Potential geographic distribution of Hantavirus reservoirs in Brazil

Hantavirus cardiopulmonary syndrome is an emerging zoonosis in Brazil. Human infections occur via inhalation of aerosolized viral particles from excreta of infected wild rodents. Necromys lasiurus and Oligoryzomys nigripes appear to be the main reservoirs of hantavirus in the Atlantic Forest and Cerrado biomes. We estimated and compared ecological niches of the two rodent species, and analyzed environmental factors influencing their occurrence, to understand the geography of hantavirus transmission. N. lasiurus showed a wide potential distribution in Brazil, in the Cerrado, Caatinga, and Atlantic Forest biomes. Highest climate suitability for O. nigripes was observed along the Brazilian Atlantic coast. Maximum temperature in the warmest months and annual precipitation were the variables that most influence the distributions of N. lasiurus and O. nigripes, respectively. Models based on occurrences of infected rodents estimated a broader area of risk for hantavirus transmission in southeastern and southern Brazil, coinciding with the distribution of human cases of hantavirus cardiopulmonary syndrome. We found no demonstrable environmental differences among occurrence sites for the rodents and for human cases of hantavirus. However, areas of northern and northeastern Brazil are also apparently suitable for the two species, without broad coincidence with human cases. Modeling of niches and distributions of rodent reservoirs indicates potential for transmission of hantavirus across virtually all of Brazil outside the Amazon Basin

Low sclerostin levels: a predictive marker of persistent inflammation in ankylosing spondylitis during anti-tumor necrosis factor therapy?

Abstract\ud \ud \ud \ud Introduction\ud \ud Sclerostin levels have been reported to be low in ankylosing spondylitis (AS), but there is no data regarding the possible role of this Wnt inhibitor during anti-tumor necrosis factor (TNF) therapy. The present study longitudinally evaluated sclerostin levels, inflammatory markers and bone mineral density (BMD) in AS patients under anti-TNF therapy.\ud \ud \ud \ud Methods\ud \ud Thirty active AS patients were assessed at baseline, 6 and 12 months after anti-TNF therapy regarding clinical parameters, inflammatory markers, BMD and baseline radiographic damage (mSASSS). Thirty age- and sex-matched healthy individuals comprised the control group. Patients' sclerostin levels, sclerostin binding low-density lipoprotein receptor-related protein 6 (LRP6) and BMD were evaluated at the same time points and compared to controls.\ud \ud \ud \ud Results\ud \ud At baseline, AS patients had lower sclerostin levels (60.5 ± 32.7 vs. 96.7 ± 52.9 pmol/L, P = 0.002) and comparable sclerostin binding to LRP6 (P = 0.387) than controls. Improvement of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Ankylosing Spondylitis quality of life (ASQoL) was observed at baseline vs. 6 vs. 12 months (P < 0.01). Concomitantly, a gradual increase in spine BMD (P < 0.001) and a positive correlation between baseline mSASSS and spine BMD was found (r = 0.468, P < 0.01). Inflammatory parameters reduction was observed comparing baseline vs. 6 vs. 12 months (P <0.01). Sclerostin levels progressively increased [baseline (60.5 ± 32.7) vs. 6 months (67.1 ± 31.9) vs. 12 months (72.7 ± 32.3) pmol/L, P <0.001]. At 12 months, the sclerostin levels remained significantly lower in patients compared to controls (72.7 ± 32.3 vs. 96.70 ± 52.85 pmol/L, P = 0.038). Moreover, sclerostin serum levels at 12 months were lower in the 10 patients with high C reactive protein (CRP) (≥ 5 mg/l) compared to the other 20 patients with normal CRP (P = 0.004). Of note, these 10 patients with persistent inflammation also had lower sclerostin serum levels at baseline compared to the other patients (P = 0.023). Univariate logistic regression analysis demonstrated that AS patients with lower sclerostin serum levels had an increased risk to have high CRP at 12 months (odds ratio = 7.43, 95% CI 1.23 to 45.01, P = 0.020) than those with higher sclerostin values.\ud \ud \ud \ud Conclusions\ud \ud Persistent low sclerostin levels may underlie continuous inflammation in AS patients under anti-TNF therapy.This study was supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP #2009/51897-5 to EB), Conselho Nacional de Desenvolvimento Científico e Tecnológico (#300248/2008-3 to CAS, #301411/2009-3 to EB and #300559/2009-7 to RMRP) Federico Foundation (to CGSS, CAS, EB and RMRP)

Isokinetic evaluation of knee muscles in soccer players: discriminant analysis [Avaliação isocinética dos músculos do joelho em jogadores de futebol: análise discriminante]; [Evaluación isocinética de los músculos de la rodilla en jugadores de fútbol: análisis discriminante]

