Epigenetic signature in human development of vascular lesions: effects of maternal hypercolesterolemia

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The M3A multi-sensor buoy network of the Mediterranean Sea

International audienceA network of three multi-sensor timeseries stations able to deliver real time physical and biochemical observations of the upper thermocline has been developed for the needs of the Mediterranean Forecasting System during the MFSTEP project. They follow the experience of the prototype M3A system that was developed during the MFSPP project and has been tested during a pilot pre-operational period of 22 months (2000?2001). The systems integrate sensors for physical (temperature, salinity, turbidity, current speed and direction) as well as optical and chemical observations (dissolved oxygen, chlorophyll-a, PAR, nitrate). The south Aegean system (E1-M3A) follows a modular design using independent mooring lines and collects biochemical data in the upper 100 m and physical data in the upper 500 m of the water column. The south Adriatic buoy system (E2-M3A) uses similar instrumentation but on a single mooring line and also tests a new method of pumping water samples from relatively deep layers, performing analysis in the protected ''dry'' environment of the buoy interior. The Ligurian Sea system (W1-M3A) is an ideal platform for air-sea interaction processes since it hosts a large number of meteorological sensors while its ocean instrumentation, with real time transmission capabilities, is confined in the upper 50 m layer. Despite their different architecture, the three systems have common sampling strategy, quality control and data management procedures. The network operates in the Mediterranean Sea since autumn 2004 collecting timeseries data for calibration and validation of the forecasting system as well for process studies of regional dynamics

Beneficial contribution to glucose homeostasis by an agro-food waste product rich in abscisic acid. A results from a randomized controlled trial

The control of glucose homeostasis represents the primary goal for the prevention and management of diabetes and prediabetes. In recent decades, the hypoglycemic hormone abscisic acid (ABA) has attracted considerable interest in the scientific literature. In this regard, the high ABA concentration in immature fruits led us to consider these food matrices as candidates for diabetes control. Therefore, the beneficial efficacy of a nutraceutical formulation based on thinned nectarines (TNs) rich in ABA was tested through a three-month, three-arm, parallel-group, randomized controlled trial (RCT) conducted on sixty-one patients with type 2 diabetes (T2D). After 3 months, both the treatments with low doses of TN (500 mg 3 times/day) and high doses of TN (750 mg 3 times/day) showed a significant reduction in glycemic parameters compared to baseline. Treatment with low doses of TN showed a greater insulin-sparing effect (fasting plasma insulin, FPI: −29.2%, p < 0.05 vs. baseline) compared to the high-dose group (FPI: −16.5%, p < 0.05 vs. baseline). Moreover, a significant correlation between glycemia and ABA plasmatic levels was observed for both intervention groups at baseline and after 3 months. Overall, our data reasonably support TN as a promising and innovative nutraceutical product able to contribute to the management of glucose homeostasis

Central and Peripheral NPY Age‐Related Regulation: A Comparative Analysis in Fish Translational Models

NPY is among the most abundant neuropeptides in vertebrate brain and is primarily involved in the regulation of food intake. The NPY system is also associated with the aging process showing beneficial effects on neuronal survival via autophagy modulation. Here, we explore the age‐related regulation of NPY in the brain and foregut of the shortest‐ and longest‐lived fish species, Nothobranchius furzeri and Danio rerio, respectively. These two research models, despite some similarities, display profound biological differences making them attractive vertebrates to elucidate the mechanisms underlying the regulation of neuropeptide synthesis and function. It is noteworthy that in both fish species only Npya has been identified, while in the other teleosts two classes of NPY (Npya and Npyb) have been annotated. Our findings document that in both species: i) NPY is centrally regulated; ii) NPY levels increase in the brain during aging; iii) NPY is localized in the enteroendocrine cells as well as in the myenteric plexus and drastically decreases in old animals. According to our data, the age‐related regulation in the gut resembles that described in other vertebrate species while the increased levels in the brain offer the unique possibility to explore the role of NPY in model organisms to develop future experimental and translatable approaches

From Vineyard to Vision: Efficacy of Maltodextrinated Grape Pomace Extract (MaGPE) Nutraceutical Formulation in Patients with Diabetic Retinopathy

Despite recent advances, pharmacological treatments of diabetic retinopathy (DR) do not directly address the underlying oxidative stress. This study evaluates the efficacy of a nutraceutical formulation based on maltodextrinated grape pomace extract (MaGPE), an oxidative stress inhibitor, in managing DR. A 6-month, randomized, placebo-controlled clinical trial involving 99 patients with mild to moderate non-proliferative DR was conducted. The MaGPE group showed improvement in best-corrected visual acuity (BCVA) values at T3 (p < 0.001) and T6 (p < 0.01), a reduction in CRT (at T3 and T6, both p < 0.0001) and a stabilization of vascular perfusion percentage, with slight increases at T3 and T6 (+3.0% and +2.7% at T3 and T6, respectively, compared to baseline). Additionally, the levels of reactive oxygen metabolite derivatives (dROMs) decreased from 1100.6 ± 430.1 UCARR at T0 to 974.8 ± 390.2 UCARR at T3 and further to 930.6 ± 310.3 UCARR at T6 (p < 0.05 vs. T0). Similarly, oxidized low-density lipoprotein (oxLDL) levels decreased from 953.9 ± 212.4 μEq/L at T0 to 867.0 ± 209.5 μEq/L at T3 and markedly to 735.0 ± 213.7 μEq/L at T6 (p < 0.0001 vs. T0). These findings suggest that MaGPE supplementation effectively reduces retinal swelling and oxidative stress, contributing to improved visual outcomes in DR patients

