TLR1/2 Activation during Heterologous Prime-Boost Vaccination (DNA-MVA) Enhances CD8+ T Cell Responses Providing Protection against Leishmania (Viannia)

Leishmania (Viannia) are the predominant agents of leishmaniasis in Latin America. Given the fact that leishmaniasis is a zoonosis, eradication is unlikely; a vaccine could provide effective prevention of disease. However, these parasites present a challenge and we do not fully understand what elements of the host immune defense prevent disease. We examined the ability of vaccination to protect against L. (Viannia) infection using the highly immunogenic heterologous prime-boost (DNA-modified vaccinia virus) modality and a single Leishmania antigen (TRYP). Although this mode of vaccination can induce protection against other leishmaniases (cutaneous, visceral), no protection was observed against L. (V.) panamensis. However, we found that if the vaccination was modified and the innate immune response was activated through Toll-like receptor1/2(TLR1/2) during the DNA priming, vaccinated mice were protected. Protection was dependent on CD8 T cells. Vaccinated mice had higher CD8 T cell responses and decreased levels of cytokines known to promote infection. Given the long-term persistence of CD8 T cell memory, these findings are encouraging for vaccine development. Further, these results suggest that modulation of TLR1/2 signaling could improve the efficacy of DNA-based vaccines, especially where CD8 T cell activation is critical, thereby contributing to effective and affordable anti parasitic vaccines

Nursing and fuzzy logic: an integrative review Enfermería y lógica fuzzy: una revisión de integradora Enfermagem e lógica fuzzy: uma revisão integrativa

This study conducted an integrative review investigating how fuzzy logic has been used in research with the participation of nurses. The article search was carried out in the CINAHL, EMBASE, SCOPUS, PubMed and Medline databases, with no limitation on time of publication. Articles written in Portuguese, English and Spanish with themes related to nursing and fuzzy logic with the authorship or participation of nurses were included. The final sample included 21 articles from eight countries. For the purpose of analysis, the articles were distributed into categories: theory, method and model. In nursing, fuzzy logic has significantly contributed to the understanding of subjects related to: imprecision or the need of an expert; as a research method; and in the development of models or decision support systems and hard technologies. The use of fuzzy logic in nursing has shown great potential and represents a vast field for research.<br>Este estudio tuvo como objetivo realizar una revisión integradora investigando como la lógica fuzzy ha sido utilizada en investigaciones con participación de enfermeros. La búsqueda de los artículos fue realizada en las bases de datos CINAHL, Embase, SCOPUS, Medline y PubMed, sin especificar un intervalo de años determinado. Fueron incluidos artículos en los idiomas: portugués, inglés y castellano; con una temática relacionada a la enfermería y a la lógica fuzzy; y con autoría o participación de enfermeros. La muestra final fue de 21 artículos, de ocho países. Para el análisis, los artículos fueron distribuidos en las categorías: teoría, método y modelo. En la enfermería, la lógica fuzzy ha contribuido significativamente para la comprensión de temas relativos a la imprecisión o a la necesidad del especialista, como método de investigación y en el desarrollo de modelos o sistemas de apoyo a la decisión y de tecnologías duras. El uso de la lógica fuzzy en la enfermería ha demostrado gran potencial y representa un vasto campo para investigaciones.<br>Este estudo teve como objetivo realizar revisão integrativa, investigando como a lógica fuzzy tem sido utilizada em pesquisas com participação de enfermeiros. A busca dos artigos foi realizada nas bases de dados CINAHL, Embase, Scopus, MEDLINE e PubMed, sem intervalo de anos especificado. Foram incluídos artigos na língua portuguesa, inglesa e espanhola; com temática relacionada à enfermagem e à lógica fuzzy, e autoria ou participação de enfermeiros. A amostra final foi de 21 artigos, de oito países. Para análise, os artigos foram distribuídos nas categorias: teoria, método e modelo. Na enfermagem, a lógica fuzzy tem contribuído significativamente para a compreensão de temas relativos à imprecisão ou à necessidade do especialista, como método de pesquisa e no desenvolvimento de modelos ou sistemas de apoio à decisão e de tecnologias duras. O uso da lógica fuzzy, na enfermagem, tem demonstrado grande potencial e representa vasto campo para pesquisas

Serious Asthma Events with Fluticasone plus Salmeterol versus Fluticasone Alone

BACKGROUND: The safe and appropriate use of long-acting beta-agonists (LABAs) for the treatment of asthma has been widely debated. In two large clinical trials, investigators found a potential risk of serious asthma-related events associated with LABAs. This study was designed to evaluate the risk of administering the LABA salmeterol in combination with an inhaled glucocorticoid, fluticasone propionate. METHODS: In this multicenter, randomized, double-blind trial, adolescent and adult patients (age, ≥12 years) with persistent asthma were assigned to receive either fluticasone with salmeterol or fluticasone alone for 26 weeks. All the patients had a history of a severe asthma exacerbation in the year before randomization but not during the previous month. Patients were excluded from the trial if they had a history of life-threatening or unstable asthma. The primary safety end point was the first serious asthma-related event (death, endotracheal intubation, or hospitalization). Noninferiority of fluticasone-salmeterol to fluticasone alone was defined as an upper boundary of the 95% confidence interval for the risk of the primary safety end point of less than 2.0. The efficacy end point was the first severe asthma exacerbation. RESULTS: Of 11,679 patients who were enrolled, 67 had 74 serious asthma-related events, with 36 events in 34 patients in the fluticasone-salmeterol group and 38 events in 33 patients in the fluticasone-only group. The hazard ratio for a serious asthma-related event in the fluticasone-salmeterol group was 1.03 (95% confidence interval [CI], 0.64 to 1.66), and noninferiority was achieved (P=0.003). There were no asthma-related deaths; 2 patients in the fluticasone-only group underwent asthma-related intubation. The risk of a severe asthma exacerbation was 21% lower in the fluticasone-salmeterol group than in the fluticasone-only group (hazard ratio, 0.79; 95% CI, 0.70 to 0.89), with at least one severe asthma exacerbation occurring in 480 of 5834 patients (8%) in the fluticasone-salmeterol group, as compared with 597 of 5845 patients (10%) in the fluticasone-only group (P<0.001). CONCLUSIONS: Patients who received salmeterol in a fixed-dose combination with fluticasone did not have a significantly higher risk of serious asthma-related events than did those who received fluticasone alone. Patients receiving fluticasone-salmeterol had fewer severe asthma exacerbations than did those in the fluticasone-only group