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Objective: Peripheral arterial disease (PAD) is the most prevalent cardiovascular (CV) condition globally. Despite the high CV risk of PAD patients, no reliable predictors of adverse clinical evolution are yet available. In this regard, previous transcriptomic analyses revealed increased expression of calprotectin (S100A8/A9) and lipocalin-2 (LCN2) in circulating extracellular vesicles (EVs) of patients with PAD. The aim of this study was to determine the prognostic value of LCN2 and calprotectin for CV risk assessment in PAD. Methods: LCN2 and the S100A9 subunit of calprotectin were examined in human femoral plaques by immunohistochemistry and qPCR. LCN2 and calprotectin were determined by ELISA in PAD (CHN cohort, n = 331, Fontaine IIeIV, serum), and PAD diagnosed by population based screening (VIVA trial, n = 413, the majority Fontaine 0eI, plasma). Patients were followed up for a mean of four years, recording the primary outcomes; CV death or amputation in the CHN cohort and CV death or major lower limb events (MALE) in the VIVA population. Secondary outcomes were all cause death or amputation, and all cause death or MALE, respectively. Results: LCN2 and S100A9 were detected in human plaques in regions rich in inflammatory cells. LCN2 and calprotectin levels were 70% and 64% lower in plasma than in serum. In the CHN cohort, high serum levels of LCN2 and calprotectin increased the risk of primary and secondary outcomes 5.6 fold (p < .001) and 1.8 fold (p = .034), respectively, after covariable adjustment. Similarly, elevated plasma levels of LCN2 and calprotectin increased by three fold the risk of primary and secondary outcomes (p

Matrix metalloproteinases have been implicated in muscular dystrophy progression and recent studies described the role of MMP-10 in skeletal muscle pathology of young dystrophic mice. Nevertheless, its implication in dystrophin deficient hearts is still missing. Here, we aimed at investigating MMP-10 implication in severe muscular dystrophic progression and characterize MMP-10 loss in skeletal and cardiac muscles of aged dystrophic mice. We examined the histopathological effect of MMP-10 ablation in aged mdx mice, both in the hind limb muscles and heart tissues. We have found that MMP-10 loss compromises survival rates of aged mdx mice, with skeletal and cardiac muscles developing a chronic inflammatory response. Our findings indicate that MMP-10 is implicated in severe muscular dystrophy progression, identifying a new area of investigation that could lead to future therapies for dystrophic muscles.

Background: Higher circulating levels of tissue inhibitor of matrix metalloproteinases (TIMP)-1 early after ischemic stroke have been associated with lower survival. The objectives of this study were to determine serum TIMP-1 levels during the first week of a severe cerebral infarction in surviving and non-surviving patients, and whether those levels during the first week could be used as a mortality biomarker for these patients. Methods: We included patients with severe malignant middle cerebral artery infarction (MMCAI) defined as computer tomography showing ischaemic changes in more than 50% of the middle cerebral artery territory and Glasgow Coma Scale (GCS) ≤ 8. We measured serum levels of matrix metalloproteinases (MMP)-9 and TIMP-1. End-point study was 30-day mortality. Results: We found higher TIMP-1 concentrations at days 1 (p < 0.001), 4 (p = 0.001), and 8 (p = 0.03) of MMCAI in nonurviving (n = 34) than in surviving (n = 34) patients. We found lower serum MMP-9 concentrations at day 1 (p = 0.03) of MMCAI and no significant differences at days 4 and 8. ROC curve analysis of TIMP-1 concentrations performed at days 1, 4, and 8 of MMCAI showed an area under curve to predict 30-day mortality of 81% (p < 0.001), 80% (p < 0.001) and 72% (p = 0.07) respectively. Conclusions: The new findings of our study were that non-surviving MMCAI patients showed higher serum TIMP-1 levels during the first week of MMCAI that surviving patients, and those levels during the first week of MMCAI could be used as mortality biomarkers.

