(R)-ketamine attenuates neurodevelopmental disease-related phenotypes in a mouse model of maternal immune activation.

Infections during pregnancy are associated with an increased risk of neuropsychiatric disorders with developmental etiologies, such as schizophrenia and autism spectrum disorders (ASD). Studies have shown that the animal model of maternal immune activation (MIA) reproduces a wide range of phenotypes relevant to the study of neurodevelopmental disorders. Emerging evidence shows that (R)-ketamine attenuates behavioral, cellular, and molecular changes observed in animal models of neuropsychiatric disorders. Here, we investigate whether (R)-ketamine administration during adolescence attenuates some of the phenotypes related to neurodevelopmental disorders in an animal model of MIA. For MIA, pregnant Swiss mice received intraperitoneally (i.p.) lipopolysaccharide (LPS; 100 µg/kg/day) or saline on gestational days 15 and 16. The two MIA-based groups of male offspring received (R)-ketamine (20 mg/kg/day; i.p.) or saline from postnatal day (PND) 36 to 50. At PND 62, the animals were examined for anxiety-like behavior and locomotor activity in the open-field test (OFT), as well as in the social interaction test (SIT). At PND 63, the prefrontal cortex (PFC) was collected for analysis of oxidative balance and gene expression of the cytokines IL-1ß, IL-6, and TGF-ß1. We show that (R)-ketamine abolishes anxiety-related behavior and social interaction deficits induced by MIA. Additionally, (R)-ketamine attenuated the increase in lipid peroxidation and the cytokines in the PFC of the offspring exposed to MIA. The present work suggests that (R)-ketamine administration may have a long-lasting attenuation in deficits in emotional behavior induced by MIA, and that these effects may be attributed to its antioxidant and anti-inflammatory activity in the PFC.

S100A9 Drives the Chronification of Psoriasiform Inflammation by Inducing IL-23/Type 3 Immunity.

Psoriasis is a chronic inflammatory skin disorder driven by the IL-23/type 3 immune response. However, molecular mechanisms sustaining the chronicity of inflammation and psoriatic lesions remain elusive. Combining systematic analyses of several transcriptomic datasets, we delineated gene signatures across human psoriatic skin, identifying S100A9 as one of the most up-regulated genes, which was confirmed in lesioned skin from patients with psoriasis and preclinical psoriasiform skin inflammation models. Genetic ablation or pharmacologic inhibition of S100A9 alleviated Aldara-induced skin inflammation. By single-cell mapping of human psoriatic skin and bone marrow chimeric mice experiments, we identified keratinocytes as the major source of S100A9. Mechanistically, S100A9 induced IL-23 production by dendritic cells, driving the IL-23/type 3 immunity in psoriasiform skin inflammation. In addition, the cutaneous IL-23/IL-17 axis induced epidermal S100A9 expression in human and experimental psoriasis. Thus, we showed an autoregulatory circuit between keratinocyte-derived S100A9 and IL-23/type 3 immunity during psoriasiform inflammation, identifying a crucial function of S100A9 in the chronification of psoriasis.

Pyruvate kinase M2 mediates IL-17 signaling in keratinocytes driving psoriatic skin inflammation.

Psoriasis is an inflammatory skin disease characterized by keratinocyte proliferation and inflammatory cell infiltration induced by IL-17. However, the molecular mechanism through which IL-17 signaling in keratinocytes triggers skin inflammation remains not fully understood. Pyruvate kinase M2 (PKM2), a glycolytic enzyme, has been shown to have non-metabolic functions. Here, we report that PKM2 mediates IL-17A signaling in keratinocytes triggering skin psoriatic inflammation. We find high expression of PKM2 in the epidermis of psoriatic patients and mice undergoing psoriasis models. Specific depletion of PKM2 in keratinocytes attenuates the development of experimental psoriasis by reducing the production of pro-inflammatory mediators. Mechanistically, PKM2 forms a complex with Act1 and TRAF6 regulating NF-κB transcriptional signaling downstream of the IL-17 receptor. As IL-17 also induces PKM2 expression in keratinocytes, our findings reveal a sustained signaling circuit critical for the psoriasis-driving effects of IL-17A, suggesting that PKM2 is a potential therapeutic target for psoriasis.

