Vacuolating cytotoxin (vacA) alleles of Helicobacter pylori comprise two geographically widespread types, m1 and m2, and have evolved through limited recombination

Vacuolating cytotoxin (vacA) alleles of Helicobacter pylori vary, particularly in their mid region (which may be type m1 or m2) and their signal peptide coding region (type s1 or s2). We investigated nucleotide diversity among vacA alleles in strains from several locales in Asia, South America, and the USA. Phylogenetic analysis of vacA mid region sequences from 18 strains validated the division into two main groups (m1 and m2) and showed further significant divisions within these groups. Informative site analysis demonstrated one example of recombination between m1 and m2 alleles, and several examples of recombination among alleles within these groups. Recombination was not sufficiently extensive to destroy phylogenetic structure entirely. Synonymous nucleotide substitution rates were markedly different between regions of vacA, suggesting different evolutionary divergence times and implying horizontal transfer of genetic elements within vacA. Non-synonymous/synonymous rate ratios were greater between m1 and m2 sequences than among m1 sequences, consistent with m1 and m2 alleles encoding functions fitting strains for slightly different ecological niches

Autoantibodies against retinal proteins in paraneoplastic and autoimmune retinopathy

BACKGROUND: Autoimmune retinal degeneration may occur in patients who present with sudden or, less commonly, subacute loss of vision of retinal origin, associated with an abnormal ERG, through the action of autoantibodies against retinal proteins. Often the patients are initially diagnosed with or suspected of having a paraneoplastic retinopathy (PR), such as cancer-associated retinopathy (CAR). However, there is limited information on the occurrence, the specificity of autoantibodies in these patients, and their association with clinical symptoms. METHODS: Sera were obtained from 193 retinopathy patients who presented with clinical symptoms resembling PR or autoimmune retinopathy (AR), including sudden painless loss of vision, typically associated with visual field defects and photopsias, and abnormal rod and/or cone responses on the electroretinogram (ERG). Sera were tested for the presence of anti-retinal autoantibodies by Western blot analysis using proteins extracted from human retina and by immunohistochemistry. Autoantibody titers against recoverin and enolase were measured by ELISA. RESULTS: We identified a higher prevalence of anti-retinal autoantibodies in retinopathy patients. Ninety-one patients' sera (47.1%) showed autoantibodies of various specificities with a higher incidence of antibodies present in retinopathy patients diagnosed with cancer (33/52; 63.5%; p = 0.009) than in retinopathy patients without cancer (58/141; 41.1%). The average age of PR patients was 62.0 years, and that of AR patients was 55.9 years. Autoantibodies against recoverin (p23) were only present in the sera of PR patients, autoantibodies against unknown p35 were more common in patients with AR, while anti-enolase (anti-p46) autoantibodies were nearly equally distributed in the sera of patients with PR and those with AR. In the seropositive patients, the autoantibodies persisted over a long period of time – from months to years. A rebound in anti-recoverin autoantibody titer was found to be associated with exacerbations in visual symptoms but not in the recurrence of cancer. When compared to sera from healthy subjects, autoantibodies against retinal proteins from both groups of patients were cytotoxic to retinal cells, indicating their pathogenic potential. CONCLUSIONS: These studies showed that patients with sudden or subacute, unexplained loss of vision of retinal origin have anti-retinal antibodies in a broad range of specificity and indicate the need for autoantibody screening. Follow-up tests of antibody levels may be useful as a biomarker of disease activity associated with worsening of vision. Moreover, the heterogeneity in autoantibody specificity may explain the variation and complexity of clinical symptoms in retinopathy patients

