DNA damage contributes to neurotoxic inflammation in Aicardi-Goutières Syndrome astrocytes

Aberrant induction of type I IFN is a hallmark of the inherited encephalopathy Aicardi-Goutières syndrome (AGS), but the mechanisms triggering disease in the human central nervous system (CNS) remain elusive. Here, we generated human models of AGS using genetically modified and patient-derived pluripotent stem cells harboring TREX1 or RNASEH2B loss-of-function alleles. Genome-wide transcriptomic analysis reveals that spontaneous proinflammatory activation in AGS astrocytes initiates signaling cascades impacting multiple CNS cell subsets analyzed at the single-cell level. We identify accumulating DNA damage, with elevated R-loop and micronuclei formation, as a driver of STING- and NLRP3-related inflammatory responses leading to the secretion of neurotoxic mediators. Importantly, pharmacological inhibition of proapoptotic or inflammatory cascades in AGS astrocytes prevents neurotoxicity without apparent impact on their increased type I IFN responses. Together, our work identifies DNA damage as a major driver of neurotoxic inflammation in AGS astrocytes, suggests a role for AGS gene products in R-loop homeostasis, and identifies common denominators of disease that can be targeted to prevent astrocyte-mediated neurotoxicity in AGS

A novel approach for Decision Support System in marine applications

This paper focuses on the development of a knowledge-based Decision Support System (DSS) or the management of the ship compartment integrated information that comprises real-time devices status and remote command, simple full-navigability on the topology of the ship by CAD drawings, operator actions sharing through Multifunction Console (MFCs), recorded video clip and others. The developed system allows sensible benefits in terms of reduced situational awareness and action time

Management of Patients Taking Oral Anticoagulants Who Need Urgent Surgery for Hip Fracture

The number of hip fractures in anticoagulated patients is predicted to increase, due to people living longer. However, evidence regarding urgent perioperative management of elderly patients with hip fracture who take oral anticoagulants (vitamin K antagonists or direct oral anticoagulants) is scarce. In this article, the authors present a narrative review of the evidence to date supporting the urgent management of hip fracture in anticoagulated elderly patients. They discuss the complexity of managing the high risk of procedure-related bleeding and, at the same time, the high risk of thromboembolism. The role of a bridging procedure and the best strategy of anticoagulation reversal are also reviewed. Further studies are required to improve the evidence in urgent surgery, especially in frail elderly patients

Photogrammetry and 3D Scanning: Assessment of Metric Accuracy for the Digital Model of Danatello's Maddalena

The deployment of 3D optical scanning technologies for measuring three-dimensional shapes of sculptures of high morphological complexity, have seen recently a development so noticeable that it emerges as one of the most promising methods for the analysis and preservation of the Cultural Heritage. In spite of an undoubted richness of information produced with this technique, the method for generating a digital model from single 3D acquisitions involves errors propagation that may deteriorate the actual metric accuracy attainable with such procedure. The activity reported in this paper describes a recent experiment in 3D scanning of a highly complex sculpture: the wooden statue <em>Maddalena</em> by Donatello, kept in the museum of the <em>Opera del Duomo</em>, in Florence. The acquisitions, taken with a commercial system based on fringe projection, give a local measurement uncertainty of about 70mm, but when the complete model is generated by automatic alignment of the raw 3D images in a common coordinate system, possible scale variations might be involved, especially along the height of the statue. With this preliminary work, the authors want to verify the metric reliability of the three-dimensional model, obtained through iterative alignments of single 3D acquisitions. For this purpose, a measurement over well-identified features of the sculpture have been performed and the distances between couples of significant points have been calculated with photogrammetric operations. By repeating the same measurements on the 3D model, a corresponding set of point-to-point distances have been evaluated and compared with the photogrammetric results.Les technologies de balayage optique 3D d\ue9ploy\ue9es pour la mesure des formes 3D de sculptures d'une forte complexit\ue9 morphologique ont connu r\ue9cemment un d\ue9veloppement tellement remarquable, qu'elles \ue9mergent comme l'un des groupes de m\ue9thodes les plus prometteuses pour l'analyse et la conservation du patrimoine culturel. Malgr\ue9 une richesse incontestable d'information produite au moyen de ces techniques, la m\ue9thode de g\ue9n\ue9ration d'un mod\ue8le num\ue9rique \ue0 partir d'acquisitions 3D individuelles comporte des erreurs de propagation susceptibles de d\ue9t\ue9riorer l'exactitude r\ue9elle de la mesure qu'on peut obtenir au moyen de cette proc\ue9dure. L'activit\ue9 signal\ue9e dans le pr\ue9sent document d\ue9crit une exp\ue9rience men\ue9e r\ue9cemment au sujet du balayage 3D d'une sculpture tr\ue8s complexe : la statue en bois Madeleine, de Donatello, conserv\ue9e au Museo dell'Opera del Duomo de Florence. Les acquisitions, prises au moyen d'un syst\ue8me commercial fond\ue9 sur la projection de franges, donnent une incertitude de mesure locale d'environ 70 mm mais, lorsque le mod\ue8le complet est g\ue9n\ue9r\ue9 par l'alignement automatique des images 3D brutes dans un syst\ue8me de coordonn\ue9es communes, il risque d'y avoir des variations d'\ue9chelle, surtout le long de la hauteur de la statue. Avec ce travail pr\ue9liminaire, les auteurs veulent v\ue9rifier la fiabilit\ue9 de la mesure du mod\ue8le 3D, obtenu au moyen d'alignements it\ue9ratifs d'acquisitions 3D individuelles. \uc0 cette fin, des mesures de traits bien identifi\ue9s de la sculpture ont \ue9t\ue9 prises, et les distances entre des paires de points significatifs ont \ue9t\ue9 calcul\ue9es au moyen d'op\ue9rations photogramm\ue9triques. La r\ue9p\ue9tition des m\ueames mesures sur le mod\ue8le 3D a permis d'\ue9valuer une s\ue9rie correspondante de distances point-\ue0-point et de la comparer avec les r\ue9sultats photogramm\ue9triques.NRC publication: Ye