Total parasite biomass but not peripheral parasitaemia is associated with endothelial and haematological perturbations in Plasmodium vivax patients.

Plasmodium vivax is the major cause of human malaria in the Americas. How P. vivax infection can lead to poor clinical outcomes, despite low peripheral parasitaemia, remains a matter of intense debate. Estimation of total P. vivax biomass based on circulating markers indicates existence of a predominant parasite population outside of circulation. In this study, we investigate associations between both peripheral and total parasite biomass and host response in vivax malaria. We analysed parasite and host signatures in a cohort of uncomplicated vivax malaria patients from Manaus, Brazil, combining clinical and parasite parameters, multiplexed analysis of host responses, and ex vivo assays. Patterns of clinical features, parasite burden, and host signatures measured in plasma across the patient cohort were highly heterogenous. Further data deconvolution revealed two patient clusters, here termed Vivaxlow and Vivaxhigh. These patient subgroups were defined based on differences in total parasite biomass but not peripheral parasitaemia. Overall Vivaxlow patients clustered with healthy donors and Vivaxhigh patients showed more profound alterations in haematological parameters, endothelial cell (EC) activation, and glycocalyx breakdown and levels of cytokines regulating different haematopoiesis pathways compared to Vivaxlow. Vivaxhigh patients presented more severe thrombocytopenia and lymphopenia, along with enrichment of neutrophils in the peripheral blood and increased neutrophil-to-lymphocyte ratio (NLCR). When patients' signatures were combined, high association of total parasite biomass with a subset of markers of EC activation, thrombocytopenia, and lymphopenia severity was observed. Finally, machine learning models defined a combination of host parameters measured in the circulation that could predict the extent of parasite infection outside of circulation. Altogether, our data show that total parasite biomass is a better predictor of perturbations in host homeostasis in P. vivax patients than peripheral parasitaemia. This supports the emerging paradigm of a P. vivax tissue reservoir, particularly in the haematopoietic niche of bone marrow and spleen.

Platelet disturbances correlate with endothelial cell activation in uncomplicated Plasmodium vivax malaria.

Platelets drive endothelial cell activation in many diseases. However, if this occurs in Plasmodium vivax malaria is unclear. As platelets have been reported to be activated and to play a role in inflammatory response during malaria, we hypothesized that this would correlate with endothelial alterations during acute illness. We performed platelet flow cytometry of PAC-1 and P-selectin. We measured platelet markers (CXCL4, CD40L, P-selectin, Thrombopoietin, IL-11) and endothelial activation markers (ICAM-1, von Willebrand Factor and E-selectin) in plasma with a multiplex-based assay. The values of each mediator were used to generate heatmaps, K-means clustering and Principal Component analysis. In addition, we determined pair-wise Pearson's correlation coefficients to generate correlation networks. Platelet counts were reduced, and mean platelet volume increased in malaria patients. The activation of circulating platelets in flow cytometry did not differ between patients and controls. CD40L levels (Median [IQ]: 517 [406-651] vs. 1029 [732-1267] pg/mL, P = 0.0001) were significantly higher in patients, while P-selectin and CXCL4 showed a nonsignificant trend towards higher levels in patients. The network correlation approach demonstrated the correlation between markers of platelet and endothelial activation, and the heatmaps revealed a distinct pattern of activation in two subsets of P. vivax patients when compared to controls. Although absolute platelet activation was not strong in uncomplicated vivax malaria, markers of platelet activity and production were correlated with higher endothelial cell activation, especially in a specific subset of patients.

Methods for predicting vaccine immunogenicity and reactogenicity.

