Early detection of gastric cancer using global, genome-wide and IRF4, ELMO1, CLIP4 and MSC DNA methylation in endoscopic biopsies

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 \u3c 0.0001). Promoter methylation of IRF4 (p \u3c 0.0001), ELMO1 (p \u3c 0.0001), CLIP4 (p \u3c 0.0001), and MSC (p \u3c 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\u3e4 are useful molecular tools for gastric cancer risk stratification in endoscopic biopsies

The Relationship and Comparison of Reaction Time Resulting from Visual, Tactile, and Auditory Stimuli, Systolic Pressure, Diastolic Pressure, and Pulse Rate Among Members of a Track Squad and Members of Physical Education Classes

Considerable research has been conducted on reaction time, blood pressure, and pulse rate in an attempt to determine their relationship to athletic performance. Slightly above average blood pressure and low pulse rate within normal limits are considered by present-day coaches to be desirable characteristics of an athlete. In sports and games in which movements of a participant are conditioned by signals, by movements of opponents, or by motion of the ball, reaction time is also of great importance. Studies which closely represent the findings of many other investigators concerning pulse rate are those by Cotton and White. Each observed unusually low pulse rates among the athletes studied. Two of these athletes, Glen Cunningham and Paavo Nurmi, both record-holding distance runners, had pulse rates of 38 and 42, respectively. The third factor involved in the present study was blood pressure. Cureton stated that young athletic subjects, those in training, average somewhat higher sitting systolic blood pressure than those not in training. Savage found relatively high diastolic pressures among 55 marathon runners measured just before their Pittsburgh marathon race of 1909. This study was designed to compare and to relate the reaction times, blood pressures, and pulse rates of freshman and varsity track teams and freshmen male students. Since pulse rate, blood pressure, and reaction time measures are considered valuable aids in predicting athletic performance, a desire to determine the relationship between each of these variables was created. This research is essentially basic in nature. It is hoped that the information obtained may eventually be added to present knowledge and may be applied to coaching and training problems. It is hoped that the results of this study may help determine the relationship of reaction time resulting from visual, auditory, and tactile stimuli to systolic pressure, diastolic pressure, and pulse rate before and after exercise. Results may help indicate some of the effects of exercise upon reaction time and pulse rate. The purpose of this study was to determine the relationship of reaction time resulting from visual, auditory and tactile stimuli, systolic pressure, diastolic pressure, and pulse rate of freshmen male students and members of the college track team before and after prescribed exercise. The purpose also was to compare freshman and varsity track teams and freshmen male students before and after exercise on the following test items: reaction times resulting from visual, auditory, and tactile stimuli; systolic pressure, diastolic pressure, and pulse rate

Identification of new Helicobacter pylori subpopulations in Native Americans and mestizos from Peru

Region-specifi

School Vouchers: Settled Questions, Continuing Disputes

Provides an assessment of the constitutional principles announced by the Court, following the June 2002 decision in the Cleveland school voucher case. Presents contrasting arguments on educational policy that address key issues about the decision

Diverse phenotypes resulting from polyphosphate kinase gene (ppk1) inactivation in different strains of Helicobacter pylori

Connections among biochemical pathways should help buffer organisms against environmental stress and affect the pace and trajectory of genome evolution. To explore these ideas, we studied consequences of inactivating the gene for polyphosphate kinase 1 (ppk1) in strains of Helicobacter pylori, a genetically diverse gastric pathogen. The PPK1 enzyme catalyzes synthesis of inorganic polyphosphate (poly P), a reservoir of high-energy phosphate bonds with multiple roles. Prior analyses in less-fastidious microbes had implicated poly P in stress resistance, motility, and virulence. In our studies, ppk1 inactivation caused the expected near-complete absence of poly P (>250-fold decrease) but had phenotypic effects that differed markedly among unrelated strains: (i) poor initial growth on standard brain heart infusion agar (five of six strains tested); (ii) weakened colonization of mice (4 of 5 strains); (iii) reduced growth on Ham's F-12 agar, a nutritionally limiting medium (8 of 11 strains); (iv) heightened susceptibility to metronidazole (6 of 17 strains); and (v) decreased motility in soft agar (1 of 13 strains). Complementation tests confirmed that the lack of growth of one Δppk1 strain on F-12 agar and the inability to colonize mice of another were each due to ppk1 inactivation. Thus, the importance of ppk1 to H. pylori differed among strains and the phenotypes monitored. We suggest that quantitative interactions, as seen here, are common among genes that affect metabolic pathways and that H. pylori's high genetic diversity makes it well suited for studies of such interactions, their underlying mechanisms, and their evolutionary consequences