The Use of Artificial Intelligence Approaches for Performance Improvement of Low-Cost Integrated Navigation Systems

In this paper, the authors investigate the possibility of applying artificial intelligence algorithms to the outputs of a low-cost Kalman filter-based navigation solution in order to achieve performance similar to that of high-end MEMS inertial sensors. To further improve the results of the prototype and simultaneously lighten filter requirements, different AI models are compared in this paper to determine their performance in terms of complexity and accuracy. By overcoming some known limitations (e.g., sensitivity on the dimension of input data from inertial sensors) and starting from Kalman filter applications (whose raw noise parameter estimates were obtained from a simple analysis of sensor specifications), such a solution presents an intermediate behavior compared to the current state of the art. It allows the exploitation of the power of AI models. Different Neural Network models have been taken into account and compared in terms of measurement accuracy and a number of model parameters; in particular, Dense, 1-Dimension Convolutional, and Long Short Term Memory Neural networks. As can be excepted, the higher the NN complexity, the higher the measurement accuracy; the models’ performance has been assessed by means of the root-mean-square error (RMSE) between the target and predicted values of all the navigation parameters

Endovascular treatment of lower extremity arteries is associated with an improved outcome in diabetic patients affected by intermittent claudication

BACKGROUND: Lower extremity peripheral arterial disease (LE-PAD) is a highly prevalent condition among diabetic patients, associated with reduced walking capacity and a high incidence of cardiovascular events. Endovascular revascularization of lower extremities arteries improves walking performance and quality of life of diabetic patients affected by intermittent claudication, but few studies evaluated the impact of revascularization on cardiovascular outcome in this high-risk population. Accordingly, in the present study we evaluated if leg-ischemia resolution by effective lower limbs percutaneous revascularization can also impact cardiovascular outcome in a homogeneous group of diabetic patients affected by intermittent claudication. METHODS: 236 diabetic patients affected by LE-PAD at stage II of Fontaine's classification, with ankle/brachial index ≤ 0.90 and one or more hemodynamically significant stenosis in at least one artery of the ileo-femoro-popliteal axis were enrolled in the study. According to the Trans-Atlantic Inter Society Consensus II recommendations, 123 (52.1%) underwent percutaneous transluminal angioplasty (PTA group), while 113 (47.9%) underwent conservative medical therapy only (MT group). The incidence of major cardiovascular events (cardiovascular death, myocardial infarction, ischemic stroke, coronary or carotid revascularization) was prospectively analyzed with Kaplan-Meier curves and the risk of developing a cardiovascular event calculated by Cox analyses. RESULTS: No baseline difference in cardiovascular risk factors were observed between the PTA and MT groups, except for a lower prevalence of males in PTA group (74.8% vs. 85.8%, p=0.034). Furthermore, patients in the PTA group showed a worse walking capacity as expressed by maximum walking distance (108.7 ± 300.9 vs 378.4 ± 552.3 meters, p<0.001). During a median follow-up of 20 months (12.0-29.0), the incidence of cardiovascular events was markedly lower in patients in the PTA group with respect to patients in the MT group (7.3% vs. 22.1%, p=0.001), and patients of the MT group had at Cox analysis a 3.9 increased risk with respect to PTA group, after adjustment for potential confounding factors (95% CI 1.1-15.3, p=0.049). CONCLUSIONS: The present study shows that lower limbs revascularization of diabetic patients affected by intermittent claudication, in addition to improve walking performance, is associated with a reduction in the incidence of future major cardiovascular events

A randomized, placebo-controlled, phase II study of obeticholic acid for primary sclerosing cholangitis

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Meta-GWAS Reveals Novel Genetic Variants Associated with Urinary Excretion of Uromodulin

Background Uromodulin, the most abundant protein excreted in normal urine, plays major roles in kidney physiology and disease. The mechanisms regulating the urinary excretion of uromodulin remain essentially unknown. Methods We conducted a meta-analysis of genome-wide association studies for raw (uUMOD) and indexed to creatinine (uUCR) urinary levels of uromodulin in 29,315 individuals of European ancestry from 13 cohorts. We tested the distribution of candidate genes in kidney segments and investigated the effects of keratin-40 (KRT40) on uromodulin processing. Results Two genome-wide significant signals were identified for uUMOD: a novel locus (P 1.24E-08) over the KRT40 gene coding for KRT40, a type 1 keratin expressed in the kidney, and the UMOD-PDILT locus (P 2.17E-88), with two independent sets of single nucleotide polymorphisms spread over UMOD and PDILT. Two genome-wide significant signals for uUCR were identified at the UMOD-PDILT locus and at the novel WDR72 locus previously associated with kidney function. The effect sizes for rs8067385, the index single nucleotide polymorphism in the KRT40 locus, were similar for both uUMOD and uUCR. KRT40 colocalized with uromodulin and modulating its expression in thick ascending limb (TAL) cells affected uromodulin processing and excretion. Conclusions Common variants in KRT40,WDR72, UMOD, and PDILT associate with the levels of uromodulin in urine. The expression of KRT40 affects uromodulin processing in TAL cells. These results, although limited by lack of replication, provide insights into the biology of uromodulin, the role of keratins in the kidney, and the influence of the UMOD-PDILT locus on kidney function