Some genes present in only certain strains of the genetically diverse gastric pathogen Helicobacter pylori may affect its phenotype and/or evolutionary potential. Here we describe a new 16.3-kb segment, 7 of whose 16 open reading frames are homologs of type IV secretion genes (virB4, virB7 to virB11, and virD4), the third such putative secretion gene cluster found in H. pylori. This segment, to be called tfs3, was discovered by subtractive hybridization and chromosome walking. Full-length and truncated tfs3 elements were found in 20 and 19%, respectively, of 94 strains tested, which were from Spain, Peru, India, and Japan. A tfs3 remnant (6 kb) was found in an archived stock of reference strain J99, although it was not included in this strain's published genome sequence. PCR and DNA sequence analyses indicated the following. (i) tfs3's ends are conserved. (ii) Right-end insertion occurred at one specific site in a chromosomal region that is varied in gene content and arrangement, the "plasticity zone." (iii) Left-end insertion occurred at different sites in each of nine strains studied. (iv) Sequences next to the right-end target in tfs3-free strains were absent from most strains carrying full-length tfs3 elements. These patterns suggested insertion by a transposition-like event, but one in which targets are chosen with little or no specificity at the left end and high specificity at the right end, thereby deleting the intervening DNA.

Background Asthma is a growing public health problem in developing countries. However, few studies have studied the role of urbanisation in this phenomenon. It was hypothesised that children living in a peri-urban setting in Peru have higher rates of asthma and allergy than rural counterparts. Methods 1441 adolescents aged 13–15 years were enrolled from two settings: a peri-urban shanty town in Lima (n=725) and 23 rural villages in Tumbes (n=716). Participants filled in questionnaires on asthma and allergy symptoms, environmental exposures and sociodemographics, and underwent spirometry, and exhaled nitric oxide (eNO) and allergy skin testing. Indoor particulate matter (PM) concentrations were measured in 170 households. Results Lima adolescents had higher rates of lifetime wheezing (22% vs 10%), current asthma symptoms (12% vs 3%) and physician-diagnosed asthma (13% vs 2%; all p <0.001). Current rhinitis (23% vs 12%), eczema (12% vs 0.4%), atopy (56% vs 38%), personal history of cigarette smoking (7.4% vs 1.3%) and mean indoor PM (31 vs 13 μg/m3) were also higher in Lima (all p <0.001). The peri-urban environment of Lima was associated with a 2.6-fold greater odds (95% CI 1.3 to 5.3) of asthma in multivariable regression. Forced expiratory volumes were higher and FEV1/FVC (forced expiratory volume in 1 s/forced vital capacity) ratios were lower in Lima (all p <0.001). Higher eNO values in Lima (p <0.001) were attributable to higher rates of asthma and atopy. Conclusions Peri-urban adolescents had more asthma, atopy and airways inflammation and were exposed to more indoor pollution. The findings provide evidence of the risks posed to lung health by peri-urban environments in developing countries.

Clinically useful molecular tools to triage gastric cancer patients are not currently available. We aimed to develop a molecular tool to predict gastric cancer risk in endoscopy-driven biopsies obtained from high-risk gastric cancer clinics in low resource settings.We discovered and validated a DNA methylation biomarker panel in endoscopic samples obtained from 362 patients seen between 2004 and 2009 in three high-risk gastric cancer clinics in Lima, Perú, and validated it in 306 samples from the Cancer Genome Atlas project (“TCGA”). Global, epigenome wide and gene-specific DNA methylation analyses were used in a Phase I Biomarker Development Trial to identify a continuous biomarker panel that combines a Global DNA Methylation Index (GDMI) and promoter DNA methylation levels of IRF4, ELMO1, CLIP4 and MSC.We observed an inverse association between the GDMI and histological progression to gastric cancer, when comparing gastritis patients without metaplasia (mean = 5.74, 95% CI, 4.97−6.50), gastritis patients with metaplasia (mean = 4.81, 95% CI, 3.77−5.84), and gastric cancer cases (mean = 3.38, 95% CI, 2.82−3.94), respectively (p < 0.0001). Promoter methylation of IRF4 (p < 0.0001), ELMO1 (p < 0.0001), CLIP4 (p < 0.0001), and MSC (p < 0.0001), is also associated with increasing severity from gastritis with no metaplasia to gastritis with metaplasia and gastric cancer.Our findings suggest that IRF4, ELMO1, CLIP4 and MSC promoter methylation coupled with a GDMI>4 are useful molecular tools for gastric cancer risk stratification in endoscopic biopsies.

Background Proximity to roadways increases the risk of asthma in developed countries; however, relatively little is known about this relationship in developing countries, where rapid and uncontrolled growth of cities has resulted in urban sprawl and heavy traffic volumes. Objective Determine the effect of distance from a heavily transited avenue on asthma symptoms and quantitative respiratory outcome measures in a peri-urban shanty town in Lima, Peru. Methods We enrolled 725 adolescents aged 13–15 years, administered a survey on asthma symptoms and measured spirometry, response to allergy skin testing and eNO. We calculated distances from the main avenue for all households and measured indoor PM in 100 households. We used multivariable regression to model the risk of asthma symptoms, risk of atopy, eNO and FEV1/FVC as a function of distance. Results Compared against 384 meters, the odds of current asthma symptoms in households living within 100 meters increased by a factor of 2 (p<0.05). The odds of atopy increased by a factor of 1.07 for every 100 meters difference in the distance from the avenue (p=0.03). We found an inverse relationship in pre-bronchodilator FEV1/FVC and distance to the avenue in females (p=0.01) but not in males. We did not find an association between eNO or household PM levels and distance. Conclusion Living in close proximity to a high traffic-density avenue in a peri-urban community in Peru was associated with a greater risk of asthma symptoms and atopy. Regulation of mobile source pollutants in peri-urban areas of developing countries may help reduce the burden of asthma symptoms and atopy.