Helicobacter pylori infection: approach of primary care physicians in a developing country

<p>Abstract</p> <p>Background</p> <p>The aim of the study was to assess the knowledge and practices of primary care physicians in diagnosis and management of <it>Helicobacter pylori (H. pylori) </it>infection in developing country.</p> <p>Methods</p> <p>This convenient sample based, cross sectional study was conducted in primary care physicians of Karachi, Pakistan from March 2008 to August 2008 through a pretested self-designed questionnaire, which contained 11 items pertaining to <it>H. pylori </it>route of transmission, diagnosis, indication for testing, treatment options, follow up and source of information.</p> <p>Results</p> <p>Out of 509 primary care physicians, 451 consented to participate with the response rate of 88.6%. Responses of 426 primary care physicians were analyzed after excluding 19 physicians. 78% of the physicians thought that contaminated water was the source of spread of infection, dyspepsia was the most frequent indication for investigating <it>H. pylori </it>infection (67% of the physicians), while 43% physicians were of the view that serology was the most appropriate test to diagnose active <it>H. pylori </it>infection. 77% of physicians thought that gastric ulcer was the most compelling indication for treatment, 61% physicians preferred Clarithromycin based triple therapy for 7–14 days. 57% of the physicians would confirm <it>H. pylori </it>eradication after treatment in selected patients and 47% physicians preferred serological testing for follow-up. In case of treatment failure, only 36% of the physicians were in favor of gastroenterologist referral.</p> <p>Conclusion</p> <p>The primary care physicians in this study lacked in knowledge regarding management of <it>H. pylori </it>infection. Internationally published guidelines and World gastroenterology organization (WGO) practice guideline on <it>H. pylori </it>for developing countries have little impact on current practices of primary care physicians. We recommend more teaching programs, continuous medical education activities regarding <it>H. pylori </it>infection.</p

Recent acquisition of Helicobacter pylori by Baka Pygmies

Both anatomically modern humans and the gastric pathogen Helicobacter pylori originated in Africa, and both species have been associated for at least 100,000 years. Seven geographically distinct H. pylori populations exist, three of which are indigenous to Africa: hpAfrica1, hpAfrica2, and hpNEAfrica. The oldest and most divergent population, hpAfrica2, evolved within San hunter-gatherers, who represent one of the deepest branches of the human population tree. Anticipating the presence of ancient H. pylori lineages within all hunter-gatherer populations, we investigated the prevalence and population structure of H. pylori within Baka Pygmies in Cameroon. Gastric biopsies were obtained by esophagogastroduodenoscopy from 77 Baka from two geographically separated populations, and from 101 non-Baka individuals from neighboring agriculturalist populations, and subsequently cultured for H. pylori. Unexpectedly, Baka Pygmies showed a significantly lower H. pylori infection rate (20.8%) than non-Baka (80.2%). We generated multilocus haplotypes for each H. pylori isolate by DNA sequencing, but were not able to identify Baka-specific lineages, and most isolates in our sample were assigned to hpNEAfrica or hpAfrica1. The population hpNEAfrica, a marker for the expansion of the Nilo-Saharan language family, was divided into East African and Central West African subpopulations. Similarly, a new hpAfrica1 subpopulation, identified mainly among Cameroonians, supports eastern and western expansions of Bantu languages. An age-structured transmission model shows that the low H. pylori prevalence among Baka Pygmies is achievable within the timeframe of a few hundred years and suggests that demographic factors such as small population size and unusually low life expectancy can lead to the eradication of H. pylori from individual human populations. The Baka were thus either H. pylori-free or lost their ancient lineages during past demographic fluctuations. Using coalescent simulations and phylogenetic inference, we show that Baka almost certainly acquired their extant H. pylori through secondary contact with their agriculturalist neighbors

Syntactic learning by mere exposure - An ERP study in adult learners

<p>Abstract</p> <p>Background</p> <p>Artificial language studies have revealed the remarkable ability of humans to extract syntactic structures from a continuous sound stream by mere exposure. However, it remains unclear whether the processes acquired in such tasks are comparable to those applied during normal language processing. The present study compares the ERPs to auditory processing of simple Italian sentences in native and non-native speakers after brief exposure to Italian sentences of a similar structure. The sentences contained a non-adjacent dependency between an auxiliary and the morphologically marked suffix of the verb. Participants were presented four alternating learning and testing phases. During learning phases only correct sentences were presented while during testing phases 50 percent of the sentences contained a grammatical violation.</p> <p>Results</p> <p>The non-native speakers successfully learned the dependency and displayed an N400-like negativity and a subsequent anteriorily distributed positivity in response to rule violations. The native Italian group showed an N400 followed by a P600 effect.</p> <p>Conclusion</p> <p>The presence of the P600 suggests that native speakers applied a grammatical rule. In contrast, non-native speakers appeared to use a lexical form-based processing strategy. Thus, the processing mechanisms acquired in the language learning task were only partly comparable to those applied by competent native speakers.</p

Reliability and Short-Term Intra-Individual Variability of Telomere Length Measurement Using Monochrome Multiplexing Quantitative PCR

