Association between Resistin Levels and All-Cause and Cardiovascular Mortality: A New Study and a Systematic Review and Meta-Analysis.

CONTEXT: Studies concerning the association between circulating resistin and mortality risk have reported, so far, conflicting results. OBJECTIVE: To investigate the association between resistin and both all-cause and cardiovascular (CV) mortality risk by 1) analyzing data from the Gargano Heart Study (GHS) prospective design (n=359 patients; 81 and 58 all-cause and CV deaths, respectively); 2) performing meta-analyses of all published studies addressing the above mentioned associations. DATA SOURCE AND STUDY SELECTION: MEDLINE and Web of Science search of studies reporting hazard ratios (HR) of circulating resistin for all-cause or CV mortality. DATA EXTRACTION: Performed independently by two investigators, using a standardized data extraction sheet. DATA SYNTHESIS: In GHS, adjusted HRs per one standard deviation (SD) increment in resistin concentration were 1.28 (95% CI: 1.07-1.54) and 1.32 (95% CI: 1.06-1.64) for all-cause and CV mortality, respectively. The meta-analyses included 7 studies (n=4016; 961 events) for all-cause mortality and 6 studies (n=4,187: 412 events) for CV mortality. Pooled HRs per one SD increment in resistin levels were 1.21 (95% CI: 1.03-1.42, Q-test p for heterogeneity<0.001) and 1.05 (95% CI: 1.01-1.10, Q-test p for heterogeneity=0.199) for all-cause and CV mortality, respectively. At meta-regression analyses, study mean age explained 9.9% of all-cause mortality studies heterogeneity. After adjusting for age, HR for all-cause mortality was 1.24 (95% CI: 1.06-1.45). CONCLUSIONS: Our results provide evidence for an association between circulating resistin and mortality risk among high-risk patients as are those with diabetes and coronary artery disease

Preliminary investigation on the water retention behaviour of cement bentonite mixtures

Cement bentonite mixtures are often used to build slurry walls for the containment of both aqueous and non aqueous pollutants, due to their quite low hydraulic conductivity and relatively high ductility and strength. Although their hydro-mechanical behaviour in saturated conditions has been studied in the past, a part of the slurry wall is expected to rest above the groundwater level. The hydraulic characterization in unsaturated conditions is then particularly relevant to evaluate the performance of the barrier, especially when it is aimed at containing non aqueous pollutant liquids which are lighter than water (LNAPL). These non wetting fluids rest above the water table and their penetration is possible just if the barrier is unsaturated. This paper presents some preliminary results of a laboratory characterization of the water retention behaviour of three different cement bentonite mixtures. The mixtures, prepared at cement - bentonite mass ratios ranging from 4:1 to 6:1, were immersed in water and cured for 28 days. Their water retention behaviour was then determined along drying and wetting paths through different techniques, namely axis translation, filter paper and vapour equilibrium. In the high suction range, the water content - suction relationship was found to be independent of cement-bentonite ratio. In the low suction range, the water content at a given suction was found to decrease for increasing cement bentonite ratios

Monitoring drying and wetting of a cement bentonite mixture with Electrical Resistivity Tomography

Cement bentonite slurry cutoff walls are used to encapsulate pollutants within contaminated areas, so avoiding their spreading in the environment. In both temperate and arid climates, at shallow depths, slurry walls are exposed to interaction with the atmosphere and thus to relative humidity values which might induce desaturation and significant shrinkage. This note presents the main results of a study aimed at investigating the impact of drying processes on the integrity and the hydraulic performance of cement bentonite slurry walls. Cement bentonite samples were cured under water for different times (1 months, 2 months and 4 months) and then dried naturally by exposing them to the laboratory environment (T = 21 °C, relative humidity approximately 38%). Once dried, the bottom of the samples was placed in contact with a thin layer of water to induce wetting. The distribution of the electrical conductivity within these samples was evaluated through Electrical Resistivity Tomography measurements, and electrical conductivity maps were converted then into maps of water contents on basis of a phenomenological relationship. The reconstructed water contents compared very well to the measured ones. Drying induced a limited cracking of the samples, which might affect to some extent the hydraulic performance of the barriers