Subjects receiving the same vaccine often show different levels of immune responses and some may even present adverse side effects to the vaccine. Systems vaccinology can combine omics data and machine learning techniques to obtain highly predictive signatures of vaccine immunogenicity and reactogenicity. Currently, several machine learning methods are already available to researchers with no background in bioinformatics. Here we described the four main steps to discover markers of vaccine immunogenicity and reactogenicity: (1) Preparing the data; (2) Selecting the vaccinees and relevant genes; (3) Choosing the algorithm; (4) Blind testing your model. With the increasing number of Systems Vaccinology datasets being generated, we expect that the accuracy and robustness of signatures of vaccine reactogenicity and immunogenicity will significantly improve.

Biologia de Sistemas de RNAs Não-Codificadores Longos na Vacinação / Systems biology of Long Non-Coding RNAs in vaccination

Entender os mecanismos responsáveis pela proteção induzida por vacinas contribui para o desenvolvimento de novas vacinas. Uma abordagem de pesquisa denominada Vacinologia de Sistemas surgiu para endereçar essa tarefa. A aplicação da Vacinologia de Sistemas gerou informações amplas relacionadas a respostas vacinais e foi aplicada no estudo de diversas vacinas. Apesar de estarem envolvidos em diversos processos imunológicos, RNAs Não-Codificadores Longos (lncRNAs) ainda não foram estudados no contexto da imunidade induzida por vacinas. Neste trabalho, fizemos a análise de mais de 2.000 amostras de transcritoma de sangue periférico, oriundas de 17 diferentes coortes vacinadas, com foco na identificação de lncRNAs potencialmente envolvidos com a resposta induzida por vacinas contra gripe e contra febre amarela. Criamos também um banco de dados online, em que todos os nossos resultados podem ser facilmente acessados. Nossos resultados indicaram que diversos lncRNAs participam de múltiplas vias imunológicas relacionadas a respostas induzidas por vacinas. Entre esses, o transcrito FAM30A se destaca por ter alta expressão em células B e ser correlacionado com a expressão de genes de imunoglobulina localizados no mesmo locus genômico. Identificamos também alterações na expressão de lncRNAs em dados de RNA-seq de uma coorte de crianças imunizadas com uma vacina atenuada contra gripe, o que sugere um papel de lncRNAs na resposta a diferentes vacinas. Nossos achados trazem evidências de que lncRNAs tem um papel significativo na resposta imune induzida por vacinas

Understanding the mechanisms of vaccine-elicited protection contributes to the development of new vaccines. The emerging field of Systems Vaccinology provides detailed information on host responses to vaccination and has been successfully applied in the study of the molecular mechanisms of several vaccines. Long Non-Coding RNAs (lncRNAs) are crucially involved in multiple biological processes, but their role in vaccine-induced immunity has not been explored. We performed an analysis of over 2,000 blood transcriptome samples from 17 vaccine cohorts to identify lncRNAs potentially involved with antibody responses to influenza and yellow fever vaccines. We have created an online database where all results from these analyses can be easily accessed. We found that lncRNAs participate in distinct immunological pathways related to vaccine-elicited responses. Among them, we showed that the expression of lncRNA FAM30A was high in B cells and correlates with the expression of immunoglobulin genes located in its genomic vicinity. We also identified altered expression of lncRNAs in RNA-sequencing (RNA-seq) data from a cohort of children vaccinated with intranasal live attenuated influenza vaccine, suggesting a common role across several diverse vaccines. Taken together, these findings provide evidence that lncRNAs have a significant impact on immune responses induced by vaccination

PLATELET-RICH PLASMA (PRP) AND TRANEXAMIC ACID (TXA) APPLIED IN TOTAL KNEE ARTHROPLASTY.

