345 research outputs found

    InSAR Time Series Analysis of Natural and Anthropogenic Coastal Plain Subsidence: The Case of Sibari (Southern Italy)

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    We applied the Small Baseline Subset multi-temporal InSAR technique (SBAS) to two SAR datasets acquired from 2003 up to 2013 by Envisat (ESA, European Space Agency) and COSMO-SkyMed (ASI, Italian Space Agency) satellites to investigate spatial and temporal patterns of land subsidence in the Sibari Plain (Southern Italy). Subsidence processes (up to ~20 mm/yr) were investigated comparing geological, hydrogeological, and land use information with interferometric results. We suppose a correlation between subsidence and thickness of the Plio-Quaternary succession suggesting an active role of the isostatic compensation. Furthermore, the active back thrusting in the Corigliano Gulf could trigger a flexural subsidence mechanism even if fault activity and earthquakes do not seem play a role in the present subsidence. In this context, the compaction of Holocene deposits contributes to ground deformation. Despite the rapid urbanization of the area in the last 50 years, we do not consider the intensive groundwater pumping and related water table drop as the main triggering cause of subsidence phenomena, in disagreement with some previous publications. Our interpretation for the deformation fields related to natural and anthropogenic factors would be a comprehensive and exhaustive justification to the complexity of subsidence processes in the Sibari Plain

    How cardiologists can manage excess body weight and related cardiovascular risk. An expert opinion

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    Obesity is an important independent cardiovascular (CV) risk factor and a chronic inflammatory disease related to the development of insulin resistance, type 2 diabetes, dyslipidaemia, coronary artery disease, hypertension, heart failure, atrial fibrillation and obstructive sleep apnoea. Body Mass Index (BMI) values >27 kg/m2 are associated with an exponential increase in the risk for Major Adverse Cardiac Events (MACE). On the other hand, weight reduction can significantly reduce metabolic, CV and oncological risk. Orlistat, bupropion/naltrexone, liraglutide and semaglutide, combined with lifestyle changes, have proven to be effective in weight loss; the last two have been tested in randomized clinical trials (RCTs) with CV outcomes only in diabetic patients, and not in obese patients. To fill a fundamental gap of knowledge, the SELECT trial on patients with obesity and CV disease treated with semaglutide is ongoing, aiming at MACE as the primary endpoint. The battle against the social and clinical stigma towards obesity must be counteracted by promoting an awareness that elevates obesity to a complex chronic disease. Several actions should be implemented to improve the management of obesity, and cardiologists have a key role for achieving a global approach to patients with excess weight also through the correct implementation of available treatment strategies

    Differential methylation of inflammatory and insulinotropic genes after metabolic surgery in women

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    Context: Biliopancreatic diversion with duodenal switch (BPD-DS), a metabolic bariatric operation, induces durable loss of excess weight and reduced cardiometabolic risk. Altered epigenetic marks are mechanistically associated with environment-driven phenotypic variations. Objective: The current study aimed to compare gene methylation levels before and after BPD-DS to identify epigenetic marks potentially linked to metabolic improvements induced by BPD-DS. Design and patients: Metabolic risk factors and gene methylation levels of 20 women studied mean 12 years (range 4-22) after BPD-DS were compared to those of 20 severely obese surgical candidates as controls, matched for pre-surgical age, body mass index and dyslipidemia and hypertension prevalences. Whole-genome blood DNA methylation analysis enabled between-group differential methylation analyses. We calculated correlations between methylation levels of the most differentially methylated CpG sites and plasma glucose and insulin levels and HOMA-IR. Results: Differential methylation analysis identified 15,343 genes demonstrating at least one differentially methylated CpG site (p<1.43x10-7). Diabetic and inflammation/immune functions were among the most overrepresented from the 200 genes exhibiting the largest group differences in methylation levels. CpG sites methylation levels of genes related to insulin action correlated significantly with fasting insulin levels and homeostatic model of insulin resistance (p≤0.002 for all). Conclusion: These findings suggest that differential methylation levels in obese controls versus treated women may partially explain the durable metabolic improvements after BPD-DS

    Liraglutide Reduces Carotid Intima-Media Thickness by Reducing Small Dense Low-Density Lipoproteins in a Real-World Setting of Patients with Type 2 Diabetes: A Novel Anti-Atherogenic Effect

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    Introduction: Liraglutide has several non-glycemic effects, including those on plasma lipids and lipoproteins, contributing to its cardiovascular benefit; however, the exact underlying mechanisms remain unclear. We investigated a novel anti-atherogenic effect of liraglutide in a real-world prospective study on patients with type 2 diabetes (T2DM). Methods: Sixty-two patients with T2DM (31 men, 31 women; mean age ± standard deviation 61 ± 9&nbsp;years) naïve to incretin-based therapies were treated with liraglutide (1.2&nbsp;mg/day) as add-on therapy to metformin (1500–3000&nbsp;mg/day) for 4&nbsp;months. Laboratory analyses included the assessment of lipoprotein subclass profile by gel electrophoresis (Lipoprint; Quantimetrix Corp., Redondo Beach, CA, USA). Carotid intima-media thickness (cIMT) was assessed by Doppler ultrasonography. Statistical analyses included the paired t test, Spearman correlation and multiple regression analysis. Results: The addition of liraglutide to metformin monotherapy resulted in significant reductions in fasting glycemia, hemoglobin A1c, body mass index, waist circumference, total cholesterol, triglycerides and low-density lipoprotein (LDL)-cholesterol, as well as in cIMT. There was an increase in the large LDL-1 subfraction, with a concomitant reduction in atherogenic small dense LDL-3 and LDL-4 subfractions. Correlation analysis revealed a significant association between changes in cIMT and changes in small dense LDL-3 subfraction (r = 0.501; p &lt; 0.0001). Multivariate analysis, including all of the measured anthropometric and laboratory parameters, revealed that only changes in the small dense LDL-3 subfraction were independent predictors of changes in cIMT (p &lt; 0.0001). Conclusion: Our findings are the first to show that the vascular benefit of liraglutide in patients with T2DM is associated with reductions in atherogenic small dense LDL. This effect is independent of glycemic control and body weight reduction and may represent one of the key mechanisms by which liraglutide is able to reduce cardiovascular events. Trial Registration: ClinicalTrials.gov: NCT01715428

