Special Issue “H. pylori Virulence Factors in the Induction of Gastric Cancer”

Twenty-five years ago, Helicobacter pylori was identified as the causative agent of gastric disorders,ranging from acute inflammation [...

Visions, values, and videos: Revisiting envisionings in service of UbiComp design for the home

UbiComp has been envisioned to bring about a future dominated by calm computing technologies making our everyday lives ever more convenient. Yet the same vision has also attracted criticism for encouraging a solitary and passive lifestyle. The aim of this paper is to explore and elaborate these tensions further by examining the human values surrounding future domestic UbiComp solutions. Drawing on envisioning and contravisioning, we probe members of the public (N=28) through the presentation and focus group discussion of two contrasting animated video scenarios, where one is inspired by 'calm' and the other by 'engaging' visions of future UbiComp technology. By analysing the reasoning of our participants, we identify and elaborate a number of relevant values involved in balancing the two perspectives. In conclusion, we articulate practically applicable takeaways in the form of a set of key design questions and challenges

Epidemiology of Helicobacter pylori and CagA-Positive Infections and Global Variations in Gastric Cancer

Gastric cancer is a major health burden and is the fifth most common malignancy and the third most common cause of death from cancer worldwide. Development of gastric cancer involves several aspects, including host genetics, environmental factors, and Helicobacter pylori infection. There is increasing evidence from epidemiological studies of the association of H. pylori infection and specific virulence factors with gastric cancer. Studies in animal models indicate H. pylori is a primary factor in the development of gastric cancer. One major virulence factor in H. pylori is the cytotoxin-associated gene A (cagA), which encodes the CagA protein in the cag pathogenicity island (cag PAI). Meta-analysis of studies investigating CagA seropositivity irrespective of H. pylori status identified that CagA seropositivity increases the risk of gastric cancer (OR = 2.87, 95% CI: 1.95–4.22) relative to the risk of H. pylori infection alone (OR = 2.31, 95% CI: 1.58–3.39). Eradicating H. pylori is a strategy for reducing gastric cancer incidence. A meta-analysis of six randomised controlled trials (RCTs) suggests that searching for and eradicating H. pylori infection reduces the subsequent incidence of gastric cancer with a pooled relative risk of 0.66 (95% CI: 0.46–0.95). The introduction in regions of high gastric cancer incidence of population-based H. pylori screening and treatment programmes, with a scientifically valid assessment of programme processes, feasibility, effectiveness and possible adverse consequences, would impact the incidence of H. pylori-induced gastric cancer. Given the recent molecular understanding of the oncogenic role of CagA, targeting H. pylori screening and treatment programmes in populations with a high prevalence of H. pylori CagA-positive strains, particularly the more oncogenic East Asian H. pylori CagA strains, may be worth further investigation to optimise the benefits of such strategies

Helicobacter pylori CagA Triggers Expression of the Bactericidal Lectin REG3γ via Gastric STAT3 Activation

Background: Most of what is known about the Helicobacter pylori (H. pylori) cytotoxin, CagA, pertains to a much-vaunted role as a determinant of gastric inflammation and cancer. Little attention has been devoted to potential roles of CagA in the majority of H. pylori infected individuals not showing oncogenic progression, particularly in relation to host tolerance. Regenerating islet-derived (REG)3c encodes a secreted C-type lectin that exerts direct bactericidal activity against Grampositive bacteria in the intestine. Here, we extend this paradigm of lectin-mediated innate immunity, showing that REG3c expression is triggered by CagA in the H. pylori-infected stomach. Methodology/Principal Findings: In human gastric mucosal tissues, REG3c expression was significantly increased in CagApositive, compared to CagA-negative H. pylori infected individuals. Using transfected CagA-inducible gastric MKN28 cells, we recapitulated REG3c induction in vitro, also showing that tyrosine phosphorylated, not unphosphorylated CagA triggers REG3c transcription. In concert with induced REG3c, pro-inflammatory signalling downstream of the gp130 cytokine coreceptor via the signal transducer and activator of transcription (STAT)3 and transcription of two cognate ligands, interleukin(IL)-11 and IL-6, were significantly increased. Exogenous IL-11, but not IL-6, directly stimulated STAT3 activation and REG3c transcription. STAT3 siRNA knockdown or IL-11 receptor blockade respectively abrogated or subdued CagAdependent REG3c mRNA induction, thus demonstrating a requirement for uncompromised signalling via the IL-11/STAT