Sequence divergence and conservation in genomes of Helicobacter cetorum strains from a dolphin and a whale

Peer reviewe

Characterization of wetting using topological principles

Hypothesis Understanding wetting behavior is of great importance for natural systems and technological applications. The traditional concept of contact angle, a purely geometrical measure related to curvature, is often used for characterizing the wetting state of a system. It can be determined from Young's equation by applying equilibrium thermodynamics. However, whether contact angle is a representative measure of wetting for systems with significant complexity is unclear. Herein, we hypothesize that topological principles based on the Gauss-Bonnet theorem could yield a robust measure to characterize wetting. Theory and Experiments We introduce a macroscopic contact angle based on the deficit curvature of the fluid interfaces that are imposed by contacts with other immiscible phases. We perform sessile droplet simulations followed by multiphase experiments for porous sintered glass and Bentheimer sandstone to assess the sensitivity and robustness of the topological approach and compare the results to other traditional approaches. Findings We show that the presented topological principle is consistent with thermodynamics under the simplest conditions through a variational analysis. Furthermore, we elucidate that at sufficiently high image resolution the proposed topological approach and local contact angle measurements are comparable. While at lower resolutions, the proposed approach provides more accurate results being robust to resolution-based effects. Overall, the presented concepts open new pathways to characterize the wetting state of complex systems and theoretical developments to study multiphase systems.Comment: 11 pages, 9 figures, 1 tabl

Evaluation of Online Consumer Health Information for Idiopathic Scoliosis Identified by a Google Search

Introduction. This study sought to assess the quality of online consumerhealth information about idiopathic scoliosis. Previous studiesshowed that quality of online health information varies and oftenlacks adherence to expert recommendations and guidelines. Nevertheless,72% of internet users seek health information online. A 2005analysis of online scoliosis information found that the informationwas limited and of poor quality. Methods. Two reviewers vetted the top 10 websites resulting from aGoogleTM search for “scoliosis.” Content was organized into categoriesand rated by three physician evaluators using a 1 - 5 scale basedon quality, accuracy, completeness of information, readability, andwillingness to recommend. Additional information, such as numberof ads and Flesch-Kinkaid reading level, also was collected. Results. The average overall physician score was 47.6 (75 possible).All websites included content that was mostly accurate but varied incompleteness. Physicians unanimously recommended Mayo Clinic,MedicineNet, and Kids Health; none recommended the GoogleTMKnowledge Graph. The Scoliosis Research Society website reachedthe highest overall physician score. Readability ranged from 7th gradeto college level; only that of Kids Health was below 10th grade level. Conclusions. Most essential information provided by the websiteswas accurate and generally well rated by physicians. Website rankingby physicians was inconsistent with the ranking order by GoogleTM,indicating that health seekers reviewing the top GoogleTM-rankedwebsites may not be viewing the websites rated highest by physicians.Physicians should consider patient literacy in website recommendations,as many have an above average literacy level.Kans J Med 2018;11(4):95-101

PCR-based genotyping of Helicobacter pylori of Gambian children and adults directly from biopsy specimens and bacterial cultures

<p>Abstract</p> <p>Background</p> <p><it>Helicobacter pylori </it>is an important agent of gastroduodenal disease in Africa and throughout the world. We sought to determine an optimum method for genotyping <it>H. pylori </it>strains from children and adults in The Gambia, West Africa.</p> <p>Results</p> <p>Virulence genes were amplified in 127 of 190 cases tested (121 adults and 6 children); each of 60 bacterial cultures, and 116 from DNA extracted directly from biopsies. The proportion of biopsies that were <it>cagA</it>+, the ratio of <it>vacAs1</it>/<it>s2</it>, and <it>vacAm1</it>/<it>m2</it>, and the proportion of mixed strain populations in individual subjects changed with age. Strains lacking virulence <it>cagA </it>and <it>vacA </it>genes and with apparently homogeneous (one predominant strain) infections were more common among infants than adults.</p> <p>Conclusions</p> <p>In order to detect the range of bacterial genotypes harbored by individual patients, direct PCR proved slightly superior to isolation of <it>H. pylori </it>by biopsy culture, but the techniques were complementary, and the combination of both culture and direct PCR produced the most complete picture. The seemingly higher virulence of strains from adult than infant infections in The Gambia merits further analysis.</p