Il Decreto Legislativo 28/2016 stabilisce i criteri per la tutela della salute della popolazione da gas radon e trizio, presenti nelle acque destinate al consumo umano, in ottemperanza della Direttiva EURATOM 2013/51. La legge definisce quali sono gli obblighi degli Enti Pubblici competenti a svolgere controlli per scopi di tutela della salute e impone alle Regioni l'elaborazione e la messa in atto di un programma di controllo che deve essere approvato dal Ministero della Salute. La realizzazione di tale programma di controllo non può prescindere dall'analisi delle caratteristiche geologiche del territorio che influenzano, spesso in modo rilevante,la concentrazione di attività del radon. In questo lavoro sono presentati i primi risultati ottenuta da una collaborazione finalizzata alla messa a punto di tecniche di misura di concentrazione di gas radon in acqua sorgiva e di una metodologia standard di campionamento, ottenuti nell'ambito di protocolli d'intesa recentemente stipulati tra ArpaCal e Dipartimento di Fisica dell'Università della Calabria (UNICAL). In particolare, sono confrontate misure di gas radon su acque prelevate da "pubblici fontanini" effettuate con due metodiche differenti, vantaggiose in circostanze diverse: la tecnica spettrometrica non richiede degassaggio ed è basata sulla spettrometria gamma al Germanio iperpuro di tipo "N" ad alta risoluzione, un secondo metodo utilizza la tecnica emanometrica e celle a scintillazione. Sono presentati i primi risultati del monitoraggio di un'area ristretta in provincia di Cosenza, ottenuti seguendo un dedicato protocollo di campionamento e di misura. La scelta delle sorgenti si basa su criteri geologici e di volume utili per l'elaborazione del programma di controllo delle acque destinate al consumo umano, come da indicazioni contenute nell'Allegato II della sopracitata legge 28/2016. I criteri geologici derivano dai risultati di recenti studi, effettuati in Calabria centro-settentrionale (Iovine et al., 2017). I risultati preliminari, ottenuti in un'area ristretta sono incoraggianti ed il metodo seguito è potenzialmente estensibile all'intera Regione Calabria.

The latest measurements of CMB electron scattering optical depth reported by Planck significantly reduces the allowed space of HI reionization models, pointing toward a later ending and/or less extended phase transition than previously believed. Reionization impulsively heats the intergalactic medium (IGM) to $\sim10^4$ K, and owing to long cooling and dynamical times in the diffuse gas, comparable to the Hubble time, memory of reionization heating is retained. Therefore, a late ending reionization has significant implications for the structure of the $z\sim5-6$ Lyman-$��$ (ly$��$) forest. Using state-of-the-art hydrodynamical simulations that allow us to vary the timing of reionization and its associated heat injection, we argue that extant thermal signatures from reionization can be detected via the Ly$��$ forest power spectrum at $5< z, 14 pages, 7 Figures. Matches version accepted by ApJ. UVB models used in this work can be downloaded from http://thermal.joseonorbe.com/uvbtables.html

Background: In the last years, circulating matrix metalloproteinases (MMP)-9 levels have been associated with functional outcome in ischemic stroke patients. However the prognostic value of circulating levels of tissue inhibitor of matrix metalloproteinases (TIMP)-1 and MMP-10 in functional outcome of ischemic stroke patients has been scarcely studied. In addition, to our knowledge, serum MMP-9, MMP-10 and TIMP-1 levels in patients with malignant middle cerebral artery infarction (MMCAI) for mortality prediction have not been studied, and these were the objectives of this study. Methods: This was a multicenter, observational and prospective study carried out in six Spanish Intensive Care Units. We included patients with severe MMCAI defined as Glasgow Coma Scale (GCS) lower than 9. We measured circulating levels of MMP-9, MMP-10, TIMP-1, in 50 patients with severe MMCAI at diagnosis and in 50 healthy subjects. Endpoint was 30-day mortality. Results: Patients with severe MMCAI showed higher serum levels of MMP-9 (p = 0.001), MMP-10 (p < 0.001), and TIMP-1 (p = 0.02) than healthy subjects. Non-surviving MMCAI patients (n = 26) compared to survivor ones (n = 24) showed higher circulating levels of TIMP-1 (p < 0.001), MMP-10 (p = 0.02) and PAI-1(p = 0.02), and lower MMP-9 levels (p = 0.04). Multiple binomial logistic regression analysis showed that serum TIMP-1 levels > 239 ng/mL are associated with 30-day mortality (OR = 5.82; 95 % CI = 1.37-24.73; P = 0.02) controlling for GCS and age. The area under the curve for TIMP-1 as predictor of 30-day mortality was 0.81 (95 % CI = 0.67-0.91; P < 0.001). We found an association between circulating levels of TIMP-1 and MMP-10 (rho = 0.45; P = 0.001), plasminogen activator inhibitor (PAI)-1 (rho = 0.53; P < 0.001), and tumor necrosis factor (TNF)-alpha (rho = 0.70; P < 0.001). Conclusions: The most relevant and new findings of our study, were that serum TIMP-1 levels in MMCAI patients were associated with mortality, and could be used as a prognostic biomarker of mortality in MMCAI patients.

