Inefficient adenoviral vector (AdV)-mediated gene transfer to the ciliated respiratory epithelium has hindered gene transfer strategies for the treatment of cystic fibrosis lung disease. In part, the inefficiency is due to an absence of the coxsackie B and adenovirus type 2 and 5 receptor (CAR) from the apical membranes of polarized epithelia. In this study, using an in vitro model of human ciliated airway epithelium, we show that providing a glycosylphosphatidylinositol (GPI)-linked AdV receptor (GPI-CAR) at the apical surface did not significantly improve AdV gene transfer efficiency because the lumenal surface glycocalyx limited the access of AdV to apical GPI-CAR. The highly glycosylated tethered mucins were considered to be significant glycocalyx components that restricted AdV access because proteolytic digestion and inhibitors of O-linked glycosylation enhanced AdV gene transfer. To determine whether these in vitro observations are relevant to the in vivo situation, we generated transgenic mice expressing GPI-CAR at the surface of the airway epithelium, crossbred these mice with mice that were genetically devoid of tethered mucin type 1 (Muc1), and tested the efficiency of gene transfer to murine airways expressing apical GPI-human CAR (GPI-hCAR) in the presence and absence of Muc1. We determined that AdV gene transfer to the murine airway epithelium was inefficient even in GPI-hCAR transgenic mice but that the gene transfer efficiency improved in the absence of Muc1. However, the inability to achieve a high gene transfer efficiency, even in mice with a deletion of Muc1, suggested that other glycocalyx components, possibly other tethered mucin types, also provide a significant barrier to AdV interacting with the airway lumenal surface.
Because lifelong exposure to estrogen is a strong determinant of bone mass, we asked whether metabolic conversion of estrogen to either inactive or active metabolites would reflect postmenopausal bone mineral density (BMD) and rate of bone loss. Biochemical markers of inactive estrogen metabolites, urinary 2-hydroxyestrogen (2OHE 1 ) and 2-methoxyestrogen (2MeOE 1 ), and active metabolites, urinary 16␣-hydroxyestrone (16␣OHE 1 ), estradiol (E 2 ), and estriol (E 3 ), were determined in 71 untreated, healthy postmenopausal women (age, 47-59 years) followed prospectively for 1 year. Urinary 2MeOE 1 was correlated negatively with baseline vertebral (anteroposterior [AP] projection, r ؍ ؊0.23 and p < 0.05; lateral view, r ؍ ؊0.27 and p < 0.05) and proximal femur bone density measured by dual-energy X-ray absorptiometry (DXA; total, r ؍ ؊0.38 and p < 0.01; neck, r ؍ ؊0.28 and p ؍ 0.02; trochanter, r ؍ ؊0.44 and p < 0.01). BMDs of women in the lowest quartile of urinary 2MeOE 1 (<15 ng/g) were significantly higher than those in the highest quartile at all skeletal sites (p < 0.05). Likewise, women in the lowest quartile of urinary 2OHE 1 /16␣OHE 1 ratio (<1.6) did not experience bone loss after 1 year, in contrast to women in the higher quartiles. We propose that the rate of inactivation of estrogens through 2-hydroxylation may contribute to postmenopausal osteoporosis. (J Bone Miner Res 2000;15:2513-2520)
This article describes the development of the Community Health clinic model for Agency in Relationships and Safer Microbicide Adherence intervention (CHARISMA), an intervention designed to address the ways in which gender norms and power differentials within relationships affect women's ability to safely and consistently use HIV pre-exposure prophylaxis (PrEP). CHARISMA development involved three main activities: (1) a literature review to identify appropriate evidence-based relationship dynamic scales and interventions; (2) the analysis of primary and secondary data collected from completed PrEP studies, surveys and cognitive interviews with PrEP-experienced and naïve women, and in-depth interviews with former vaginal ring trial participants and male partners; and (3) the conduct of workshops to test and refine key intervention activities prior to pilot testing. These steps are described along with the final clinic and community-based intervention, which was tested for feasibility, acceptability, and preliminary effectiveness in Johannesburg, South Africa.
