Compartmentalised expression of meprin in small intestinal mucosa: enhanced expression in lamina propria in coeliac disease

Epithelial cells in the human small intestine express meprin, an astacin-like metalloprotease, which accumulates normally at the brush border membrane and in the gut lumen. Therefore, meprin is targeted towards luminal components. In coeliac disease patients, peptides from ingested cereals trigger mucosal inflammation in the small intestine, disrupting epithelial cell differentiation and function. Using in situ hybridisation on duodenal tissue sections, we observed a marked shift of meprin mRNA expression from epithelial cells, the predominant expression site in normal mucosa, to lamina propria leukocytes in coeliac disease. Meprin thereby gains access to the substrate repertoire present beneath the epitheliu

Modelo estratégico integral para el proceso de salud ocupacional con énfasis en la gestión del conocimiento para la empresa Saludrogas

En el presente trabajo se identifican aspectos relevantes dentro de la gerencia del talento humano, diseñando un modelo estratégico integral para el proceso de salud ocupacional con énfasis en la gestión del conocimiento para la empresa Saludrogas.In the present work, relevant aspects are identified within the management of human talent, designing a comprehensive strategic model for the occupational health process with emphasis on the management of knowledge for the health-care company

A consultation-level intervention to improve care of frequently attending patients: a cluster randomised controlled feasibility trial

Background: Frequent attenders (FAs) to primary care receive considerable NHS resources without necessarily gaining benefit, and may even be harmed. Aim: To assess the feasibility of a consultation-level intervention to improve care and address service use of FAs. Design & setting: A cluster randomised controlled feasibility trial was undertaken. The study used a mixed-methods process evaluation and took place in six practices in England. Method: All practices screened the top 3% of all attending patients over the previous 12 months for eligibility. Following randomisation, intervention patients were matched with named GPs, trained to use the Background, Affect, Trouble, Handling, Empathy (BATHE) technique during consultations. Telephone consultations were encouraged. Feasibility outcomes assessed were recruitment, retention, data collection and completeness, implementation fidelity, and acceptability Results: A total of 599/1328 (45.1%) FAs were eligible. Four practices were randomised to the intervention (n = 451) and two to usual care (n = 148). A total of 96 (23.7%) patients were recruited to complete questionnaires. Retention and completeness of data were good; for example, 76% of those agreeing to complete questionnaires did so at the 12-month assessment point. Thirty-four GPs were trained and delivered BATHE ≥1 times to 50.1% of patients (n = 577 consultations). There were minimal increases in continuity and telephone consultations. Patients were positive about the intervention, but noticed little change in their care. Despite valuing BATHE, low adherence to training was indicated and GPs used it less than anticipated. Conclusion: It was feasible to identify FAs and collect trial data. GPs were keen to engage and there was evidence that the BATHE technique was taken into practice. Optimising training is likely to improve fidelity. The intervention was low cost and low risk

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Addressing the environmental, community and health impacts of resource development: Challenges across scales, sectors and sites

Work that addresses the cumulative impacts of resource extraction on environment, community, and health is necessarily large in scope. This paper presents experiences from initiating research at this intersection and explores implications for the ambitious, integrative agenda of planetary health. The purpose is to outline origins, design features, and preliminary insights from our intersectoral and international project, based in Canada and titled the “Environment, Community, Health Observatory” (ECHO) Network. With a clear emphasis on rural, remote, and Indigenous communities, environments, and health, the ECHO Network is designed to answer the question: How can an Environment, Community, Health Observatory Network support the integrative tools and processes required to improve understanding and response to the cumulative health impacts of resource development? The Network is informed by four regional cases across Canada where we employ a framework and an approach grounded in observation, “taking notice for action”, and collective learning. Sharing insights from the foundational phase of this five-year project, we reflect on the hidden and obvious challenges of working across scales, sectors, and sites, and the overlap of generative and uncomfortable entanglements associated with health and resource development. Yet, although intersectoral work addressing the cumulative impacts of resource extraction presents uncertainty and unresolved tensions, ultimately we argue that it is worth staying with the trouble

Addressing the environmental, community and health impacts of resource development: Challenges across scales, sectors and sites

Work that addresses the cumulative impacts of resource extraction on environment, community, and health is necessarily large in scope. This paper presents experiences from initiating research at this intersection and explores implications for the ambitious, integrative agenda of planetary health. The purpose is to outline origins, design features, and preliminary insights from our intersectoral and international project, based in Canada and titled the “Environment, Community, Health Observatory” (ECHO) Network. With a clear emphasis on rural, remote, and Indigenous communities, environments, and health, the ECHO Network is designed to answer the question: How can an Environment, Community, Health Observatory Network support the integrative tools and processes required to improve understanding and response to the cumulative health impacts of resource development? The Network is informed by four regional cases across Canada where we employ a framework and an approach grounded in observation, “taking notice for action”, and collective learning. Sharing insights from the foundational phase of this five-year project, we reflect on the hidden and obvious challenges of working across scales, sectors, and sites, and the overlap of generative and uncomfortable entanglements associated with health and resource development. Yet, although intersectoral work addressing the cumulative impacts of resource extraction presents uncertainty and unresolved tensions, ultimately we argue that it is worth staying with the trouble

Exploring gender and fear retrospectively:stories of women’s fear during the ‘Yorkshire Ripper’ murders

The murder of 13 women in the North of England between 1975 and 1979 by Peter Sutcliffe who became known as the Yorkshire Ripper can be viewed as a significant criminal event due to the level of fear generated and the impact on local communities more generally. Drawing upon oral history interviews carried out with individuals living in Leeds at the time of the murders, this article explores women’s accounts of their fears from the time. This offers the opportunity to explore the gender/fear nexus from the unique perspective of a clearly defined object of fear situated within a specific spatial and historical setting. Findings revealed a range of anticipated fear-related emotions and practices which confirm popular ‘high-fear’ motifs; however, narrative analysis of interviews also highlighted more nuanced articulations of resistance and fearlessness based upon class, place and biographies of violence, as well as the way in which women drew upon fear/fearlessness in their overall construction of self. It is argued that using narrative approaches is a valuable means of uncovering the complexity of fear of crime and more specifically provides renewed insight onto women’s fear

Genome-Wide Phylogenetic Comparative Analysis of Plant Transcriptional Regulation: A Timeline of Loss, Gain, Expansion, and Correlation with Complexity

Evolutionary retention of duplicated genes encoding transcription-associated proteins (TAPs, comprising transcription factors and other transcriptional regulators) has been hypothesized to be positively correlated with increasing morphological complexity and paleopolyploidizations, especially within the plant kingdom. Here, we present the most comprehensive set of classification rules for TAPs and its application for genome-wide analyses of plants and algae. Using a dated species tree and phylogenetic comparative (PC) analyses, we define the timeline of TAP loss, gain, and expansion among Viridiplantae and find that two major bursts of gain/expansion occurred, coinciding with the water-to-land transition and the radiation of flowering plants. For the first time, we provide PC proof for the long-standing hypothesis that TAPs are major driving forces behind the evolution of morphological complexity, the latter in Plantae being shaped significantly by polyploidization and subsequent biased paleolog retention. Principal component analysis incorporating the number of TAPs per genome provides an alternate and significant proxy for complexity, ideally suited for PC genomics. Our work lays the ground for further interrogation of the shaping of gene regulatory networks underlying the evolution of organism complexity