Hotspots of microplastic accumulation at the land-sea transition and their spatial heterogeneity: The Po River prodelta (Adriatic Sea).

Deltas are the locus of river-borne sediment accumulation, however, their role in sequestering plastic pollutants is still overlooked. By combining geomorphological, sedimentological, and geochemical analyses, which include time-lapse multibeam bathymetry, sediment provenance, and µFT-IR analyses, we investigate the fate of plastic particles after a river flood event providing an unprecedented documentation of the spatial distribution of sediment as well as of microplastics (MPs), including particles fibers, and phthalates (PAEs) abundances in the subaqueous delta. Overall sediments are characterized by an average of 139.7 ± 80 MPs/kg d.w., but display spatial heterogeneity of sediment and MPs accumulation: MPs are absent within the active sandy delta lobe, reflecting dilution by clastic sediment (ca. 1.3 Mm3) and sediment bypass. The highest MP concentration (625 MPs/kg d.w.) occurs in the distal reaches of the active lobe where flow energy dissipates. In addition to MPs, cellulosic fibers are relevant (of up to 3800 fibers/kg d.w.) in all the analyzed sediment samples, and dominate (94 %) with respect to synthetic polymers. Statistically significant differences in the relative concentration of fiber fragments ≤0.5 mm in size were highlighted between the active delta lobe and the migrating bedforms in the prodelta. Fibers were found to slightly follow a power law size distribution coherent with a one-dimensional fragmentation model and thus indicating the absence of a size dependent selection mechanism during burial. Multivariate statistical analysis suggests traveling distance and bottom-transport regime as the most relevant factors controlling particle distribution. Our findings suggest that subaqueous prodelta should be considered hot spots for the accumulation of MPs and associated pollutants, albeit the strong lateral heterogeneity in their abundances reflects changes in the relative influence of fluvial and marine processes.

Distinguishable DNA methylation defines a cardiac-specific epigenetic clock.

BACKGROUND: The present study investigates whether epigenetic differences emerge in the heart of patients undergoing cardiac surgery for an aortic valvular replacement (AVR) or coronary artery bypass graft (CABG). An algorithm is also established to determine how the pathophysiological condition might influence the human biological cardiac age. RESULTS: Blood samples and cardiac auricles were collected from patients who underwent cardiac procedures: 94 AVR and 289 CABG. The CpGs from three independent blood-derived biological clocks were selected to design a new blood- and the first cardiac-specific clocks. Specifically, 31 CpGs from six age-related genes, ELOVL2, EDARADD, ITGA2B, ASPA, PDE4C, and FHL2, were used to construct the tissue-tailored clocks. The best-fitting variables were combined to define new cardiac- and blood-tailored clocks validated through neural network analysis and elastic regression. In addition, telomere length (TL) was measured by qPCR. These new methods revealed a similarity between chronological and biological age in the blood and heart; the average TL was significantly higher in the heart than in the blood. In addition, the cardiac clock discriminated well between AVR and CABG and was sensitive to cardiovascular risk factors such as obesity and smoking. Moreover, the cardiac-specific clock identified an AVR patient's subgroup whose accelerated bioage correlated with the altered ventricular parameters, including left ventricular diastolic and systolic volume. CONCLUSION: This study reports on applying a method to evaluate the cardiac biological age revealing epigenetic features that separate subgroups of AVR and CABG.

Sodium nitroprusside for advanced heart failure. A metanalysis of literature data.

Advanced heart failure (HF) is associated with a very poor prognosis and places a big burden on health-care services. The gold standard treatment, i.e. long-term mechanical circulatory support or heart transplantation, is precluded in many patients but observational studies suggest that the use of SNP might be associated with favourable long-term clinical outcomes. We performed a metanalysis of published studies that compared sodium nitroprusside (SNP) with optimal medical therapy to examine the safety and efficacy of SNP as part of the treatment regimen of patients hospitalized for advanced heart failure (HF). We searched PUBMED, EMBASE and WEB OF SCIENCE for studies that compared SNP with optimal medical therapy in advanced HF on July 2022. After screening 700 full-text articles, data from two original articles were included in a combined analysis. The analysis demonstrated a 66% reduction in the odds of death in advanced HF patients treated with SNP. The results show the potential importance of the inclusion of SNP in the treatment regimen of patients hospitalized because of advanced HF and underlines that controlled, randomized studies are still required in this condition.

