How Is Exposure to Tobacco Outlets Within Activity Spaces Associated With Daily Tobacco Use Among Youth? A Mediation Analysis

INTRODUCTION: We investigated associations between exposure to tobacco outlets within activity spaces and daily tobacco use, and whether exposure to adults or peers using tobacco mediate these relationships. METHODS: We used Geographic Ecological Momentary Assessment data over 14 days from 85 youth aged 16-20 years in eight mid-sized California city areas. Tobacco outlet addresses and global positioning systems locations were geocoded and activity spaces were constructed by joining sequential points. We assessed daily number of tobacco outlets within 50 or 100 m of activity space polylines and number of minutes participants were within 50 or 100 m of tobacco outlets each day; daily use of tobacco; and whether participants saw (1) adults and (2) people their age (peers) using tobacco each day. RESULTS: Controlling for demographics, results of multilevel structural equation models showed no association between number of tobacco outlets within 50 m of polylines and tobacco use (probit regression coefficient: 0.01, p = .82). However, we found evidence of an indirect effect (p = .001) through daily exposure to peers using tobacco. Specifically, greater number of tobacco outlets within 50 m of polylines was positively associated with seeing peers use tobacco (probit regression coefficient: 0.10, p < .001). In turn, seeing peers use tobacco was positively associated with tobacco use on that day (probit regression coefficient: 2.23, p < .001). Similar results were found for number of tobacco outlets within 100 m of polylines. CONCLUSIONS: Exposure to tobacco outlets within activity spaces affects youth tobacco use through daily exposure to peers who use tobacco. IMPLICATIONS: Using real-time-ordered data, this article examines whether exposure to adults and peers using tobacco mediate associations between exposure to tobacco outlets within activity spaces and daily tobacco use among youth. Results suggest that exposure to tobacco outlets within activity spaces affects daily tobacco use through exposure to peers who use tobacco. These findings provide additional significant support for policy makers who are considering regulating the number and density of tobacco retailers and point to the importance of interventions focused on peer tobacco use and youths' daily environments to reduce tobacco use

Retro-1-oligonucleotide conjugates. Synthesis and biological evaluation

Addition of small molecule Retro-1 has been described to enhance antisense and splice switching oligonucleotides. With the aim of assessing the effect of covalently linking Retro-1 to the biologically active oligonucleotide, three different derivatives of Retro-1 were prepared that incorporated a phosphoramidite group, a thiol or a 1,3-diene, respectively. Retro-1-oligonucleotide conjugates were assembled both on-resin (coupling of the phosphoramidite) and from reactions in solution (Michael-type thiol-maleimide reaction and Diels-Alder cycloaddition). Splice switching assays with the resulting conjugates showed that they were active but that they provided little advantage over the unconjugated oligonucleotide in the well-known HeLa Luc705 reporter system

Pseudomonas aeruginosa diversification during infection development in cystic fibrosis lungs - A review

Pseudomonas aeruginosa is the most prevalent pathogen of cystic fibrosis (CF) lung disease. Its long persistence in CF airways is associated with sophisticated mechanisms of adaptation, including biofilm formation, resistance to antibiotics, hypermutability and customized pathogenicity in which virulence factors are expressed according the infection stage. CF adaptation is triggered by high selective pressure of inflamed CF lungs and by antibiotic treatments. Bacteria undergo genetic, phenotypic, and physiological variations that are fastened by the repeating interplay of mutation and selection. During CF infection development, P. aeruginosa gradually shifts from an acute virulent pathogen of early infection to a host-adapted pathogen of chronic infection. This paper reviews the most common changes undergone by P. aeruginosa at each stage of infection development in CF lungs. The comprehensive understanding of the adaptation process of P. aeruginosa may help to design more effective antimicrobial treatments and to identify new targets for future drugs to prevent the progression of infection to chronic stages.The authors thank the project FCT PTDC/SAUSAP/113196/2009/FCOMP-01-0124-FEDER-016012, the Strategic Project PEst-OE/EQB/LA0023/2013, the Project. BioHealth-Biotechnology and Bioengineering approaches to improve health quality., Ref. NORTE-07-0124-FEDER-000027, co-funded by the Programa Operacional Regional do Norte (ON.2-O Novo Norte), QREN, FEDER, the project. RECI/BBB-EBI/0179/2012-Consolidating Research Expertise and Resources on Cellular and Molecular Biotechnology at CEB/IBB., Ref. FCOMP-01-0124-FEDER-027462, FEDER. The authors also acknowledge PhD Grant of Ana MargaridaSousa SFRH/BD/72551/2010

Expression and localization of epithelial aquaporins in the adult human lung

Aquaporins (AQPs) facilitate water transport across epithelia and play an important role in normal physiology and disease in the human airways. We used in situ hybridization and immunofluorescence to determine the expression and cellular localization of AQPs 5, 4, and 3 in human airway sections. In nose and bronchial epithelia, AQP5 is expressed at the apical membrane of columnar cells of the superficial epithelium and submucosal gland acinar cells. AQP4 was detected in basolateral membranes in ciliated ducts and by in situ in gland acinar cells. AQP3 is present on basal cells of both superficial epithelium and gland acinus. In these regions AQPs 5, 4, and 3 are appropriately situated to permit transepithelial water permeability. In the small airways (proximal and terminal bronchioles) AQP3 distribution shifts from basal cell to surface expression (i.e., localized to the apical membrane of proximal and terminal bronchioles) and is the only AQP identified in this region of the human lung. The alveolar epithelium has all three AQPs represented, with AQP5 and AQP4 localized to type I pneumocytes and AQP3 to type II cells. This study describes an intricate network of AQP expression that mediates water transport across the human airway epithelium

VAMP8 is a vesicle SNARE that regulates mucin secretion in airway goblet cells

Mucin secretion in the lung is regulated by the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) exocytotic core, which has not been defined in airway goblet cells. In this study, the SNARE vesicle-associated membrane protein 8 (VAMP8) was found to be expressed in human airway epithelial goblet cells. VAMP8 knockdown by RNA interference techniques reduced airway epithelial mucin secretion induced by PAR agonists, neutrophil elastase and ATP. Basal (non-agonist elicited) mucin secretion was also reduced as a result of VAMP8 knockdown. Importantly, mucin secretion was reduced in the lungs of VAMP8 knockout mice compared to wild-type littermates. Our data suggest that VAMP8 is an essential SNARE in airway mucin granule exocytosis. Reduction of VAMP8 activity/expression may provide a novel therapeutic target to ameliorate airway mucus obstruction in lung diseases

Thrombin-promoted release of UDP-glucose from human astrocytoma cells: Thrombin-promoted release of UDP-glucose

The P2Y14 receptor is activated by UDP-sugars, most potently by UDP-glucose, but not by free nucleotides, suggesting that UDP-glucose is the cognate agonist for this receptor. However, evidence for regulated release of UDP-glucose is scarce. In the present study, the occurrence of receptor-promoted release of UDP-glucose was investigated, using 1321N1 human astrocytoma cells