We present the development and testing of a Micromegas detector prototype and its front end intended to be a candidate for the substitutions of some of the Multiwire Proportional Chambers in the ...future AMBER (NA66) experiment at CERN. Results of the test of the first small size prototype are discussed.
•The Apparatus for Mesons and Baryon Experimental Research at CERN is requiring new detectors.•Micro-Pattern Gaseous Detector technology is a good candidate for the future upgrades.•MICRO-MEsh GAS detector read-out by the Torino Integrated Gem Electronics for Read-out ASIC.
Background and purpose
Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired immunomediated condition affecting the peripheral nervous system where probably macrophages are the ...primary effector cells for demyelination. Reactive oxygen species (ROS), catalyzed by the NOX family of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase enzymes, can induce peroxidation and are potentially injurious to myelin. Our aim was to assess the activity of NOX2, an isoform of NOX, in a series of CIDP patients and to analyze the effect of intravenous immunoglobulin (IVIg) on NOX2.
Methods
Thirty CIDP patients treated with IVIg and 30 control subjects were enrolled. To evaluate NOX2 activity, neutrophil and monocyte oxidative burst was measured directly in fresh whole blood using the Phagoburst™ assay, a fluorescence‐activated cell sorting method. The mean fluorescence intensity, emitted in response to different stimuli, leads to the production of ROS and corresponds to the percentage of oxidizing cells and their enzymatic activity.
Results
Mean fluorescence intensity values for granulocyte and monocyte burst in patients (mean 633.3, SD 191; mean 111.8, SD 28.5) were different from those measured in healthy controls (granulocytes, mean 436.6, SD 137.0, P = 0.0003; monocytes, mean 78.2, SD 17.3, P = 0.000001). Moreover, IVIg administration increased both granulocyte (P = 0.005) and monocyte (P = 0.0009) burst.
Conclusion
Our findings demonstrate that oxidative burst is significantly increased in CIDP patients and that treatment with IVIg enhances oxidative values, thus representing a possible IVIg therapeutic effect linked to a regulatory effect of ROS. Based on this, the development of treatments targeting the specific activation of NOX may be beneficial in autoimmune disorders.
Since the coronavirus disease 2019 (COVID-19) outbreak started, children have been considered marginally involved compared to adults, with a quite significant percentage of asymptomatic carriers. ...Very recently, an overwhelming inflammatory activation, which shares clinical similarities with Kawasaki disease (KD), has been described in children exposed to COVID-19. We report three KD-like cases that occurred during the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a highly affected area of Northern Italy. The clinical presentation was characterized by the presence of unremitting fever, diarrhea and elevated inflammatory markers. Case #1 and Case #2 occurred one week apart and shared other clinical features: laboratory tests confirmed COVID-19 exposure and high inflammatory activation with myocardial involvement. Case #3 followed a more typical pattern for KD. Interestingly, this patient showed lower levels of procalcitonin, C-reactive protein, D-dimers, and ferritin compared to the other two cases, whereas platelet count was higher. We hypothesize that SARS-CoV-2 might act in children as a trigger, either inducing a classical KD phenotype or causing a systemic inflammatory response leading to a severe KD-like phenotype, eventually characterized by myocardial impairment. We think that bringing these cases and their differences to the attention of the rheumatology community during the COVID-19 pandemic will be beneficial in order to highlight the importance of early diagnosis and to increase awareness of this new phenomenon.
Hereditary Diffuse Gastric Cancer (HDGC) syndrome is an autosomal dominant hereditary cancer predisposition associated with germline pathogenic/likely pathogenic variants in the CDH1 gene. ...Identifying early stage HDGC is difficult, and prophylactic measures can be effective in preventing incidence. Preimplantation Genetic Testing (PGT) can provide information about CDH1 variant status, HDGC risk, and limit familial transmission of CDH1 variants. To date, however, little is known about the attitudes of individuals with CDH1 variants towards PGT.
Given that little is known about the reproductive attitudes of individuals with HDGC, we recruited participants with CDH1 variants from a familial gastric cancer registry and administered a cross-sectional survey with open- and closed-ended response items. We assessed attitudes regarding PGT and the effect of HDGC on quality of life.