Spontaneous NaCl-doped ices Ih, Ic, III, V and VI. Understanding the mechanism of ion inclusion and its dependence on the crystalline structure of ice.

Direct coexistence simulations on a microsecond time scale have been performed for different types of ice (Ih, Ic, III, V, and VI) in contact with a NaCl aqueous solution at different pressures. In line with the previous results obtained for ice Ih [Conde et al., Phys. Chem. Chem. Phys., 2017, 19, 9566-9574], our results reveal the spontaneous growth of a new ice doped phase and the formation of a brine rejection phase in all ices studied. However, both the preferential incorporation of ions into the ice lattice and the inclusion mechanisms depend on the crystalline structure of each ice. This work shows the inclusion of Cl- and Na+ ions in ice from salt using molecular dynamics simulation, in agreement with the experimental evidence found in the literature. The model used for water is TIP4P/2005. For NaCl we employ a set of potential parameters that uses unit charges for the ions.

The management of patients with acute ischemic stroke while on direct oral anticoagulants (DOACs): data from an Italian cohort and a proposed algorithm.

Approximately 1-2% of patients with non-valvular atrial fibrillation have an acute ischemic stroke (AIS) while on direct oral anticoagulant (DOAC) treatment every year. However, current evidence on stroke subtypes, pathophysiology and factors leading to the failure of DOAC preventive therapy in a "real world" setting is still scanty. This study aimed at investigating whether there is any relationship between DOAC plasma levels and the stroke occurrence, on the basis of the phenotypic classification and pathophysiology of the stroke, in a cohort of DOAC-treated patients admitted to our hospital for AIS over 1-year period. A total of 28 patients had DOAC plasma levels determined in emergency and were included in the study, nine patients receiving dabigatran, 11 rivaroxaban and 8 apixaban. The DOAC levels were low in 8/28 patients (28.6% of the sample), intermediate in 4 (14.3%) and high in 16 (57.1%). The most prevalent stroke subtype was the small vessel disease, according to the A-S-C-O phenotypic classification, in 53.6% of our sample. The most common clinical presentation was "minor stroke" in 71.4% of the cases. There was a significantly higher proportion of patients with high DOAC levels in the small vessel group, compared to the cardioembolic group without other phenotypes. The question arises as to the most suitable clinical management of AIS in these patients on DOACs. In the current absence of clear evidence, taking into account the DOAC levels (low/intermediate/high) and the underlying stroke pathophysiology, we present a flowchart of our proposed clinical management of ischemic stroke in patients while on DOAC.

Heterogeneous Reconstruction of Tracks and Primary Vertices With the CMS Pixel Tracker.

The High-Luminosity upgrade of the Large Hadron Collider (LHC) will see the accelerator reach an instantaneous luminosity of 7 × 1034 cm-2 s-1 with an average pileup of 200 proton-proton collisions. These conditions will pose an unprecedented challenge to the online and offline reconstruction software developed by the experiments. The computational complexity will exceed by far the expected increase in processing power for conventional CPUs, demanding an alternative approach. Industry and High-Performance Computing (HPC) centers are successfully using heterogeneous computing platforms to achieve higher throughput and better energy efficiency by matching each job to the most appropriate architecture. In this paper we will describe the results of a heterogeneous implementation of pixel tracks and vertices reconstruction chain on Graphics Processing Units (GPUs). The framework has been designed and developed to be integrated in the CMS reconstruction software, CMSSW. The speed up achieved by leveraging GPUs allows for more complex algorithms to be executed, obtaining better physics output and a higher throughput.

HIV-1 Vpr mediates the depletion of the cellular repressor CTIP2 to counteract viral gene silencing.

Mammals have evolved many antiviral factors impacting different steps of the viral life cycle. Associated with chromatin-modifying enzymes, the cellular cofactor CTIP2 contributes to HIV-1 gene silencing in latently infected reservoirs that constitute the major block toward an HIV cure. We report, for the first time, that the virus has developed a strategy to overcome this major transcriptional block. Productive HIV-1 infection results in a Vpr-mediated depletion of CTIP2 in microglial cells and CD4+ T cells, two of the major viral reservoirs. Associated to the Cul4A-DDB1-DCAF1 ubiquitin ligase complex, Vpr promotes CTIP2 degradation via the proteasome pathway in the nuclei of target cells and notably at the latent HIV-1 promoter. Importantly, Vpr targets CTIP2 associated with heterochromatin-promoting enzymes dedicated to HIV-1 gene silencing. Thereby, Vpr reactivates HIV-1 expression in a microglial model of HIV-1 latency. Altogether our results suggest that HIV-1 Vpr mediates the depletion of the cellular repressor CTIP2 to counteract viral gene silencing.