Mild cognitive impairment (MCI) is a classification reserved for nondemented elderly individuals at increased risk for future decline to dementia, compared to those with normal cognition. Cognitive tests, particularly those assessing verbal recall, have been found to be useful in the identification of elderly people with MCI. We argue that a variety of motor/psychomotor evaluations are also sensitive to MCI. Motor assessments described as complex correctly categorize normal versus MCI elderly with comparable accuracies to those obtained by cognitive tests. Unlike performance on verbally based cognitive measures, motor-test scores appear to be relatively independent of educational attainment, indicating that the use of certain motor tests may be particularly valuable in the identification of MCI among elderly with widely varying educational backgrounds.
Artigo recebido em 16 de dezembro de 2015, versão final aceita em 3 de agosto de 2016. RESUMO:Tendo como pano de fundo o debate sobre a relação entre uso dos recursos naturais, economia e sustentabilidade, neste trabalho objetiva-se discutir o lugar do extrativismo no contexto do Desenvolvimento considerando as diferentes perspectivas sobre essa atividade na Amazônia brasileira. Com base em revisão de literatura e dados secundários, contextualiza-se que historicamente as estratégias de desenvolvimento pensadas para a região amazônica brasileira são pautadas em atividades extrativistas promovidas pelos detentores de poder político e econômico e fomentadas pelo Estado. Atualmente, é recorrente no discurso de acadêmicos e de porta-vozes do governo, de movimentos sociais e de empresas, a necessidade do repensar o uso dos recursos naturais, agregando valor aos produtos extrativistas e valorizando o conhecimento das populações tradicionais. Discute-se o reconhecimento da diversidade de populações, de ecossistemas e de formas de gestão dos recursos naturais, emergindo novos atores, novos produtos e conflitos. Todavia, nesse cenário de disputas, segue o desafio da operacionalização de tais princípios em termos de estratégias para o desenvolvimento.Palavras-chave: atividades extrativistas; recursos naturais; desenvolvimento sustentável. ABSTRACT:Having as background the debate about the relationship between the use of natural resources, economy and sustainability, the objective of this paper is to discuss the place for extraction in the context of development considering the different perspectives of this activity in the Brazilian Amazon. Based on literature review and secondary data it is contextualized that historically the development strategies designed to Brazil's Amazon region are guided in extractive activities promoted by the holders of political and economical power and promoted by the state. Currently, it recurs in academic discourses and government spokesmen, social movements and companies, the need to rethink the use of natural resources, adding value to extractive products and enhancing
Este artigo apresenta uma pesquisa realizada de forma participativa na Amazônia brasileira, na região de Santarém, Pará. O objetivo foi entender como as grandes mudanças socioambientais estão afetando os agricultores familiares. Nos últimos 20 anos, a agricultura familiar, na área de estudo, tem sido confrontada com a rápida expansão de monoculturas de grande escala, principalmente o cultivo de soja. Como parte do Observatório Socioambiental Odyssea, pesquisadores acadêmicos e organizações de agricultura familiar firmaram uma parceria para coproduzir dados que poderiam ser estrategicamente úteis para estas organizações. Um processo de coconstrução de demandas por conhecimento permitiu o estabelecimento de prioridades e a definição da estratégia de coleta de dados. Três níveis de análise foram escolhidos para permitir uma compreensão integrada das dinâmicas das mudanças socioambientais: o nível do território do Planalto de Santarém, o nível da comunidade rural (lugar de vida reconhecido pelos agricultores) e as famílias dos agricultores. Jovens pesquisadores comunitários aplicaram um questionário através de um aplicativo de celular com 544 famílias nos municípios de Santarém, Mojuí dos Campos e Belterra. Anteriormente, foram realizadas reuniões nas comunidades rurais e aplicados questionários com representantes de 32 comunidades. Os dados foram coletados entre abril e junho de 2019. Os pesquisadores comunitários e acadêmicos se reuniram então para duas sessões coletivas de análise e interpretação de dados, em julho e outubro de 2019. Os dados foram padronizados e limpos usando o software SPSS, entre setembro e dezembro de 2019. Os metadados e bancos de dados estão disponíveis no dataverse do CIRAD.
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