Gender-Specific Effects of Genetic Variants within Th1 and Th17 Cell-Mediated Immune Response Genes on the Risk of Developing Rheumatoid Arthritis.

The present study was conducted to explore whether single nucleotide polymorphisms (SNPs) in Th1 and Th17 cell-mediated immune response genes differentially influence the risk of rheumatoid arthritis (RA) in women and men. In phase one, 27 functional/tagging polymorphisms in C-type lectins and MCP-1/CCR2 axis were genotyped in 458 RA patients and 512 controls. Carriers of Dectin-2 rs4264222T allele had an increased risk of RA (OR = 1.47, 95%CI 1.10-1.96) whereas patients harboring the DC-SIGN rs4804803G, MCP-1 rs1024611G, MCP-1 rs13900T and MCP-1 rs4586C alleles had a decreased risk of developing the disease (OR = 0.66, 95%CI 0.49-0.88; OR = 0.66, 95%CI 0.50-0.89; OR = 0.73, 95%CI 0.55-0.97 and OR = 0.68, 95%CI 0.51-0.91). Interestingly, significant gender-specific differences were observed for Dectin-2 rs4264222 and Dectin-2 rs7134303: women carrying the Dectin-2 rs4264222T and Dectin-2 rs7134303G alleles had an increased risk of RA (OR = 1.93, 95%CI 1.34-2.79 and OR = 1.90, 95%CI 1.29-2.80). Also five other SNPs showed significant associations only with one gender: women carrying the MCP-1 rs1024611G, MCP-1 rs13900T and MCP-1 rs4586C alleles had a decreased risk of RA (OR = 0.61, 95%CI 0.43-0.87; OR = 0.67, 95%CI 0.47-0.95 and OR = 0.60, 95%CI 0.42-0.86). In men, carriers of the DC-SIGN rs2287886A allele had an increased risk of RA (OR = 1.70, 95%CI 1.03-2.78), whereas carriers of the DC-SIGN rs4804803G had a decreased risk of developing the disease (OR = 0.53, 95%CI 0.32-0.89). In phase 2, we genotyped these SNPs in 754 RA patients and 519 controls, leading to consistent gender-specific associations for Dectin-2 rs4264222, MCP-1 rs1024611, MCP-1 rs13900 and DC-SIGN rs4804803 polymorphisms in the pooled sample (OR = 1.38, 95%CI 1.08-1.77; OR = 0.74, 95%CI 0.58-0.94; OR = 0.76, 95%CI 0.59-0.97 and OR = 0.56, 95%CI 0.34-0.93). SNP-SNP interaction analysis of significant SNPs also showed a significant two-locus interaction model in women that was not seen in men. This model consisted of Dectin-2 rs4264222 and Dectin-2 rs7134303 SNPs and suggested a synergistic effect between the variants. These findings suggest that Dectin-2, MCP-1 and DC-SIGN polymorphisms may, at least in part, account for gender-associated differences in susceptibility to RA.

Immunologic evaluation and validation of methods using synthetic peptides derived from Mycobacterium tuberculosis for the diagnosis of tuberculosis infection

The goal of this study was to demonstrate the usefulness of an enzyme-linked immunosorbent assay (ELISA) for the serodiagnosis of pulmonary tuberculosis (PTB) and extrapulmonary TB (EPTB). This assay used 20 amino acid-long, non-overlapped synthetic peptides that spanned the complete Mycobacterium tuberculosis ESAT-6 and Ag85A sequences. The validation cohort consisted of 1,102 individuals who were grouped into the following five diagnostic groups: 455 patients with PTB, 60 patients with EPTB, 40 individuals with non-EPTB, 33 individuals with leprosy and 514 healthy controls. For the PTB group, two ESAT-6 peptides (12033 and 12034) had the highest sensitivity levels of 96.9% and 96.2%, respectively, and an Ag85A-peptide (29878) was the most specific (97.4%) in the PTB groups. For the EPTB group, two Ag85A peptides (11005 and 11006) were observed to have a sensitivity of 98.3% and an Ag85A-peptide (29878) was also the most specific (96.4%). When combinations of peptides were used, such as 12033 and 12034 or 11005 and 11006, 99.5% and 100% sensitivities in the PTB and EPTB groups were observed, respectively. In conclusion, for a cohort that consists entirely of individuals from Venezuela, a multi-antigen immunoassay using highly sensitive ESAT-6 and Ag85A peptides alone and in combination could be used to more rapidly diagnose PTB and EPTB infection.

