Changes in endotoxin levels in T2DM subjects on anti-diabetic therapies

Introduction Chronic low-grade inflammation is a significant factor in the development of obesity associated diabetes. This is supported by recent studies suggesting endotoxin, derived from gut flora, may be key to the development of inflammation by stimulating the secretion of an adverse cytokine profile from adipose tissue. Aims The study investigated the relationship between endotoxin and various metabolic parameters of diabetic patients to determine if anti-diabetic therapies exerted a significant effect on endotoxin levels and adipocytokine profiles. Methods Fasting blood samples were collected from consenting Saudi Arabian patients (BMI: 30.2 ± (SD)5.6 kg/m2, n = 413), consisting of non-diabetics (ND: n = 67) and T2DM subjects (n = 346). The diabetics were divided into 5 subgroups based on their 1 year treatment regimes: diet-controlled (n = 36), metformin (n = 141), rosiglitazone (RSG: n = 22), a combined fixed dose of metformin/rosiglitazone (met/RSG n = 100) and insulin (n = 47). Lipid profiles, fasting plasma glucose, insulin, adiponectin, resistin, TNF-α, leptin, C-reactive protein (CRP) and endotoxin concentrations were determined. Results Regression analyses revealed significant correlations between endotoxin levels and triglycerides (R2 = 0.42; p < 0.0001); total cholesterol (R2 = 0.10; p < 0.001), glucose (R2 = 0.076; p < 0.001) and insulin (R2 = 0.032; p < 0.001) in T2DM subjects. Endotoxin showed a strong inverse correlation with HDL-cholesterol (R2 = 0.055; p < 0.001). Further, endotoxin levels were elevated in all of the treated diabetic subgroups compared with ND, with the RSG treated diabetics showing significantly lower endotoxin levels than all of the other treatment groups (ND: 4.2 ± 1.7 EU/ml, RSG: 5.6 ± 2.2 EU/ml). Both the met/RSG and RSG treated groups had significantly higher adiponectin levels than all the other groups, with the RSG group expressing the highest levels overall. Conclusion We conclude that sub-clinical inflammation in T2DM may, in part, be mediated by circulating endotoxin. Furthermore, that whilst the endotoxin and adipocytokine profiles of diabetic patients treated with different therapies were comparable, the RSG group demonstrated significant differences in both adiponectin and endotoxin levels. We confirm an association between endotoxin and serum insulin and triglycerides and an inverse relationship with HDL. Lower endotoxin and higher adiponectin in the groups treated with RSG may be related and indicate another mechanism for the effect of RSG on insulin sensitivity

The gut microbiota, bile acids and their correlation in primary sclerosing cholangitis associated with inflammatory bowel disease.

BACKGROUND: Patients with primary sclerosing cholangitis associated with inflammatory bowel disease (PSC-IBD) have a very high risk of developing colorectal neoplasia. Alterations in the gut microbiota and/or gut bile acids could account for the increase in this risk. However, no studies have yet investigated the net result of cholestasis and a potentially altered bile acid pool interacting with a dysbiotic gut flora in the inflamed colon of PSC-IBD. AIM: The aim of this study was to compare the gut microbiota and stool bile acid profiles, as well as and their correlation in patients with PSC-IBD and inflammatory bowel disease alone. METHODS: Thirty patients with extensive colitis (15 with concomitant primary sclerosing cholangitis) were prospectively recruited and fresh stool samples were collected. The microbiota composition in stool was profiled using bacterial 16S rRNA sequencing. Stool bile acids were assessed by high-performance liquid chromatography tandem mass spectrometry. RESULTS: The total stool bile acid pool was significantly reduced in PSC-IBD. Although no major differences were observed in the individual bile acid species in stool, their overall combination allowed a good separation between PSC-IBD and inflammatory bowel disease. Compared with inflammatory bowel disease alone, PSC-IBD patients demonstrated a different gut microbiota composition with enrichment in Ruminococcus and Fusobacterium genus compared with inflammatory bowel disease. At the operational taxonomic unit level major shifts were observed within the Firmicutes (73%) and Bacteroidetes phyla (17%). Specific microbiota-bile acid correlations were observed in PSC-IBD, where 12% of the operational taxonomic units strongly correlated with stool bile acids, compared with only 0.4% in non-PSC-IBD. CONCLUSIONS: Patients with PSC-IBD had distinct microbiota and microbiota-stool bile acid correlations as compared with inflammatory bowel disease. Whether these changes are associated with, or may predispose to, an increased risk of colorectal neoplasia needs to be further clarified.info:eu-repo/semantics/publishedVersio

Candida tropicalis biofilms matrix - involvement on its resistance to amphotericin B

