Helicobacter pylori virulence factors in duodenal ulceration: A primary cause or a secondary infection causing chronicity

Reports from countries with a high prevalence of Helicobacter pylori. (H pylori) infection do not show a proportionately high prevalence of duodenal ulceration, suggesting the possibility that H pylori cannot be a primary cause of duodenal ulceration. It has been mooted that this discrepancy might be explained by variations in the prevalence of virulence factors in different populations. The aim of this paper is to determine whether the published literature gives support to this possibility. The relevant literature was reviewed and analyzed separately for countries with a high and low prevalence of H pylori infection and virulence factors. Although virulent strains of H pylori were significantly more often present in patients with duodenal ulcer than without the disease in countries with a low prevalence of H pylori infection in the population, there was no difference in the prevalence of virulence factors between duodenal ulcer, non - ulcer dyspepsia or normal subjects in many countries, where the prevalence of both H pylori infection and of virulence factors was high. In these countries, the presence of virulence factors was not predictive the clinical outcome. To explain the association between virulence factors and duodenal ulcer in countries where H pylori prevalence is low, only two papers were found that give little support to the usual model proposed, namely that organisms with the virulence factors are more likely than those without them to initiate a duodenal ulcer. We offer an alternative hypothesis that suggests virulence factors are more likely to interfere with the healing of a previously produced ulcer. The presence of virulence factors only correlates with the prevalence of duodenal ulcer in countries where the prevalence of H pylori is low. There is very little evidence that virulence factors initiate duodenal ulceration, but they may be related to failure of the ulcer to heal

Precise role of H pylori in duodenal ulceration

The facts that H pylori infection is commoner in duodenal ulcer (DU) patients than in the normal population, and that eradication results in most cases being cured, have led to the belief that it causes DU. However, early cases of DU are less likely than established ones to be infected. H pylori-negative cases are usually ascribed to specific associated factors such as non-steroidal anti-inflammatory drugs (NSAIDs), Crohn’s disease, and hypergastrinaemia, but even after excluding these, several H pylori-negative cases remain and are particularly common in areas of low prevalence of H pylori infection. Moreover, this incidence of H pylori negative DU is not associated with a fall in overall DU prevalence when compared with countries with a higher H pylori prevalence. In countries with a high H pylori prevalence there are regional differences in DU prevalence, but no evidence of an overall higher prevalence of DU than in countries with a low H pylori prevalence. There is no evidence that virulence factors are predictive of clinical outcome. After healing following eradication of H pylori infection DU can still recur. Medical or surgical measures to reduce acid output can lead to long-term healing despite persistence of H pylori infection. Up to half of cases of acute DU perforation are H pylori negative. These findings lead to the conclusion that H pylori infection does not itself cause DU, but leads to resistance to healing, i.e., chronicity. This conclusion is shown not to be incompatible with the universally high prevalence of DU compared with controls

(Im)mobilising Youth Citizenship / Youth Citizenship (im)mobilities

Mobility is a vital component to many conceptual, empirical and philosophical debates surrounding age, ageing and the life-course. In this paper we focus on how the relationship between mobility and citizenship shapes young people’s life-courses and life-chances, and, in turn, how this influences how young people engage with, produce, manage and promote everyday spaces. More than ever before, contemporary youth experience a myriad of expectations (both chances and needs) for mobility, all of which have allied opportunities and challenges that feed into their everyday and future lives. Specifically, mobility has clear implications for notions of citizenship and ‘being mobile’ is closely aligned to contrasting perceptions of ‘being footloose’ and ‘living precariously’ in terms of young people’s education, employment, housing and leisure biographies. We therefore seek to critically engage with the nexus of mobility, citizenship and youth/life-course studies so as to develop a conceptual framework that better understands how young people might imagine and realise the benefits of mobility whilst avoiding the pitfalls of precarity. This includes thinking critically about how youth citizens are im/mobilised in terms of shaping citizenship practice; if, and how, citizenship practices produce or obstruct young people’s spatial and social mobilities; the multi-locational citizenship/s that exist across the life-course, such as learning citizenship through mobility (university, gap years, internships, graduate schemes etc.); and the geopolitical implications for im/mobility upon youth citizenship and wider life-course discourses (Brexit, Trump, nationalism etc.)

Bordered YouthAnalysing Citizenship and Identities in Post-Brexit Northern Ireland

“Young people living in the North of Ireland are put into boxes which perhaps do not adequately represent their views and opinions – the Bordered Youth Project seeks to change that”. This project analyses how young people negotiate the complex and overlapping identities and citizenships produced by living in border regions. We are working with young people aged 18 to 24 living in Northern Ireland, using creative participatory methods to assess how their interpretations, imaginations and encounters with bordered spaces shape, or are shaped by, their everyday movements and cultural interactions. The question of citizenship in a Northern Irish context is of critical importance as it has significant implications for any future decision-making around the constitutional question of whether Northern Ireland should remain in the United Kingdom or become part of a united Ireland. Any change to the constitution - and potentially the very existence of Northern Ireland - will have far reaching ramifications for the nature and shape of both the United Kingdom and the Republic of Ireland

Towards the spatial resolution of metalloprotein charge states by detailed modeling of XFEL crystallographic diffraction.

