Altered expression of caspases-4 and -5 during inflammatory bowel disease and colorectal cancer : diagnostic and therapeutic potential

Caspases are a group of proteolytic enzymes involved in the co-ordination of cellular processes, including cellular homeostasis, inflammation and apoptosis. Altered activity of caspases, particularly caspase-1, has been implicated in the development of intestinal diseases, such as inflammatory bowel disease (IBD) and colorectal cancer (CRC). However, the involvement of two related inflammatory caspase members, caspases-4 and -5, during intestinal homeostasis and disease has not yet been established. This study demonstrates that caspases-4 and -5 are involved in IBD-associated intestinal inflammation. Furthermore, we found a clear correlation between stromal caspase-4 and -5 expression levels, inflammation and disease activity in ulcerative colitis patients. Deregulated intestinal inflammation in IBD patients is associated with an increased risk of developing CRC. We found robust expression of caspases-4 and -5 within intestinal epithelial cells, exclusively within neoplastic tissue, of colorectal tumours. An examination of adjacent normal, inflamed and tumour tissue from patients with colitis-associated CRC confirmed that stromal expression of caspases-4 and -5 is increased in inflamed and dysplastic tissue, while epithelial expression is restricted to neoplastic tissue. In addition to identifying caspases-4 and -5 as potential targets for limiting intestinal inflammation, this study has identified epithelial-expressed caspases-4 and -5 as biomarkers with diagnostic and therapeutic potential in CRC

Pilot Study of the Effects of Tai Chi on Elderly Fall Risks

Introduction. Falls in the elderly are a significant public health concern. Tai Chi has been shown to reduce falls in this population and increase muscle strength, balance, mood, confidence and sleep.https://scholarworks.uvm.edu/comphp_gallery/1087/thumbnail.jp

Acute unilateral hearing loss as an unusual presentation of cholesteatoma

BACKGROUND: Cholesteatomas are epithelial cysts that contain desquamated keratin. Patients commonly present with progressive hearing loss and a chronically discharging ear. We report an unusual presentation of the disease with an acute hearing loss suffered immediately after prolonged use of a pneumatic drill. CASE PRESENTATION: A 41 year old man with no previous history of ear problems presented with a sudden loss of hearing in his right ear immediately following the prolonged use of a pneumatic drill on concrete. The cause was found to be a fractured long process of incus which had been eroded by the presence of an attic cholesteatoma. A tympanomastoidectomy and ossiculoplasty was performed with good result. CONCLUSION: Cholesteatomas may be asymptomatic and insidious in their onset. This case illustrates the point that an indolent disease such as this may present in unusual ways and the clinician must always have a high index of suspicion combined with thorough assessment and examination of every patient

Teaching across disciplines: a case study of a project-based short course to teach holistic coastal adaptation design

Climate change has led to the need for innovation in resilient infrastructure and the social policies which will support those. This requires greater interdisciplinary interactions and knowledge building among emerging professionals. This paper presents a case study of a pilot short course intended to immerse graduate students in the design of resilient infrastructure using place-based and interdisciplinary active team learning. This course helps graduate students bridge the gap between research and practice on the social science and engineering of resilient infrastructure for coastal adaptation. The intellectual framework for the course (the Adaptive Gradients Framework) provides a holistic evaluation of adaptation design proposals and was used to recognize the complexity of social, ecological and engineering aspects and varied social benefits. The course provides a model to move outside rigid boundaries of institutions and disciplines to begin to build, in both students and instructors, the ability to work more effectively on complex social-ecological-engineering problems. Finally, this paper presents a summary of lessons learned from this pilot short course

Virus–Host Interactions Between Nonsecretors and Human Norovirus

BACKGROUND & AIMS: Human norovirus infection is the leading cause of acute gastroenteritis. Genetic polymorphisms, mediated by the FUT2 gene (secretor enzyme), define strain susceptibility. Secretors express a diverse set of fucosylated histoblood group antigen carbohydrates (HBGA) on mucosal cells; nonsecretors (FUT2-/-) express a limited array of HBGAs. Thus, nonsecretors have less diverse norovirus strain infections, including resistance to the epidemiologically dominant GII.4 strains. Because future human norovirus vaccines will comprise GII.4 antigen and because secretor phenotype impacts GII.4 infection and immunity, nonsecretors may mimic young children immunologically in response to GII.4 vaccination, providing a needed model to study crossprotection in the context of limited pre-exposure. METHODS: By using specimens collected from the first characterized nonsecretor cohort naturally infected with GII.2 human norovirus, we evaluated the breadth of serologic immunity by surrogate neutralization assays, and cellular activation and cytokine production by flow cytometry. RESULTS: GII.2 infection resulted in broad antibody and cellular immunity activation that persisted for at least 30 days for T cells, monocytes, and dendritic cells, and for 180 days for blocking antibody. Multiple cellular lineages expressing interferon-g and tumor necrosis factor-a dominated the response. Both T-cell and B-cell responses were cross-reactive with other GII strains, but not GI strains. To promote entry mechanisms, inclusion of bile acids was essential for GII.2 binding to nonsecretor HBGAs. CONCLUSIONS: These data support development of withingenogroup, cross-reactive antibody and T-cell immunity, key outcomes that may provide the foundation for eliciting broad immune responses after GII.4 vaccination in individuals with limited GII.4 immunity, including young children

