Desenvolvimento e caracterização de um novo sistema microparticulado contendo polímero catiônico para a administração pulmonar da dapsona e avaliação toxicológica em modelos animais in vivo

A pneumonia causada por Pneumocystis carinii (PCP) é uma das principais doenças oportunistas que acomete pacientes portadores do vírus HIV. Segundo dados da Organização Mundial da Saúde, cerca de 80 - 85% das pessoas portadoras do vírus sofrem de PCP. Essa infecção é pulmonar e o agente patológico permanece apenas nos pulmões. O tratamento convencional desta doença (sulfametoxazol e trimetoprima) apresenta efeitos colaterais severos (febre, neutropenia, nefrotoxicidade). Neste contexto, a dapsona (DDS) surge como um tratamento alternativo eficaz contra a PCP. A dapsona é um fármaco da classe das sulfonas, com atividade bacteriostática e que quando administrada pela via oral, apesar de apresentar menos efeitos adversos que a terapia convencional, pode causar efeitos adversos nas células do sangue. Desta forma, o objetivo do presente trabalho é desenvolver micropartículas de quitosana pela técnica de spray-drying, visando à administração pulmonar com efeito local da dapsona, para o tratamento da PCP. O racional da proposta baseia-se na administração localizada do fármaco, a qual pode contribuir para a redução da dose administrada e, consequentemente, dos efeitos adversos. As análises através de microscopia eletrônica de varredura (MEV) mostraram que o tamanho das partículas obtidas foi reduzido e adequado para administração pulmonar (1 – 5 μm). O perfil de dissolução in vitro demonstrou uma liberação biexponencial da dapsona a partir das micropartículas, sendo essa caracterizada por uma fase de liberação rápida e outra lenta, o que indica a sustentação da liberação do fármaco. Os resultados de deposição das partículas in vitro mostraram uma distribuição adequada e uma elevada fração de partículas finas respiráveis (FPF = 50%). O experimento de toxicidade in vivo mostrou uma baixa toxicidade das micropartículas em relação ao fármaco livre, mostrando um potencial efeito protetor para a administração da dapsona.Pneumonia caused by Pneumocystis (jiroveci) carinii (PCP) is a major opportunistic infection that affects patients with HIV. According to the World Health Organization, between 80 - 85% of patients with the HIV virus suffers from PCP. This infection is pulmonary disease and the pathologic agent remains in the lungs. The conventional treatment of this disease leads to severe side effects (fever, neutropenia, nephrotoxicity). In this context, dapsone appears as an effective alternative for the treatment against PCP. Dapsone is a drug of sulfones class and its mechanism of action is based on the bacteriostatic activity. When dapsone is administered orally, although it has fewer side effects than the conventional therapy, this drug can cause adverse effects on blood cells. In this way, the aim of this work was to develop chitosan microparticles by spray-drying technique, aiming to pulmonary administration with local effect of dapsone for the treatment of PCP. The propose of this work is based on the localized administration of the drug, which may contribute to the reduction of the dose and therefore adverse effects. Analyses by scanning electron microscopy (SEM) showed that the particle size obtained was reduced and appropriate for pulmonary delivery (1 – 5 μm). The in vitro dissolution profile showed a biexponential release of dapsone from the microparticles, characterized by a burst phase release and a subsequent slow release, which indicates the sustaining delivery of dapsone. The in vitro deposition of microparticles measured in a Andersen cascade impactor showed an adequate distribution and high fine particles fraction (FPF = 50%). The in vivo toxicity experiment showed low toxicity of microparticles compared to free drug, indicating a potential protective effect of dapsone administration when microencapsulated

A coordenação agroindustrial citrícola brasileira e os novos recursos de poder: dos políticos aos jurídicos

O presente trabalho mostra que os recursos políticos e jurídicos tornaram-se tão ou mais estratégicos para citricultores e processadores de suco no Brasil que os próprios recursos financeiros, tecnológicos e organizacionais. Também, apresenta uma análise da governança citrícola brasileira atual, que está pautada por estratégias diferentes entre citricultores e processadoras: os citricultores e sua principal associação pautam suas principais ações nas utilizações de recursos políticos e algumas grandes processadoras de suco avançam com utilizações de recursos jurídicos. Esse embate revela um novo entrave para a conquista de resultados positivos pelos citricultores na rede de poder atual, pois os mandados judiciais revelam que o contrato de fornecimento de laranja tornou-se um instrumento de poder fundamental nessa rede de coordenação, causando ganhos estratégicos para as processadoras de suco após quatro anos de conquistas de recursos políticos significativos por parte dos citricultores, especialmente do estado de São Paulo.------------------------------------This essay shows that the political and legal resources, for citrus farmers, became as much strategic as financial, technological and organizational resources themselves. It This essay shows that the political and legal resources, for citrus farmers, became as much strategic as financial, technological and organizational resources themselves. ItThis essay shows that the political and legal resources, for citrus farmers, became as much strategic as financial, technological and organizational resources themselves. It presents an analysis of Brazilian citrus business governance, which is guided by different strategies between citrus farmers and processing plants: the citrus farmers and their main association guide their actions into using political resources while some big juice processing plants advance by using legal resources. This opposition represents a new obstacle to the conquest of positive results by citrus farmers in the current power network, because court orders shows that the supplying contracts of orange became an instrument of fundamental power into this coordination network, causing strategic gains for the juice processing plants after four years of significant political resource conquests by citrus farmers, specially in Sao Paulo state.Citricultores, recursos de poder, processadores de suco, governança citrícola, citrus farmers, resources of power, juice processing plants, citrus business governance, Agribusiness, Crop Production/Industries,

