Cigarette smoke exposure is a major determinant of adverse lung health, but the molecular processes underlying its effects on inflammation and immunity remain poorly understood. Therefore, we sought to understand whether inflammatory and host defense determinants are affected during subchronic cigarette smoke exposure. Dose-response and time course studies of lungs from Balb/c mice exposed to smoke generated from 3, 6, and 9 cigarettes/day for 4 days showed macrophage- and S100A8-positive neutrophil-rich inflammation in lung tissue and bronchoalveolar lavage (BAL) fluid, matrix metalloproteinase (MMP) and serine protease induction, sustained NF-kappaB translocation and binding, and mucus cell induction but very small numbers of CD3+CD4+ and CD3+CD8+ lymphocytes. Cigarette smoke had no effect on phospho-Akt but caused a small upregulation of phospho-Erk1/2. Activator protein-1 and phospho-p38 MAPK could not be detected. Quantitative real-time PCR showed upregulation of chemokines (macrophage inflammatory protein-2, monocyte chemoattractant protein-1), inflammatory mediators (TNF-alpha, IL-1beta), leukocyte growth and survival factors [granulocyte-macrophage colony-stimulating factor, colony-stimulating factor (CSF)-1, CSF-1 receptor], transforming growth factor-beta, matrix-degrading MMP-9 and MMP-12, and Toll-like receptor (TLR)2, broadly mirroring NF-kappaB activation. No upregulation was observed for MMP-2, urokinase-type plasminogen activator, tissue-type plasminogen activator, and TLRs 3, 4, and 9. In mouse strain comparisons the rank order of susceptibility was Balb/c > C3H/HeJ > 129SvJ > C57BL6. Partition of responses into BAL macrophages vs. lavaged lung strongly implicated macrophages in the inflammatory responses. Strikingly, except for IL-10 and MMP-12, macrophage and lung gene profiles in Balb/c and C57BL/6 mice were very similar. The response pattern we observed suggests that subchronic cigarette smoke exposure may be useful to understand pathogenic mechanisms triggered by cigarette smoke in the lungs including inflammation and alteration of host defense.

BackgroundThe Edinburgh Postnatal Depression Scale (EPDS), originally developed in Britain, is one of the most widely used screening instruments for assessing symptoms of the Perinatal Common Mental Disorders (PCMDs) of depression and anxiety. However, its potential to detect PCMDs in culturally diverse low- and lower-middle income countries (LALMICs) is unclear. This systematic review aimed to appraise formally validated local language versions of the EPDS from these resource-constrained settings.MethodsFollowing the PRISMA protocol, we searched MEDLINE-OVID, CINAHL-Plus and PUBMED to identify studies reporting translation, cultural adaptation and formal validation of the EPDS to detect PCMDs among women in LALMICs. The quality of the studies meeting inclusion criteria was assessed using standard criteria and a new process-based criteria; which was developed specifically for this study.ResultsWe identified 1281 records among which 16 met inclusion criteria; three further papers were identified by hand-searching reference lists. The publications reported findings from 12 LALMICs in14 native languages. Most of these local language versions of the EPDS (LLV-EPDS) had lower precision for identifying true cases of PCMDs among women in the general perinatal population compared to the original English version. Only one study met all criteria for culturally sensitive translation, the others had not established the comprehensibility of the local version amongst representative groups of women in pre-testing. Many studies tested the LLV-EPDS only amongst convenience samples recruited at single health facilities. Diagnostic interviews for confirmation of mental disorders could have been influenced by the mental health professionals’ lack of blinding to the initial screening results. Additionally, even when diagnostic-interviews were carried out in the local language, questions might not have been understood as most studies followed standard diagnostic protocol which had not been culturally adapted.ConclusionsMost of the LLV-EPDS from non-English speaking low- and middle-income-countries did not meet all criteria for formal validation of a screening instrument. Psychometric properties of LLV-EPDS could be enhanced by adopting the new process-based criteria for translation, adaptation and validation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12884-016-0859-2) contains supplementary material, which is available to authorized users.

Background: Cigarette smoke has both pro-inflammatory and immunosuppressive effects. Both active and passive cigarette smoke exposure are linked to an increased incidence and severity of respiratory virus infections, but underlying mechanisms are not well defined. We hypothesized, based on prior gene expression profiling studies, that upregulation of pro-inflammatory mediators by short term smoke exposure would be protective against a subsequent influenza infection.

A genomic-length cDNA clone corresponding to the RNA of dengue virus type 2 (DEN-2) New Guinea C strain (NGC) was constructed in a low copy number vector. The cloned cDNA was stably propagated in Escherichia coli and designated pDVWS501. RNA transcripts produced in vitro from the cDNA using T7 RNA polymerase yielded infectious virus (MON501) upon electroporation into BHK-21 cells. When compared with parental NGC virus, MON501 replicated to similar levels in Aedes albopictus C6/36 cells and showed similar neurovirulence in suckling mice. In contrast, a second genomic-length cDNA clone (pDVWS310) used as an intermediate in the construction of pDVWS501 produced virus