The n-acetyl phenylalanine glucosamine derivative attenuates the inflammatory/catabolic environment in a chondrocyte-synoviocyte co-culture system

Osteoarthritis (OA), the most prevalent degenerative joint disease, still lacks a true disease-modifying therapy. The involvement of the NF-κB pathway and its upstream activating kinases in OA pathogenesis has been recognized for many years. The ability of the N-acetyl phenylalanine glucosamine derivative (NAPA) to increase anabolism and reduce catabolism via inhibition of IKKα kinase has been previously observed in vitro and in vivo. The present study aims to confirm the chondroprotective effects of NAPA in an in vitro model of joint OA established with primary cells, respecting both the crosstalk between chondrocytes and synoviocytes and their phenotypes. This model satisfactorily reproduces some features of the previously investigated DMM model, such as the prominent induction of ADAMTS-5 upon inflammatory stimulation. Both gene and protein expression analysis indicated the ability of NAPA to counteract key cartilage catabolic enzymes (ADAMTS-5) and effectors (MCP-1). Molecular analysis showed the ability of NAPA to reduce IKKα nuclear translocation and H3Ser10 phosphorylation, thus inhibiting IKKα transactivation of NF-κB signalling, a pivotal step in the NF-κB-dependent gene expression of some of its targets. In conclusion, our data confirm that NAPA could truly act as a disease-modifying drug in OA

Seismic Vulnerability of the Italian Roadway Bridge Stock

This study focuses on the seismic vulnerability evaluation of the Italian roadway bridge stock, within the framework of a Civil Protection sponsored project. A comprehensive database of existing bridges (17,000 bridges with different level of knowledge) was implemented. At the core of the study stands a procedure for automatically carrying out state-of-the-art analytical evaluation of fragility curves for two performance levels – damage and collapse – on an individual bridge basis. A webGIS was developed to handle data and results. The main outputs are maps of bridge seismic risk (from the fragilities and the hazard maps) at the national level and real-time scenario damage-probability maps (from the fragilities and the scenario shake maps). In the latter case the webGIS also performs network analysis to identify routes to be followed by rescue teams. Consistency of the fragility derivation over the entire bridge stock is regarded as a major advantage of the adopted approach

Thermodynamics of the classical spin-ice model with nearest neighbour interactions using the Wang-Landau algorithm

In this article we study the classical nearest-neighbour spin-ice model (nnSI) by means of Monte Carlo simulations, using the Wang-Landau algorithm. The nnSI describes several of the salient features of the spin-ice materials. Despite its simplicity it exhibits a remarkably rich behaviour. The model has been studied using a variety of techniques, thus it serves as an ideal benchmark to test the capabilities of the Wang Landau algorithm in magnetically frustrated systems. We study in detail the residual entropy of the nnSI and, by introducing an applied magnetic field in two different crystallographic directions ([111] and [100],) we explore the physics of the kagome-ice phase, the transition to full polarisation, and the three dimensional Kasteleyn transition. In the latter case, we discuss how additional constraints can be added to the Hamiltonian, by taking into account a selective choice of states in the partition function and, then, show how this choice leads to the realization of the ideal Kasteleyn transition in the system.Comment: 9 pages, 9 figure

The Christmas 2018 eruption at Mt. Etna: enlightening how the volcano factory works through a multi‐parametric inspection