Validação da Inteligência Artificial na viabilidade de testes da COVID-19: Validation of Artificial Intelligence in the viability of COVID-19 tests

O estudo de caráter exploratório e análise de dados sobre os modelos de testes para a detecção do vírus SARS-CoV-2 por meio do julgamento de especialistas com o intuito de detectar a presença ou não da doença em um indivíduo. Em se tratando de uma pandemia global cujo vírus é altamente transmissível a aplicação de testes laboratoriais passa a ser de extrema importância para a identificação de agentes de infecção e no controle da disseminação. Surge então a questão de como se avaliar de forma combinada (qualitativa e quantitativa) o nível de viabilidade dos testes de Covid-19 frente a esse vírus contemporâneo. O objetivo do trabalho é demonstrar algumas definições sobre o tema e qual a testagem mais viável para este cenário a fim de acelerar o processo dos exames e atribuir resultados mais precisos em menor tempo. Com os resultados obtidos verificou-se que a testagem de maior viabilidade segundo o julgamento dos criterios diante dos métodos avaliados foi por meio da Inteligência Artificial

Redes de políticas no agronegócio no estado de São Paulo: Formas de orquestração de interesses produtivos nos complexos agroindustriais citrícola e sucroalcooleiro

Agribusiness is organized into policy networks. The orchestrations of interests associations are important to reveal the field of agroindustrial political governance which grew with the agricultural policies at the corporatist level, under the state regulation of Brazilian agriculture in the years 1960s and 1970s, and which have become more plural governances or in networks coordinated and oriented by business, agricultural product or agroindustrial sector. This article presents, through the citrical and sugar- alcohol agroindustrial case study in the State of São Paulo in the period 1964-2010, and the most important transformations in the two most important networks of agribusiness in São Paulo from the theoretical field of political neoinstitutionalism.El agronegocio se organiza en redes de políticas. Las orquestaciones de asociaciones de interés son importantes para revelar el campo de la gobernanza política agroindustrial que creció con las políticas agrícolas a nivel corporativo en Brasil, es decir, bajo la regulación estatal de la agricultura brasileña en los años sesenta y setenta, y que se convirtió en una gobernanza más pluralista o en redes coordinadas y orientadas a los negocios, productos agrícolas o sector agroindustrial. El presente artículo muestra los casos agroindustriales de cítricos y sucroalcoholero en el estado de São Paulo en el período 1964/2010 y presenta las transformaciones más importantes en las dos redes de políticas más importantes del agronegocio paulista, a partir del campo teórico del neoinstitucionalismo político.O agronegócio se organiza em redes de políticas. Orquestrações das associações de interesses são importantes para revelar o campo da governança política agroindustrial que cresceu com as políticas agrícolas em nível corporativista no Brasil, isto é, sob a regulação estatal da agricultura brasileira nos anos 1960 e 1970, e que se transformaram em governanças mais plurais ou em redes coordenadas e orientadas por negócio, por produto agrícola ou setor agroindustrial. O presente artigo mostra, por meio dos estudos dos casos agroindustriais citrícola e sucroalcooleiro no estado de São Paulo no período 1964/2010, as transformações mais importantes nas duas redes de políticas mais importantes do agronegócio paulista, a partir do campo teórico do neoinstitucionalismo político

Aprendizagem significativa do ensino metacognitivo utilizando AHP para definição das práticas pedagógicas

Essa pesquisa tem como objetivo prover um referencial teórico que compreende temas sobre teoria da aprendizagem, fundamentos de ensino metacognitivo e aprendizagem significativa. Analisando as obras selecionadas, buscou estabelecer correlações que serviram como contribuições de autores para melhorar a compreensão dos fundamentos da temática estudada. Além disso, tem o propósito de descrever os modelos conceitos a partir de revisão da literatura de modo a estabelecer métodos de planejamento de ensino para o melhor desenvolvimento dos estudantes. Para tal escolha, é utilizado o AHP (Analityc Hierarchy Process) para escolher as melhores práticas de ensino