Lessons learned in developing family medicine residency training programs in Japan

BACKGROUND: While family medicine is not well established as a discipline in Japan, a growing number of Japanese medical schools and training hospitals have recently started sougoushinryoubu (general medicine departments). Some of these departments are incorporating a family medicine approach to residency training. We sought to learn from family medicine pioneers of these programs lessons for developing residency training. METHODS: This qualitative project utilized a long interview research design. Questions focused on four topics: 1) circumstances when becoming chair/faculty member; 2) approach to starting the program; 3) how Western ideas of family medicine were incorporated; and 4) future directions. We analyzed the data using immersion/crystallization to identify recurring themes. From the transcribed data, we selected representative quotations to illustrate them. We verified the findings by emailing the participants and obtaining feedback. RESULTS: Participants included: five chairpersons, two program directors, and three faculty members. We identified five lessons: 1) few people understand the basic concepts of family medicine; 2) developing a core curriculum is difficult; 3) start with undergraduates; 4) emphasize clinical skills; and 5) train in the community. CONCLUSION: While organizational change is difficult, the identified lessons suggest issues that merit consideration when developing a family medicine training program. Lessons from complexity science could inform application of these insights in other countries and settings newly developing residency training

Designing an information system for updating land records in Bangladesh: action design ethnographic research (ADER)

Open Access. This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.This article has been made available through the Brunel Open Access Publishing Fund.Information Systems (IS) has developed through adapting, generating and applying diverse methodologies, methods, and techniques from reference disciplines. Further, Action Design Research (ADR) has recently developed as a broad research method that focuses on designing and redesigning IT and IS in organizational contexts. This paper reflects on applying ADR in a complex organizational context in a developing country. It shows that ADR requires additional lens for designing IS in such a complex organizational context. Through conducting ADR, it is seen that an ethnographic framework has potential complementarities for understanding complex contexts thereby enhancing the ADR processes. This paper argues that conducting ADR with an ethnographic approach enhances design of IS and organizational contexts. Finally, this paper aims presents a broader methodological framework, Action Design Ethnographic Research (ADER), for designing artefacts as well as IS. This is illustrated through the case of a land records updating service in Bangladesh

Beyond “yesterday’s tomorrow”: future-focused mobile interaction design by and for emergent users

Mobile and ubiquitous computing researchers have long envisioned future worlds for users in developed regions. Steered by such visions, they have innovated devices and services exploring the value of alternative propositions with and for individuals, groups and communities. Meanwhile, such radical and long-term explorations are uncommon for what have been termed emergent users; users, that is, for whom advanced technologies are just within grasp. Rather, a driving assumption is that today’s high-end mobile technologies will “trickle down” to these user groups in due course. In this paper, we open the debate about what mobile technologies might be like if emergent users were directly involved in creating their visions for the future 5–10 years from now. To do this, we report on a set of envisioning workshops in India, South Africa and Kenya that provide a roadmap for valued, effective devices and services for these regions in the next decade. © 2016, The Author(s)

Caveolin-1 protects B6129 mice against Helicobacter pylori gastritis.

Caveolin-1 (Cav1) is a scaffold protein and pathogen receptor in the mucosa of the gastrointestinal tract. Chronic infection of gastric epithelial cells by Helicobacter pylori (H. pylori) is a major risk factor for human gastric cancer (GC) where Cav1 is frequently down-regulated. However, the function of Cav1 in H. pylori infection and pathogenesis of GC remained unknown. We show here that Cav1-deficient mice, infected for 11 months with the CagA-delivery deficient H. pylori strain SS1, developed more severe gastritis and tissue damage, including loss of parietal cells and foveolar hyperplasia, and displayed lower colonisation of the gastric mucosa than wild-type B6129 littermates. Cav1-null mice showed enhanced infiltration of macrophages and B-cells and secretion of chemokines (RANTES) but had reduced levels of CD25+ regulatory T-cells. Cav1-deficient human GC cells (AGS), infected with the CagA-delivery proficient H. pylori strain G27, were more sensitive to CagA-related cytoskeletal stress morphologies ("humming bird") compared to AGS cells stably transfected with Cav1 (AGS/Cav1). Infection of AGS/Cav1 cells triggered the recruitment of p120 RhoGTPase-activating protein/deleted in liver cancer-1 (p120RhoGAP/DLC1) to Cav1 and counteracted CagA-induced cytoskeletal rearrangements. In human GC cell lines (MKN45, N87) and mouse stomach tissue, H. pylori down-regulated endogenous expression of Cav1 independently of CagA. Mechanistically, H. pylori activated sterol-responsive element-binding protein-1 (SREBP1) to repress transcription of the human Cav1 gene from sterol-responsive elements (SREs) in the proximal Cav1 promoter. These data suggested a protective role of Cav1 against H. pylori-induced inflammation and tissue damage. We propose that H. pylori exploits down-regulation of Cav1 to subvert the host's immune response and to promote signalling of its virulence factors in host cells