Characterization of hydration water in supercooled water-trehalose solutions: The role of the hydrogen bonds network.

The structural and dynamical properties of hydration water in aqueous solutions of trehalose are studied with molecular dynamics simulation. We simulate the systems in the supercooled region to investigate how the interaction with the trehalose molecules modifies the hydrogen bond network, the structural relaxation, and the diffusion properties of hydration water. The analysis is performed by considering the radial distribution functions, the residence time of water molecules in the hydration shell, the two body excess entropy, and the hydrogen bond water-water and water-trehalose correlations of the hydration water. The study of the two body excess entropy shows the presence of a fragile to strong crossover in supercooled hydration water also found in the relaxation time of the water-water hydrogen bond correlation function, and this is in agreement with predictions of the mode coupling theory and of previous studies of the oxygen-oxygen density correlators [A. Iorio et al., J. Mol. Liq. 282, 617 (2019); Sci. China: Phys., Mech. Astron. 62, 107011 (2019)]. The water-trehalose hydrogen bond correlation function instead evidences a strong to strong crossover in the relaxation time, and this crossover is related to a trehalose dynamical transition. This signals the role that the strong interplay between the soluted molecules and the surrounding solvent has in determining the dynamical transition common to both components of the system that happens upon cooling and that is similar to the well known protein dynamical transition. We connect our results with the cryoprotecting role of trehalose molecules.

High density liquid structure enhancement in glass forming aqueous solution of LiCl.

We investigate using molecular dynamics simulations the dynamical and structural properties of LiCl:6H2O aqueous solution upon supercooling. This ionic solution is a glass forming liquid of relevant interest in connection with the study of the anomalies of supercooled water. The LiCl:6H2O solution is easily supercooled and the liquid state can be maintained over a large decreasing temperature range. We performed simulations from ambient to 200 K in order to investigate how the presence of the salt modifies the behavior of supercooled water. The study of the relaxation time of the self-density correlation function shows that the system follows the prediction of the mode coupling theory and behaves like a fragile liquid in all the range explored. The analysis of the changes in the water structure induced by the salt shows that while the salt preserves the water hydrogen bonds in the system, it strongly affects the tetrahedral hydrogen bond network. Following the interpretation of the anomalies of water in terms of a two-state model, the modifications of the oxygen radial distribution function and the angular distribution function of the hydrogen bonds in water indicate that LiCl has the role of enhancing the high density liquid component of water with respect to the low density component. This is in agreement with recent experiments on aqueous ionic solutions.

Freezing Temperatures, Ice Nanotubes Structures, and Proton Ordering of TIP4P/ICE Water inside Single Wall Carbon Nanotubes.

A very recent experimental paper importantly and unexpectedly showed that water in carbon nanotubes is already in the solid ordered phase at the temperature where bulk water boils. The water models used so far in literature for molecular dynamics simulations in carbon nanotubes show freezing temperatures lower than the experiments. We present here results from molecular dynamics simulations of water inside single walled carbon nanotubes using an extremely realistic model for both liquid and icy water, the TIP4P/ICE. The water behavior inside nanotubes of different diameters has been studied upon cooling along the isobars at ambient pressure starting from temperatures where water is in a liquid state. We studied the liquid/solid transition, and we observed freezing temperatures higher than in bulk water and that depend on the diameter of the nanotube. The maximum freezing temperature found is 390 K, which is in remarkable agreement with the recent experimental measurements. We have also analyzed the ice structure called "ice nanotube" that water forms inside the single walled carbon nanotubes when it freezes. The ice forms observed are in agreement with previous results obtained with different water models. A novel finding, a partial proton ordering, is evidenced in our ice nanotubes at finite temperature.

Structural properties and fragile to strong transition in confined water.