Molecular identification of Sporothrix species involved in the first familial outbreak of sporotrichosis in the state of Espírito Santo, southeastern Brazil

Sporotrichosis is a widespread subcutaneous mycosis caused by the dimorphic fungi now known as the Sporothrix schenckii complex. This complex is comprised of at least six species, including Sporothrix albicans, Sporothrix brasiliensis, Sporothrix globosa, Sporothrix luriei, Sporothrix mexicana and S. schenckii. Cases of sporotrichosis have significantly increased in Brazil over the past decade, especially in the state of Rio de Janeiro (RJ), where an epidemic among cat owners has been observed. The zoonotic transmission from cats to humans suggests a common source of infection and indicates that animals can act as vectors. We performed a molecular characterisation of samples collected during the first outbreak of familial sporotrichosis caused by S. brasiliensis in the state of Espírito Santo, Brazil. These results represent the first description of such an outbreak outside the endemic area of zoonotic sporotrichosis in RJ.

Diets based on virgin olive oil or fish oil but not on sunflower oil prevent age-related alveolar bone resorption by mitochondrial-related mechanisms.

BACKGROUND/OBJECTIVES Aging enhances frequency of chronic diseases like cardiovascular diseases or periodontitis. Here we reproduced an age-dependent model of the periodontium, a fully physiological approach to periodontal conditions, to evaluate the impact of dietary fat type on gingival tissue of young (6 months old) and old (24 months old) rats. METHODS/FINDINGS Animals were fed life-long on diets based on monounsaturated fatty acids (MUFA) as virgin olive oil, n-6 polyunsaturated fatty acids (n-6PUFA), as sunflower oil, or n-3PUFA, as fish oil. Age-related alveolar bone loss was higher in n-6PUFA fed rats, probably as a consequence of the ablation of the cell capacity to adapt to aging. Gene expression analysis suggests that MUFA or n-3PUFA allowed mitochondria to maintain an adequate turnover through induction of biogenesis, autophagy and the antioxidant systems, and avoiding mitochondrial electron transport system alterations. CONCLUSIONS The main finding is that the enhanced alveolar bone loss associated to age may be targeted by an appropriate dietary treatment. The mechanisms involved in this phenomenon are related with an ablation of the cell capacity to adapt to aging. Thus, MUFA or n-3PUFA might allow mitochondrial maintaining turnover through biogenesis or autophagy. They might also be able to induce the corresponding antioxidant systems to counteract age-related oxidative stress, and do not inhibit mitochondrial electron transport chain. From the nutritional and clinical point of view, it is noteworthy that the potential treatments to attenuate alveolar bone loss (a feature of periodontal disease) associated to age could be similar to some of the proposed for the prevention and treatment of cardiovascular diseases, a group of pathologies recently associated with age-related periodontitis.

Estudio del síndrome metabólico y de la obesidad en pacientes en hemodiálisis.

INTRODUCTION: The metabolic syndrome (MS) consists of a set of clinical and biochemical changes. It is very common among chronic hemodialysis patients, being the leading cause of death in these patients, 44% of all patients undergoing this therapy. AIMS: The aim of this study was to investigate the prevalence of MS and risk factors associated with its development, as well as the prevalence of obesity in HD patients. METHODS: This study has followed 90 patients of both sexes with chronic renal failure (CRF) who were treated with hemodialysis periodically in our unit for ten years. All patients were performed quarterly measurements of plasma albumin (A1b) and other biochemical analysis; besides, they underwent some anthropometric measurements like weight, height and body mass index (BMI). This was calculated using weight / size2 formula and grouped in BMI values according to WHO criteria. The data concerning hypertension and glucose were also considered. RESULTS: The prevalence of MS was 25% and obesity was presented as follows: 45% with type I overweight; 30.8% with type II overweight and 12 patients (2%) were obese. Being statistically significant as risk factors, BMI, overweight, triglycerides, total cholesterol, HDL cholesterol as well as hypertension and elevated glucose levels were obtained. CONCLUSIONS: The metabolic syndrome compromises the patient survival causing a high prevalence in these patients. The principal risk factors in MS are monitoring weight, BMI, triglycerides, HDL cholesterol, hypertension and diabetes.