OBJECTIVE: To evaluate the efficacy of platelet-rich plasma (PRP) and tranexamic acid (TXA) applied in total knee arthroplasty. METHODS: We selected and randomized 84 patients. TXA was applied in 23 patients, PRP in 20, and PRP in combination with TXA in 20. Hemoglobin was measured preoperatively and 24 and 48 hours postoperatively. The function questionnaire, pain scale and gain of knee flexion were monitored until the second postoperative year. RESULTS: There was a difference (p <0.01) in the decrease in hemoglobin 48 hours after surgery between the TXA group and the control and PRP groups. In terms of pain, the TXA group at 24 and 48 hours after surgery and the PRP group at 48 hours after surgery showed advantages (p <0.01). Knee flexion gain in the first 24 hours postoperatively was better in the TXA group (p <0.05). CONCLUSION: TXA was effective in lowering the drop in hemoglobin level, reducing pain and improving movement gain 48 hours after the procedure. PRP was not effective in reducing bleeding or improving knee function after arthroplasty, but provided better control of postoperative pain. Level of Evidence I, Randomized, blinded, prospective clinical trial.

OBJETIVO: Avaliar a eficácia do plasma rico em plaquetas (PRP) e do ácido tranexâmico (ATX) aplicados na artroplastia total do joelho. MÉTODOS: Selecionamos e randomizamos 84 pacientes. ATX foi aplicado em 23 pacientes, PRP em 20, e PRP associado a ATX em 20. A hemoglobina foi medida no pré-operatório e nas 24 e 48 horas após a cirurgia. O questionário de função, a escala de dor e o ganho de flexão do joelho foram verificados até o segundo ano de pós-operatório. RESULTADOS: Houve diferença(p < 0,01) na diminuição da hemoglobina 48 horas após a cirurgia entre o grupo ATX e os grupos controle e PRP. Na dor, o grupo ATX 24 e 48 horas após a cirurgia e o grupo PRP 48 horas após a cirurgia apresentaram vantagens (p < 0,01). O ganho de flexão do joelho nas primeiras 24 horas de pós-operatório foi melhor no grupo ATX (p < 0,05). CONCLUSÃO: O ATX foi eficaz na diminuição da queda da hemoglobina, reduzindo a dor e melhorando o ganho de movimento em 48 horas após o procedimento. O PRP não foi eficaz na redução do sangramento ou na melhora da função do joelho após a artroplastia, mas proporcionou melhor controle da dor pós-operatória. Nível de Evidência I, Randomizado, duplo cego, ensaio clínico prospectivo.

Platelet-rich plasma (prp) and tranexamic acid (txa) applied in total knee arthroplasty / Plasma rico em plaquetas (prp) e ácido tranexâmico (atx) aplicados na artroplastia total do joelho

ABSTRACT Objective: To evaluate the efficacy of platelet-rich plasma (PRP) and tranexamic acid (TXA) applied in total knee arthroplasty. Methods: We selected and randomized 84 patients. TXA was applied in 23 patients, PRP in 20, and PRP in combination with TXA in 20. Hemoglobin was measured preoperatively and 24 and 48 hours postoperatively. The function questionnaire, pain scale and gain of knee flexion were monitored until the second postoperative year. Results: There was a difference (p <0.01) in the decrease in hemoglobin 48 hours after surgery between the TXA group and the control and PRP groups. In terms of pain, the TXA group at 24 and 48 hours after surgery and the PRP group at 48 hours after surgery showed advantages (p <0.01). Knee flexion gain in the first 24 hours postoperatively was better in the TXA group (p <0.05). Conclusion: TXA was effective in lowering the drop in hemoglobin level, reducing pain and improving movement gain 48 hours after the procedure. PRP was not effective in reducing bleeding or improving knee function after arthroplasty, but provided better control of postoperative pain. Level of Evidence I, Randomized, blinded, prospective clinical trial.

