Influence of disordered porous media in the anomalous properties of a simple water model

The thermodynamic, dynamic and structural behavior of a water-like system confined in a matrix is analyzed for increasing confining geometries. The liquid is modeled by a two dimensional associating lattice gas model that exhibits density and diffusion anomalies, in similarity to the anomalies present in liquid water. The matrix is a triangular lattice in which fixed obstacles impose restrictions to the occupation of the particles. We show that obstacules shortens all lines, including the phase coexistence, the critical and the anomalous lines. The inclusion of a very dense matrix not only suppress the anomalies but also the liquid-liquid critical point

Ab initio simulations of Cu binding sites in the N-terminal region of PrP

The prion protein (PrP) binds Cu2+ ions in the octarepeat domain of the N-terminal tail up to full occupancy at pH=7.4. Recent experiments show that the HGGG octarepeat subdomain is responsible for holding the metal bound in a square planar coordination. By using first principle ab initio molecular dynamics simulations of the Car-Parrinello type, the Cu coordination mode to the binding sites of the PrP octarepeat region is investigated. Simulations are carried out for a number of structured binding sites. Results for the complexes Cu(HGGGW)+(wat), Cu(HGGG) and the 2[Cu(HGGG)] dimer are presented. While the presence of a Trp residue and a H2O molecule does not seem to affect the nature of the Cu coordination, high stability of the bond between Cu and the amide Nitrogens of deprotonated Gly's is confirmed in the case of the Cu(HGGG) system. For the more interesting 2[Cu(HGGG)] dimer a dynamically entangled arrangement of the two monomers, with intertwined N-Cu bonds, emerges. This observation is consistent with the highly packed structure seen in experiments at full Cu occupancy.Comment: 4 pages, conference proceedin

Is depression a real risk factor for acute myocardial infarction mortality? A retrospective cohort study

Background: Depression has been associated with a higher risk of cardiovascular events and a higher mortality in patients with one or more comorbidities. This study investigated whether continuative use of antidepressants (ADs), considered as a proxy of a state of depression, prior to acute myocardial infarction (AMI) is associated with a higher mortality afterwards. The outcome to assess was mortality by AD use. Methods: A retrospective cohort study was conducted in the Veneto Region on hospital discharge records with a primary diagnosis of AMI in 2002-2015. Subsequent deaths were ascertained from mortality records. Drug purchases were used to identify AD users. A descriptive analysis was conducted on patients' demographics and clinical data. Survival after discharge was assessed with a Kaplan-Meier survival analysis and Cox's multiple regression model. Results: Among 3985 hospital discharge records considered, 349 (8.8%) patients were classified as AD users'. The mean AMI-related hospitalization rate was 164.8/100,000 population/year, and declined significantly from 204.9 in 2002 to 130.0 in 2015, but only for AD users (-40.4%). The mean overall follow-up was 4.64.1years. Overall, 523 patients (13.1%) died within 30days of their AMI. The remainder survived a mean 5.3 +/- 4.0years. After adjusting for potential confounders, use of antidepressants was independently associated with mortality (adj OR=1.75, 95% CI: 1.40-2.19). Conclusions: Our findings show that AD users hospitalized for AMI have a worse prognosis in terms of mortality. The use of routinely-available records can prove an efficient way to monitor trends in the state of health of specific subpopulations, enabling the early identification of AMI survivors with a history of antidepressant use

Caspase-independent programmed cell death triggers Ca2PO4 deposition in an in vitro model of nephrocalcinosis

We provide evidence of caspase-independent cell death triggering the calcification process in GDNF-silenced HK-2 cells

Dose escalation of desmoteplase for acute ischemic stroke (DEDAS): evidence of safety and efficacy 3 to 9 hours after stroke onset

<p><b>Background and Purpose:</b> Desmoteplase is a novel plasminogen activator with favorable features in vitro compared with available agents. This study evaluated safety and efficacy of intravenous (IV) desmoteplase in patients with perfusion/diffusion mismatch on MRI 3 to 9 hours after onset of acute ischemic stroke.</p> <p><b>Methods:</b> DEDAS was a placebo-controlled, double-blind, randomized, dose-escalation study investigating doses of 90 μg/kg and 125 μg/kg desmoteplase. Eligibility criteria included baseline National Institute of Health Stroke Scale (NIHSS) scores of 4 to 20 and MRI evidence of perfusion/diffusion mismatch. The safety end point was the rate of symptomatic intracranial hemorrhage. Primary efficacy co-end points were MRI reperfusion 4 to 8 hours after treatment and good clinical outcome at 90 days. The primary analyses were intent-to-treat. Before unblinding, a target population, excluding patients violating specific MRI criteria, was defined.</p> <p><b>Results:</b> Thirty-seven patients were randomized and received treatment (intent-to-treat; placebo: n=8; 90 μg/kg: n=14; 125 μg/kg: n=15). No symptomatic intracranial hemorrhage occurred. Reperfusion was achieved in 37.5% (95% CI [8.5; 75.5]) of placebo patients, 18.2% (2.3; 51.8) of patients treated with 90 μg/kg desmoteplase, and 53.3% (26.6; 78.7) of patients treated with 125 μg/kg desmoteplase. Good clinical outcome at 90 days occurred in 25.0% (3.2; 65.1) treated with placebo, 28.6% (8.4; 58.1) treated with 90 μg/kg desmoteplase and 60.0% (32.3; 83.7) treated with 125 μg/kg desmoteplase. In the target population (n=25), the difference compared with placebo increased and was statistically significant for good clinical outcome with 125 μg/kg desmoteplase (P=0.022).</p> <p><b>Conclusions:</b> Treatment with IV desmoteplase 3 to 9 hours after ischemic stroke onset appears safe. At a dose of 125 μg/kg desmoteplase appeared to improve clinical outcome, especially in patients fulfilling all MRI criteria. The results of DEDAS generally support the results of its predecessor study, Desmoteplase in Acute Ischemic Stroke (DIAS).</p&gt

Properties and occurrence rates of KeplerKepler exoplanet candidates as a function of host star metallicity from the DR25 catalog

Correlations between the occurrence rate of exoplanets and their host star properties provide important clues about the planet formation processes. We studied the dependence of the observed properties of exoplanets (radius, mass, and orbital period) as a function of their host star metallicity. We analyzed the planetary radii and orbital periods of over 2800 $Kepler$ candidates from the latest $Kepler$ data release DR25 (Q1-Q17) with revised planetary radii based on $Gaia$~DR2 as a function of host star metallicity (from the Q1-Q17 (DR25) stellar and planet catalog). With a much larger sample and improved radius measurements, we are able to reconfirm previous results in the literature. We show that the average metallicity of the host star increases as the radius of the planet increases. We demonstrate this by first calculating the average host star metallicity for different radius bins and then supplementing these results by calculating the occurrence rate as a function of planetary radius and host star metallicity. We find a similar trend between host star metallicity and planet mass: the average host star metallicity increases with increasing planet mass. This trend, however, reverses for masses $> 4.0\, M_\mathrm{J}$: host star metallicity drops with increasing planetary mass. We further examined the correlation between the host star metallicity and the orbital period of the planet. We find that for planets with orbital periods less than 10 days, the average metallicity of the host star is higher than that for planets with periods greater than 10 days.Comment: 14 pages, 13 Figures, Accepted for publication in The Astronomical Journa