Phage therapy is effective against infection by Mycobacterium ulcerans in a murine footpad model

Author Summary: Buruli Ulcer (BU), caused by Mycobacterium ulcerans, is a necrotizing disease of the skin, subcutaneous tissue and bone. Standard treatment of BU patients consists of a combination of the antibiotics rifampicin and streptomycin for 8 weeks. However, in advanced stages of the disease, surgical resection of the destroyed skin is still required. The use of bacterial viruses (bacteriophages) for the control of bacterial infections has been considered as an alternative or a supplement to antibiotic chemotherapy. By using a mouse model of M. ulcerans footpad infection, we show that mice treated with a single subcutaneous injection of the mycobacteriophage D29 present decreased footpad pathology associated with a reduction of the bacterial burden. In addition, D29 treatment induced increased levels of IFN-γ and TNF in M. ulcerans -infected footpads, correlating with a predominance of a mononuclear infiltrate. These findings suggest the potential use of phage therapy in BU, as a novel therapeutic approach against this disease, particularly in advanced stages where bacteria are found primarily in an extracellular location in the subcutaneous tissue, and thus immediately accessible by lytic phages.This work was supported by a grant from the Health Services of Fundacao Calouste Gulbenkian, and the Portuguese Science and Technology Foundation (FCT) fellowships SFRH/BPD/64032/2009, SFRH/BD/41598/2007, and SFRH/BPD/68547/2010 to GT, TGM, and AGF, respectively. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Tradução, validação e adaptação cultural da escala de atividade esportiva Translation, validation and cultural adaptation of the "sports activities scale"

OBJETIVOS: Realizar a tradução e adaptação cultural do "Sports Activities Scale" para a língua portuguesa, e verificar suas propriedades de medida, reprodutibilidade e validade. MÉTODO: baseado na revisão da literatura de Guillemin et al. foi realizado a tradução, adaptação cultural e validação. Para a análise estatística foi utilizado a análise descritiva, o teste t, o coeficiente de correlação intraclasse e o coeficiente de correlação de Spearman, com nível de significância igual a 5% (alfa = 0,05). RESULTADOS: O questionário traduzido apresentou: boa compreensão e equivalência cultural de 95% dos pacientes após algumas modificações; uma excelente reprodutibilidade (alfa=0,01, ro<0,001) ao correlacionar intra-entrevistador e inter-entrevistador; uma correlação com o questionário SF-36 significante nos itens Capacidade Funcional, Aspecto Físico, Dor, Estado Geral e Aspectos Sociais; uma correlação fraca com o questionário SF-36 nos itens Vitalidade, Aspectos Emocionais e a Saúde Mental; uma correlação significante com o Lysholm (alfa =0,01, ro<0,001); e uma correlação negativa moderada com a escala análogo visual da dor (alfa =0,05, ro<0,013). CONCLUSÃO: A versão em português do questionário "Sports Activities Scale" é um parâmetro de fácil administração, reprodutível e válido para ser utilizado na avaliação específica de sintomas e limitações do joelho durante a prática esportiva de pacientes brasileiros.<br>OBJECTIVES: to translate and adapt the "Sports Activities Scale" as well as to check its measurement, reproduction and validity properties. METHOD: the translation, cultural adaptation and validation were made by reviewing the work by Guillemin et al. For statistical analysis, we used descriptive analysis, t-test, inter-class correlation coefficient and Spearman correlation coefficient, with significance level equal to 5% (alpha = 0.05). RESULTS: the translated questionnaire showed to be understandable and culturally equivalent for 95% of Brazilian patients after some modifications were made; an excellent reproducibility (alpha = 0.01, rho < 0.001) when correlating intra- and inter-interviewers; a significant correlation with the SF-36 questionnaire on the following items: functional capacity, pain, general aspects and social aspects, a weak association with SF-36 questionnaire on vitality, emotional aspects and mental health; a significant correlation with Lysholm (alpha = 0.01, rho > 0.001); and a moderate negative correlation with the visual analog scale for pain (alpha = 0.05, rho = 0.0013). CONCLUSION: The Brazilian version of the "Sports Activities Scale" questionnaire is an easily-manageable, reproducible and valid parameter for a specific evaluation of knee's symptoms and restraints during sports activities, in Brazilian patients

Efficiency or bounded rationality? Drivers of firm diversification strategies in Vietnam

Considering the case of diversified firms within a developing/transition country such as Vietnam, this paper investigates diversification relatedness while taking into account both firm- and industry-specific components. The high volatility of the dynamics of diversification observed in Vietnam suggests the hypothesis that firms decide to enter into new industries following a trial and error process, initiated by boundedly rational herding behaviors, i.e., firms follow the most commonly observed business combinations. Using a survivor-based (SB) measure of relatedness, we test the hypothesis of boundedly rational behavior. We find that both the probability of exit and the different performance measures (Return on sales and Total factor productivity) are not or are negatively correlated with SB-related diversification. This is in contrast to what has been observed in developed countries. However, using the SIC distance approach, we obtain the expected positive relationship between performance and relatedness in diversified firms. The conflicting result between these two relatedness indices therefore suggests there has been a trend in follow-up among inexperienced firms that imitate the direction and intensity of the diversification of dominating players within the industry (herd behavior). However, diversified firms gain experience over time and choose more efficient business combinations in subsequent entries. When we use the classical SIC-based approach, we find that greater diversification raises profitability, but only to an optimum relatedness point, beyond which the positive effect fades away. To control for the endogeneity of diversification relatedness and the serial correlation in error terms, we adopt an instrumental-variable two-stage least-squares estimation approach (IV-2SLS) with GMM treatment

Fluorescent nanodiamond tracking reveals intraneuronal transport abnormalities induced by brain-disease-related genetic risk factors

International audienceBrain diseases such as autism and Alzheimer's disease (each inflicting >1% of the world population) involve a large network of genes displaying subtle changes in their expression. Abnormalities in intraneuronal transport have been linked to genetic risk factors found in patients, suggesting the relevance of measuring this key biological process. However, current techniques are not sensitive enough to detect minor abnormalities. Here we report a sensitive method to measure the changes in intraneuronal transport induced by brain-disease-related genetic risk factors using fluorescent nanodiamonds (FNDs). We show that the high brightness, photostability and absence of cytotoxicity allow FNDs to be tracked inside the branches of dissociated neurons with a spatial resolution of 12 nm and a temporal resolution of 50 ms. As proof of principle, we applied the FND tracking assay on two transgenic mouse lines that mimic the slight changes in protein concentration (∼30%) found in the brains of patients. In both cases, we show that the FND assay is sufficiently sensitive to detect these changes