Human serum-derived hydroxy long-chain fatty acids exhibit anti-inflammatory and anti-proliferative activity

<p>Abstract</p> <p>Background</p> <p>Circulating levels of novel long-chain hydroxy fatty acids (called GTAs) were recently discovered in the serum of healthy subjects which were shown to be reduced in subjects with colorectal cancer (CRC), independent of tumor burden or disease stage. The levels of GTAs were subsequently observed to exhibit an inverse association with age in the general population. The current work investigates the biological activity of these fatty acids by evaluating the effects of enriched human serum extracts on cell growth and inflammation.</p> <p>Methods</p> <p>GTAs were extracted from commercially available bulk human serum and then chromatographically separated into enriched (GTA-positive) and depleted (GTA-negative) fractions. SW620, MCF7 and LPS stimulated RAW264.7 cells were treated with various concentrations of the GTA-positive and GTA-negative extracts, and the effects on cell growth and inflammation determined.</p> <p>Results</p> <p>Enriched fractions resulted in poly-ADP ribose polymerase (PARP) cleavage, suppression of NFκB, induction of IκBα, and reduction in NOS2 mRNA transcript levels. In RAW264.7 mouse macrophage cells, incubation with enriched fractions prior to treatment with LPS blocked the induction of several pro-inflammatory markers including nitric oxide, TNFα, IL-1β, NOS2 and COX2.</p> <p>Conclusions</p> <p>Our results show that human serum extracts enriched with endogenous long-chain hydroxy fatty acids possess anti-inflammatory and anti-proliferative activity. These findings support a hypothesis that the reduction of these metabolites with age may result in a compromised ability to defend against uncontrolled cell growth and inflammation, and could therefore represent a significant risk for the development of CRC.</p

A Reliability-Generalization Study of Journal Peer Reviews: A Multilevel Meta-Analysis of Inter-Rater Reliability and Its Determinants

Background: This paper presents the first meta-analysis for the inter-rater reliability (IRR) of journal peer reviews. IRR is defined as the extent to which two or more independent reviews of the same scientific document agree. Methodology/Principal Findings: Altogether, 70 reliability coefficients (Cohen’s Kappa, intra-class correlation [ICC], and Pearson product-moment correlation [r]) from 48 studies were taken into account in the meta-analysis. The studies were based on a total of 19,443 manuscripts; on average, each study had a sample size of 311 manuscripts (minimum: 28, maximum: 1983). The results of the meta-analysis confirmed the findings of the narrative literature reviews published to date: The level of IRR (mean ICC/r 2 =.34, mean Cohen’s Kappa =.17) was low. To explain the study-to-study variation of the IRR coefficients, meta-regression analyses were calculated using seven covariates. Two covariates that emerged in the metaregression analyses as statistically significant to gain an approximate homogeneity of the intra-class correlations indicated that, firstly, the more manuscripts that a study is based on, the smaller the reported IRR coefficients are. Secondly, if the information of the rating system for reviewers was reported in a study, then this was associated with a smaller IRR coefficient than if the information was not conveyed. Conclusions/Significance: Studies that report a high level of IRR are to be considered less credible than those with a low level o

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Effective use of tansfer plates in mixed development

The need for providing car parking within apartment buildings often lead to a situation where different grid arrangements exist in the parking and apartment floors. In most cases, a setback is also present to accommodate this change over. This requires the use of a transfer system such as a transfer plate or transfer beams. In mixed development, there is a possibility to change the location of the transfer floor. This paper explores the added advantage of using a transfer plate in such situations due to its outrigger behaviour and how it changes when its location is changed. A case study of a highrise apartment building is used to demonstrate different trends in outrigger behaviour with respect to dynamic wind and earthquake loading

Importance of accurate modeling input and assumptions in 3D finite element analysis of tall buildings

With ever increasing land prices, design and construction of high-rise buildings are becoming very common. There is a trend among design Engineers to resort to 3D Finite Element Analysis (FEA) during the design of such high rise buildings. This is due to the fact that challenging architectural concepts, when combined with inherent complexities and scale of such projects, require the need of complex structural systems and components such as outriggers, transfer plates, etc. However incorrect modeling input and assumptions could lead to a situation where predictions made using such models may differ greatly from the actual behaviour. In this paper, the importance of accuracy in modeling FEA of high rise buildings is demonstrated through the use of a case study of a 34 storey hotel building with outriggers. The impact of modeling accuracy and assumptions on the predicted performance of the outrigger is also evaluated

The Influence of transfer plates on the lateral behaviour of apartment buildings

Senate Research Gran

Research Papers Atropine therapy in acute anticholinesterase (Organophosphorus / carbamate) poisoning; adherence to current guidelines

Purpose: Atropine is a life saving drug in acute anticholinesterase poisoning. Proper atropinization is associated with better clinical outcome. Hence we aimed to look at the adherence to existing guidelines on atropine therapy in anticholinesterase poisoning. Method: A cross-sectional study at two tertiary care hospitals was carried out by using a semi-structured questionnaire.Association between atropine toxicity and death were analyzed by Chi-squared test. Results: Among the 144 patients with anticholinesterase poisoning (105 organophosphorus, 39 carbamate) 110 were males. Mean (SD) age was 37 (16) years. In 52 patients, atropine was started at peripheral hospitals where as atropine was commenced in 89 of the patients at the collaborating hospitals. Three patients were not treated with atropine. Fourteen (16%) patients did not have cholinergic features at the time of commencing atropine. Features of atropine toxicity developed in 122 (90%) patients. Twenty-four (17%) patients died in spite of the treatment.Atropine toxicity was associated with the occurrence of deaths; p&lt; 0.05. Conclusion: The occurrence of death due to anticholinesterase poisoning was high when compared to national figure which was 12%; attention should be focused on identifying the causative factors of the high death rate. Association between atropine toxicity and death were statistically significant