Vaccine effectiveness of heterologous CoronaVac plus BNT162b2 in Brazil

There is considerable interest in the waning of effectiveness of coronavirus disease 2019 (COVID-19) vaccines and vaccine effectiveness (VE) of booster doses. Using linked national Brazilian databases, we undertook a test-negative design study involving almost 14 million people (~16 million tests) to estimate VE of CoronaVac over time and VE of BNT162b2 booster vaccination against RT-PCR-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe COVID-19 outcomes (hospitalization or death). Compared with unvaccinated individuals, CoronaVac VE at 14-30 d after the second dose was 55.0% (95% confidence interval (CI): 54.3-55.7) against confirmed infection and 82.1% (95% CI: 81.4-82.8) against severe outcomes. VE decreased to 34.7% (95% CI: 33.1-36.2) against infection and 72.5% (95% CI: 70.9-74.0) against severe outcomes over 180 d after the second dose. A BNT162b2 booster, 6 months after the second dose of CoronaVac, improved VE against infection to 92.7% (95% CI: 91.0-94.0) and VE against severe outcomes to 97.3% (95% CI: 96.1-98.1) 14-30 d after the booster. Compared with younger age groups, individuals 80 years of age or older had lower protection after the second dose but similar protection after the booster. Our findings support a BNT162b2 booster vaccine dose after two doses of CoronaVac, particularly for the elderly

Two-dose ChAdOx1 nCoV-19 vaccine protection against COVID-19 hospital admissions and deaths over time : a retrospective, population-based cohort study in Scotland and Brazil

Funding Information: This study is part of the EAVE II project. EAVE II is funded by the MRC (MC_PC_19075) with the support of BREATHE—The Health Data Research Hub for Respiratory Health (MC_PC_19004), which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. This research is part of the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant ref MC_PC_20058). Additional support has been provided through Public Health Scotland and Scottish Government Director General Health and Social Care. The original EAVE project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme (11/46/23). The views expressed are those of the authors and not necessarily those of the NIHR, the Department of Health and Social Care, or the UK government. The Brazilian component is part of the Fiocruz VigiVac project on continuous digital evaluation of the national anti-COVID-19 immunisation programme. SVK and SA acknowledge funding from an NHS Research Scotland Senior Clinical Fellowship (SCAF/15/02), the MRC (MC_UU_00022/2), and the Scottish Government Chief Scientist Office (SPHSU17). This partnership between Brazil and Scotland was established through funding from the NIHR (GHRG /16/137/99) using UK aid from the UK Government to support global health research. This study was partially supported by a donation from the Fazer o Bem Faz Bem programme. The authors thank DATASUS for its excellent work in providing unidentified databases. GLW, MLB, and MB-N are research fellows from the Brazilian National Research Council. GLW acknowledges funding from FAPERJ (Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro; E-26/210.180/2020). We thank Dave Kelly from Albasoft (Inverness, UK) for his support with making primary care data available; Wendy Inglis-Humphrey, Vicky Hammersley, and Laura Brook (University of Edinburgh, Edinburgh, UK); and Pam McVeigh, Amanda Burridge, and Afshin Dastafshan (Public Health Scotland, Glasgow, UK) for their support with project management and administration. Funding Information: SVK is a member of the UK Government's Scientific Advisory Group on Emergencies subgroup on ethnicity, the Cabinet Office's International Best Practice Advisory Group, and was co-chair of the Scottish Government's Expert Reference Group on Ethnicity and COVID-19. CR reports grants from the Medical Research Council (MRC) and Public Health Scotland, during the conduct of the study, and is a member of the Scottish Government Chief Medical Officer's COVID-19 Advisory Group, Scientific Pandemic Influenza Group on Modelling, and Medicines and Healthcare products Regulatory Agency Vaccine Benefit and Risk Working Group. AS is a member of the Scottish Government Chief Medical Officer's COVID-19 Advisory Group and its Standing Committee on Pandemics; he is also a member of the UK Government's New and Emerging Respiratory Virus Threats Risk Stratification Subgroup and a member of AstraZeneca's Thrombotic Thrombocytopenic Taskforce. All roles are unremunerated. VdAO, VB, MLB, and MB-N are employees of Fiocruz, a federal public institution, which manufactures Vaxzevria in Brazil, through a full technology transfer agreement with AstraZeneca. Fiocruz allocates all its manufactured products to the Ministry of Health for the public health service use. All other authors declare no competing interests. Funding Information: This study is part of the EAVE II project. EAVE II is funded by the MRC (MC_PC_19075) with the support of BREATHE?The Health Data Research Hub for Respiratory Health (MC_PC_19004), which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. This research is part of the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant ref MC_PC_20058). Additional support has been provided through Public Health Scotland and Scottish Government Director General Health and Social Care. The original EAVE project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme (11/46/23). The views expressed are those of the authors and not necessarily those of the NIHR, the Department of Health and Social Care, or the UK government. The Brazilian component is part of the Fiocruz VigiVac project on continuous digital evaluation of the national anti-COVID-19 immunisation programme. SVK and SA acknowledge funding from an NHS Research Scotland Senior Clinical Fellowship (SCAF/15/02), the MRC (MC_UU_00022/2), and the Scottish Government Chief Scientist Office (SPHSU17). This partnership between Brazil and Scotland was established through funding from the NIHR (GHRG /16/137/99) using UK aid from the UK Government to support global health research. This study was partially supported by a donation from the Fazer o Bem Faz Bem programme. The authors thank DATASUS for its excellent work in providing unidentified databases. GLW, MLB, and MB-N are research fellows from the Brazilian National Research Council. GLW acknowledges funding from FAPERJ (Funda??o Carlos Chagas Filho de Amparo ? Pesquisa do Estado do Rio de Janeiro; E-26/210.180/2020). We thank Dave Kelly from Albasoft (Inverness, UK) for his support with making primary care data available; Wendy Inglis-Humphrey, Vicky Hammersley, and Laura Brook (University of Edinburgh, Edinburgh, UK); and Pam McVeigh, Amanda Burridge, and Afshin Dastafshan (Public Health Scotland, Glasgow, UK) for their support with project management and administration. Publisher Copyright: © 2022 The author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licensePeer reviewedPublisher PD

