Extracellular cyclophilins contribute to the regulation of inflammatory responses.

The main regulators of leukocyte trafficking during inflammatory responses are chemokines. However, another class of recently identified chemotactic agents is extracellular cyclophilins, the proteins mostly known as receptors for the immunosuppressive drug, cyclosporine A. Cyclophilins can induce leukocyte chemotaxis in vitro and have been detected at elevated levels in inflamed tissues, suggesting that they might contribute to inflammatory responses. We recently identified CD147 as the main signaling receptor for cyclophilin A. In the current study we examined the contribution of cyclophilin-CD147 interactions to inflammatory responses in vivo using a mouse model of acute lung injury. Blocking cyclophilin-CD147 interactions by targeting CD147 (using anti-CD147 Ab) or cyclophilin (using nonimmunosuppressive cyclosporine A analog) reduced tissue neutrophilia by up to 50%, with a concurrent decrease in tissue pathology. These findings are the first to demonstrate the significant contribution of cyclophilins to inflammatory responses and provide a potentially novel approach for reducing inflammation-mediated diseases.

Why Public Health Agencies Cannot Depend on Good Laboratory Practices as a Criterion for Selecting Data: The Case of Bisphenol A

In their safety evaluations of bisphenol A (BPA), the U.S. Food and Drug Administration (FDA) and a counterpart in Europe, the European Food Safety Authority (EFSA), have given special prominence to two industry-funded studies that adhered to standards defined by Good Laboratory Practices (GLP). These same agencies have given much less weight in risk assessments to a large number of independently replicated non-GLP studies conducted with government funding by the leading experts in various fields of science from around the world. OBJECTIVES: We reviewed differences between industry-funded GLP studies of BPA conducted by commercial laboratories for regulatory purposes and non-GLP studies conducted in academic and government laboratories to identify hazards and molecular mechanisms mediating adverse effects. We examined the methods and results in the GLP studies that were pivotal in the draft decision of the U.S. FDA declaring BPA safe in relation to findings from studies that were competitive for U.S. National Institutes of Health (NIH) funding, peer-reviewed for publication in leading journals, subject to independent replication, but rejected by the U.S. FDA for regulatory purposes. DISCUSSION: Although the U.S. FDA and EFSA have deemed two industry-funded GLP studies of BPA to be superior to hundreds of studies funded by the U.S. NIH and NIH counterparts in other countries, the GLP studies on which the agencies based their decisions have serious conceptual and methodologic flaws. In addition, the U.S. FDA and EFSA have mistakenly assumed that GLP yields valid and reliable scientific findings (i.e., "good science"). Their rationale for favoring GLP studies over hundreds of publically funded studies ignores the central factor in determining the reliability and validity of scientific findings, namely, independent replication, and use of the most appropriate and sensitive state-of-the-art assays, neither of which is an expectation of industry-funded GLP research. CONCLUSIONS: Public health decisions should be based on studies using appropriate protocols with appropriate controls and the most sensitive assays, not GLP. Relevant NIH-funded research using state-of-the-art techniques should play a prominent role in safety evaluations of chemicals.

Sources of pre-analytical variations in yield of DNA extracted from blood samples: analysis of 50,000 DNA samples in EPIC.

The European Prospective Investigation into Cancer and nutrition (EPIC) is a long-term, multi-centric prospective study in Europe investigating the relationships between cancer and nutrition. This study has served as a basis for a number of Genome-Wide Association Studies (GWAS) and other types of genetic analyses. Over a period of 5 years, 52,256 EPIC DNA samples have been extracted using an automated DNA extraction platform. Here we have evaluated the pre-analytical factors affecting DNA yield, including anthropometric, epidemiological and technical factors such as center of subject recruitment, age, gender, body-mass index, disease case or control status, tobacco consumption, number of aliquots of buffy coat used for DNA extraction, extraction machine or procedure, DNA quantification method, degree of haemolysis and variations in the timing of sample processing. We show that the largest significant variations in DNA yield were observed with degree of haemolysis and with center of subject recruitment. Age, gender, body-mass index, cancer case or control status and tobacco consumption also significantly impacted DNA yield. Feedback from laboratories which have analyzed DNA with different SNP genotyping technologies demonstrate that the vast majority of samples (approximately 88%) performed adequately in different types of assays. To our knowledge this study is the largest to date to evaluate the sources of pre-analytical variations in DNA extracted from peripheral leucocytes. The results provide a strong evidence-based rationale for standardized recommendations on blood collection and processing protocols for large-scale genetic studies.