Objective-Thrombin induces CD40 ligand (CD40L) and matrix metalloproteinases (MMPs) under inflammatory/prothrombotic conditions. Thrombin and CD40L could modulate endothelial MMP-10 expression in vitro and in vivo. Methods and Results-Human endothelial cells were stimulated with thrombin (0.1-10 U/mL), CD40L (0.25-1 µg/mL), or their combination (thrombin/CD40L) to assess MMP-10 expression and microparticle generation. Thrombin/CD40L elicited higher MMP-10 mRNA (5-fold; P

This article has been accepted for publication in Monthly Notices of the Royal Astronomical Society ©: 2011 RAS © 2011 The AuthorsPublished by Oxford University Press on behalf of the Royal Astronomical Society. All rights reserved, We have studied the mass assembly and star formation histories of massive galaxies identified at low redshift in different cosmological hydrodynamical simulations. To this end, we have carried out a detailed follow-up backwards in time of their constituent mass elements (sampled by particles) of different types. After that, the configurations they depict at progressively higher zs were carefully analysed. The analyses show that these histories share common generic patterns, irrespective of particular circumstances. In any case, however, the results we have found are different depending on the particle type. The most outstanding differences follow. We have found that by z∼ 3.5-6, mass elements identified as stellar particles at z= 0 exhibit a gaseous cosmic-web-like morphology with scales of ∼1 physical Mpc, where the densest mass elements have already turned into stars by z∼ 6. These settings are in fact the densest pieces of the cosmic web, where no hot particles show up, and dynamically organized as a hierarchy of flow convergence regions (FCRs), that is, attraction basins for mass flows. At high z FCRs undergo fast contractive deformations with very low angular momentum, shrinking them violently. Indeed, by z∼ 1 most of the gaseous or stellar mass they contain shows up as bound to a massive elliptical-like object at their centres, with typical half-mass radii of rmass star∼ 2-3kpc. After this, a second phase comes about where the mass assembly rate is much slower and characterized by mergers involving angular momentum. On the other hand, mass elements identified at the diffuse hot coronae surrounding massive galaxies at z= 0 do not display a clear web-like morphology at any z. Diffuse gas is heated when FCRs go through contractive deformations. Most of this gas remains hot and with low density throughout the evolution. To shed light on the physical foundations of the behaviour revealed by our analyses (i.e. a two-phase formation process with different implications for diffuse or shocked mass elements), as well as on their possible observational implications, these patterns have been confronted with some generic properties of singular flows as described by the adhesion model (i.e. potential character of the velocity field, singular versus regular points, dressing, locality when a spectrum of perturbations is implemented). We have found that the common patterns the simulations show can be interpreted as a natural consequence of flow properties that, moreover, could explain different generic observational results from massive galaxies or their samples. We briefly discuss some of them, This work was partially supported by the DGES (Spain) through the grants AYA2009-12792-C03-02 and AYA2009-12792- C03-03 from the PNAyA, as well as by the regional Madrid V PRICIT programme through the ASTROMADRID network (CAM S2009/ESP-1496)