Studies examining the association between telomere length and cancer risk have often relied on measurement of telomere length from a single blood draw using a real-time PCR technique. We examined the reliability of telomere length measurement using sequential samples collected over a 9-month period.Relative telomere length in peripheral blood was estimated using a single tube monochrome multiplex quantitative PCR assay in blood DNA samples from 27 non-pregnant adult women (aged 35 to 74 years) collected in 7 visits over a 9-month period. A linear mixed model was used to estimate the components of variance for telomere length measurements attributed to variation among women and variation between time points within women. Mean telomere length measurement at any single visit was not significantly different from the average of 7 visits. Plates had a significant systematic influence on telomere length measurements, although measurements between different plates were highly correlated. After controlling for plate effects, 64% of the remaining variance was estimated to be accounted for by variance due to subject. Variance explained by time of visit within a subject was minor, contributing 5% of the remaining variance.Our data demonstrate good short-term reliability of telomere length measurement using blood from a single draw. However, the existence of technical variability, particularly plate effects, reinforces the need for technical replicates and balancing of case and control samples across plates

Telomere Shortening Impairs Regeneration of the Olfactory Epithelium in Response to Injury but Not Under Homeostatic Conditions

Atrophy of the olfactory epithelium (OE) associated with impaired olfaction and dry nose represents one of the most common phenotypes of human aging. Impairment in regeneration of a functional olfactory epithelium can also occur in response to injury due to infection or nasal surgery. These complications occur more frequently in aged patients. Although age is the most unifying risk factor for atrophic changes and functional decline of the olfactory epithelium, little is known about molecular mechanisms that could influence maintenance and repair of the olfactory epithelium. Here, we analyzed the influence of telomere shortening (a basic mechanism of cellular aging) on homeostasis and regenerative reserve in response to chemical induced injury of the OE in late generation telomere knockout mice (G3 mTerc−/−) with short telomeres compared to wild type mice (mTerc+/+) with long telomeres. The study revealed no significant influence of telomere shortening on homeostatic maintenance of the OE during mouse aging. In contrast, the regenerative response to chemical induced injury of the OE was significantly impaired in G3 mTerc−/− mice compared to mTerc+/+ mice. Seven days after chemical induced damage, G3 mTerc−/− mice exhibited significantly enlarged areas of persisting atrophy compared to mTerc+/+ mice (p = 0.031). Telomere dysfunction was associated with impairments in cell proliferation in the regenerating epithelium. Deletion of the cell cycle inhibitor, Cdkn1a (p21) rescued defects in OE regeneration in telomere dysfunctional mice. Together, these data indicate that telomere shortening impairs the regenerative capacity of the OE by impairing cell cycle progression in a p21-dependent manner. These findings could be relevant for the impairment in OE function in elderly people

Genome-Wide Association Study of Relative Telomere Length

Telomere function is essential to maintaining the physical integrity of linear chromosomes and healthy human aging. The probability of forming proper telomere structures depends on the length of the telomeric DNA tract. We attempted to identify common genetic variants associated with log relative telomere length using genome-wide genotyping data on 3,554 individuals from the Nurses' Health Study and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial that took part in the National Cancer Institute Cancer Genetic Markers of Susceptibility initiative for breast and prostate cancer. After genotyping 64 independent SNPs selected for replication in additional Nurses' Health Study and Women's Genome Health Study participants, we did not identify genome-wide significant loci; however, we replicated the inverse association of log relative telomere length with the minor allele variant [C] of rs16847897 at the TERC locus (per allele β = −0.03, P = 0.003) identified by a previous genome-wide association study. We did not find evidence for an association with variants at the OBFC1 locus or other loci reported to be associated with telomere length. With this sample size we had >80% power to detect β estimates as small as ±0.10 for SNPs with minor allele frequencies of ≥0.15 at genome-wide significance. However, power is greatly reduced for β estimates smaller than ±0.10, such as those for variants at the TERC locus. In general, common genetic variants associated with telomere length homeostasis have been difficult to detect. Potential biological and technical issues are discussed

Sequence variation in telomerase reverse transcriptase (TERT) as a determinant of risk of cardiovascular disease: the Atherosclerosis Risk in Communities (ARIC) study

Abstract Background Telomerase reverse transcriptase (TERT) maintains telomere ends during DNA replication by catalyzing the addition of short telomere repeats. The expression of telomerase is normally repressed in somatic cells leading to a gradual shortening of telomeres and cellular senescence with aging. Interindividual variation in leukocyte telomere length has been previously associated with susceptibility to cardiovascular disease. The aim of the present study was to determine whether six variants in the TERT gene are associated with risk of incident coronary heart disease, incident ischemic stroke, and mortality in participants in the biracial population-based Atherosclerosis Risk in Communities (ARIC) study, including rs2736100 that was found to influence mean telomere length in a genome-wide analysis. Methods ARIC is a prospective study of the etiology and natural history of atherosclerosis in 15,792 individuals aged 45 to 64 years at baseline in 1987–1989. Haplotype tagging SNPs in TERT were genotyped using a custom array containing nearly 49,000 SNPs in 2,100 genes associated with cardiovascular and metabolic phenotypes. Cox proportional hazards models were used to assess the association between the TERT polymorphisms and incident cardiovascular disease and mortality over a 20-year follow-up period in 8,907 whites and 3,022 African-Americans with no history of disease at the baseline examination, while individuals with prevalent cardiovascular disease were not excluded from the analyses of mortality. Results After adjustment for age and gender, and assuming an additive genetic model, rs2736122 and rs2853668 were nominally associated with incident coronary heart disease (hazards rate ratio = 1.20, p = 0.02, 95 % confidence interval = 1.03– 1.40) and stroke (hazards rate ratio = 1.17, p = 0.05, 95 % confidence interval = 1.00 - 1.38), respectively, in African-Americans. None of the variants was significantly associated with cardiovascular disease in white study participants or with mortality in either racial group. Conclusions Replication in additional population-based samples combined with genotyping of polymorphisms in other genes involved in maintenance of telomere length may help to determine whether genetic variants associated with telomere homeostasis influence the risk of cardiovascular disease in middle-aged adults