Candida tropicalis has emerged as one of the most prevalent fungal pathogens, and its ability to form biofilms has been considered one of the most important virulence factors, since they represent high tolerance to antifungal agents. However, the mechanisms of biofilm resistance to antifungal agents remain poorly understood. Thus, the main goal of this study was to infer about the ability of amphotericin B (AMB) to control and combat C. tropicalis biofilms. Additionally, it was also intended to determine the influence of matrix components in bio- film resistance. AMB was unable to totally prevent biofilm formation and to eradicate C. tropicalis preformed biofilms. Moreover, AMB led to a significant increase of the biofilm production due to an augment of the total protein and carbohydrate contents of the matrix. The C. tropicalis biofilm matrix assumes an important role on its resistance to AMB.This work was supported by the Programa Operacional, Fatores de competitividade and by national funds through Fundacao para a Ciencia e a Tecnologia on the scope of the projects FCT PTDC/SAU-MIC/119069/2010, RECI/EBB-EBI/0179/2012, and PEst-OE/EQB/LA0023/2013. The authors also thank the Project "BioHealth - Biotechnology and Bioengineering approaches to improve health quality; Ref. NORTE-07-0124-FEDER-000027, co-funded by the Programa Operacional Regional do Norte (ON.2 - O Novo Norte), QREN, FEDER

Thrombus aspiration in patients with ST-elevation myocardial infarction: results of a national registry of interventional cardiology.

BACKGROUND: We aimed to evaluate the impact of thrombus aspiration (TA) during primary percutaneous coronary intervention (P-PCI) in 'real-world' settings. METHODS: We performed a retrospective study, using data from the National Registry of Interventional Cardiology (RNCI 2006-2012, Portugal) with ST-elevation myocardial infarction (STEMI) patients treated with P-PCI. The primary outcome, in-hospital mortality, was analysed through adjusted odds ratio (aOR) and 95% confidence intervals (95%CI). RESULTS: We assessed data for 9458 STEMI patients that undergone P-PCI (35% treated with TA). The risk of in-hospital mortality with TA (aOR 0.93, 95%CI:0.54-1.60) was not significantly decreased. After matching patients through the propensity score, TA reduced significantly the risk of in-hospital mortality (OR 0.58, 95%CI:0.35-0.98; 3500 patients). CONCLUSIONS: The whole cohort data does not support the routine use of TA in P-PCI, but the results of the propensity-score matched cohort suggests that the use of selective TA may improve the short-term risks of STEMI.info:eu-repo/semantics/publishedVersio

A generic tool to assess impact of changing edit rules in a business survey - an application to the UK Annual Business Inquiry part 2

Business surveys often use complex sets of edit rules (edits, for short) to check returned questionnaires (records), locate suspicious or unacceptable responses, and support data cleaning operations prior to using the survey responses for estimation of the required target parameters. These sets of edits are complex because they may involve large numbers of survey questionnaires and variables, they may contain a large number of edits, and the edits may depend on a large number of tolerance parameters. When such sets of edits are used, they may cause large numbers of record failures and generate substantial costs of revision, especially if edit failures are dealt with by means of clerical operations, like reviewing original paper questionnaires or digital images of these, and re-contacting businesses for clarification and/or correction of the responses provided. Costs can be high both in terms of the resources required, as well as in terms of timeliness of survey processing, by delaying availability of the survey data for estimation and publication.In this paper we describe a generic tool, developed as a result of the collaboration between the University of Southampton and the ONS. This tool can help to assess the potential impact of changing the edits in a specified business survey. It is a SAS macro using the IML language which enables calculation of a number of edit performance and data quality indicators. Changes to the set of edits aiming to ‘relax’ the existing edits so that failure rates decrease and efficiency savings are achieved are assessed by means of several edit-related performance indicators, like failure and hit rates, false hit rates, etc.. Data quality indicators include proportion of errors missed and estimates of the bias resulting from missing errors for a specified revision of the set of edits. Edit designers and managers can then aim to fine tune their edits so that failure rates, false hit rates and editing costs are reduced, while data quality is preserved. An illustration is provided by the application of the tool to revise the edits used for the UK Annual Business Inquiry Part 2 to the reference year 2007

Innovation in Teaching Transboundary Water Courses – An Interdisciplinary Approach

In this session we will present four curriculum approaches to transboundary courses. Each of the speakers will share the methodologies used in their program and/or class (majors in geography, water engineering, international relations, and international policies). Tools such as class discussions and simulations, student research benefiting from exchange with real world transboundary officials, use of special software for planning and evaluating cooperation, will be discussed and demonstrated

Size-dependent bandgap and particle size distribution of colloidal semiconductor nanocrystals

A new analytical expression for the size-dependent bandgap of colloidal semiconductor nanocrystals is proposed within the framework of the finite-depth square-well effective mass approximation in order to provide a quantitative description of the quantum confinement effect. This allows one to convert optical spectroscopic data (photoluminescence spectrum and absorbance edge) into accurate estimates for the particle size distributions of colloidal systems even if the traditional effective mass model is expected to fail, which occurs typically for very small particles belonging to the so-called strong confinement limit. By applying the reported theoretical methodologies to CdTe nanocrystals synthesized through wet chemical routes, size distributions are inferred and compared directly to those obtained from atomic force microscopy and transmission electron microscopy. This analysis can be used as a complementary tool for the characterization of nanocrystal samples of many other systems such as the II-VI and III-V semiconductor materials.Comment: 9 pages, 5 figure