Social distancing measures to control the COVID-19 pandemic: potential impacts and challenges in Brazil.

The COVID-19 pandemic has challenged researchers and policy makers to identify public safety measures forpreventing the collapse of healthcare systems and reducingdeaths. This narrative review summarizes the available evidence on the impact of social distancing measures on the epidemic and discusses the implementation of these measures in Brazil. Articles on the effect of social distancing on COVID-19 were selected from the PubMed, medRXiv and bioRvix databases. Federal and state legislation was analyzed to summarize the strategies implemented in Brazil. Social distancing measures adopted by the population appear effective, particularly when implemented in conjunction with the isolation of cases and quarantining of contacts. Therefore, social distancing measures, and social protection policies to guarantee the sustainability of these measures, should be implemented. To control COVID-19 in Brazil, it is also crucial that epidemiological monitoring is strengthened at all three levels of the Brazilian National Health System (SUS). This includes evaluating and usingsupplementary indicators to monitor the progression of the pandemic and the effect of the control measures, increasing testing capacity, and making disaggregated notificationsand testing resultstransparentand broadly available

Insights into the Musa genome: Syntenic relationships to rice and between Musa species

<p>Abstract</p> <p>Background</p> <p><it>Musa </it>species (Zingiberaceae, Zingiberales) including bananas and plantains are collectively the fourth most important crop in developing countries. Knowledge concerning <it>Musa </it>genome structure and the origin of distinct cultivars has greatly increased over the last few years. Until now, however, no large-scale analyses of <it>Musa </it>genomic sequence have been conducted. This study compares genomic sequence in two <it>Musa </it>species with orthologous regions in the rice genome.</p> <p>Results</p> <p>We produced 1.4 Mb of <it>Musa </it>sequence from 13 BAC clones, annotated and analyzed them along with 4 previously sequenced BACs. The 443 predicted genes revealed that Zingiberales genes share GC content and distribution characteristics with eudicot and Poaceae genomes. Comparison with rice revealed microsynteny regions that have persisted since the divergence of the Commelinid orders Poales and Zingiberales at least 117 Mya. The previously hypothesized large-scale duplication event in the common ancestor of major cereal lineages within the Poaceae was verified. The divergence time distributions for <it>Musa</it>-Zingiber (Zingiberaceae, Zingiberales) orthologs and paralogs provide strong evidence for a large-scale duplication event in the <it>Musa </it>lineage after its divergence from the Zingiberaceae approximately 61 Mya. Comparisons of genomic regions from <it>M. acuminata </it>and <it>M. balbisiana </it>revealed highly conserved genome structure, and indicated that these genomes diverged circa 4.6 Mya.</p> <p>Conclusion</p> <p>These results point to the utility of comparative analyses between distantly-related monocot species such as rice and <it>Musa </it>for improving our understanding of monocot genome evolution. Sequencing the genome of <it>M. acuminata </it>would provide a strong foundation for comparative genomics in the monocots. In addition a genome sequence would aid genomic and genetic analyses of cultivated <it>Musa </it>polyploid genotypes in research aimed at localizing and cloning genes controlling important agronomic traits for breeding purposes.</p