CHANTI: a Fast and Efficient Charged Particle Veto Detector for the NA62 Experiment at CERN

The design, construction and test of a charged particle detector made of scintillation counters read by Silicon Photomultipliers (SiPM) is described. The detector, which operates in vacuum and is used as a veto counter in the NA62 experiment at CERN, has a single channel time resolution of 1.14 ns, a spatial resolution of ~2.5 mm and an efficiency very close to 1 for penetrating charged particles

Cardiopulmonary assessment in primary ciliary dyskinesia.

Background Primary ciliary dyskinesia (PCD) is a rare, usually autosomal recessive disorder of ciliary dysfunction associated with lung involvement, which has a great impact on health. There is limited information concerning the aerobic fitness of children and adolescents with PCD. The aim of this study was to assess cardiopulmonary functional capacity and its relationship with pulmonary function and physical activity (PA) levels in patients with PCD. Design Ten patients with PCD (age 13·2±2·8years) underwent spirometry and cardiopulmonary exercise testing. PA was investigated through a questionnaire. Eight age- and body mass index-matched healthy children were enrolled as controls. Main variables were forced expiratory volume at 1s, peak oxygen uptake (VO 2peak) and time spent in PA. Results Forty per cent of patients with PCD had impaired lung function as expressed by FEV 1<85% predicted. Only patients with impaired lung function exhibited reduced VO 2peak (18·1±7·9mL/kg/min). Time spent in total daily PA was slightly lower in patients than controls, with no difference between patients with normal or reduced lung function. In multiple regression models, male gender (??=0·518, P=0·018), age (??=0·752, P=0·035) and time spent in vigorous PA (??=0·353, P=0·049) were independent predictors of aerobic fitness. Conclusions Assessment of resting pulmonary function and cardiopulmonary functional capacity could contribute to the evaluation of pulmonary impairment in PCD. Given the benefit of physical exercise on airway clearance and on general health and quality of life, patients with PCD should be encouraged to adopt an active lifestyle

Muon Radiography Investigations in Boreholes with a Newly Designed Cylindrical Detector

Muons are constantly produced in cosmic-rays and reach the Earth surface with a flux of about 160 particles per second per square meter. The abundance of muons with respect to other cosmic particles and their capability to cross dense materials with low absorption rate allow them to be exploited for large scale geological or human-made object imaging. Muon radiography is based on similar principles as X-ray radiography, measuring the surviving rate of muons escaping the target and relating it to the mass distribution inside the object. In the course of decades, after the first application in 1955, the methodology has been applied in several different fields. Muography allows us to measure the internal density distribution of the investigated object, or to simply highlight the presence of void regions by observing any excess of muons. Most of these applications require the detector to be installed below the rock being probed. In case that possible installation sites are not easily accessible by people, common instrumentation cannot be installed. A novel borehole cylindrical detector for muon radiography has been recently developed to deal with these conditions. It has been realized with a cylindrical geometry to fit typical borehole dimensions. Its design maximizes the geometrical acceptance, minimizing the dead spaces by the use of arc-shaped scintillators. The details of the construction and preliminary results of the first usage are described in this paper. © 2022 by the authors

The Non-Canonical Wnt/PKC Pathway Regulates Mitochondrial Dynamics through Degradation of the Arm-Like Domain-Containing Protein Alex3

The regulation of mitochondrial dynamics is vital in complex cell types, such as neurons, that transport and localize mitochondria in high energy-demanding cell domains. The Armcx3 gene encodes a mitochondrial-targeted protein (Alex3) that contains several arm-like domains. In a previous study we showed that Alex3 protein regulates mitochondrial aggregation and trafficking. Here we studied the contribution of Wnt proteins to the mitochondrial aggregation and dynamics regulated by Alex3. Overexpression of Alex3 in HEK293 cells caused a marked aggregation of mitochondria, which was attenuated by treatment with several Wnts. We also found that this decrease was caused by Alex3 degradation induced by Wnts. While the Wnt canonical pathway did not alter the pattern of mitochondrial aggregation induced by Alex3, we observed that the Wnt/PKC non-canonical pathway regulated both mitochondrial aggregation and Alex3 protein levels, thereby rendering a mitochondrial phenotype and distribution similar to control patterns. Our data suggest that the Wnt pathway regulates mitochondrial distribution and dynamics through Alex3 protein degradation

The hidden fragility in the heart of the athletes: A review of genetic biomarkers

