The oral and gastrointestinal mucosae represent the main targets of the toxic effect of chemo and/or radiotherapy administered during the conditioning regimen before hematopoietic stem cell ...transplant (HSCT). These harmful consequences and the immunological complications that may occur after the transplant (such as Graft versus Host Disease, GvHD) are responsible for the clinical symptoms associated with mucositis during the aplasia phase, like pain, nausea, vomiting, and diarrhea. These toxicities could play a critical role in the oral and gastrointestinal microbiomes during the post-transplant phase, and the degree of microbial dysbiosis and dysregulation among different bacterial species could also be crucial in intestinal mucosa homeostasis, altering the host's innate and adaptive immune responses and favoring abnormal immune responses responsible for the occurrence of GvHD. This prospective pediatric study aims to analyze longitudinally oral and gut microbiomes in 17 pediatric patients who received allogeneic HSCT for malignant and non-malignant diseases. The oral mucositis was mainly associated with an increased relative abundance of Fusobacteria, and Prevotella species, while Streptococcus descendants showed a negative correlation. The fecal microbiome of subjects affected by cutaneous acute GvHD (aGvHD) correlated with Proteobacteria. Oral mucosal microbiota undergoes changes after HSCT, Fusobacteria, and Prevotella represent bacterial species associated with mucositis and they could be the target for future therapeutic approaches, while fecal microbiome in patients with acute GvHD (aGvHD) revealed an increase of different class of Proteobacteria (Alphaproteobacteria and Deltaproteobacteria) and a negative correlation with the class of Gammaproteobacteria.
Inflammatory Bowel Diseases (IBD) are known to occur in association with Hirschsprung disease (HSCR). Most of cases are represented by Crohn Disease (CD) occurring in patients with Total Colonic ...Aganglionosis (TCSA) with an estimated prevalence of around 2%. Based on these considerations and on a number of provisional data belonging to our Center for Digestive Diseases, we developed a unicentric cross-sectional observational study aimed at describing phenotype, genotype, pathology and metagenomics of all patients with TCSA and Crohn-like lesions. Out of a series of 62 eligible TCSA patients, 48 fulfilled inclusion criteria and were enrolled in the study. Ten patients did not complete the study due to non-compliance or withdrawal of consent and were subsequently dropped out. A total of 38 patients completed the study. All patients were tested for chronic intestinal inflammation by a combination of fecal calprotectine (FC) or occult fecal blood (OFB) and underwent fecal metagenomics. Nineteen (50%) tested positive for FC, OFB, or both and subsequently underwent retrograde ileoscopy. Fourteen patients (36.8%) presented Crohn-like lesions, occurring after a median of 11.5 years after surgery (range 8 months - 21.5 years). No statistically significant differences regarding demographic, phenotype and genotype were observed comparing patients with and without lesions, except for need for blood transfusion that was more frequent in those with lesions. Faecal microbiome of patients with lesions (not that of caregivers) was less biodiverse and characterized by a reduction of Bacteroidetes, and an overabundance of Proteobacteria. FC tested negative in 3/14 patients with lesions (21%). Our study demonstrated an impressive 10-folds higher incidence of chronic inflammation in TCSA. Up to 50% of patients may develop IBD-like lesions postoperatively. Nonetheless, we failed in identifying specific risk factors to be used to implement prevention strategies. Based on the results of our study, we suggest screening all TCSA patients with retrograde ileoscopy regardless of FC/OFB values. The frequency of endoscopic assessments and the role of FC/OFB screening in prompting endoscopy is yet to be determined.
Abstract
Cerium-doped Lutetium-Yttrium Oxyorthosilicate (LYSO:Ce) is
one of the most widely used Cerium-doped Lutetium based
scintillation crystals. Initially developed for medical detectors it
...rapidly became attractive for High Energy Particle Physics (HEP)
applications, especially in the frame of high luminosity particle
colliders.
In this paper, a comprehensive and systematic study of LYSO:Ce
(Lu
(1-
x
)
Y
x
2
SiO
5
:Ce) crystals
is presented. It involves for the first time a large number of
crystal samples (180) of the same size from a dozen of producers.
The study consists of a comparative characterization of LYSO:Ce
crystal products available on the market by mechanical, optical and
scintillation measurements and aims specifically, to investigate key
parameters of timing applications for HEP.
Aims/hypothesis
Enhanced vascular inflammation, immune cell infiltration and elevated production of reactive oxygen species (ROS) contribute significantly to pro-atherogenic responses in diabetes. We ...assessed the immunomodulatory role of NADPH oxidase (NOX)-derived ROS in diabetes-accelerated atherosclerosis.
Methods
Diabetes was induced in male
Apoe
−/−
mice with five daily doses of streptozotocin (55 mg kg
−1
day
−1
). Atherosclerotic plaque size, markers of ROS and immune cell accumulation were assessed in addition to flow cytometric analyses of cells isolated from the adjacent mediastinal lymph nodes (meLNs). The role of NOX-derived ROS was investigated using the NOX inhibitor, GKT137831 (60 mg/kg per day; gavage) administered to diabetic and non-diabetic
Apoe
−/−
mice for 10 weeks.