Differential in vitro activity of the DNA topoisomerase inhibitor idarubicin against Trypanosoma rangeli and Trypanosoma cruzi

In this study the effect of eight DNA topoisomerase inhibitors on the growth Trypanosoma rangeli epimastigotes in cell culture was investigated. Among the eight compounds tested, idarubicin was the only compound that displayed promising trypanocidal activity with a half-maximal growth inhibition (GI50) value in the sub-micromolar range. Fluorescence-activated cell sorting analysis showed a reduction in DNA content in T. rangeli epimastigotes when treated with idarubicin. In contrast to T. rangeli, against Trypanosoma cruzi epimastigotes idarubicin was much less effective exhibiting a GI50 value in the mid-micromolar range. This result indicates that idarubicin displays differential toxic effects in T. rangeli and T. cruzi. Compared with African trypanosomes, it seems that American trypanosomes are generally less susceptible to DNA topoisomerase inhibitors.

Schistosoma mansoni in a low-prevalence area in Brazil: the importance of additional methods for the diagnosis of hard-to-detect individual carriers by low-cost immunological assays

Schistosomiasis diagnosis is based on the detection of eggs in the faeces, which is laborious and lacks sensitivity, especially for patients with a low parasite burden. Immunological assays for specific antibody detection are available, but they usually demonstrate low sensitivity and/or specificity. In this study, two simple immunological assays were evaluated for the detection of soluble Schistosoma mansoni adult worm preparation (SWAP) and egg-specific IgGs. These studies have not yet been evaluated for patients with low parasite burdens. Residents of an endemic area in Brazil donated sera and faecal samples for our study. The patients were initially diagnosed by a rigorous Kato-Katz analysis of 18 thick smears from four different stool samples. The ELISA-SWAP was successful for human diagnosis with 90% sensitivity and specificity, confirming the Kato-Katz diagnosis with nearly perfect agreement, as seen by the Kappa index (0.85). Although the ELISA-soluble S. mansoni egg antigen was 85% sensitive, it exhibited low specificity (80%; Kappa index: 0.75) and was more susceptible to cross-reactivity. We believe that immunological assays should be used in conjunction with Kato-Katz analysis as a supplementary tool for the diagnosis of schistosomiasis for patients with low infection burdens, which are usually hard to detect.

Cuidado transpessoal em enfermagem: uma análise pautada em modelo conceitual

Estudo teórico que objetivou analisar os atributos, antecedentes e consequências do conceito cuidado transpessoal, mediante utilização do Modelo de Análise de Conceito. Para isso, elencaram-se livros publicados pela teórica Jean Watson, em português e em inglês, no período de 1979 a 2012. Cumpridos os critérios de inclusão, permaneceram seis obras literárias. Os antecedentes mais citados foram o momento de cuidado e a intenção em estar na relação. Os atributos mais presentes foram a intersubjetividade e as relações entre os envolvidos no processo. Com relação às consequências, o fato de o cuidado transpessoal propiciar restauração/reconstituição (healing) foi o elemento mais presente. O estudo possibilitou constatar ínfimas alterações na definição do conceito com o passar dos anos e das publicações da teórica. Assim, analisar os atributos, os antecedentes e as consequências do conceito propiciou melhor entendimento deste e compreensão da sua importância na Teoria do Cuidado Humano proposta pela teórica americana.

The relation of body mass index and abdominal adiposity with dyslipidemia in 27 general populations of the WHO MONICA Project.

The association between adiposity measures and dyslipidemia has seldom been assessed in a multipopulational setting. 27 populations from Europe, Australia, New Zealand and Canada (WHO MONICA project) using health surveys conducted between 1990 and 1997 in adults aged 35-64 years (n = 40,480). Dyslipidemia was defined as the total/HDL cholesterol ratio >6 (men) and >5 (women). Overall prevalence of dyslipidemia was 25% in men and 23% in women. Logistic regression showed that dyslipidemia was strongly associated with body mass index (BMI) in men and with waist circumference (WC) in women, after adjusting for region, age and smoking. Among normal-weight men and women (BMI<25 kg/m(2)), an increase in the odds for being dyslipidemic was observed between lowest and highest WC quartiles (OR = 3.6, p < 0.001). Among obese men (BMI ≥ 30), the corresponding increase was smaller (OR = 1.2, p = 0.036). A similar weakening was observed among women. Classification tree analysis was performed to assign subjects into classes of risk for dyslipidemia. BMI thresholds (25.4 and 29.2 kg/m(2)) in men and WC thresholds (81.7 and 92.6 cm) in women came out at first stages. High WC (>84.8 cm) in normal-weight men, menopause in women and regular smoking further defined subgroups at increased risk. standard categories of BMI and WC, or their combinations, do not lead to optimal risk stratification for dyslipidemia in middle-age adults. Sex-specific adaptations are necessary, in particular by taking into account abdominal obesity in normal-weight men, post-menopausal age in women and regular smoking in both sexes.