RESUMO Objetivo: Avaliar a eficácia do plasma rico em plaquetas (PRP) e do ácido tranexâmico (ATX) aplicados na artroplastia total do joelho. Métodos: Selecionamos e randomizamos 84 pacientes. ATX foi aplicado em 23 pacientes, PRP em 20, e PRP associado a ATX em 20. A hemoglobina foi medida no pré-operatório e nas 24 e 48 horas após a cirurgia. O questionário de função, a escala de dor e o ganho de flexão do joelho foram verificados até o segundo ano de pós-operatório. Resultados: Houve diferença(p < 0,01) na diminuição da hemoglobina 48 horas após a cirurgia entre o grupo ATX e os grupos controle e PRP. Na dor, o grupo ATX 24 e 48 horas após a cirurgia e o grupo PRP 48 horas após a cirurgia apresentaram vantagens (p < 0,01). O ganho de flexão do joelho nas primeiras 24 horas de pós-operatório foi melhor no grupo ATX (p < 0,05). Conclusão: O ATX foi eficaz na diminuição da queda da hemoglobina, reduzindo a dor e melhorando o ganho de movimento em 48 horas após o procedimento. O PRP não foi eficaz na redução do sangramento ou na melhora da função do joelho após a artroplastia, mas proporcionou melhor controle da dor pós-operatória. Nível de Evidência I, Randomizado, duplo cego, ensaio clínico prospectivo.

Long noncoding RNAs are involved in multiple immunological pathways in response to vaccination.

Understanding the mechanisms of vaccine-elicited protection contributes to the development of new vaccines. The emerging field of systems vaccinology provides detailed information on host responses to vaccination and has been successfully applied to study the molecular mechanisms of several vaccines. Long noncoding RNAs (lncRNAs) are crucially involved in multiple biological processes, but their role in vaccine-induced immunity has not been explored. We performed an analysis of over 2,000 blood transcriptome samples from 17 vaccine cohorts to identify lncRNAs potentially involved with antibody responses to influenza and yellow fever vaccines. We have created an online database where all results from this analysis can be accessed easily. We found that lncRNAs participate in distinct immunological pathways related to vaccine-elicited responses. Among them, we showed that the expression of lncRNA FAM30A was high in B cells and correlates with the expression of immunoglobulin genes located in its genomic vicinity. We also identified altered expression of these lncRNAs in RNA-sequencing (RNA-seq) data from a cohort of children following immunization with intranasal live attenuated influenza vaccine, suggesting a common role across several diverse vaccines. Taken together, these findings provide evidence that lncRNAs have a significant impact on immune responses induced by vaccination.

CEMiTool: a Bioconductor package for performing comprehensive modular co-expression analyses.

BACKGROUND: The analysis of modular gene co-expression networks is a well-established method commonly used for discovering the systems-level functionality of genes. In addition, these studies provide a basis for the discovery of clinically relevant molecular pathways underlying different diseases and conditions. RESULTS: In this paper, we present a fast and easy-to-use Bioconductor package named CEMiTool that unifies the discovery and the analysis of co-expression modules. Using the same real datasets, we demonstrate that CEMiTool outperforms existing tools, and provides unique results in a user-friendly html report with high quality graphs. Among its features, our tool evaluates whether modules contain genes that are over-represented by specific pathways or that are altered in a specific sample group, as well as it integrates transcriptomic data with interactome information, identifying the potential hubs on each network. We successfully applied CEMiTool to over 1000 transcriptome datasets, and to a new RNA-seq dataset of patients infected with Leishmania, revealing novel insights of the disease's physiopathology. CONCLUSION: The CEMiTool R package provides users with an easy-to-use method to automatically implement gene co-expression network analyses, obtain key information about the discovered gene modules using additional downstream analyses and retrieve publication-ready results via a high-quality interactive report.

Toxicogenomic and bioinformatics platforms to identify key molecular mechanisms of a curcumin-analogue DM-1 toxicity in melanoma cells.