Evaluación del estado nutricional en pacientes trasplantados renales durante 5 años de seguimiento.

INTRODUCTION: Weight gain and malnutrition after kidney transplantation is common and the resulting overweight and obesity is associated with serious health complications. By contrast, the prevalence of malnutrition in patients with renal transplantation and its impact on the outcome of kidney transplantation is underestimated. OBJECTIVES: The aim of this study was to evaluate the nutritional status of renal transplant patients and determine if the five-year follow-up, these patients undergo alterations that suggest nutritional deterioration. METHODS: The sample consisted of 119 renal transplant patients who attended for five years post-transplant consultation. All patients measurements of total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), triglycerides and ferritin (Ft) were performed. and anthropometric measurements were made of weight, height and BMI. Patients were divided into three groups according to GFR Group 1: <60 mL/min, Group 2: 89-60 mL/min Group 3: ≥ 90 mL/min. RESULTS: The weight and BMI tended to decrease in group 3 while increasing in the other groups. A decrease in total cholesterol, HDL, LDL, Triglycerides and Ferritin less pronounced in group 3 occurs. CONCLUSIONS: After five years you can see a significant reduction in nutritional biochemical parameters in general, likewise the nutritional status is closely related, and is directly proportional to the function of the graft.

Impact of inadequate empirical therapy on the mortality of patients with bloodstream infections: a propensity score-based analysis.

The impact of the adequacy of empirical therapy on outcome for patients with bloodstream infections (BSI) is key for determining whether adequate empirical coverage should be prioritized over other, more conservative approaches. Recent systematic reviews outlined the need for new studies in the field, using improved methodologies. We assessed the impact of inadequate empirical treatment on the mortality of patients with BSI in the present-day context, incorporating recent methodological recommendations. A prospective multicenter cohort including all BSI episodes in adult patients was performed in 15 hospitals in Andalucía, Spain, over a 2-month period in 2006 to 2007. The main outcome variables were 14- and 30-day mortality. Adjusted analyses were performed by multivariate analysis and propensity score-based matching. Eight hundred one episodes were included. Inadequate empirical therapy was administered in 199 (24.8%) episodes; mortality at days 14 and 30 was 18.55% and 22.6%, respectively. After controlling for age, Charlson index, Pitt score, neutropenia, source, etiology, and presentation with severe sepsis or shock, inadequate empirical treatment was associated with increased mortality at days 14 and 30 (odds ratios [ORs], 2.12 and 1.56; 95% confidence intervals [95% CI], 1.34 to 3.34 and 1.01 to 2.40, respectively). The adjusted ORs after a propensity score-based matched analysis were 3.03 and 1.70 (95% CI, 1.60 to 5.74 and 0.98 to 2.98, respectively). In conclusion, inadequate empirical therapy is independently associated with increased mortality in patients with BSI. Programs to improve the quality of empirical therapy in patients with suspicion of BSI and optimization of definitive therapy should be implemented.

Spain in Europe 2004-2008

In March of 2004, the Observatory of European Foreign Policy published a special monograph about Spain in Europe (1996-2004) in digital format. The objective of the monograph was to analyse Spain’s foreign policy agenda and strategy during the period of José María Aznar’s presidency. As the title suggests, one of the initial suppositions of the analysis is the Europeanization of Spanish foreign activities. Is that how it was? Did Aznar’s Spain see the world and relate to it through Brussels? The publication was well received, considering the number of visits received and above all the institutions which asked to link the publication to their web pages. Among these, the EUobserver published the introduction to the piece in English titled Aznar: thinking locally, acting in Europe (described by the EUobserver as a paper of utmost importance). The fact that the elections were held three days after the tragic events of the 11th of March dramatically increased interest in Spain and the implications for Europe. This publication is the second of its type, in this case analysing the period of the Zapatero government (2004-2008). Once again the starting premise (the Europeanization of the agenda and the methods employed) has been considered by the analysts. And once again the articles collected in this publication serve to “triangulate” the analysis. Spain and Europe are two vertices (more or less distant, in essence and in form) which the authors handle in their analysis of the case (third vertex).

