Rifapentine, a synthetic derivate of rifampicin which was developed in 1965, has interesting pharmacological properties, including a long terminal half-life (13 h, compared to 2-3 h for rifampicin) ...and promising bactericidal activity against Mycobacterium tuberculosis. Despite being approved in 1998 by the US Food and Drug Administration (FDA) for the treatment of pulmonary tuberculosis, its global use has been limited by unavailability. In the past decade, new evidence has emerged to define rifapentine as a key component for treatment of active disease and latent infection with M. tuberculosis (LTBI).
Abstract
Background
The role of the immune system in the pathobiology of Idiopathic Pulmonary Fibrosis (IPF) is controversial.
Methods
To investigate it, we calculated immune signatures with Gene Set ...Variation Analysis (GSVA) and applied them to the lung transcriptome followed by unbiased cluster analysis of GSVA immune-enrichment scores, in 109 IPF patients from the Lung Tissue Research Consortium (LTRC). Results were validated experimentally using cell-based methods (flow cytometry) in lung tissue of IPF patients from the University of Pittsburgh (n = 26). Finally, differential gene expression and hypergeometric test were used to explore non-immune differences between clusters.
Results
We identified two clusters (C#1 and C#2) of IPF patients of similar size in the LTRC dataset. C#1 included 58 patients (53%) with enrichment in GSVA immune signatures, particularly cytotoxic and memory T cells signatures, whereas C#2 included 51 patients (47%) with an overall lower expression of GSVA immune signatures (results were validated by flow cytometry with similar unbiased clustering generation). Differential gene expression between clusters identified differences in cilium, epithelial and secretory cell genes, all of them showing an inverse correlation with the immune response signatures. Notably, both clusters showed distinct features despite clinical similarities.
Conclusions
In end-stage IPF lung tissue, we identified two clusters of patients with very different levels of immune signatures and gene expression but with similar clinical characteristics. Weather these immune clusters differentiate diverse disease trajectories remains unexplored.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Sufficient iodine intake is needed during pregnancy to ensure proper fetal development. The iodine levels of women in their first trimester of pregnancy in Catalonia are currently unknown. This data ...would help to determine whether our public health services should establish recommendations or interventions in this line. The aim of this study was to investigate the iodine nutritional status, prevalence of urinary iodine <150 μg/L, and tobacco use in the first trimester of pregnancy in our setting.
Cross-sectional study. Data were collected during 2008-2009 from women in their first trimester at the primary care centers of the province of Barcelona (Spain). Pregnant women included in the study completed a questionnaire on eating habits and underwent urinary iodine concentration (UIC) assessment.
Nine hundred forty five women completed the dietary questionnaire and urinary iodine testing. Median UIC was 172 μg/L, with 407 participants (43.1%) showing levels <150 μg/L. On multivariate logistic regression analysis, intake of 1-2 glasses of milk per day, OR = 0.636 95% CI (0.45-0.90) or >2 glasses, OR = 0.593 95% CI (0.37-0.95); iodized salt consumption, OR = 0.678 95% CI (0.51-0. 90); and use of iodine supplementation, OR = 0.410 95% CI (0.31-0.54), protected against the risk of UIC <150 μg/L. Simultaneous consumption of iodized salt and milk (≥1 glass/day) showed a larger protective effect: OR = 0.427, 95% CI (0.31-0.54).
The median UIC of the pregnant women surveyed indicated an acceptable iodine nutritional status according to the criteria established by the WHO and ICCIDD. The risk of urinary iodine <150 μg/L decreased with simultaneous consumption of milk and iodized salt, similar to the decrease seen with iodine supplementation.
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