How to democratize Internet of Things devices. A participatory design research

The global introduction of affordable Internet of Things (IoT) devices offers an opportunity to empower a large variety of users with different needs. However, many off-the-shelf digital products are still not widely adopted by people who are hesitant technology users or by older adults, notwithstanding that the design and user-interaction of these devices is recognized to be user-friendly. In view of the potential of IoT-based devices, how can we reduce the obstacles of a cohort with low digital literacy and technology anxiety and enable them to be equal participants in the digitalized world? This article shows the method and results achieved in a community-stakeholder workshop, developed through the participatory design methodology, aiming at brainstorming problems and scenarios through a focus group and a structured survey. The research activity focused on understanding factors to increase the usability of off-the-shelf IoT devices for hesitant users and identify strategies for improving digital literacy and reducing technology anxiety. A notable result was a series of feedback items pointing to the importance of creating learning resources to support individuals with different abilities, age, gender expression, to better adopt off-the-shelf IoT-based solutions.Comment: 8 pages, 5 figure

Mammography: EUSOBI recommendations for women’s information

This paper summarises the basic information to be offered to women who undergo mammography. After a delineation of the general aim of early diagnosis of breast cancer, the main difference between screening mammography and diagnostic mammography is explained. The best time for scheduling mammography in fertile women is defined. The need to bring images and reports from the previous mammogram (and from other recent breast imaging examinations) is highlighted. The technique and procedure of mammography are briefly described with particular attention to discomfort and pain experienced by a fraction of women who undergo the test. Information is given on the recall during a screening program and on the request for further work-up after a diagnostic mammography. The logic of the diagnostic mammography report and of classification systems such as BI-RADS and R1-R5 is illustrated, and brief but clear information is given about the diagnostic performance of the test, with particular reference to interval cancers. Moreover, the breast cancer risk due to radiation exposure from mammography is compared to the reduction in mortality obtained with the test, and the concept of overdiagnosis is presented. Finally, five frequently asked questions are answered

Success factors of global goal-setting for sustainable development:Learning from the millennium development goals

The Millennium Development Goals (MDGs) were an important precursor to the Sustainable Development Goals (SDGs). Hence, identifying the conditions that made the MDGs successful enhances our understanding of global goal-setting and informs the global endeavour to achieve the SDGs. Drawing on a comprehensive review of 316 articles published between 2009 and 2018, we identify six factors that have enabled or hindered MDG implementation. Our analysis stresses the importance of path dependencies and shows that the MDGs catalysed changes only for those countries with sufficient resource availability, administrative capacity and economic development, as well as adequate support from external donors. National ownership and NGO pressure bolstered efforts to implement the MDGs. These findings suggest that globally agreed goals do not easily trickle down from the global to the national level. Thus, this article adopts a forward-looking perspective and draws key lessons for the current implementation of the SDGs in developing countries

Helicobacter pylori (H pylori) infection in Greece: the changing prevalence during a ten-year period and its antigenic profile

BACKGROUND: To evaluate changes in H pylori infection prevalence in Greece during a ten-year period, and to examine its antigenic profile. METHODS: Three groups of patients were studied. Group O-87: Banked serum samples of 200 consecutive adult outpatients, from the Hepato-Gastroenterology clinic of a teaching hospital at Athens, collected in 1987. Group O-97: Serum samples of 201 similarly selected outpatients from the same Unit, collected in 1997. Group BD-97: Serum samples of 120 consecutive blood donors from the same hospital, collected in 1997. H pylori IgG antibody seroprevalence was studied by a quantitative ELISA. Antigenic profile was studied by western-blot IgG assay, in 62 IgG positive patients of O-97 and BD-97. Results were analyzed by conventional statistics and multivariate regression analysis. RESULTS: The H pylori seroprevalence increased with age in the three tested groups. In O-97, seroprevalence did not differ from that, in BD-97. On the contrary, there was a significant decrease in seropositivity between O-87 and O-97 (59.5% vs 49.2%, p = 0.039). Multiple regression analysis showed that age over 35 years (OR:3.45, 95% CI:1.59–7.49, p = 0.002) and year of patients' selection – that is 1987 or 1997 – (OR:1.73, 95% CI:1.14–2.65 for 1987, p = 0.010), were independent risk factors of H pylori infection. The seroprevalence of CagA+ and VacA+ strains was 77.4% and 58.5%, respectively, and type I(CagA+/VacA+) strains were significantly more common than type II(CagA-/VacA-) strains (59.7% vs 22.6%, p < 0.001). CONCLUSIONS: During a ten-year period, we found a significant decrease of H pylori infection in Greece and our data support the birth cohort phenomenon as an explanation for the age-dependent increase of H pylori infection. The prevalence of CagA and/or VacA positive strains is relatively high, in a country with low incidence of gastric cancer