Melanoma is a highly invasive and metastatic cancer with high mortality rates and chemoresistance. Around 50% of melanomas are driven by activating mutations in BRAF that has led to the development of potent anti-BRAF inhibitors. However resistance to anti-BRAF therapy usually develops within a few months and consequently there is a need to identify alternative therapies that will bypass BRAF inhibitor resistance. The curcumin analogue DM-1 (sodium 4-[5-(4-hydroxy-3-methoxy-phenyl)-3-oxo-penta-1,4-dienyl]-2-methoxy-phenolate) has substantial anti-tumor activity in melanoma, but its mechanism of action remains unclear. Here we use a synthetic lethal genetic screen in Saccharomyces cerevisiae to identify 211 genes implicated in sensitivity to DM-1 toxicity. From these 211 genes, 74 had close human orthologues implicated in oxidative phosphorylation, insulin signaling and iron and RNA metabolism. Further analysis identified 7 target genes (ADK, ATP6V0B, PEMT, TOP1, ZFP36, ZFP36L1, ZFP36L2) with differential expression during melanoma progression implicated in regulation of tumor progression, cell differentiation, and epithelial-mesenchymal transition. Of these TOP1 and ADK were regulated by DM-1 in treatment-naïve and vemurafenib-resistant melanoma cells respectively. These data reveal that the anticancer effect of curcumin analogues is likely to be mediated via multiple targets and identify several genes that represent candidates for combinatorial targeting in melanoma.

Factors Associated with Infant Mortality in a Northeastern Brazilian Capital / Fatores associados à mortalidade infantil em uma capital do Nordeste brasileiro

Abstract Purpose Identify factors associated with infant mortality by a hierarchical model based on socioeconomic, health care, obstetric and biological determinants in a northeastern Brazilian capital. Methods Observational, retrospective cohort study based on secondary data of births and deaths of infants of mothers living in the city of Teresina. Results Based on the distal level of determination of infant mortality, the characteristics that remained statistically significant were maternal age, maternal education and maternal occupation (p< 0.001). In the intermediate level, all variables were statistically significant, particularly the type of pregnancy and delivery (p< 0.001). The gender of the baby was the proximal level feature that had no significant association with the outcome, while the other variables of this level had association (p< 0.001). Conclusions This study evidenced that, in addition to biological factors, socioeconomic status and maternal and child health care are important to determine infant mortality.

Resumo Objetivo Identificar os fatores associados à mortalidade infantil por modelo hierárquico segundo determinantes socioeconômicos, assistenciais, obstétricos e biológicos em uma capital do Nordeste brasileiro. Métodos Estudo observacional, de coorte retrospectiva, com base em dados secundários de nascimentos e óbitos de crianças menores de um ano, de mães residentes no município de Teresina (PI). Resultados Para o nível distal de determinação da mortalidade infantil, as características que se mantiveram estatisticamente significativas foram idade materna, escolaridade materna e ocupação materna, com p< 0,001. No intermediário, todas as variáveis apresentaram significância estatística, com destaque para o tipo de gravidez e de parto, com p< 0,001. O sexo do bebê representou a característica do nível proximal que não obteve associação significativa com o desfecho, enquanto as demais variáveis desse nível estavam associadas, com p< 0,001. Conclusões Além da determinação da mortalidade infantil pelos fatores biológicos, destacou-se a importância da condição socioeconômica e da assistência à saúde materno-infantil.

Factors Associated with Infant Mortality in a Northeastern Brazilian Capital.

Purpose Identify factors associated with infant mortality by a hierarchical model based on socioeconomic, health care, obstetric and biological determinants in a northeastern Brazilian capital. Methods Observational, retrospective cohort study based on secondary data of births and deaths of infants of mothers living in the city of Teresina. Results Based on the distal level of determination of infant mortality, the characteristics that remained statistically significant were maternal age, maternal education and maternal occupation (p < 0.001). In the intermediate level, all variables were statistically significant, particularly the type of pregnancy and delivery (p < 0.001). The gender of the baby was the proximal level feature that had no significant association with the outcome, while the other variables of this level had association (p < 0.001). Conclusions This study evidenced that, in addition to biological factors, socioeconomic status and maternal and child health care are important to determine infant mortality.

[Prenatal care and risk factors associated with premature birth and low birth weight in the a capital in the Brazilian Northeast]. / Atenção pré-natal e fatores de risco associados à prematuridade e baixo peso ao nascer em capital do nordeste brasileiro.