España en Europa 2004-2008

En marzo de 2004 el Observatorio de Política Exterior Europea publicó, en versión digital, un monográfico especial sobre España en Europa (1996-2004). Su objetivo era analizar la agenda y la estrategia de España durante el período de José María Aznar en materia de relaciones internacionales. Como bien indicaba el título de aquella publicación, uno de los supuestos de partida del análisis era la europeización de la actividad internacional de España. ¿Era así?, ¿la España de Aznar veía el mundo y se aproximaba a él a través de Bruselas? Aquella publicación tuvo una buena acogida, a la vista de las visitas recibidas y sobre todo de las instituciones que nos pidieron vincular dicha publicación a sus páginas web y, entre ellas, hay que destacar que EUObserver publicó como comentario su artículo introductorio, en versión inglesa, Aznar: thinking locally, acting in Europe (calificado por EUObserver como lectura de máxima relevancia). El hecho de que las elecciones de 2004 se celebraran tres días después de los trágicos acontecimientos del 11-M hizo que el interés por España y por su proyección europea e internacional aumentara de manera destacada. La presente publicación constituye un segundo ejercicio de dicho tipo, en este caso para analizar el período del gobierno Zapatero (2004-2008). Una vez más, el supuesto de partida (la europeización de la agenda y del método) está en la mente de los analistas. Y una vez más los artículos recogidos en esta publicación hacen el ejercicio de “triangular” el análisis. España y Europa son dos vértices (más o menos alejados, en el fondo y en la forma) que los autores manejan en sus análisis de caso (tercer vértice)

España en Europa 1996-2004

Pensar globalmente, actuar localmente” es un slogan imprescindible en el discurso político de nuestros días. Pues bien, la práctica política, en materia de Unión Europea, de los dos gobiernos del Partido Popular, presididos por José María Aznar (1996-2004), nos permite acuñar un slogan de signo bien diferente: “pensar localmente, actuar en Europa”. En efecto, si algo caracteriza a estos ocho años de práctica política de José María Aznar es haber convertido sus preocupaciones domésticas en factor exclusivo de su estrategia europea, con independencia del contexto de cada momento y de la necesidad de encajar objetivos nacionales con objetivos europeos. De ahí que sea lógico que la campaña electoral que ha precedido a las elecciones generales del 14 de marzo no haya recogido ninguno de los temas que dominan en la agenda de la UE en el momento actual. Ni la ampliación, ni la Constitución, ni tampoco el proceso de conformación de un núcleo duro tienen cabida en el debate político españo

Spain in Europe 1996-2004

“Thinking globally, acting locally" is an essential slogan in the current political discourse. Yet, in view of the policies on the European Union carried out by the two governments of the People’s Party (PP) headed by José María Aznar between 1996 and 2004, we could coin a quite different slogan: "thinking locally, acting in Europe". Indeed, José María Aznar’s policy-making during the last eight years has been characterised by turning his domestic concerns into the ‘exclusive factor’ of his European strategy, regardless of the context and the need for fitting in national objectives with Europeans’. Hence, it was natural that the electoral campaign preceding the general elections held on Sunday, 14 March, did not deal with any of the topics prevailing in the EU’s current agenda. Neither enlargement nor the Constitution, nor the process of shaping a core group within the EU, seem to have room in Spain’s political debate...

Musée de l'histoire du costume, France , Louis VI, 1787 [32 rue Beaujon, Hôtel de Madrazo, Paris, 8e arrondissement, ouvert au public le 24 janvier 1920] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 57818

Terapias alternativas/complementares: o saber e o fazer das enfermeiras do distrito administrativo 71 - Santo Amaro - São Paulo

Este estudo objetivou verificar o saber e o fazer das enfermeiras que atuam nas unidades municipais de Saúde do Distrito Administrativo 71-Santo Amaro -São Paulo, frente às Terapias Alternativas/Complementares(TA/C). A pesquisa, de abordagem quantitativa com análise qualitativa dos dados, permitiu evidenciar que 89% dos enfermeiros acreditam nas TA/C porém, apenas 22,2% têm conhecimento do respaldo legal e 5,5% têm cursos nesta área; 44,4% aplicam em si mesma e 11,1% aplicam nos pacientes, sete TA/C distintas, classificadas em cinco grupos de HILL. Desvendou-se que há necessidade de buscar novos saberes como opções de assistência à promoção da saúde da população.