Financiamento dos Sistema de Saude

Este Relatório sobre a Saúde no Mundo foi produzido sob a direcção geral de Carissa Etienne, Assistente do Director-Geral, Sistemas e Serviços de Saúde e Anarfi Asamoa-Baah, Director Geral Adjunto. Os redactores principais froam David B Evans, Riku Elovainio e Gary Humphreys; com contribuições de Daniel Chisholm, Joseph Kutzin, Sarah Russell, Priyanka Saksena e Ke Xu. Contribuições sob a forma de caixas de texto e análises foram fornecidos por: Ole Doetinchem, Adelio Fernandes Antunes, Justine Hsu, Chandika K. Indikadahena, Jeremy Lauer, Nathalie van de Maele, Belgacem Sabri, Hossein Salehi, Xenia Scheil-Adlung (ILO) and Karin Stenberg. Sugestões e comentários foram recebidos dos Directores Regionais, Assistentes do Director-Geral e respectivas equipas. Análises, dados e revisões da organização do texto, vários rascunhos ou secções específicas foram fornecidos por (em adição às pessoas jáacima mencionadas): Dele Abegunde, Michael Adelhardt, Hector Arreola, Guitelle Baghdadi-Sabeti, Dina Balabanova, Dorjsuren Bayarsaikhan, Peter Berman, Melanie Bertram, Michael Borowitz, Reinhard Busse, Alexandra Cameron, Guy Carrin, Andrew Cassels, Eleonora Cavagnero, John Connell, David de Ferranti, Don de Savigny, Varatharajan Durairaj, Tamás Evetovits, Josep Figueras, Emma Fitzpatrick, Julio Frenk, Daniela Fuhr, Ramiro Guerrero, Patricia Hernandez Pena, Hans V Hogerzeil, Kathleen Holloway, Melitta Jakab, Elke Jakubowski, Christopher James, Mira Johri, Matthew Jowett, Joses Kirigia, Felicia Knaul, Richard Laing, Nora Markova, Awad Mataria, Inke Mathauer, Don Matheson, Anne Mills, Eduardo Missoni, Laurent Musango, Helena Nygren-Krug, Ariel Pablos-Mendez, Anne-Marie Perucic, Claudia Pescetto, Jean Perrot, Alexander Preker, Magdalena Rathe, Dag Rekve, Ritu Sadana, Rocio Saenz, Thomas Shakespeare, Ian Smith, Peter C Smith, Alaka Singh, Ruben Suarez Berenguela, Tessa Tan-Torres Edejer, Richard Scheffler, Viroj Tangcharoensathien, Fabrizio Tediosi, Sarah Thomson, Ewout van Ginneken, Cornelis van Mosseveld e Julia Watson. A redacção do Relatório foi informada por muitos indivíduos de várias instituições que forneceram documentos de suporte; estes documentos de suporte podem ser encontrados em: http://www.who.int/healthsystems/topics/financing/healthreport/whr_background/en Michael Reid editou as cópias do Relatório, Gaël Kernen produziu as figuras e Evelyn Omukubi forneceu o valioso apoio secretarial e administrativo. O desenho e paginação foi feito por Sophie Guetaneh Aguettant e Cristina Ortiz. Ilustração por Edel Tripp (http://edeltripp.daportfolio.com). A tradução foi realizada por Jorge Cabral e Aurélio Floriano e revista por Aurélio Floriano e Paulo Ferrinho, do Instituto de Higiene e Medicina Tropical, da Universidade Nova de Lisboa - Lisboa, Portugal. A publicação foi produzida com o apoio da Comunidade dos Países de Língua Portuguesa (CPLP), sob autorização do Director Geral da Organização Mundial da Saúde (OMS). As informações contidas neste Relatório não podem, de forma alguma, ser tomadas como a expressão das posições da CPLP

Estimação da média com observações

Neste trabalho abordamos o problema da estimação da média de uma variável aleatória que depende de outra (ou outras) através de um modelo de regressão. O conhecimento completo da amostra permite o tratamento deste problema utilizando os métodos clássicos para a estimação da regressão. Aqui iremos estudar uma solução para o problema quando parte da informação que compõe a amostra se perde, nomeadamente, quando, na amostra que permite o tratamento do problema de regressão, algumas das ordenadas não são conhecidas, mas sim apenas o valor para variável explicativa. A solução mais simples neste caso consistiria em ignorar os pontos correspondentes da amostra. Contudo, aqui, pretende-se estudar um método que tenta tirar partido do conhecimento de que houve uma observação e que o valor desta está relacionado com a abcissa disponível através de um modelo de regressão que será aproximado à custa dos pontos da amostra conhecidos na totalidade. Numa primeira instância introduzimos os métodos não paramétricos de aproximação da regressão, a explorar, regressograma e Nadaraya- Watson. Em capítulos posteriores, descrevemos a adaptação do estimador Nadaraya-Watson ao problema das amostras incompletas. Discutemse ainda adaptações que tentam minimizar as dificuldades deste estimador quando o espaço das abcissas é de dimensão grande, assumindo que parte da função de regressão tem um comportamento linear, portanto paramétrico. Neste trabalho apresentamos resultados que asseguram a normalidade assimptótica dos estimadores definidos.