We derive by computer simulation the radial distribution functions of water confined in a silica pore modeled to reproduce MCM-41. We perform the calculations in a range of temperatures from ambient to deep supercooling for the subset of water molecules that reside in the inner shell (free water) by applying the excluded volume corrections. By comparing with bulk water we find that the first shell of the oxygen-oxygen and hydrogen-hydrogen radial distribution functions is less sharp and the first minimum fills in while the oxygen-hydrogen structure does not significantly change, indicating that the free water keeps the hydrogen bond short range order. The two body excess entropy of supercooled water is calculated from the radial distribution functions. We connect the behavior of this function to the relaxation time of the same system already studied in previous simulations. We show that the two body entropy changes its behavior in coincidence with the crossover of the relaxation time from the mode coupling fragile to the strong Arrhenius regime. As for bulk water also in confinement, the two body entropy has a strict connection with the dynamical relaxation.

Microscopic origin of the fragile to strong crossover in supercooled water: The role of activated processes.

We perform an accurate analysis of the density self-correlation functions of TIP4P/2005 supercooled water on approaching the region of the liquid-liquid critical point. In a previous work on this model, we provided evidence of a fragile to strong crossover of the dynamical behavior in the deep supercooled region. The structural relaxation follows the Mode Coupling theory in the fragile region and then deviates from Mode Coupling regime to a strong Arrhenius behavior. This crossover is particularly important in water because it is connected to the thermodynamics of the supercooled region. To better understand the origin of this crossover, we compute now the Van Hove self-correlation functions. In particular we aim at investigating the presence and the role of the hopping phenomena that are the cause of the fragile to strong crossover in simple liquids. In TIP4P/2005 water, we find hopping processes too and we analyze how they depend on temperature and density upon approaching the fragile to strong crossover and the Mode Coupling ideal crossover temperature. Our results show that water behaves like a simple glass former. After an initial ballistic regime, the cage effect dominates the mild supercooled region, with diffusion taking place at long time. At the fragile to strong crossover, we find that hopping (activated) processes start to play a role. This is evidenced by the appearance of peaks in the Van Hove correlation functions. In the deep supercooled regime, our analysis clearly indicates that activated processes dominate the dynamics. The comparison between the Van Hove functions and the radial distribution functions allows to better understand the mechanism of hopping phenomena in supercooled water and to connect their onset directly with the crossing of the Widom Line.

Spontaneous NaCl-doped ice at seawater conditions: focus on the mechanisms of ion inclusion.

Molecular dynamics simulations on the microsecond time scale have been performed on an aqueous solution of TIP4P/2005 water and NaCl by using the direct coexistence technique to study the ice growth and the ice/liquid interface water. At ambient pressure, for temperatures above the eutectic point of the salt and at seawater concentrations the brine rejection phenomenon and the spontaneous growth of an ice slab doped by the salt are obtained, as found in natural terrestrial and planetary environments. Experiments indicate that Cl- goes via substitution to ice sites. In line with this evidence we find a new result: the Cl- ion included in the lattice always substitutes not one but two water molecules, leaving the surrounding ice structure not distorted. The Na+ ion shows a lower probability of being included in the ice and it occupies an interstitial site, causing a local distortion of the lattice. No signs of significant ion diffusion are observed in the lattice.

High precision determination of the melting points of water TIP4P/2005 and water TIP4P/Ice models by the direct coexistence technique.

An exhaustive study by molecular dynamics has been performed to analyze the factors that enhance the precision of the technique of direct coexistence for a system of ice and liquid water. The factors analyzed are the stochastic nature of the method, the finite size effects, and the influence of the initial ice configuration used. The results obtained show that the precision of estimates obtained through the technique of direct coexistence is markedly affected by the effects of finite size, requiring systems with a large number of molecules to reduce the error bar of the melting point. This increase in size causes an increase in the simulation time, but the estimate of the melting point with a great accuracy is important, for example, in studies on the ice surface. We also verified that the choice of the initial ice Ih configuration with different proton arrangements does not significantly affect the estimate of the melting point. Importantly this study leads us to estimate the melting point at ambient pressure of two of the most popular models of water, TIP4P/2005 and TIP4P/Ice, with the greatest precision to date.

Additional predictive value of nutritional status in the prognostic assessment of heart failure patients.