Participants (n = 21) were predominantly partnered (61.9%), had a personal cancer history (71.4%), and had biological children (71.4%). Interest in learning about PGT was high; 66.7% of participants were interested in PGT and 90.5% approved of healthcare providers discussing PGT with individuals with CDH1 variants. Attitudes regarding personal use were varied. Among all participants, 35% would not, 25% were uncertain, and 40% would use PGT. Personal philosophy and preferences for family and reproduction were key factors related to PGT attitudes. HDGC had moderate effects on participants' quality of life, including social relationships, health behaviors, and emotional experiences including worry about cancer risk and guilt regarding familial implications.
PGT was identified by participants as acceptable for use in a variety of contexts and benefits of reproductive counseling involving PGT may extend beyond CDH1 carriers to family members' reproductive behaviors. Dispositions towards PGT are governed by personal philosophy or belief systems. These findings can help guide providers counseling individuals with CDH1 variants.
Chronic liver disease (CLD) is a cause of morbidity and mortality worldwide, due to haemodynamic and metabolic complications of liver cirrhosis. During CLD the extracellular matrix undergoes a ...process of remodelling, leading to new collagen formation and deposition. Tissue remodelling is regulated by fine molecular mechanisms, involving proteases, inhibitors and growth factors. The major role in matrix degradation is played by matrix metalloproteinases (MMPs), a class of zinc and calcium-dependent enzymes, and their tissue inhibitors (TIMPs). Along with the progress in diagnostic techniques, leading to more precise and less invasive methods, the concept of monitoring has gained importance for the clinical management of CLD. At the present state of our knowledge, liver biopsy still represents an essential procedure for staging liver disease. However, despite its importance, liver biopsy presents some limitations: the risk of a disease underestimation is the most significant one, as hepatic lesions are often irregularly located within the liver. Parallel to the limitations of liver biopsy, clinical needs for an early identification of progressive fibrosis require additional non-invasive techniques to be developed. In this review we discuss the major problems concerning this important clinical necessity. Moreover, we focus on the role of MMPs and TIMPs in the pathogenesis of CLD, as well as their possible use as non-invasive serum markers for inflammation and fibrosis in this pathology.
This study presents, for the first time, long-term data of sub-μm particle number size distributions in the particle size range of 14–670 nm in the Mediterranean area of Rome. Data are analysed in ...terms of possible aerosol populations.
A particular “event” including also measurements of nitrous acid mixing ratios in the atmosphere is further analysed. High statistical correlations are established: At daytime, between the unknown HONO formation rate and the product of NO
2,
J
NO
2
, relative humidity, and sub-μm particle surface area concentration. At nighttime, between the volume concentration of the small Aitken mode particles and the HONO mixing ratios.
The study would provide information on fine and ultrafine aerosol particle size distribution down to 14 nm in the Mediterranean suburban area of Rome. Besides, it would support previous works which have already provided several evidences for the existence of relations between the sub-μm aerosol populations and HONO. Our conclusions include speculations on possible daytime HONO formation mechanisms on particle surfaces in the accumulation mode size range, and nighttime mass formation mechanisms in common for the small Aitken mode particles and HONO.
The snowpack is a complex photochemical reactor that emits a wide variety of reactive molecules to the atmosphere. In particular, the photolysis of nitrate ions, NO3 −, produces NO, NO2, and HONO, ...which affects the oxidative capacity of the atmosphere. We report measurements in the European High Arctic where we observed for the first time emissions of NO, NO2, and HONO by the seasonal snowpack in winter, in the complete or near-complete absence of sunlight and in the absence of melting. We also detected unusually high concentrations of nitrite ions, NO2 −, in the snow. These results suggest that microbial activity in the snowpack is responsible for the observed emissions. Isotopic analysis of NO2 − and NO3 − in the snow confirm that these ions, at least in part, do not have an atmospheric origin and are most likely produced by the microbial oxidation of NH4 + coming from clay minerals into NO2 − and NO3 −. These metabolic pathways also produce NO. Subsequent dark abiotic reactions lead to NO2 and HONO production. The snow cover is therefore not only an active photochemical reactor but also a biogeochemical reactor active in the cycling of nitrogen and it can affect atmospheric composition all year round.
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