New resources for functional analysis of omics data for the genus Aspergillus

<p>Abstract</p> <p>Background</p> <p>Detailed and comprehensive genome annotation can be considered a prerequisite for effective analysis and interpretation of omics data. As such, Gene Ontology (GO) annotation has become a well accepted framework for functional annotation. The genus <it>Aspergillus </it>comprises fungal species that are important model organisms, plant and human pathogens as well as industrial workhorses. However, GO annotation based on both computational predictions and extended manual curation has so far only been available for one of its species, namely <it>A. nidulans</it>.</p> <p>Results</p> <p>Based on protein homology, we mapped 97% of the 3,498 GO annotated <it>A. nidulans </it>genes to at least one of seven other <it>Aspergillus </it>species: <it>A. niger</it>, <it>A. fumigatus</it>, <it>A. flavus</it>, <it>A. clavatus</it>, <it>A. terreus</it>, <it>A. oryzae </it>and <it>Neosartorya fischeri</it>. GO annotation files compatible with diverse publicly available tools have been generated and deposited online. To further improve their accessibility, we developed a web application for GO enrichment analysis named FetGOat and integrated GO annotations for all <it>Aspergillus </it>species with public genome sequences. Both the annotation files and the web application FetGOat are accessible via the Broad Institute's website (<url>http://www.broadinstitute.org/fetgoat/index.html</url>). To demonstrate the value of those new resources for functional analysis of omics data for the genus <it>Aspergillus</it>, we performed two case studies analyzing microarray data recently published for <it>A. nidulans</it>, <it>A. niger </it>and <it>A. oryzae</it>.</p> <p>Conclusions</p> <p>We mapped <it>A. nidulans </it>GO annotation to seven other <it>Aspergilli</it>. By depositing the newly mapped GO annotation online as well as integrating it into the web tool FetGOat, we provide new, valuable and easily accessible resources for omics data analysis and interpretation for the genus <it>Aspergillus</it>. Furthermore, we have given a general example of how a well annotated genome can help improving GO annotation of related species to subsequently facilitate the interpretation of omics data.</p

Predicting Bison Migration out of Yellowstone National Park Using Bayesian Models

Long distance migrations by ungulate species often surpass the boundaries of preservation areas where conflicts with various publics lead to management actions that can threaten populations. We chose the partially migratory bison (Bison bison) population in Yellowstone National Park as an example of integrating science into management policies to better conserve migratory ungulates. Approximately 60% of these bison have been exposed to bovine brucellosis and thousands of migrants exiting the park boundary have been culled during the past two decades to reduce the risk of disease transmission to cattle. Data were assimilated using models representing competing hypotheses of bison migration during 1990–2009 in a hierarchal Bayesian framework. Migration differed at the scale of herds, but a single unifying logistic model was useful for predicting migrations by both herds. Migration beyond the northern park boundary was affected by herd size, accumulated snow water equivalent, and aboveground dried biomass. Migration beyond the western park boundary was less influenced by these predictors and process model performance suggested an important control on recent migrations was excluded. Simulations of migrations over the next decade suggest that allowing increased numbers of bison beyond park boundaries during severe climate conditions may be the only means of avoiding episodic, large-scale reductions to the Yellowstone bison population in the foreseeable future. This research is an example of how long distance migration dynamics can be incorporated into improved management policies