Implementation of the Xpert MTB/RIF assay for tuberculosis in Mongolia: A qualitative exploration of barriers and enablers

© 2017 Rendell et al. Objective. The aim of our study was to identify barriers and enablers to implementation of the Xpert MTB/RIF test within Mongolia's National Tuberculosis Program. Methods. Twenty-four semi-structured interviews were conducted between June and September 2015 with laboratory staffand tuberculosis physicians in Mongolia's capital Ulaanbaatar and regional towns where Xpert MTB/RIF testing had been implemented. Interviews were recorded, transcribed, translated and analysed thematically using NVIVO qualitative analysis software. Results. Eight laboratory staff(five from the National Tuberculosis Reference Labo- ratory in Ulaanbaatar and three from provincial laboratories) and sixteen tuberculosis physicians (five from the Mongolian National Center for Communicable Diseases in Ulaanbaatar, four from district tuberculosis clinics in Ulaanbaatar and seven from provincial tuberculosis clinics) were interviewed. Major barriers to Xpert MTB/RIF implementation identified were: lack of awareness of program guidelines; inadequate staffing arrangements; problems with cartridge supply management; lack of local repair options for the Xpert machines; lack of regular formal training; paper based system; delayed treatment initiation due to consensus meeting and poor sample quality. Enablers to Xpert MTB/RIF implementation included availability of guidelines in the local language; provision of extra laboratory staff, shift working arrangements and additional modules; capacity for troubleshooting internally; access to experts; opportunities for peer learning; common understanding of diagnostic algorithms and decentralised testing. Conclusion. Our study identified a number of barriers and enablers to implementation of Xpert MTB/RIF in the Mongolian National Tuberculosis Program. Lessons learned from this study can help to facilitate implementation of Xpert MTB/RIF in other Mongolian locations as well as other low-and middle-income countries

Chronic adolescent stress sex-specifically alters the hippocampal transcriptome in adulthood

Chronic adolescent stress alters behavior in a sex-specific manner at the end of adolescence and in adulthood. Although prolonged behavioral repercussions of chronic adolescent stress have been documented, the potential underlying mechanisms are incompletely understood. In this study we demonstrate that a history of chronic adolescent stress modified the adult stress response, as measured by corticosterone concentration, such that a history of chronic adolescent stress resulted in a blunted response to a novel acute stressor. In order to begin to address potential mechanistic underpinnings, we assessed the extent to which chronic adolescent stress impacted global DNA methylation. Reduced global hippocampal methylation was evident in females with a history of chronic adolescent stress; thus, it was possible that chronic adolescent stress altered global transcription in the whole hippocampi of adult male and female rats. In addition, because acute stress can stimulate a genomic response, we assessed the transcriptome following exposure to an acute novel stressor to determine the extent to which a history of chronic adolescent stress modifies the adult transcriptional response to an acute stressor in males and females. In addition to the reduction in global methylation, chronic adolescent stress resulted in distinct patterns of gene expression in the adult hippocampus that differentiated by sex. Furthermore, both sex and a history of chronic adolescent stress influenced the transcriptional response to an acute novel stressor in adulthood, suggesting both latent and functional effects of chronic adolescent stress at the level of gene transcription. Pathway analysis indicated that ESR1 and IFN-a may be particularly influential transcription factors mediating these transcriptional differences and suggest candidate mechanisms for future studies. Collectively, these studies demonstrate sexspecific and enduring effects of adolescent stress exposure that are more pronounced in females than in males

Metabolomic and inflammatory signatures of symptom dimensions in major depression.

BACKGROUND: Major depressive disorder (MDD) is a highly heterogenous disease, both in terms of clinical profiles and pathobiological alterations. Recently, immunometabolic dysregulations were shown to be correlated with atypical, energy-related symptoms but less so with the Melancholic or Anxious distress symptom dimensions of depression in The Netherlands Study of Depression and Anxiety (NESDA) study. In this study, we aimed to replicate these immunometabolic associations and to characterize the metabolomic correlates of each of the three MDD dimensions. METHODS: Using three clinical rating scales, Melancholic, and Anxious distress, and Immunometabolic (IMD) dimensions were characterized in 158 patients who participated in the Predictors of Remission to Individual and Combined Treatments (PReDICT) study and from whom plasma and serum samples were available. The NESDA-defined inflammatory index, a composite measure of interleukin-6 and C-reactive protein, was measured from pre-treatment plasma samples and a metabolomic profile was defined using serum samples analyzed on three metabolomics platforms targeting fatty acids and complex lipids, amino acids, acylcarnitines, and gut microbiome-derived metabolites among other metabolites of central metabolism. RESULTS: The IMD clinical dimension and the inflammatory index were positively correlated (r=0.19, p=.019) after controlling for age, sex, and body mass index, whereas the Melancholic and Anxious distress dimensions were not, replicating the previous NESDA findings. The three symptom dimensions had distinct metabolomic signatures using both univariate and set enrichment statistics. IMD severity correlated mainly with gut-derived metabolites and a few acylcarnitines and long chain saturated free fatty acids. Melancholia severity was significantly correlated with several phosphatidylcholines, primarily the ether-linked variety, lysophosphatidylcholines, as well as several amino acids. Anxious distress severity correlated with several medium and long chain free fatty acids, both saturated and polyunsaturated ones, sphingomyelins, as well as several amino acids and bile acids. CONCLUSION: The IMD dimension of depression appears reliably associated with markers of inflammation. Metabolomics provides powerful tools to inform about depression heterogeneity and molecular mechanisms related to clinical dimensions in MDD, which include a link to gut microbiome and lipids implicated in membrane structure and function