Thoracic Endovascular Aortic Repair for Type B Acute Aortic Dissection Complicated by Descending Thoracic Aneurysm

OBJECTIVES: To analyse the results and review the literature about thoracic aortic endovascular repair (TEVAR) for type B acute aortic dissection (TBAAD) complicated by descending thoracic aortic aneurysm (DTA) in the hyperacute or acute phases. METHODS: This was a multicentre, observational descriptive study. Inclusion criteria were TBAAD with a DTA of 6550 mm, TBAAD on an already known aneurysmal descending thoracic aorta, and TBAAD presenting with an enlarged aorta with a total diameter &lt;50 mm, but with &gt;50% diameter increase compared with a previous computed tomography angiography (CTA) showing a non-dissected aorta with normal sizing. Primary endpoints were early and long-term survival, freedom from TEVAR and aortic related mortality (ARM), and freedom from re-intervention. RESULTS: Twenty-two patients were included in the analysis. The mean aortic diameter was 66 \ub1 26 mm (range 42-130; IQR 51-64). The in hospital TEVAR related mortality was 14% (n = 3). The mean radiological follow-up was 56 \ub1 45 months (range 6-149; IQR 12-82), and the follow-up index 0.97 \ub1 0.1. All surviving patients were available for follow-up. During follow-up the cumulative mortality was 26% (n = 5) and TEVAR related mortality was 5% (n = 1). Overall the estimate of survival was 82% (95%CI: 61.5-93) at 1 year, and 64% at 5 years. Ongoing primary clinical success was 79% (re-intervention n = 4). Freedom from aortic related mortality was 86% (95%CI: 66-95) at 1 and 5 year, while freedom from re-intervention was 95% (95%CI: 75.5-95) at 1 year, and 77% (95%CI: 50-92) at 5 years. CONCLUSIONS: In our experience, DTA is a frequent complication from the very beginning of the clinical onset of TBAAD. In this high-risk cohort, TEVAR showed satisfactory results, better than those predicted by the risk score for open repair, with favourable stability of the aortic diameter and no aortic related adverse events during follow-up

ENPP1 Affects Insulin Action and Secretion: Evidences from In Vitro Studies

The aim of this study was to deeper investigate the mechanisms through which ENPP1, a negative modulator of insulin receptor (IR) activation, plays a role on insulin signaling, insulin secretion and eventually glucose metabolism. ENPP1 cDNA (carrying either K121 or Q121 variant) was transfected in HepG2 liver-, L6 skeletal muscle- and INS1E beta-cells. Insulin-induced IR-autophosphorylation (HepG2, L6, INS1E), Akt-Ser473, ERK1/2-Thr202/Tyr204 and GSK3-beta Ser9 phosphorylation (HepG2, L6), PEPCK mRNA levels (HepG2) and 2-deoxy-D-glucose uptake (L6) was studied. GLUT 4 mRNA (L6), insulin secretion and caspase-3 activation (INS1E) were also investigated. Insulin-induced IR-autophosphorylation was decreased in HepG2-K, L6-K, INS1E-K (20%, 52% and 11% reduction vs. untransfected cells) and twice as much in HepG2-Q, L6-Q, INS1E-Q (44%, 92% and 30%). Similar data were obtained with Akt-Ser473, ERK1/2-Thr202/Tyr204 and GSK3-beta Ser9 in HepG2 and L6. Insulin-induced reduction of PEPCK mRNA was progressively lower in untransfected, HepG2-K and HepG2-Q cells (65%, 54%, 23%). Insulin-induced glucose uptake in untransfected L6 (60% increase over basal), was totally abolished in L6-K and L6-Q cells. GLUT 4 mRNA was slightly reduced in L6-K and twice as much in L6-Q (13% and 25% reduction vs. untransfected cells). Glucose-induced insulin secretion was 60% reduced in INS1E-K and almost abolished in INS1E-Q. Serum deficiency activated caspase-3 by two, three and four folds in untransfected INS1E, INS1E-K and INS1E-Q. Glyburide-induced insulin secretion was reduced by 50% in isolated human islets from homozygous QQ donors as compared to those from KK and KQ individuals. Our data clearly indicate that ENPP1, especially when the Q121 variant is operating, affects insulin signaling and glucose metabolism in skeletal muscle- and liver-cells and both function and survival of insulin secreting beta-cells, thus representing a strong pathogenic factor predisposing to insulin resistance, defective insulin secretion and glucose metabolism abnormalities

Application of the rainbow trout derived intestinal cell line (RTgutGC) for ecotoxicological studies: molecular and cellular responses following exposure to copper.