    Multiscenario flood hazard assessment using probabilistic runoff hydrograph estimation and 2D hydrodynamic modelling

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    In this paper, we aim to define a procedure of flood hazard assessment applicable to large river basins in which flood events can be induced/sustained by the full basin area or by fractions of the total area as functions of the extent of the triggering precipitation event. The proposed procedure is based on a combined approach accounting for (1) the reconstruction of intensity–duration–frequency curves expressing the magnitude in terms of intensity for multiple return periods; (2) the application of the soil conservation service method for runoff estimation from a selected rainfall scenario considering some characteristics of the basin (i.e. soil type, land use/treatment, surface condition, and antecedent moisture conditions); (3) 2D hydrodynamic modelling conducted by the HEC-RAS model using runoff hydrographs as hydrological input data; (4) the reconstruction of flood hazard maps by overlaying multiple inundation maps depicting flood extent for different return periods. To account for the variability in the extent of the triggering precipitation event and the resulting input hydrograph, multiple contributing areas are considered. The procedure is tested at the archaeological site of Sybaris in southern Italy, which is periodically involved in flood events of variable magnitude. The obtained results highlight that the variable extent of the floodable area is strongly conditioned by the extent of the contributing area and return period, as expected. The archaeological site is always involved in the simulated flooding process, except for the smallest contributing area for which only a 300-year event involves this part of the site. Our findings may be useful for developing and supporting flood risk management plans in the area. The developed procedure might be easily exported and tested in other fluvial contexts in which evaluations of multiple flood hazard scenarios, due to the basin geometry and extent, are needed

    Association of adipocyte genes with ASP expression: a microarray analysis of subcutaneous and omental adipose tissue in morbidly obese subjects

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    <p>Abstract</p> <p>Background</p> <p>Prevalence of obesity is increasing to pandemic proportions. However, obese subjects differ in insulin resistance, adipokine production and co-morbidities. Based on fasting plasma analysis, obese subjects were grouped as Low Acylation Stimulating protein (ASP) and Triglyceride (TG) (LAT) vs High ASP and TG (HAT). Subcutaneous (SC) and omental (OM) adipose tissues (n = 21) were analysed by microarray, and biologic pathways in lipid metabolism and inflammation were specifically examined.</p> <p>Methods</p> <p>LAT and HAT groups were matched in age, obesity, insulin, and glucose, and had similar expression of insulin-related genes (InsR, IRS-1). ASP related genes tended to be increased in the HAT group and were correlated (factor B, adipsin, complement C3, p < 0.01 each). Differences between LAT and HAT group were almost exclusively in SC tissue, with little difference in OM tissue. Increased C5L2 (p < 0.01), an ASP receptor, in HAT suggests a compensatory ASP pathway, associated with increased TG storage.</p> <p>Results</p> <p>HAT adipose tissue demonstrated increased lipid related genes for storage (CD36, DGAT1, DGAT2, SCD1, FASN, and LPL), lipolysis (HSL, CES1, perilipin), fatty acid binding proteins (FABP1, FABP3) and adipocyte differentiation markers (CEBPα, CEBPβ, PPARγ). By contrast, oxidation related genes were decreased (AMPK, UCP1, CPT1, FABP7). HAT subjects had increased anti-inflammatory genes TGFB1, TIMP1, TIMP3, and TIMP4 while proinflammatory PIG7 and MMP2 were also significantly increased; all genes, p < 0.025.</p> <p>Conclusion</p> <p>Taken together, the profile of C5L2 receptor, ASP gene expression and metabolic factors in adipose tissue from morbidly obese HAT subjects suggests a compensatory response associated with the increased plasma ASP and TG.</p

    The diacylglycerol kinase α/Atypical PKC/β1 integrin pathway in SDF-1α mammary carcinoma invasiveness

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    Diacylglycerol kinase α (DGKα), by phosphorylating diacylglycerol into phosphatidic acid, provides a key signal driving cell migration and matrix invasion. We previously demonstrated that in epithelial cells activation of DGKα activity promotes cytoskeletal remodeling and matrix invasion by recruiting atypical PKC at ruffling sites and by promoting RCP-mediated recycling of α5β1 integrin to the tip of pseudopods. In here we investigate the signaling pathway by which DGKα mediates SDF-1α-induced matrix invasion of MDA-MB-231 invasive breast carcinoma cells. Indeed we showed that, following SDF-1α stimulation, DGKα is activated and localized at cell protrusion, thus promoting their elongation and mediating SDF-1α induced MMP-9 metalloproteinase secretion and matrix invasion. Phosphatidic acid generated by DGKα promotes localization at cell protrusions of atypical PKCs which play an essential role downstream of DGKα by promoting Rac-mediated protrusion elongation and localized recruitment of β1 integrin and MMP-9. We finally demonstrate that activation of DGKα, atypical PKCs signaling and β1 integrin are all essential for MDA-MB-231 invasiveness. These data indicates the existence of a SDF-1α induced DGKα - atypical PKC - β1 integrin signaling pathway, which is essential for matrix invasion of carcinoma cells
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