BACKGROUND AND AIMS: Nutritional status (NS) is not routinely assessed in HF. We sought to evaluate whether NS may be additive to a comprehensive pre-discharge evaluation based on a clinical score that includes BMI (MAGGIC) and on an index of functional capacity (six minute walking test, 6mWT) in HF patients. METHODS AND RESULTS: The CONUT (Controlling Nutritional Status) score (including serum albumin level, total cholesterol and lymphocyte count) was computed in 466 consecutive patients (mean age 61 ± 11 years, NYHA class 2.6 ± 0.6, LVEF 34 ± 11%, BMI 27.2 ± 4.5) who had pre-discharge MAGGIC and 6MWT. The endpoint was all-cause mortality. Mild or moderate undernourishment was present in 54% of patients with no differences across BMI strata. The 12-month event rate was 7.7%. Deceased patients had a more compromised NS (CONUT 2.8 ± 1.5 vs 1.7 ± 1.3, p < 0.0001), and a more advanced HF (MAGGIC 28.2 ± 6.0 vs 22.0 ± 6.6, p < 0.0001; 6MWT 311.1 ± 102.2 vs. 408.9 ± 95.9 m, p < 0.0001). The 12-month mortality rate varied from 4% for well-nourished to 11% for undernourished patients (p = 0.008). At univariate analysis, the CONUT was predictive for all-cause mortality with a Hazard Ratio of 1.701 [95% CI 1.363-2.122], p < 0.0001. Multivariable analysis showed that the CONUT significantly added to the combination of MAGGIC and 6MWT and improved predictive discrimination and risk classification (c-index 0.82 [95% CI 0.75-0.88], integrated discrimination improvement 0.028 [95% CI 0.015-0.081]). CONCLUSIONS: In HF patients assessment of NS, significantly improves prediction of 12-month mortality on top of the information provided by clinical evaluation and functional capacity and should be incorporated in the overall assessment of HF patients.

Mode coupling theory and fragile to strong transition in supercooled TIP4P/2005 water.

We study by molecular dynamics simulations supercooled water with the TIP4P/2005 potential. This model is able to predict many properties of water in a large range of the thermodynamic space in agreement with experiments. We explore the dynamical behavior and, in particular, the self intermediate scattering function of the oxygen atoms. We find that the structural relaxation in the range of mild supercooling is in agreement with the Mode Coupling Theory (MCT). The ideal MCT crossover takes place at decreasing temperature with increasing density. Deviations from the MCT behavior are found upon further supercooling. A crossover from the MCT, fragile, regime to a strong, Arrhenius, regime is found and it is connected to the presence of a liquid-liquid phase transition and the Widom line emanating from the liquid-liquid critical point.

The Widom line and dynamical crossover in supercritical water: Popular water models versus experiments.

In a previous study [Gallo et al., Nat. Commun. 5, 5806 (2014)], we have shown an important connection between thermodynamic and dynamical properties of water in the supercritical region. In particular, by analyzing the experimental viscosity and the diffusion coefficient obtained in simulations performed using the TIP4P/2005 model, we have found that the line of response function maxima in the one phase region, the Widom line, is connected to a crossover from a liquid-like to a gas-like behavior of the transport coefficients. This is in agreement with recent experiments concerning the dynamics of supercritical simple fluids. We here show how different popular water models (TIP4P/2005, TIP4P, SPC/E, TIP5P, and TIP3P) perform in reproducing thermodynamic and dynamic experimental properties in the supercritical region. In particular, the comparison with experiments shows that all the analyzed models are able to qualitatively predict the dynamical crossover from a liquid-like to a gas-like behavior upon crossing the Widom line. Some of the models perform better in reproducing the pressure-temperature slope of the Widom line of supercritical water once a rigid shift of the phase diagram is applied to bring the critical points to coincide with the experimental ones.

Relation between the two-body entropy and the relaxation time in supercooled water.

The two-body excess entropy of supercooled water is calculated from the radial distribution functions obtained from computer simulation of the TIP4P model for different densities upon supercooling. This quantity is considered in connection with the relaxation time of the self intermediate scattering function. The relaxation time shows a mode coupling theory (MCT) behavior in the region of mild supercooling and a strong behavior in the deep supercooled region. We find here that the two-body entropy is connected to the relaxation time and shows a logarithmic behavior with an apparent asymptotic divergence at the mode coupling crossover temperature. There is also evidence of a change in behavior of the two-body entropy upon crossing from the fragile (hopping-free) state to the strong (hopping-dominated) state of supercooled water, and the relation that connects the two-body entropy and the relxation time in the MCT region no longer holds.