Quantum Dots for Tracking Dendritic Cells and Priming an Immune Response In Vitro and In Vivo

Dendritic cells (DCs) play a key role in initiating adaptive immune response by presenting antigen to T cells in lymphoid organs. Here, we investigate the potential of quantum dots (QDs) as fluorescent nanoparticles for in vitro and in vivo imaging of DCs, and as a particle-based antigen-delivery system to enhance DC-mediated immune responses. We used confocal, two-photon, and electron microscopies to visualize QD uptake into DCs and compared CD69 expression, T cell proliferation, and IFN-γ production by DO11.10 and OT-II T cells in vivo in response to free antigen or antigen-conjugated to QDs. CD11c+ DCs avidly and preferentially endocytosed QDs, initially into small vesicles near the plasma membrane by an actin-dependent mechanism. Within 10 min DCs contained vesicles of varying size, motion, and brightness distributed throughout the cytoplasm. At later times, endocytosed QDs were compartmentalized inside lysosomes. LPS-induced maturation of DCs reduced the rate of endocytosis and the proportion of cells taking up QDs. Following subcutaneous injection of QDs in an adjuvant depot, DCs that had endocytosed QDs were visualized up to 400 µm deep within draining lymph nodes. When antigen-conjugated QDs were used, T cells formed stable clusters in contact with DCs. Antigen-conjugated QDs induced CD69 expression, T cell proliferation, and IFN-γ production in vivo with greater efficiency than equivalent amounts of free antigen. These results establish QDs as a versatile platform for immunoimaging of dendritic cells and as an efficient nanoparticle-based antigen delivery system for priming an immune response

Genome sequence analysis of Helicobacter pylori strains associated with gastric ulceration and gastric cancer

<p>Abstract</p> <p>Background</p> <p>Persistent colonization of the human stomach by <it>Helicobacter pylori </it>is associated with asymptomatic gastric inflammation (gastritis) and an increased risk of duodenal ulceration, gastric ulceration, and non-cardia gastric cancer. In previous studies, the genome sequences of <it>H. pylori </it>strains from patients with gastritis or duodenal ulcer disease have been analyzed. In this study, we analyzed the genome sequences of an <it>H. pylori </it>strain (98-10) isolated from a patient with gastric cancer and an <it>H. pylori </it>strain (B128) isolated from a patient with gastric ulcer disease.</p> <p>Results</p> <p>Based on multilocus sequence typing, strain 98-10 was most closely related to <it>H. pylori </it>strains of East Asian origin and strain B128 was most closely related to strains of European origin. Strain 98-10 contained multiple features characteristic of East Asian strains, including a type s1c <it>vacA </it>allele and a <it>cagA </it>allele encoding an EPIYA-D tyrosine phosphorylation motif. A core genome of 1237 genes was present in all five strains for which genome sequences were available. Among the 1237 core genes, a subset of alleles was highly divergent in the East Asian strain 98-10, encoding proteins that exhibited <90% amino acid sequence identity compared to corresponding proteins in the other four strains. Unique strain-specific genes were identified in each of the newly sequenced strains, and a set of strain-specific genes was shared among <it>H. pylori </it>strains associated with gastric cancer or premalignant gastric lesions.</p> <p>Conclusion</p> <p>These data provide insight into the diversity that exists among <it>H. pylori </it>strains from diverse clinical and geographic origins. Highly divergent alleles and strain-specific genes identified in this study may represent useful biomarkers for analyzing geographic partitioning of <it>H. pylori </it>and for identifying strains capable of inducing malignant or premalignant gastric lesions.</p

Use of cancer-specific yeast-secreted in vivo biotinylated recombinant antibodies for serum biomarker discovery

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