The main determinants of the risk of mortality in the neonatal period are low birth weight and premature birth. The study sought to analyze the adequacy of prenatal care and risk factors associated with premature birth and low birth weight in a northeastern Brazilian capital. This is a case-control study. A model for adequacy of prenatal conditions composed of four indicators was created. Descriptive statistics for univariate analysis were used; as well as Wald linear trend tests, Student's t and chi-square test for bivariate analysis and multiple logistic regression for multivariate analysis with p <0.05. Multivariate analysis showed that poor education, not performing gainful activity, caesarean section, oligohydramnios, placental abruption and pre-eclampsia are independent factors associated with premature birth and/or low birth weight. For adequacy of prenatal care, variable indicator III remained significant, showing that mothers who had inadequate prenatal care had an increased chance for the occurrence of the outcome, highlighting the need for adequate public health policies of care for pregnant women in the municipality under scrutiny.

Atenção pré-natal e fatores de risco associados à prematuridade e baixo peso ao nascer em capital do nordeste brasileiro / Prenatal care and risk factors associated with premature birth and low birth weight in the a capital in the Brazilian Northeast

Resumo Os principais determinantes do risco de morrer no período neonatal são o baixo peso ao nascer e a prematuridade. O estudo teve como objetivo analisar a adequação do pré-natal e fatores de risco associados à prematuridade e ao baixo peso ao nascerem uma capital do nordeste brasileiro. Trata-se de um estudo caso-controle. Foi construído um modelo de adequação do pré-natal composto por quatro indicadores. Utilizou-se estatística descritiva para análise univariada; testes de Wald, de tendência linear, t de Student e qui-quadrado para a análise bivariada e regressão logística múltipla para análise multivariada com p<0,05. A análise multivariada mostrou que baixa escolaridade, não realizar atividade remunerada, parto cesáreo, oligodrâmnio, descolamento prematuro da placenta e pré-eclâmpsia são fatores independentes associados com a prematuridade e/ou baixo peso ao nascer. Para adequação do pré-natal, a variável Indicador III permaneceu significativa, mostrando que as mães que apresentaram inadequação da atenção pré-natal tiveram chance aumentada para a ocorrência do desfecho, evidenciando a necessidade de adequação de políticas públicas de saúde de atenção às gestantes no município estudado.

Abstract The main determinants of the risk of mortality in the neonatal period are low birth weight and premature birth. The study sought to analyze the adequacy of prenatal care and risk factors associated with premature birth and low birth weight in a northeastern Brazilian capital. This is a case-control study. A model for adequacy of prenatal conditions composed of four indicators was created. Descriptive statistics for univariate analysis were used; as well as Wald linear trend tests, Student’s t and chi-square test for bivariate analysis and multiple logistic regression for multivariate analysis with p <0.05. Multivariate analysis showed that poor education, not performing gainful activity, caesarean section, oligohydramnios, placental abruption and pre-eclampsia are independent factors associated with premature birth and/or low birth weight. For adequacy of prenatal care, variable indicator III remained significant, showing that mothers who had inadequate prenatal care had an increased chance for the occurrence of the outcome, highlighting the need for adequate public health policies of care for pregnant women in the municipality under scrutiny.

[Use of the linkage method to identify the risk factors associated with infant mortality: an integrative review of the literature]. / Utilização do método linkage na identificação dos fatores de risco associados à mortalidade infantil: revisão integrativa da literatura.

Global concern in relation to child mortality gained visibility with the release of the Millennium Development Goals in 2000 in which the reduction of child mortality is included under goal number four, which proposes to reduce the mortality rate of children under five years by two thirds between 1990 and 2015. Reducing child mortality has been a major priority of social health policies of the Brazilian government. The identification of risk factors associated with infant mortality can assist in the planning of actions to restructure and improve care for pregnant women and newborns in order to reduce child mortality. With this in mind, this study sets out to analyze the use of the linkage method to identify risk factors associated with infant mortality. An integrative review of the literature was conducted for this purpose and eight complete articles published between 2008 and 2013 were analyzed using the following key words: infant mortality, risk factors and information systems. The use of the linkage method proved to be very useful, enabling adequate investigation of the factors most strongly related to child mortality, showing its relevance to the study of public health problems.