Advancing the 3Rs in regulatory ecotoxicology: A pragmatic cross-sector approach

The ecotoxicity testing of chemicals for prospective environmental safety assessment is an area in which a high number of vertebrates are used across a variety of industry sectors. Refining, reducing, and replacing the use of animals such as fish, birds, and amphibians for this purpose addresses the ethical concerns and the increasing legislative requirements to consider alternative test methods. Members of the UK-based National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) Ecotoxicology Working Group, consisting of representatives from academia, government organizations, and industry, have worked together over the past 6 y to provide evidence bases to support and advance the application of the 3Rs in regulatory ecotoxicity testing. The group recently held a workshop to identify the areas of testing, demands, and drivers that will have an impact on the future of animal use in regulatory ecotoxicology. As a result of these discussions, we have developed a pragmatic approach to prioritize and realistically address key opportunity areas, to enable progress toward the vision of a reduced reliance on the use of animals in this area of testing. This paper summarizes the findings of this exercise and proposes a pragmatic strategy toward our key long-term goals-the incorporation of reliable alternatives to whole-organism testing into regulations and guidance, and a culture shift toward reduced reliance on vertebrate toxicity testing in routine environmental safety assessment. Integr Environ Assess Manag 2016;12:417-421. © 2015 SETAC

A review of climate change and the implementation of marine biodiversity legislation in the United Kingdom

1. Marine legislation, the key means by which the conservation of marine biodiversity is achieved, has been developing since the 1960s. In recent decades, an increasing focus on ‘holistic’ policy development is evident, compared with earlier ‘piecemeal’ sectoral approaches. Important marine legislative tools being used in the United Kingdom, and internationally, include the designation of marine protected areas and the Marine Strategy Framework Directive (MSFD) with its aim of meeting ‘Good Environmental Status’ (GES) for European seas by 2020. 2. There is growing evidence of climate change impacts on marine biodiversity, which may compromise the effectiveness of any legislation intended to promote sustainable marine resource management. 3. A review of key marine biodiversity legislation relevant to the UK shows climate change was not considered in the drafting of much early legislation. Despite the huge increase in knowledge of climate change impacts in recent decades, legislation is still limited in how it takes these impacts into account. There is scope, however, to account for climate change in implementing much of the legislation through (a) existing references to environmental variability; (b) review cycles; and (c) secondary legislation and complementary policy development. 4. For legislation relating to marine protected areas (e.g. the EC Habitats and Birds Directives), climate change has generally not been considered in the site-designation process, or for ongoing management, with the exception of the Marine (Scotland) Act. Given that changing environmental conditions (e.g. rising temperatures and ocean acidification) directly affect the habitats and species that sites are designated for, how this legislation is used to protect marine biodiversity in a changing climate requires further consideration. 5. Accounting for climate change impacts on marine biodiversity in the development and implementation of legislation is vital to enable timely, adaptive management responses. Marine modelling can play an important role in informing management decisions

Immunomagnetic t-lymphocyte depletion (ITLD) of rat bone marrow using OX-19 monoclonal antibody

Graft versus host disease (GVHD) may be abrogated and host survival prolonged by in vitro depletion of T lymphocytes from bone marrow (BM) prior to allotransplantation. Using a mouse anti-rat pan T-lymphocyte monoclonal antibody (0×19) bound to monosized, magnetic, polymer beads, T lymphocytes were removed in vitro from normal bone marrow. The removal of the T lymphocytes was confirmed by flow cytometry. Injection of the T-lymphocyte-depleted bone marrow into fully allogeneic rats prevents the induction of GVHD and prolongs host survival. A highly efficient technique of T-lymphocyte depletion using rat bone marrow is described. It involves the binding of OX-19, a MoAb directed against all rat thy-mocytes and mature peripheral T lymphocytes, to monosized, magnetic polymer spheres. Magnetic separation of T lymphocytes after mixing the allogeneic bone marrow with the bead/OX-19 complex provides for a simple, rapid depletion of T lymphocytes from the bone marrow. In vitro studies using flow cytometry and the prevention of GVHD in a fully allogeneic rat bone marrow model have been used to demonstrate the effectiveness of the depletion procedure. © 1989 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted