Dietary red meat aggravates dextran sulfate sodium-induced colitis in mice whereas resistant starch attenuates inflammation

Although a genetic component has been identified as a risk factor for developing inflammatory bowel disease, there is evidence that dietary factors also play a role in the development of this disease. Aims The aim of this study was to determine the effects of feeding a red meat diet with and without resistant starch (RS) to mice with dextran sulfate sodium (DSS)-induced colitis. Methods Colonic experimental colitis was induced in Balb/c mice using DSS. The severity of colitis was evaluated based on a disease activity index (based on bodyweight loss, stool consistency, rectal bleeding, and overall condition of the animal) and a histological score. Estimations were made of numbers of a range of different bacteria in the treatment pools of cecal digesta using quantitative real-time PCR. Results Consumption of a diet high in red meat increased DSS-induced colitis as evidenced by higher disease activity and histopathological scores. Addition of RS to the red meat diet exerted a beneficial effect in acute DSS-induced colitis. Subjective analysis of numbers of a range of bacterial targets suggest changes in the gut microbiota abundance were induced by red meat and RS treatments and these changes could contribute to the reported outcomes. Conclusions A dietary intake of red meat aggravates DSS-induced colitis whereas co-consumption of resistant starch reduces the severity of colitis.This work was supported by the National Health and Medical Research Council (grant ID 535079) and CSIRO Preventative Health National Research Flagship

Accumulation of promutagenic DNA adducts in the mouse distal colon after consumption of heme does not induce colonic neoplasms in the western diet model of spontaneous colorectal cancer

Author version made available in accordance with Publisher copyright policy.Scope: Red meat is considered a risk factor for colorectal cancer (CRC). Heme is considered to promote colonic hyperproliferation and cell damage. Resistant starch (RS) is a food that ferments in the colon with studies demonstrating protective effects against CRC. By utilizing the western diet model of spontaneous CRC, we determined if feeding heme (as hemin chloride) equivalent to a high red meat diet would increase colonic DNA adducts and CRC and whether RS could abrogate such effects. Methods and results: Four groups of mice: control, heme, RS and heme + RS were fed diets for 1 or 18 months. Colons were analyzed for apoptosis, proliferation, DNA adducts “8-hydroxy-2-deoxyguanosine” and “O6-methyl-2-deoxyguanosine” (O6MeG), and neoplasms. In the short term, heme increased cell proliferation (p < 0.05). Changes from 1 to 18 months showed increased cell proliferation (p<0.01) and 8-hydroxy-2-deoxyguanosine adducts (p < 0.05) in all groups, but only heme-fed mice showed reduced apoptosis (p < 0.01) and increasedO6MeGadducts (p<0.01). The incidence of colon neoplasms was not different between any interventions. Conclusion: We identified heme to increase proliferation in the short term, inhibit apoptosis over the long term, and increase O6MeG adducts in the colon over time although these changes did not affect colonic neoplasms within this mouse model.Funding for this project was provided by the National Health and Medical Research Council of Australia (Project number 535079).We would like to acknowledge the Royal Society of Edinburgh for funding a visit for Dr. SilviaGratz fromUKto Australia to carry out work associated with this project

Peru's ancient water systems can help protect communities from shortages caused by climate change

Water is essential for human life, but in many parts of the world water supplies are under threat from more extreme, less predictable weather conditions due to climate change. Nowhere is this clearer than in the Peruvian Andes, where rising temperatures and receding glaciers forewarn of imminent water scarcity for the communities that live there.Throwing money and resources into engineering projects does not always guarantee success when trying to combat the effects of climate change and protect vulnerable communities. But the marriage of ancient and modern technologies offers promising solutions to the threat of water scarcity in Peru, and places like it all across the world.Fil: Conlon, Susan. University of Bristol; Reino UnidoFil: Lane, Kevin John. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Arqueología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Incidence and risk factors of delirium in patients post pancreaticoduodenectomy

AbstractBackgroundPost-operative delirium is an important and common complication of major abdominal surgery characterized by acute confusion with fluctuating consciousness. The aim of this study was to establish the incidence of post-operative delirium in patients undergoing a pancreaticoduodenectomy and to determine the risk factors for its development.MethodsFrom a prospectively maintained database, a retrospective cohort analysis was performed of 50 consecutive patients who underwent a pancreaticoduodenectomy at the National Surgical Centre for Pancreatic Cancer in St. Vincent's University Hospital, Dublin and whose entire post-operative stay was in this institution, between July 2011 and December 2012. Two independent medical practitioners assessed all data and delirium was diagnosed according to criteria of the Diagnostic and Statistical Manual Disorder (DSM), fourth edition. Univariate and multivariate analyses were performed.ResultsSeven patients (14%) developed post-operative delirium. The median onset was on the second post-operative day. Older age was predictive of an increased risk of delirium post-operatively. Those who developed delirium had a significantly increased length of stay (LOS) as well as a significantly increased risk of developing at least a grade 3 complication (Clavien-Dindo classification).ConclusionThis study demonstrates that post-operative delirium is associated with a more complicated recovery after a pancreaticoduodenectomy and that older age is independently predictive of its development. Focused screening may allow targeted preventative strategies to be used in the peri-operative period to reduce complications and costs associated with delirium

Evaluation of Four Structural Best Management Practices for Highway Runoff in Beaufort and Colleton Counties, South Carolina, 2005-2006

2008 S.C. Water Resources Conference - Addressing Water Challenges Facing the State and Regio

Design and Approach of a Storm Runoff Investigation at Selected South Carolina Department of Transportation Maintenance Yards

2010 S.C. Water Resources Conference - Science and Policy Challenges for a Sustainable Futur

Impacts on the Electrical System Economics from Critical Design Factors of Wave Energy Converters and Arrays

It is expected that ultimately, like offshore wind farms, electrical systems will make up to a quarter of the overall Capex of wave farms. This is a significant element of cost and consideration must be taken in the design of both individual wave energy converters (WECs) and arrays of WECs to ensure that these costs can be minimised. In a worst case scenario design decisions could increase the cost of the electrical system by several orders and ultimately make the technology uncompetitive. This paper outlines the impacts on the cost of the electrical system arising from design factors of WECs and WEC arrays or wave farms. The paper uses a cost model to examine the impact to the cost of WEC array electrical systems caused by changing of key design factors. The design factors examined include WEC unit rating, capacity factor, interface to the electrical network, array spacing, export voltage, array design, site selection, export distance, and WEC dynamic response. All of these design factors have an impact on the economics of the electrical system and hence the economics of the wave farm as a whole. The paper concludes that there are some critical design choices which should be avoided if a cost-effective wave farm is to be established. It is also concluded that some design choices could ultimately reduce the overall Capex of WEC arrays enhancing their competiveness

Evaluation of Four Structural Best Management Practices for Highway Runoff in Beaufort and Colleton Counties, South Carolina, 2005-2006

2008 S.C. Water Resources Conference - Addressing Water Challenges Facing the State and Regio

The Domestic and Export Market for Large Scale Wave Energy in Ireland and the Economics of Export Transmission

Ireland is on track to meet its 2020 renewable energy targets with over 2 GW of onshore wind installed in the all island market as of 2013, and a multiple of this capacity in various stages of planning and development. It is currently unclear how much of this potential capacity will ultimately be installed but it has become clear that the wind industry in Ireland will change focus to export opportunities post 2020. This presents some interesting challenges for wave energy in Ireland. There is some early activity in the installation of wave farms off the west coast of Ireland and it is evident that the potential resource is extremely large. This wave resource is concentrated on the west coast of Ireland, remote of domestic load centres and export markets. To fully exploit this resource the wave energy industry may ultimately depend on the export market opportunity due to limited domestic demand. This paper examines the domestic potential for wave energy penetration and the benefits this may bring. It is concluded that there is a potential domestic market for wave energy in Ireland with the right conditions, although this market may be limited. Ultimately it is concluded that large scale wave energy may require a transmission route to an export market and this will be challenging and expensive, requiring the use o

Phase I study of single agent NIZ985, a recombinant heterodimeric IL-15 agonist, in adult patients with metastatic or unresectable solid tumors

BACKGROUND: NIZ985 is a recombinant heterodimer of physiologically active interleukin (IL-)15 and IL-15 receptor alpha. In preclinical models, NIZ985 promotes cytotoxic lymphocyte proliferation, killing function, and organ/tumor infiltration, with resultant anticancer effects. In this first-in-human study, we assessed the safety, pharmacokinetics, and immune effects of NIZ985 in patients with metastatic or unresectable solid tumors. METHODS: Single agent NIZ985 dose escalation data are reported from a phase I dose escalation/expansion study of NIZ985 as monotherapy. Adult patients (N=14) received 0.25, 0.5, 1, 2 or 4 µg/kg subcutaneous NIZ985 three times weekly (TIW) for the first 2 weeks of each 28-day cycle, in an accelerated 3+3 dose escalation trial design. IL-15 and endogenous cytokines were monitored by ELISA and multiplexed electrochemiluminescent assays. Multiparameter flow cytometry assessed the frequency, phenotype and proliferation of peripheral blood mononuclear cells. Preliminary antitumor activity was assessed by overall response rate (Response Evaluation Criteria in Solid Tumors V.1.1). RESULTS: As of March 2, 2020, median treatment duration was 7.5 weeks (range 1.1-77.1). Thirteen patients had discontinued and one (uveal melanoma) remains on treatment with stable disease. Best clinical response was stable disease (3 of 14 patients; 21%). The most frequent adverse events (AEs) were circular erythematous injection site reactions (100%), chills (71%), fatigue (57%), and fever (50%). Treatment-related grade 3/4 AEs occurred in six participants (43%); treatment-related serious AEs (SAEs) in three (21%). The per-protocol maximum tolerated dose was not reached. Pharmacokinetic accumulation of serum IL-15 in the first week was followed by significantly lower levels in week 2, likely due to more rapid cytokine consumption by an expanding lymphocyte pool. NIZ985 treatment was associated with increases in several cytokines, including interferon (IFN)-γ, IL-18, C-X-C motif chemokine ligand 10, and tumor necrosis factor-β, plus significant induction of cytotoxic lymphocyte proliferation (including natural killer and CD8 CONCLUSIONS: Subcutaneous NIZ985 TIW was generally well tolerated in patients with advanced cancer and produced immune activation paralleling preclinical observations, with induction of IFN-γ and proliferation of cytotoxic lymphocytes. Due to delayed SAEs at the two highest dose levels, administration is being changed to once-weekly in a revised protocol, as monotherapy and combined with checkpoint inhibitor spartalizumab. These alterations are expected to maximize the potential of NIZ985 as a novel immunotherapy. TRIAL REGISTRATION NUMBER: NCT02452268