Aromatherapy and nursing: historical and theoretical conception

Abstract Aromatherapy is a Practical or Complementary Health Therapy that uses volatile concentrates extracted from plants called essential oils, in order to improve physical, mental and emotional well-being. Aromatherapy has been practiced historically and worldwide by nurses and, as in Brazil is supported by the Federal Nursing Council, it is relevant to discuss this practice in the context of Nursing through Theories of Nursing. This study of theoretical reflection, exploratory and descriptive, aims to discuss the pharmacognosy of essential oils, the historical trajectory of Aromatherapy in Nursing and the conceptions to support Aromatherapy in light of eight Nursing Theorists (Florence Nightingale, Myra Levine, Hildegard Peplau, Martha Rogers, Callista Roy, Wanda Horta, Jean Watson and Katharine Kolcaba), contributing to its inclusion as a nursing care practice.

Tornabenea ribeirensis (Apiaceaeb a new species from São Nicolau, Cape Verde Islands (West Africa)

Many species of Apiaceae are found in the Macaronesien Region. Several have been introduccd by human activities, but a number of taxa is endemic to the different archipelagos or even rrstrictcd to a single island. The following enumeration is based mainly on HANSEN & SUNDING ( 1993). In the Arores 28 different taxa of Apiaceae occur; among them four endemic species [AUIMI; hrrrrii WATSON, A. trifoliatum (WATSON) TKEL., Clrtrc~,y~l~~ll~r~~~ cl:oricrm TREL.. SOErich trwrictr GUTIINICK ex SEUB.]. In Madeira the Apiaceae are very diverse and consist ol’ 29 species and subspecies. From the archipelago two monotypic genera, rC/c/trtio. velitru~rr t/ccipicvr.s (SCHRAD. & J. C. WENDL.) Ho~+hl. md kJorli:ia edu[is LOWE and ~hrcc cndcmic species [Oemmrlre diwricore (R. BR.) MABB.. I/nperrr/orio lotvei COSS. and Burrirr~r hre~$~lirrnr LOWE] are described. The Canary Islands have the highest numbcr of plant-species and a high level of endemism. 5-l taxa of Apiaceae are recorded including three endemic genera (Rtrrheopsis A. HANSEX & KUNKEL, Todm-oa PARL. and Tiqyrmm PARL.) and further I5 endemic taxa. The Apiaceae are represented in the Cape Verde Islands by I2 species. Most of the taxa have been introduced by human activities (LOBIN & ZIZKA 1957) like Amvhm grm’eo- 1efr.s L., Apirm grmvolerrs L, Foerricrrhrr urlgore MILL.. Corimrtlru~t~ srrtirvrrrr L. or Petrosilerrm crisprrm (FRILL.) A.W.HILL. These species are cultivated and some of them later became \\esdy. Other species like Ciclosper- UWL /e/~fo/~/l~ll~rrtr (PER%) SPRAGUE (= Apimr leproplr~llrr~rr) are weeds of cultivated grounds or wasted lands. All these species are today widespread in temperate. subtropical or tropical regions all over the world. The only native species are to be found in the endemic genus To~wI~~I~~~ PARL.

Weighted Kernel regression

In the fixed design regression model, additional weights areconsidered for the Nadaraya--Watson and Gasser--M\"uller kernel estimators.We study their asymptotic behavior and the relationships between new andclassical estimators. For a simple family of weights, and considering theIMSE as global loss criterion, we show some possible theoretical advantages.An empirical study illustrates the performance of the weighted estimatorsin finite samples.

The implications of alternative splicing in the ENCODE protein complement.

Alternative premessenger RNA splicing enables genes to generate more than one gene product. Splicing events that occur within protein coding regions have the potential to alter the biological function of the expressed protein and even to create new protein functions. Alternative splicing has been suggested as one explanation for the discrepancy between the number of human genes and functional complexity. Here, we carry out a detailed study of the alternatively spliced gene products annotated in the ENCODE pilot project. We find that alternative splicing in human genes is more frequent than has commonly been suggested, and we demonstrate that many of the potential alternative gene products will have markedly different structure and function from their constitutively spliced counterparts. For the vast majority of these alternative isoforms, little evidence exists to suggest they have a role as functional proteins, and it seems unlikely that the spectrum of conventional enzymatic or structural functions can be substantially extended through alternative splicing.