Utilização do método linkage na identificação dos fatores de risco associados à mortalidade infantil: revisão integrativa da literatura / Use of the linkage method to identify the risk factors associated with infant mortality: an integrative review of the literature

A preocupação mundial em relação à mortalidade infantil ganhou visibilidade com a divulgação no ano 2000 dos Objetivos do Desenvolvimento do Milênio, em que sua redução ganha destaque com a meta de número quatro, que propõe diminuir em dois terços sua taxa para crianças menores de cinco anos, no período entre 1990 e 2015. Reduzir a mortalidade infantil tem sido uma das prioridades das políticas sociais de saúde do governo brasileiro. A identificação de fatores de risco relacionados com a mortalidade infantil pode auxiliar no planejamento de ações para a reestruturação e melhoria da assistência à gestante e aos recém-nascidos, visando à redução da mortalidade infantil. Nesta perspectiva, o presente estudo tem como objetivo analisar a utilização do método de linkage na identificação de fatores de risco associados à mortalidade infantil. Utilizou-se a Revisão Integrativa da Literatura. Foram analisados oito artigos na íntegra publicados entre 2008 e 2013, através dos descritores: mortalidade infantil, fatores de risco e sistemas de informação. O uso da técnica de linkage mostrou-se bastante útil, permitindo a adequada investigação dos fatores mais fortemente relacionados à mortalidade infantil, mostrando sua relevância para o estudo de problemas de saúde pública.

Global concern in relation to child mortality gained visibility with the release of the Millennium Development Goals in 2000 in which the reduction of child mortality is included under goal number four, which proposes to reduce the mortality rate of children under five years by two thirds between 1990 and 2015. Reducing child mortality has been a major priority of social health policies of the Brazilian government. The identification of risk factors associated with infant mortality can assist in the planning of actions to restructure and improve care for pregnant women and newborns in order to reduce child mortality. With this in mind, this study sets out to analyze the use of the linkage method to identify risk factors associated with infant mortality. An integrative review of the literature was conducted for this purpose and eight complete articles published between 2008 and 2013 were analyzed using the following key words: infant mortality, risk factors and information systems. The use of the linkage method proved to be very useful, enabling adequate investigation of the factors most strongly related to child mortality, showing its relevance to the study of public health problems.

Hollow-fiber liquid-phase microextraction and gas chromatography-mass spectrometry of barbiturates in whole blood samples.

Here, we present a method for measuring barbiturates (butalbital, secobarbital, pentobarbital, and phenobarbital) in whole blood samples. To accomplish these measurements, analytes were extracted by means of hollow-fiber liquid-phase microextraction in the three-phase mode. Hollow-fiber pores were filled with decanol, and a solution of sodium hydroxide (pH 13) was introduced into the lumen of the fiber (acceptor phase). The fiber was submersed in the acidified blood sample, and the system was subjected to an ultrasonic bath. After a 5 min extraction, the acceptor phase was withdrawn from the fiber and dried under a nitrogen stream. The residue was reconstituted with ethyl acetate and trimethylanilinium hydroxide. An aliquot of 1.0 µL of this solution was injected into the gas chromatograph/mass spectrometer, with the derivatization reaction occurring in the hot injector port (flash methylation). The method proved to be simple and rapid, and only a small amount of organic solvent (decanol) was needed for extraction. The detection limit was 0.5 µg/mL for all the analyzed barbiturates. The calibration curves were linear over the specified range (1.0 to 10.0 µg/mL). This method was successfully applied to postmortem samples (heart blood and femoral blood) collected from three deceased persons previously exposed to barbiturates.

Biculturalism: an endless enigma

Neste trabalho discutiremos, de maneira sucinta, o conceito de cultura relacionado ao ensino e à aprendizagem de línguas estrangeira. A relação existente entre bilingüismo e biculturalismo é também levada em consideração dentro de uma perspectiva sociolingüística. (AU)