Introduction: Muscle activity in soccer players can be measured by isokinetic dynamometer, which is a reliable tool for assessing human performance. Objectives: To perform isokinetic analyses and to determine which variables differentiate the under-17 (U17) soccer category from the professional (PRO). Methods: Thirty four players were assessed (n=17 for each category). The isokinetic variables used for the knee extension-flexion analysis were: peak torque (Nm), total work (J), average power (W), angle of peak torque (deg.), agonist/ antagonist ratio (%), measured for three velocities (60°/s, 120°/s and 300°/s), with each series containing five repetitions. Three Wilks' Lambda discriminant analyses were performed, to identify which variables were more significant for the definition of each of the categories. Results: The discriminative variables at 60°/s in the PRO category were: extension peak torque, flexion total work, extension average power and agonist/antagonist ratio; and for the U17s were: extension total work, flexion peak torque and flexion average power. At 120°/s for the PRO category the discriminant variables were: flexion peak torque and extension average power; for the U17s they were: extension total work and flexion average power. Finally at 300°/s, the variables found in the PRO and U17 categories respectively were: extension average power and extension total work. Conclusion: Isokinetic variables for flexion and extension knee muscles were able to significantly discriminate between PRO and U17 soccer players. RESUMO Introdução: A atividade muscular em jogadores de futebol pode ser medida por meio do dinamômetro isocinético, que é um instrumento confiável para avaliação do desempenho humano. Objetivos: Conduzir análises isocinéticas e discriminar quais variáveis diferenciam a categoria sub-17 (S17) da profissional (PRO). Métodos: Trinta e quatro jogadores de futebol (n=17 para cada categoria) foram avaliados. As variáveis isocinéticas utilizadas para a análise de extensão-flexão do joelho foram: pico de torque (Nm), trabalho total (J), potência média (W), ângulo de pico de torque (graus), razão agonista/antagonista (%), testadas em três velocidades (60°/s, 120°/s e 300°/s), com cada série contendo cinco repetições. Três análises discriminantes foram feitas usando o método Wilk's Lambda para identificar quais variáveis fariam uma discriminação significativa entre as duas categorias. Resultados: As variáveis discriminantes a 60°/s na categoria PRO foram: pico de torque extensores, trabalho total flexores, potência média de extensores e razão agonista/antagonista; e para os S17 foram: trabalho total de extensores, pico de torque de flexores e potência média de flexores. A 120°/s para a categoria PRO as variáveis discriminantes foram: pico de torque de flexores e potência média de extensores; para os S17 foram: trabalho total de extensores e potência média de flexores. A 300°/s, as variáveis encontradas para as categorias PRO e S17 foram, respectivamente: potência média de extensores e trabalho total de extensores. Conclusão: As variáveis isocinéticas para os músculos do joelho flexores e extensores foram capazes de fazer uma discriminação significativa entre jogadores de futebol PRO e S17. RESUMEN Introducción: La actividad muscular en jugadores de fútbol puede ser medida por medio del dinamómetro isocinético, que es un instrumento confiable para evaluación del desempeño humano. Objetivos: Conducir análisis isocinéticos y discriminar qué variables diferencian la categoría sub-17 (S17) de la profesional (PRO). Métodos: Fueron evaluados treinta y cuatro jugadores de fútbol (n=17 para cada categoría). Las variables isocinéticas utilizadas para el análisis de extensión-flexión de la rodilla fueron: pico de torque (Nm), trabajo total (J), potencia media (W), ángulo de pico de torque (grados), razón agonista/antagonista (%), probadas en tres velocidades (60°/s, 120°/s y 300°/s), con cada serie conteniendo cinco repeticiones. Fueron realizados tres análisis discriminantes usando el método Wilk's Lambda para identificar qué variables harían una discriminación significativa entre las dos categorías. Resultados: Las variables discriminantes a 60°/s en la categoría PRO fueron: pico de torque extensores, trabajo total flexores, potencia media de extensores y razón agonista/antagonista; y para los S17 fueron: trabajo total de extensores, pico de torque de flexores y potencia media de flexores. A 120°/s para la categoría PRO las variables discriminantes fueron: pico de torque de flexores y potencia media de extensores; para los S17 fueron: trabajo total de extensores y potencia media de flexores. A 300°/s, las variables encontradas para las categorías PRO y S17 fueron, respectivamente: potencia media de extensores y trabajo total de extensores. Conclusión: Las variables isocinéticas para los músculos de la rodilla flexores y extensores fueron capaces de hacer una discriminación significativa entre jugadores de fútbol PRO y S17

A DNA Vaccine Encoding Multiple HIV CD4 Epitopes Elicits Vigorous Polyfunctional, Long-Lived CD4+ and CD8+ T Cell Responses

T-cell based vaccines against HIV have the goal of limiting both transmission and disease progression by inducing broad and functionally relevant T cell responses. Moreover, polyfunctional and long-lived specific memory T cells have been associated to vaccine-induced protection. CD4+ T cells are important for the generation and maintenance of functional CD8+ cytotoxic T cells. We have recently developed a DNA vaccine encoding 18 conserved multiple HLA-DR-binding HIV-1 CD4 epitopes (HIVBr18), capable of eliciting broad CD4+ T cell responses in multiple HLA class II transgenic mice. Here, we evaluated the breadth and functional profile of HIVBr18-induced immune responses in BALB/c mice. Immunized mice displayed high-magnitude, broad CD4+/CD8+ T cell responses, and 8/18 vaccine-encoded peptides were recognized. In addition, HIVBr18 immunization was able to induce polyfunctional CD4+ and CD8+ T cells that proliferate and produce any two cytokines (IFNγ/TNFα, IFNγ/IL-2 or TNFα/IL-2) simultaneously in response to HIV-1 peptides. For CD4+ T cells exclusively, we also detected cells that proliferate and produce all three tested cytokines simultaneously (IFNγ/TNFα/IL-2). The vaccine also generated long-lived central and effector memory CD4+ T cells, a desirable feature for T-cell based vaccines. By virtue of inducing broad, polyfunctional and long-lived T cell responses against conserved CD4+ T cell epitopes, combined administration of this vaccine concept may provide sustained help for CD8+ T cells and antibody responses- elicited by other HIV immunogens