Results
Diabetes increased atherosclerotic plaque development in the aortic sinus and this correlated with increased lesional accumulation of T cells and CD11c
+
cells and altered T cell activation in the adjacent meLNs. Diabetic
Apoe
−/−
mice demonstrated an elevation in vascular ROS production and expression of the proinflammatory markers monocyte chemoattractant protein 1, vascular adhesion molecule 1 and IFNγ. Blockade of NOX-derived ROS using GKT137831 prevented the diabetes-mediated increase in atherosclerotic plaque area and associated vascular T cell infiltration and also significantly reduced vascular ROS as well as markers of inflammation and plaque necrotic core area.
Conclusions/interpretation
Diabetes promotes pro-inflammatory immune responses in the aortic sinus and its associated lymphoid tissue. These changes are associated with increased ROS production by NOX. Blockade of NOX-derived ROS using the NOX inhibitor GKT137831 is associated with attenuation of these changes in the immune response and reduces the diabetes-accelerated development of atherosclerotic plaques in
Apoe
−/−
mice.
Combined readout of a triple-GEM detector Antochi, V.C.; Baracchini, E.; Cavoto, G. ...
Journal of instrumentation,
05/2018, Letnik:
13, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Optical readout of GEM based devices by means of high granularity and low noise CMOS sensors allows to obtain very interesting tracking performance. Space resolution of the order of tens of μm were ...measured on the GEM plane along with an energy resolution of 20%÷30%. The main limitation of CMOS sensors is represented by their poor information about time structure of the event. In this paper, the use of a concurrent light readout by means of a suitable photomultiplier and the acquisition of the electric signal induced on the GEM electrode are exploited to provide the necessary timing informations. The analysis of the PMT waveform allows a 3D reconstruction of each single clusters with a resolution on z of 100 μm. Moreover, from the PMT signals it is possible to obtain a fast reconstruction of the energy released within the detector with a resolution of the order of 25% even in the tens of keV range useful, for example, for triggering purpose.
Time Projection Chambers (TPCs) working in combination with Gas Electron Multipliers (GEMs) produce a very sensitive detector capable of observing low energy events. This is achieved by capturing ...photons generated during the GEM electron multiplication process by means of a high-resolution camera. The CYGNO experiment has recently developed a TPC Triple GEM detector coupled to a low noise and high spatial resolution CMOS sensor. For the image analysis, an algorithm based on an adapted version of the well-known DBSCAN was implemented, called iDBSCAN. In this paper a description of the iDBSCAN algorithm is given, including test and validation of its parameters, and a comparison with DBSCAN itself and a widely used algorithm known as Nearest Neighbor Clustering (NNC). The results show that the adapted version of DBSCAN is capable of providing full signal detection efficiency and very good energy resolution while improving the detector background rejection.
The CYGNO project has the goal to use a gaseous TPC with optical readout to detect dark matter and solar neutrinos with low energy threshold and directionality. The CYGNO demonstrator will consist of ...1 m3 volume filled with He:CF4 gas mixture at atmospheric pressure. Optical readout with high granularity CMOS sensors, combined with fast light detectors, will provide a detailed reconstruction of the event topology. This will allow to discriminate the nuclear recoil signal from the background, mainly represented by low energy electron recoils induced by radioactivity. Thanks to the high reconstruction efficiency, CYGNO will be sensitive to low mass dark matter, and will have the potential to overcome the neutrino floor, that ultimately limits non-directional dark matter searches.
The goal of the CYGNO project is to deploy at Laboratori Nazionali del Gran Sasso (LNGS) an high resolution Time Projection Chamber (TPC) with Gas Electron Multipliers (GEMs) amplification and ...optical 3D readout of an Helium/Fluorine based gas mixture for directional Dark Matter (DM) searches at low 1-10 GeV WIMP masses. The determination of the incoming direction of WIMP particles can in fact offer not only additional handles for discrimination of the annoying backgrounds, but especially an unique key for a positive, unambiguous identification of a DM signal.
The CYGNO/INITIUM experiment Amaro, F. D.; Baracchini, Elisabetta; Benussi, L. ...
SciPost physics proceedings,
07/2023
12
Journal Article
Recenzirano
Odprti dostop
The CYGNO project for the development of a high precision optical readout gaseous TPC for directional Dark Matter search and solar neutrino spectroscopy will be presented. It is to be hosted at ...Laboratori Nazionali del Gran Sasso. CYGNO peculiar features are the use of sCMOS cameras and PMTs coupled to GEMs amplification of a helium-based gas mixture at atmospheric pressure, in order to achieve 3D tracking with head tail capability and background rejection down to O(keV) energy, to boost sensitivity to low WIMP masses. The latest R&D results within the CYGNO project will be discussed along with the underground installation and operation of a 50 l prototype, soon to be followed by a O(1) m3 experiment demonstrator in 2024-2026. The latest results on the negative ion drift operation at atmospheric pressure within CYGNO optical readout approach will be illustrated, which is the aim of the ERC Consolidator Grant project INITIUM.
A growing body of evidence links the analysis of the KIR genotype and the presence of their HLA-B and -C ligands to a wide repertoire of human diseases.
We noticed that, using a panel of 184 ...Caucasoid donors, a limited number of HLA alleles were incorrectly supratyped by previously described pyrosequence-based assays. Here we describe a simple implementation of the reported methods that corrects all the discrepancies found with HLA-B and -C molecular typing and allows establishing a quick and high-throughput method for the determination of HLA-Bw4 I80, Bw4T80, Bw6 and HLA-C1 or -C2 supratype.
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