There is an acknowledged need for in vitro fish intestinal model to help understand dietary exposure to chemicals in the aquatic environment. The presence and use of such models is however largely restrictive due to technical difficulties in the culturing of enterocytes in general and the availability of appropriate established cell lines in particular. In this study, the rainbow trout (Oncorhynchus mykiss) intestinal derived cell line (RTgutGC) was used as a surrogate for the "gut sac" method. To facilitate comparison, RTgutGC cells were grown as monolayers (double-seeded) on permeable Transwell supports leading to a two-compartment intestinal model consisting of polarised epithelium. This two-compartment model divides the system into an upper apical (lumen) and a lower basolateral (portal blood) compartment. In our studies, these cells stained weakly for mucosubstances, expressed the tight junction protein ZO-1 in addition to E-cadherin and revealed the presence of polarised epithelium in addition to microvilli protrusions. The cells also revealed a comparable transepithelial electrical resistance (TEER) to the in vivo situation. Importantly, the cell line tolerated apical saline (1:1 ratio) thus mimicking the intact organ to allow assessment of uptake of compounds across the intestine. Following an exposure over 72 h, our study demonstrated that the RTgutGC cell line under sub-lethal concentrations of copper sulphate (Cu) and modified saline solutions demonstrated uptake of the metal with saturation levels comparable to short term ex situ gut sac preparations. Gene expression analysis revealed no significant influence of pH or time on mRNA expression levels of key stress related genes (i.e. CYP3A, GST, mtA, Pgp and SOD) in the Transwell model. However, significant positive correlations were found between all genes investigated suggesting a co-operative relationship amongst the genes studied. When the outlined characteristics of the cell line are combined with the division of compartments, the RTgutGC double seeded model represents a potential animal replacement model for ecotoxicological studies. Overall, this model could be used to study the effects and predict aquatic gastrointestinal permeability of metals and other environmentally relevant contaminants in a cost effective and high throughput manner

PPARA polymorphism influences the cardiovascular benefit of fenofibrate in type 2 diabetes: Findings from accord-lipid

The cardiovascular benefits of fibrates have been shown to be heterogeneous and to depend on the presence of atherogenic dyslipidemia. We investigated whether genetic variability in the PPARA gene, coding for the pharmacological target of fibrates (PPAR-a), could be used to improve the selection of patients with type 2 diabetes who may derive cardiovascular benefit from addition of this treatment to statins. We identified a common variant at the PPARA locus (rs6008845, C/T) displaying a study-wide significant influence on the effect of fenofibrate on major cardiovascular events (MACE) among 3,065 self-reported white subjects treated with simvastatin and randomized to fenofibrate or placebo in the ACCORD-Lipid trial. T/T homozygotes (36% of participants) experienced a 51% MACE reduction in response to fenofibrate (hazard ratio 0.49; 95% CI 0.34–0.72), whereas no benefit was observed for other genotypes (Pinteraction 5 3.7 3 1024). The rs6008845-by-fenofibrate interaction on MACE was replicated in African Americans from ACCORD (N 5 585, P 5 0.02) and in external cohorts (ACCORD-BP, ORIGIN, and TRIUMPH, total N 5 3059, P 5 0.005). Remarkably, rs6008845 T/T homozygotes experienced a cardiovascular benefit from fibrate even in the absence of atherogenic dyslipidemia. Among these individuals, but not among carriers of other genotypes, fenofibrate treatment was associated with lower circulating levels of CCL11—a proinflammatory and atherogenic chemokine also known as eotaxin (P for rs6008845-by-fenofibrate interaction 5 0.003). The GTEx data set revealed regulatory functions of rs6008845 on PPARA expression in many tissues. In summary, we have found a common PPARA regulatory variant that influences the cardiovascular effects of fenofibrate and that could be used to identify patients with type 2 diabetes who would derive benefit from fenofibrate treatment, in addition to those with atherogenic dyslipidemia