Oxidation states of individual metal atoms within a metalloprotein can be assigned by examining X-ray absorption edges, which shift to higher energy for progressively more positive valence numbers. Indeed, X-ray crystallography is well suited for such a measurement, owing to its ability to spatially resolve the scattering contributions of individual metal atoms that have distinct electronic environments contributing to protein function. However, as the magnitude of the shift is quite small, about +2 eV per valence state for iron, it has only been possible to measure the effect when performed with monochromated X-ray sources at synchrotron facilities with energy resolutions in the range 2-3 × 10-4 (ΔE/E). This paper tests whether X-ray free-electron laser (XFEL) pulses, which have a broader bandpass (ΔE/E = 3 × 10-3) when used without a monochromator, might also be useful for such studies. The program nanoBragg is used to simulate serial femtosecond crystallography (SFX) diffraction images with sufficient granularity to model the XFEL spectrum, the crystal mosaicity and the wavelength-dependent anomalous scattering factors contributed by two differently charged iron centers in the 110-amino-acid protein, ferredoxin. Bayesian methods are then used to deduce, from the simulated data, the most likely X-ray absorption curves for each metal atom in the protein, which agree well with the curves chosen for the simulation. The data analysis relies critically on the ability to measure the incident spectrum for each pulse, and also on the nanoBragg simulator to predict the size, shape and intensity profile of Bragg spots based on an underlying physical model that includes the absorption curves, which are then modified to produce the best agreement with the simulated data. This inference methodology potentially enables the use of SFX diffraction for the study of metalloenzyme mechanisms and, in general, offers a more detailed approach to Bragg spot data reduction

Widespread occurrence of Mycobacterium tuberculosis DNA from 18th-19th century Hungarians

A large number (265) of burials from 1731-1838 were discovered in sealed crypts of the Dominican Church, Vac, Hungary in 1994. Many bodies were naturally mummified, so that both soft tissues and bones were available. Contemporary archives enabled the determination of age at death, and the identification of family groups. In some cases, symptoms before death were described and, occasionally, occupation. Initial radiological examination of a small number of individuals had indicated calcified lung lesions and demonstrable acid-fast bacteria suggestive of tuberculosis infection. Tuberculosis was endemic in 18th-19th century Europe, so human remains should contain detectable Mycobacterium tuberculosis complex (MTB) DNA, enabling comparisons with modern isolates. Therefore, a comprehensive examination of 168 individuals for the presence of MTB DNA was undertaken. Specific DNA amplification methods for MTB showed that 55% of individuals were positive and that the incidence varied according to age at death and sampling site in the body. Radiographs were obtained from 27 individuals and revealed an association between gross pathology and the presence of MTB DNA. There was an inverse relationship between PCR positivity and MTB target sequence size. In some cases, the preservation of MTB DNA was excellent, and several target gene sequences could be detected from the same sample. This information, combined with MTB DNA sequencing data and molecular typing techniques, will enable us to study the past epidemiology of TB infection, and extends the timeframe for studying changes in molecular fingerprints. Am J Phys Anthropol 120:144-152, 2003. (C) 2003 Wiley-Liss, Inc

Implementing High-Intensity Trauma-Informed Sexual Behavior Risk Reduction in Justice-Involved Women

Sexually transmitted infections continue to be a source of significant morbidity in people with a history of incarceration, particularly women. Justice-involved women are at exceptionally high risk of long-lasting and severe health consequences of contracting an STI. This evidence-based practice implementation project used a repeated measures design to compare sexually transmitted infection knowledge acquisition and condom use self-efficacy in a group of incarcerated women before, immediately after, and three weeks following participation in the Safer Sex Self-Efficacy Workshop. Of the participants (N= 21), 100% demonstrated a significant increase in sexually transmitted infection knowledge and condom use self-efficacy between pre- and post-test scores of the Sexually Transmitted Disease Questionnaire and the Condom use Self-efficacy Scale and maintained those increases at the three-week follow-up

A beginner’s guide to radiation damage

Radiation damage considerations affecting data collection by more than a factor of two are summarized and damage avoidance strategies are suggested

Experiment requirements: Vitamin D metabolites and bone demineralization, Spacelab 2, experiment no. 1

As a contribution toward an understanding of the molecular basis of bone loss, mineral imbalance, and increasing fecal calcium under conditions of prolonged space flight, the blood levels of biologically active vitamin D metabolites of flight crew members will be quantitatively measured. Prior to the mission, the refinement of existing and the development of new techniques for the assay of all vitamin D metabolites will provide an arsenal of methods suitable for a wide range of metabolite levels. In terms of practical application, the analysis of human and animal plasma samples, Spacelab crew plasma samples, and flight hardware are envisioned