with cell proliferation and migration in MDA-MB-231, a human breast cancer cell line. Methods: Based on previous studies, disintegrin was isolated by FPLC, through two chromatographic steps, both on reversed phase C-18 columns. The isolated disintegrin was structurally characterized by Tris-Tricine-SDS-PAGE, mass spectrometry and N-terminal sequencing. For the functional assays, MTT and wound-healing assays were performed in order to investigate cytotoxicity and effect on cell migration in vitro, respectively. Results: Disintegrin presented a molecular mass of 7287.4 Da and its amino acid sequence shared similarity with the disintegrin domain of P-II metalloproteases. Using functional assays, the disintegrin showed low cytotoxicity (15% and 17%, at 3 and 6 μg/mL, respectively) after 24 h of incubation and in the wound-healing assay, the disintegrin (3 μg/mL) was able to significantly inhibit cell migration (24%, p < 0.05), compared to negative control. Conclusion: Thus, our results demonstrate that non-RGD disintegrin from C. d. collilineatus induces low cytotoxicity and inhibits migration of human breast cancer cells. Therefore, it may be a very useful molecular tool for understanding ECM-cell interaction cancer-related mechanisms involved in an important integrin family that highlights molecular aspects of tumorigenesis. Also, non-RGD disintegrin has potential to serve as an agent in anticancer therapy or adjuvant component combined with other anticancer drugs.

RESUMO Objetivo Avaliar o Programa Mais Médicos (PMM) no Brasil estimando o aumento proporcional do número de médicos nos municípios participantes e os custos do programa, estratificado pelo componente de custo e fonte de financiamento. Métodos Os dados oficiais da edição de Demografia médica no Brasil de 2013 foram usados para estimar o número de médicos anterior ao PMM. O número de médicos ao final do quarto ciclo de recrutamento do PMM (julho de 2014) foi fornecido pelo Ministério da Saúde. Os componentes de custo foram identificados e calculados de acordo com a legislação e as diretrizes do PMM. Os municípios participantes foram selecionados segundo quatro critérios relacionados à vulnerabilidade. Resultados O PMM proveu um adicional de 14.462 médicos para áreas remotas bastante vulneráveis em 3.785 municípios (68% do total) e 34 distritos sanitários especiais indígenas. Houve aumento maior do número de médicos nas regiões mais pobres (Norte e Nordeste). O custo anual estimado de US$ 1,1 bilhão cobriu provisões médicas, educação continuada e supervisão/mentoria. O financiamento foi em grande parte centralizado ao nível federal (92,6%). Conclusão Considera-se que o custo do PMM seja relativamente moderado em relação aos benefícios em potencial à saúde da população. O aumento maior no número de médicos para atender a população mais pobres e vulnerável alcançou a meta de corrigir a má distribuição de profissionais da saúde. A experiência do PMM no Brasil pode subsidiar o debate visando reduzir a escassez de médicos.

ABSTRACT Objective To evaluate the Programa Mais Médicos (More Doctors Program; PMM) in Brazil by estimating the proportional increase in the number of doctors in participating municipalities and the program costs, stratified by cost component and funding source. Methods Official data from the 2013 edition of Demografia Médica no Brasil (Medical Demography in Brazil) was used to estimate the number of doctors prior to PMM. The number of doctors at the end of the fourth PMM recruiting cycle (July 2014) was obtained from the Ministry of Health. Cost components were identified and estimated based on PMM legislation and guidelines. The participating municipalities were chosen based on four criteria, all related to vulnerability. Results The PMM provided an additional 14 462 physicians to highly vulnerable, remote areas in 3 785 municipalities (68% of the total) and 34 Special Indigenous Sanitary Districts. There was a greater increase of physicians in the poorest regions (North and Northeast). The estimated annual cost of US$ 1.1 billion covered medical provision, continuing education, and supervision/mentoring. Funding was largely centralized at the federal level (92.6%). Conclusion The cost of PMM is considered relatively moderate in comparison to its potential benefits for population health. The greater increase of doctors for the poorest and most vulnerable met the target of correcting imbalances in health worker distribution. The PMM experience in Brazil can contribute to the debate on reducing physician shortages.

