No abstract

SummaryThe growth of Mycobacterium tuberculosis mutants unable to synthesize phthiocerol dimycocerosates (DIMs) was recently shown to be impaired in mouse lungs. However, the precise role of these molecules in the course of infection remained to be determined. Here, we provide evidence that the attenuation of a DIM-deficient strain takes place during the acute phase of infection in both lungs and spleen of mice, and that this attenuation results in part from the increased sensitivity of the mutant to the cidal activity of reactive nitrogen intermediates released by activated macrophages. We also show that the DIM-deficient mutant, the growth and survival of which were not impaired within resting macrophages and dendritic cells, induced these cells to secrete more tumour necrosis factor (TNF)-a a a a and interleukin (IL)-6 than the wild-type strain. Although purified DIM molecules by themselves had no effect on the activation of macrophages and dendritic cells in vitro , we found that the proper localization of DIMs in the cell envelope of M. tuberculosis is critical to their biological effects. Thus, our findings suggest that DIM production contributes to the initial growth of M. tuberculosis by protecting it from the nitric oxide-dependent killing of macrophages and modulating the early immune response to infection.

Although the vast majority of refugees have suffered trauma and extended separation from their families in exile, little is known about the interactions between these two types of experience. The qualitative and quantitative analyses of data gathered from 113 refugees from Latin America and Africa suggest that the joint occurrence of trauma and separation has a significant impact on emotional distress and confirm that the family plays a key role as an anchor of emotion and identity.

The Outline for Cultural Formulation (OCF) introduced with DSM-IV provided a framework for clinicians to organize cultural information relevant to diagnostic assessment and treatment planning. However, use of the OCF has been inconsistent, raising questions about the need for guidance on implementation, training, and application in diverse settings. To address this need, DSM-5 introduced a cultural formulation interview (CFI) that operationalizes the process of data collection for the OCF. The CFI includes patient and informant versions and 12 supplementary modules addressing specific domains of the OCF. This article summarizes the literature reviews and analyses of experience with the OCF conducted by the DSM-5 Cross-Cultural Issues Subgroup (DCCIS) that informed the development of the CFI. We review the history and contents of the DSM-IV OCF, its use in training programs, and previous attempts to render it operational through questionnaires, protocols, and semi-structured interview formats. Results of research based on the OCF are discussed. For each domain of the OCF, we summarize findings from the DCCIS that led to content revision and operationalization in the CFI. The conclusion discusses training and implementation issues essential to service delivery.