The 24–27 December 2018 flank eruption at Mount Etna (Southern Italy) has been investigated through a multidisciplinary approach in which olivine chemical zoning and diffusion chronometry data were integrated with models inferred by GNSS (Global Navigation Satellite System) measurements. Inspection of the olivine chemical zoning from core to rim allowed the identification of some dominant ways of transfer and interaction between magmas pertaining to different magmatic environments. Most of crystal cores are representative of crystallization at pressure of 290–230 and 160–120 MPa. Olivine rims suggest re‐equilibration at shallow pressure (≤30 MPa). Geodetic‐based models indicate pressurization of near‐vertical prolate spheroidal sources centered at ∼7.2 km below sea level (bsl) between 9 June 2017 and 28 June 2018 and later at ∼5.1 km bsl between 28 June 2018 and the eruption onset. Geodetic data also highlight a change in the inflation rate since late June 2018 and later around November 2018, which has been here related to both replenishment phases and magma uprising across the plumbing system. Timescales of magma replenishment are in agreement with prolonged recharge from deep levels upward to shallow environments started about 6 months before the eruption, with further replenishment involving the upper magmatic environments just 3–16 days before the eruption. At present, the eruptive activity at the volcano is primarily controlled by pressure imbalances affecting extensive sections of the plumbing system, with possibility to develop persistent eruptive activity at the summit versus flank eruptions depending on fortuitous interruptions of the steady magma recharge/discharge rate at shallow levels

Functional assessment of the collateral-dependent circulation in chronic total coronary occlusion using transthoracic Doppler ultrasound and venous adenosine infusion

The measurement of collateral flow reserve (CFR; the hyperemic/baseline collateral flow velocity ratio) in patients with chronic total coronary occlusion requires invasive and expensive techniques. Noninvasive transthoracic coronary Doppler echocardiography may be an alternative option. Fifty-one patients with chronic total coronary occlusion were evaluated by transthoracic coronary Doppler echocardiography and venous adenosine infusion to measure CFR in occluded coronary arteries (the left anterior descending artery in 44 patients and the artery supplying the posterior descending artery in 7 patients). CFR data were plotted against 3 angiographic parameters: (1) grade of the epicardial filling of the occluded artery (1=absent, 2=partial, 3=complete), (2) stenosis of the donor artery, and (3) the extent of coronary artery disease (vessels with >or=70% stenosis). Collateral flow was maintained at stress in 34 patients (CFR>or=1, range 1.0 to 2.2) but was withdrawn in 17 patients (CFR<1, range 0.25 to 0.90). CFR increased with the degree of angiographic collateral flow (grade 1: 0.73+/-0.29; grade 2: 1.16+/-0.31; grade 3: 1.34+/-0.49; F=5.31, p=0.008). A multivariate model of CFR prediction showed a direct relation with angiographic collateral grade and the number of diseased vessels and an inverse relation with stenosis of the donor artery. In conclusion, CFR measurement is feasible by transthoracic coronary Doppler echocardiography. One third of the patients with chronic total coronary occlusion had collateral flow withdrawal at stress, which occurs when collateral circulation is poor and when the donor artery is stenotic. CFR correlates with angiographic collateral grade and with the extent of coronary artery disease

Hydrogeochemical and isotopic signature of surface and groundwater in a highly industrialized sector of the Rio de la Plata coastal plain (Argentina)

The coastal plain of the middle estuary of the Río de la Plata is a highly industrialized area and is densely populated by sectors. The main human activity in the sector encompassed between the cities of Ensenada and Berisso is associated with the petrochemical industry. In this work, hydrogeochemical and isotopic characteristics of surface and groundwater in the impacted area are analyzed and the results are contrasted with those obtained in an undisturbed protected area. Major and trace elements were determined using standardized methods while the stable isotopes δ18O y δ2H were analyzed by mass spectroscopy. Human impact is evidenced by the occurrence of large variations in the major chemical composition of water, and also by the elevated concentrations of some trace elements that are not contributed from natural sources. These results may contribute to the understanding of chemical processes and pollutants distribution in highly industrialized coastal plain areas.Centro de Investigaciones Geológica

An Overview of Major Health Information Technology, Public Health, Medicaid, and COBRA Provisions of the American Recovery and Reinvestment Act of 2009

A detailed side-by-side analysis of the individual components of the American Recovery and Reinvestment Act of 2009 (ARRA), signed into law on February 17, 2009. One of the most sweeping pieces of economic legislation ever enacted, ARRA not only provides hundreds of billions of dollars in new health and health care spending but also makes comprehensive reforms in health law and policy, particularly in the area of health information law, including health information technology (HIT) adoption and health information privacy