Sorteio intradomiciliar em inquéritos de saúde

OBJETIVO : Comparar a eficiência e a acurácia de delineamentos de amostragem com e sem sorteio intradomiciliar em inquéritos de saúde. MÉTODOS : Com base nos dados de um inquérito realizado na Baixada Santista, SP, entre 2006 e 2007, foram retiradas 1.000 amostras sob cada um dos delineamentos e, em cada amostra, foram obtidas estimativas para pessoas de 18 a 59 anos de idade e de 18 anos e mais. Sob o primeiro, foram sorteados 40 setores censitários, 12 domicílios por setor e uma pessoa por domicílio. Na análise, os dados foram ponderados pelo número de adultos residentes nos domicílios. Sob o segundo, foram sorteados 40 setores, seis domicílios por setor para o grupo de 18 a 59 anos de idade e cinco ou seis domicílios para o grupo de 18 anos e mais. Não houve sorteio dentro do domicílio. Medidas de precisão e de vício das estimativas de proporção para 11 indicadores foram calculadas nos dois conjuntos finais das amostras selecionadas para os dois tipos de delineamentos. Estes foram comparados por meio das medidas relativas: coeficiente de variação, razão vício/média, razão vício/erro padrão e erro quadrático médio relativo. O custo foi comparado considerando custo básico por pessoa, custo por domicílio e números de pessoas e domicílios. RESULTADOS : Os vícios mostraram-se desprezíveis nos dois delineamentos. A precisão foi maior para o delineamento sem sorteio e o custo foi menor. CONCLUSÕES : O delineamento sem sorteio intradomicilar mostrou-se superior em termos de eficiência e acurácia, devendo ser a opção preferencial do pesquisador. O sorteio de moradores deve ser adotado quando houver razões referentes ao objeto de estudo que possam levar à introdução de vícios nas respostas dos entrevistados no caso de vários moradores responderem ao questionário proposto

Immunoregulation of bovine macrophages by factors in the salivary glands of Rhipicephalus microplus

<p>Abstract</p> <p>Background</p> <p>Alternative strategies are required to control the southern cattle tick, <it>Rhipicephalus microplus</it>, due to evolving resistance to commercially available acaricides. This invasive ectoparasite is a vector of economically important diseases of cattle such as bovine babesiosis and anaplasmosis. An understanding of the biological intricacies underlying vector-host-pathogen interactions is required to innovate sustainable tick management strategies that can ultimately mitigate the impact of animal and zoonotic tick-borne diseases. Tick saliva contains molecules evolved to impair host innate and adaptive immune responses, which facilitates blood feeding and pathogen transmission. Antigen presenting cells are central to the development of robust T cell responses including Th1 and Th2 determination. In this study we examined changes in co-stimulatory molecule expression and cytokine response of bovine macrophages exposed to salivary gland extracts (SGE) obtained from 2-3 day fed, pathogen-free adult <it>R. microplus</it>.</p> <p>Methods</p> <p>Peripheral blood-derived macrophages were treated for 1 hr with 1, 5, or 10 μg/mL of SGE followed by 1, 6, 24 hr of 1 μg/mL of lipopolysaccharide (LPS). Real-time PCR and cytokine ELISA were used to measure changes in co-stimulatory molecule expression and cytokine response.</p> <p>Results</p> <p>Changes were observed in co-stimulatory molecule expression of bovine macrophages in response to <it>R</it>. <it>microplus </it>SGE exposure. After 6 hrs, CD86, but not CD80, was preferentially up-regulated on bovine macrophages when treated with 1 μg/ml SGE and then LPS, but not SGE alone. At 24 hrs CD80, CD86, and CD69 expression was increased with LPS, but was inhibited by the addition of SGE. SGE also inhibited LPS induced upregulation of TNFα, IFNγ and IL-12 cytokines, but did not alter IL-4 or CD40 mRNA expression.</p> <p>Conclusions</p> <p>Molecules from the salivary glands of adult <it>R. microplus </it>showed bimodal concentration-, and time-dependent effects on differential up-regulation of CD86 in bovine macrophages activated by the TLR4-ligand, LPS. Up regulation of proinflammatory cytokines and IL-12, a Th1 promoting cytokine, were inhibited in a dose-dependent manner. The co-stimulatory molecules CD80, as well as the cell activation marker, CD69, were also suppressed in macrophages exposed to SGE. Continued investigation of the immunomodulatory factors will provide the knowledge base to research and develop therapeutic or prophylactic interventions targeting <it>R. microplus</it>-cattle interactions at the blood-feeding interface.</p

Field template-based design and biological evaluation of new sphingosine kinase 1 inhibitors

Purpose: Sphingosine kinase 1 (SK1) is a protooncogenic enzyme expressed in many human tumours and is associated with chemoresistance and poor prognosis. It is a potent therapy target and its inhibition chemosensitises solid tumours. Despite recent advances in SK1 inhibitors synthesis and validation, their clinical safety and chemosensitising options are not well described. In this study, we have designed, synthesised and tested a new specific SK1 inhibitor with a low toxicity profile. Methods: Field template molecular modelling was used for compound design. Lead compounds were tested in cell and mouse cancer models. Results: Field template analysis of three known SK1 inhibitors, SKI-178, 12aa and SK1-I, was performed and compound screening identified six potential new SK1 inhibitors. SK1 activity assays in both cell-free and in vitro settings showed that two compounds were effective SK1 inhibitors. Compound SK-F has potently decreased cancer cell viability in vitro and sensitised mouse breast tumours to docetaxel (DTX) in vivo, without significant whole-body toxicity. Conclusion: Through field template screening, we have identified a new SK1 inhibitor, SK-F, which demonstrated antitumour activity in vitro and in vivo without overt toxicity when combined with DTX

Screening for frailty in older adults using a self-reported instrument

OBJECTIVE To validate a screening instrument using self-reported assessment of frailty syndrome in older adults. METHODS This cross-sectional study used data from the Saúde, Bem-estar e Envelhecimento study conducted in Sao Paulo, SP, Southeastern Brazil. The sample consisted of 433 older adult individuals (≥ 75 years) assessed in 2009. The self-reported instrument can be applied to older adults or their proxy respondents and consists of dichotomous questions directly related to each component of the frailty phenotype, which is considered the gold standard model: unintentional weight loss, fatigue, low physical activity, decreased physical strength, and decreased walking speed. The same classification proposed in the phenotype was utilized: not frail (no component identified); pre-frail (presence of one or two components), and frail (presence of three or more components). Because this is a screening instrument, “process of frailty” was included as a category (pre-frail and frail). Cronbach’s α was used in psychometric analysis to evaluate the reliability and validity of the criterion, the sensitivity, the specificity, as well as positive and negative predictive values. Factor analysis was used to assess the suitability of the proposed number of components. RESULTS Decreased walking speed and decreased physical strength showed good internal consistency (α = 0.77 and 0.72, respectively); however, low physical activity was less satisfactory (α = 0.63). The sensitivity and specificity for identifying pre-frail individuals were 89.7% and 24.3%, respectively, while those for identifying frail individuals were 63.2% and 71.6%, respectively. In addition, 89.7% of the individuals from both the evaluations were identified in the “process of frailty” category. CONCLUSIONS The self-reported assessment of frailty can identify the syndrome among older adults and can be used as a screening tool. Its advantages include simplicity, rapidity, low cost, and ability to be used by different professionals