Sudden cardiac death (SCD) is a devastating event which can also affect people in apparent good health, such as young athletes. It is known that intense and continuous exercise along with a genetic background that predisposes a person to the risk of fatal arrhythmias is a trigger for SCD. Therefore, knowledge of the athlete’s genetic conditions underlying the onset of SCD must be extended, in order to develop new effective prevention and/or therapeutic strategies. Arrhythmic features occur across a broad spectrum of cardiac diseases, sometimes presenting with overlapping phenotypes. The genetic basis of arrhythmogenic disorders has been greatly highlighted in the last 30 years, and has shown marked heterogeneity. The advent of next-generation sequencing has constantly updated our understanding of the genetic basis of arrhythmogenic diseases and is laying the foundation for precision medicine. With the exception of a few clinical cases involving a single athlete showing a highly suspected phenotype for the presence of a heart disease, there are few studies to date that analysed the applicability of genetic testing on cohorts of athletes. This evidence shows that genetic testing can contribute to the diagnosis of up to 13% of athletes; however, the presence of clinical markers is essential. This review aims to provide a reference collection on current knowledge of the genetic basis of sudden cardiac death in athletes and to review updated evidence on the effectiveness of genetic testing in early identification of athletes at risk for SCD

Bivalirudin in patients undergoing pci: state of art and future perspectives

Acute coronary syndrome (ACS) represents the most common cause of death worldwide. Percutaneous coronary intervention (PCI) is the management of choice in patients with ACS and occurrence of intra procedural thrombotic complications are an independent predictor of mortality and other major adverse cardiovascular events in patients undergoing PCI. According to current guideline, anticoagulation therapy is indicated during PCI in order to reduce the risk of thrombotic complications such as stent thrombosis. Among currently available anticoagulant drugs, bivalirudin demonstrates a lower incidence of bleeding risk, despite it is associated with an increased risk of stent thrombosis. The aim of this paper is to discuss the pharmacology of bivalirudin and the clinical evidences of its use in patients undergoing PCI for ACS

A factor analytic study of the Italian National Institute of Health Quality of Life – Core Evaluation Form (ISSQoL-CEF)

Objectives: The Italian National Institute of Health Quality of Life - Core Evaluation Form (ISSQoL-CEF) is a specific questionnaire measuring health-related quality of life for human immunodeficiency virus-infected people in the era of highly active antiretroviral therapy. The main goal of this study was to examine the construct validity of this questionnaire by confirmation of its hypothesized dimensional structure. Methods: Baseline quality of life data from four clinical studies were collected and a confirmatory factor analysis of the ISSQoL-CEF items was carried out. Both first-order and secondorder factor models were tested: Model 1 with nine correlated first-order factors; Model 2 with three correlated second-order factors (Physical, Mental, and Social Health); Model 3 with two correlated second-order factors (Physical and Mental/Social Health); Model 4 with only one second-order factor (General Health). Results: A total of 261 patients were surveyed. Model 1 had a good fit to the data. Model 2 had an acceptable fit to the data and it was the best of all hierarchical models. However, Model 2 fitted the data worse than Model 1. Conclusions: The findings of in this study, consistent with the results of previous study, pointed out the construct validity of the ISSQoL-CEF. © 2010 Lauriola et al, publisher and licensee Dove Medical Press Ltd

GRP78 Mediates Cell Growth and Invasiveness in Endometrial Cancer.

Abstract Recent studies have indicated that endoplasmic reticulum stress, the unfolded protein response activation and altered GRP78 expression can play an important role in a variety of tumors development and progression. Very recently we reported for the first time that GRP78 is increased in endometrial tumors. However, whether GRP78 could play a role in the growth and/or invasiveness of endometrial cancer cells is still unknown. Here we report that the silencing of GRP78 expression affects both cell growth and invasiveness of Ishikawa and AN3CA cells, analyzed by the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and transwell migration assay, respectively. At variance with Ishikawa cells, AN3CA cells showed, besides an endoplasmic reticulum, also a plasma membrane GRP78 localization, evidenced by both immunofluorescence and cell membrane biotinylation experiments. Intriguingly, flow cytometry experiments showed that the treatment with a specific antibody targeting GRP78 C-terminal domain caused apoptosis in AN3CA but not in Ishikawa cells. Induction of apoptosis in AN3CA cells was not mediated by the p53 pathway activation but was rather associated to reduced AKT phosphorylation. Interestingly, immunofluorescence analysis evidenced that endometrioid adenocarcinoma tissues displayed, similarly to AN3CA cells, also a GRP78 plasma membrane localization. These data suggest that GRP78 and its plasma membrane localization, might play a role in endometrial cancer development and progression and might constitute a novel target for the treatment of endometrial cancer