Paradoxical upgrading reaction in extra-pulmonary tuberculosis: association with vitamin D therapy

SETTING: Glasgow, Scotland, UK. BACKGROUND: Paradoxical reactions in tuberculosis (TB) are a notable example of our incomplete understanding of host-pathogen interactions during anti-tuberculosis treatment. OBJECTIVES: To determine risk factors for a TB paradoxical reaction, and specifically to assess for an independent association with vitamin D use. DESIGN: Consecutive human immunodeficiency virus (HIV) negative adult patients treated for extra-pulmonary TB were identified from an Extended Surveillance of Mycobacterial Infections database. In our setting, vitamin D was variably prescribed for newly diagnosed TB patients. A previously published definition of paradoxical TB reaction was retrospectively applied to, and data on all previously described risk factors were extracted from, centralised electronic patient records. The association with vitamin D use was assessed using multivariate logistic regression. RESULTS: Of the 249 patients included, most had TB adenopathy; 222/249 had microbiologically and/or histologically confirmed TB. Vitamin D was prescribed for 57/249 (23%) patients; 37/249 (15%) were classified as having paradoxical reactions. Younger age, acid-fast bacilli-positive invasive samples, multiple disease sites, lower lymphocyte count and vitamin D use were found to be independent risk factors. CONCLUSION: We speculate that vitamin D-mediated signalling of pro-inflammatory innate immune cells, along with high antigenic load, may mediate paradoxical reactions in anti-tuberculosis treatment

Diastereoselective Synthesis of C60/Steroid Conjugates

The design and synthesis of fullerene–steroid hybrids by using Prato’s protocol has afforded new fullerene derivatives endowed with epiandrosterone, an important naturally occurring steroid hormone. Since the formation of the pyrrolidine ring resulting from the 1,3-dipolar cyloaddition reaction takes place with generation of a new stereogenic center on the C2 of the five-membered ring, the reaction proceeds with formation of a diastereomeric mixture [compounds 6 and 7 in 70:30 ratio, 8 and 9 in 26:74 ratio (HPLC)] in which the formation of the major diasteroisomers 6 and 9 is consistent with an electrophilic attack of [60]fullerene on the Re face of the azomethine ylide directed by the steroidic unit. The chiroptical properties of these conjugates reveal typical Cotton effects in CD spectra that have been used to assign the absolute configuration of the new fulleropyrrolidines. The electrochemical study of the new compounds reveals the presence of four quasi-reversible reduction waves which are cathodically shifted in comparison with the parent C60, thus ascertaining the proposed structures.Financial support by the Ministerio de Ciencia e Innovación (MINECO) of Spain (CTQ2011-24652, CTQ2011-27253, PIB2010JP-00196, and CSD2007-00010 projects) and CAM (Madrisolar-2) is acknowledged; A.R. thanks UCM for financial support; M.S. is indebted to Programa del Grupo Santander 2012

A holistic, learning-centred approach to building evaluation capacity in development organizations

There is growing pressure on development organizations to improve their evaluation systems and capacities. This presents considerable challenges for time- and resource-poor organizations in developing countries. Evaluation capacity development (ECD) approaches are needed that are appropriate and effective for such organizations. We argue that this requires a long-term, holistic, participatory, learning-centred approach that aims to develop learning organizations and build the capacity of whole organizations and their stakeholders. It also needs to incorporate local knowledge and ideas and ongoing meta-evaluation of ECD activities. We describe this approach and how it was applied in a four-year action research project with a non-governmental organization in Nepal. Drawing on findings from this project and various follow up activities, we suggest some principles and strategies for designing and implementing an effective and sustainable approach to ECD that can help to address the many challenges and issues we have identified