High informative content management in shipboard applications

This paper focuses on the implementation of a crucial application in naval field, named Damage Control System (DCS), in the development of which the researchers of the Centro Cultura Innovativa d’Impresa (CCII) of University of Salento have been involved by its industrial partner Avio S.p.A.

Damage Control System: an Application for Ship Safety and Security

A crucial application in naval field called Damage Control System (DCS) is the focus of this paper. DCS is an information-retrieval and equipment-control system that allows ship personnel to detect, analyze, and handle various types of situations which are hazardous for shipboard safety. The DCS is embedded in the Integrated Platform Management System (IPMS) and developed by researches of, Apphia s.r.l., CCII (Centro Cultura Innovativa d'Impresa) of University of Salento and Avio S.p.A

Evaluation of hygienic conditions of food contact surfaces in retail outlets: Six years of monitoring

A total of 68 food contact surfaces in five different retail outlets of the following food categories: raw meat (17 surfaces), fishery products (12), deli (11), pastry (18), and dairy products (10) were monitored for hygienic conditions during the years 2010–2015. Each retail outlet was visited three times per year, except for that of dairy products which was monitored once a year. The samples were collected by hygiene swabs used on the sanitized surfaces before coming in contact with any type of food and analyzed for total aerobic count and presence of Salmonella spp. and Listeria monocytogenes. On the basis of the results, the surfaces were classified according to compliance criteria with good hygienic conditions: compliant (from not detectable to 49 CFU/cm2), improvable (between 50 and 499 CFU/cm2) and not compliant (>500 CFU/cm2). The highest rates of improvable or not compliant data were found in the stores of raw meat (38 and 29%, respectively) and fishery products (23 and 31%), followed by deli (21 and 13%). As no regulatory limits have been established for food contact surfaces, the compliance criteria proposed in this study could be used to monitor the cleaning and sanitation procedures in the food distribution system

Heme oxygenase-1 is an important modulator in limiting glucose-induced apoptosis in human umbilical vein endothelial cells

Hyperglycaemia is associated with oxidative stress. The inducible isoform of heme oxygenase (HO-1) is an effective system to counteract oxidative stress, yet it is unclear how hyperglycaemia affects HO-1. In this study, we explored: 1) the HO-1 protein content and HO activity in human umbilical vein endothelial cells (HUVECs) exposed to different glucose concentrations, and 2) the mechanisms which account for the high glucose-induced effects on HO-1. We evaluated HO-1 protein expression, HO activity, apoptosis and reactive oxygen species (ROS) in HUVECs treated for 48 h with 5.5, 10 and 20 mM glucose. A dose-dependent production of reactive oxygen species was observed. At 10 mM glucose, an increase of HO-1 protein expression and HO activity was observed, whereas at 20 mM, there was no change in protein content and activity relative to at 5.5 mM glucose. HO-1 protein expression in HUVECs exposed to 20 mM of glucose was increased in the presence of 20 U/ml superoxide dismutase (SOD). HO-1 gene silencing augments ROS production both at 5.5 and 10 mM glucose, leading to an increased apoptosis. We conclude that, in endothelial cells, the regulation of HO-1 by glucose is dependent upon levels of glucose itself. Lack of homeostatic HO-1 upregulation fails to protect from oxidative damage and results in a higher rate of apoptotic cell death