RESUMEN Objetivo Evaluar el Programa “Mais Médicos” en el Brasil mediante el cálculo del aumento proporcional del número de médicos en los municipios participantes y los costos del programa, con estratificación por componente del costo y fuente de financiamiento. Métodos Se utilizaron datos oficiales de la edición del 2013 de Demografia médica no Brasil [demografía médica en el Brasil] para calcular el número de médicos antes del Programa “Mais Medicos”. El número de médicos al final del cuarto ciclo de reclutamiento del programa (julio del 2014) se obtuvo del Ministerio de Salud. Se determinaron y calcularon los componentes de costos sobre la base de la legislación y las directrices del programa. Se eligieron los municipios participantes según cuatro criterios, todos relacionados con la vulnerabilidad. Resultados Mediante el Programa “Mais Médicos” se destinaron 14 462 médicos más a zonas sumamente vulnerables y remotas en 3 785 municipios (68% del total) y 34 distritos sanitarios indígenas especiales. El aumento del número de médicos fue mayor en las zonas más pobres (al Norte y Nordeste). El costo anual estimado de US$ 1 100 millones incluyó la dotación de médicos, la educación continua y la supervisión y tutoría. El financiamiento estuvo principalmente centralizado en el nivel federal (92,6%). Conclusiones Se considera que el costo del Programa “Mais Médicos” es relativamente moderado en relación con los posibles beneficios para la salud de la población. Con el mayor aumento de la dotación de médicos en las poblaciones más pobres y vulnerables se cumplió el objetivo de corregir los desequilibrios en la distribución del personal de salud. La experiencia de este programa en el Brasil puede contribuir al debate sobre cómo paliar la escasez de médicos.

Abstract Background In Brazil, accidents with venomous animals are considered a public health problem. Tityus serrulatus (Ts), popularly known as the yellow scorpion, is most frequently responsible for the severe accidents in the country. Ts envenoming can cause several signs and symptoms classified according to their clinical manifestations as mild, moderate or severe. Furthermore, the victims usually present biochemical alterations, including hyperglycemia. Nevertheless, Ts envenoming and its induced hyperglycemia were never studied or documented in a patient with diabetes mellitus (DM). Therefore, this is the first study to evaluate the glycemia during Ts envenoming using a diabetic animal model (NOD, non-obese diabetic). Methods Female mice (BALB/c or NOD) were challenged with a non-lethal dose of Ts venom. Blood glucose level was measured (tail blood using a glucose meter) over a 24-h period. The total glycosylated hemoglobin (HbA1c) levels were measured 30 days after Ts venom injection. Moreover, the insulin levels were analyzed at the glycemia peak. Results The results demonstrated that the envenomed NOD animals presented a significant increase of glycemia, glycosylated hemoglobin (HbA1c) and insulin levels compared to the envenomed BALB/c control group, corroborating that DM victims present great risk of developing severe envenoming. Moreover, the envenomed NOD animals presented highest risk of death and sequelae. Conclusions This study demonstrated that the diabetic victims stung by Ts scorpion should be always considered a risk group for scorpion envenoming severity.

Abstract Background In the Atlantic forest of the North and Northeast regions of Brazil, local population often uses the fruit juice and the aqueous extract of leaves of soursop (Annona muricata L.) to treat Lachesis muta rhombeata envenomation. Envenomation is a relevant health issue in these areas, especially due to its severity and because the production and distribution of antivenom is limited in these regions. The aim of the present study was to evaluate the relevance of the use of soursop leaf extract and its juice against envenomation by Lachesis muta rhombeata. Methods We evaluated the biochemical, hematological and hemostatic parameters, the blood pressure, the inflammation process and the lethality induced by Lachesis muta rhombeata snake venom. We also assessed the action of the aqueous extract of leaves (AmL) and juice (AmJ) from A. muricata on the animal organism injected with L. m. rhombeata venom (LmrV) in the laboratory environment. Results LmrV induced a decrease of total protein, albumin and glucose; and increase of creatine kinase, aspartate aminotransferase, and urea concentrations. It provoked hemoconcentration followed by reduction of hematocrit, an increase in prothrombin time and partial thromboplastin time and a decrease of the blood pressure. LmrV induced the release of interleukin-6, an increase in neutrophils and changes in the serum protein profile, characteristic of the acute inflammatory process. LD50 values were similar for the groups injected with LmrV and treated or untreated with AmJ and AmL. Both treatments play a role on the maintenance of blood glucose, urea and coagulation parameters and exert a protective action against the myotoxicity. However, they seem to worsen the hypotension caused by LmrV. Conclusion The treatments with AmJ and AmL present some beneficial actions, but they might intensify some effects of the venom. Therefore, additional studies on A. muricata are necessary to enable its use as natural antivenom for bushmaster snakebite.

The phytopathogenic fungus Moniliophthora perniciosa (Stahel) Aime & Philips-Mora, causal agent of witches' broom disease of cocoa, causes countless damage to cocoa production in Brazil. Molecular studies have attempted to identify genes that play important roles in fungal survival and virulence. In this study, sequences deposited in the M. perniciosa Genome Sequencing Project database were analyzed to identify potential biological targets. For the first time, the ergosterol biosynthetic pathway in M. perniciosa was studied and the lanosterol 14α-demethylase gene (ERG11) that encodes the main enzyme of this pathway and is a target for fungicides was cloned, characterized molecularly and its phylogeny analyzed. ERG11 genomic DNA and cDNA were characterized and sequence analysis of the ERG11 protein identified highly conserved domains typical of this enzyme, such as SRS1, SRS4, EXXR and the heme-binding region (HBR). Comparison of the protein sequences and phylogenetic analysis revealed that the M. perniciosa enzyme was most closely related to that of Coprinopsis cinerea.