The ghrelin paradox in the control of equine chondrocyte function: The good and the bad

Increasing evidence suggests a role for ghrelin in the control of articular inflammatory diseases like osteoarthritis (OA). In the present study we examined the ability of ghrelin to counteract LPS-induced necrosis and apoptosis of chondrocytes and the involvement of GH secretagogue receptor (GHS-R)1a in the protective action of ghrelin. The effects of ghrelin (10-7-10-11\u202fmol/L) on equine primary cultured chondrocytes viability and necrosis in basal conditions and under LPS treatment (100\u202fng/ml) were detected by using both acridine orange/propidium iodide staining and annexin-5/propidium iodide staining. The presence of GHS-R1a on chondrocytes was detected by Western Blot. The involvement of the GHS-R1a in the ghrelin effect against LPS-induced cytotoxicity was examined by pretreating chondrocytes with D-Lys3-GHRP-6, a specific GHS-R1a antagonist, and by using des-acyl ghrelin (DAG, 10-7and 10-9\u202fmol/L) which did not recognize the GHS-R 1a. Low ghrelin concentrations reduced chondrocyte viability whereas 10-7\u202fmol/L ghrelin protects against LPS-induced cellular damage. The protective effect of ghrelin depends on the interaction with the GHS-R1a since it is significantly reduced by D-Lys3-GHRP-6. The negative action of ghrelin involves caspase activation and could be due to an interaction with a GHS-R type different from the GHS-R1a recognized by both low ghrelin concentrations and DAG. DAG, in fact, induces a dose-dependent decrease in chondrocyte viability and exacerbates LPS-induced damage. These data indicate that ghrelin protects chondrocytes against LPS-induced damage via interaction with GHS-R1a and suggest the potential utility of local GHS-R1a agonist administration to treat articular inflammatory diseases such as OA

Study of cosmogenic activation above ground for the DarkSide-20k experiment

The activation of materials due to exposure to cosmic rays may become an important background source for experiments investigating rare event phenomena. DarkSide-20k, currently under construction at the Laboratori Nazionali del Gran Sasso, is a direct detection experiment for galactic dark matter particles, using a two-phase liquid-argon Time Projection Chamber (TPC) filled with 49.7 tonnes (active mass) of Underground Argon (UAr) depleted in 39Ar. Despite the outstanding capability of discriminating / background in argon TPCs, this background must be considered because of induced dead time or accidental coincidences mimicking dark-matter signals and it is relevant for low-threshold electron-counting measurements. Here, the cosmogenic activity of relevant long-lived radioisotopes induced in the experiment has been estimated to set requirements and procedures during preparation of the experiment and to check that it is not dominant over primordial radioactivity; particular attention has been paid to the activation of the 120 t of UAr used in DarkSide-20k. Expected exposures above ground and production rates, either measured or calculated, have been considered in detail. From the simulated counting rates in the detector due to cosmogenic isotopes, it is concluded that activation in copper and stainless steel is not problematic. The activity of 39Ar induced during extraction, purification and transport on surface is evaluated to be 2.8% of the activity measured in UAr by DarkSide-50 experiment, which used the same underground source, and thus considered acceptable. Other isotopes in the UAr such as 37Ar and 3H are shown not to be relevant due to short half-life and assumed purification methods

Sensitivity projections for a dual-phase argon TPC optimized for light dark matter searches through the ionization channel

Dark matter lighter than 10  GeV/c2 encompasses a promising range of candidates. A conceptual design for a new detector, DarkSide-LowMass, is presented, based on the DarkSide-50 detector and progress toward DarkSide-20k, optimized for a low-threshold electron-counting measurement. Sensitivity to light dark matter is explored for various potential energy thresholds and background rates. These studies show that DarkSide-LowMass can achieve sensitivity to light dark matter down to the solar neutrino fog for GeV-scale masses and significant sensitivity down to 10  MeV/c2 considering the Migdal effect or interactions with electrons. Requirements for optimizing the detector’s sensitivity are explored, as are potential sensitivity gains from modeling and mitigating spurious electron backgrounds that may dominate the signal at the lowest energies

Entropy solutions to a strongly degenerate anisotropic convection-diffusion equation, with application to the backward-forward stochastic differential utility

Consiglio Nazionale delle Ricerche - Biblioteca Centrale - P.le Aldo Moro, 7 Rome / CNR - Consiglio Nazionale delle RichercheSIGLEITItal

Ultra-low-dose CT for left atrium and pulmonary veins imaging using new model-based iterative reconstruction algorithm

Aims To evaluate the feasibility of ultra-low-dose CT for left atrium and pulmonary veins using new model-based iterative reconstruction (MBIR) algorithm. Methods and results Two hundred patients scheduled for catheter ablation were randomized into two groups: Group 1 (100 patients, Multidetector row CT (MDCT) with MBIR, no ECG triggering, tube voltage and tube current of 100 kV and 60 mA, respectively) and Group 2 [100 patients, MDCT with adaptive statistical iterative reconstruction algorithm (ASIR), no ECG triggering, and kV and mA tailored on patient BMI]. Image quality, CT attenuation, image noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) of left atrium (LA) and pulmonary veins, and effective dose (ED) were evaluated for each exam and compared between two groups. No significant differences between groups in terms of population characteristics, cardiovascular risk factors, anatomical features, prevalence of persistent atrial fibrillation and image quality score. Statistically significant differences were found between Group 1 and Group 2 in mean attenuation, SNR, and CNR of LA. Significantly, lower values of noise were found in Group 1 versus Group 2. Group 1 showed a significantly lower mean ED in comparison with Group 2 (0.41\ub10.04 versus 4.17\ub12.7 mSv). Conclusion The CT for LA and pulmonary veins imaging using MBIR is feasible and allows examinations with very low-radiation exposure without loss of image quality

Low-Dose Coronary CT Angiography in Patients with Atrial Fibrillation: Comparison of Image Quality and Radiation Exposure with Two Different Approaches

Rationale and Objectives: To evaluate image quality, coronary interpretability and radiation exposure of coronary CT angiography (CCTA)performed in patients with atrial fibrillation (AF)with the latest scanner generation, comparing two different technical approaches. A new scanner that combines a 0.23 mm spatial resolution, a new generation of iterative reconstruction, fast gantry rotation time and the intracycle motion-correction algorithm to improve the temporal resolution was recently introduced in the clinical field. Materials and Methods: We enrolled 105 consecutive patients with chronic AF who performed CCTA with a whole-heart coverage high-definition CT scanner (16-cm z-axis coverage with 256 detector rows, 0.28 s gantry rotation time). Five of them were excluded for impaired renal function. Patients were randomized between a double acquisition protocol (50 patients, group 1)or a single acquisition protocol (50 patients, group 2). The image quality, coronary segment interpretability and effective dose (ED)of CCTA were assessed. Results: The mean HR during the scan was 85.6\ub121 bpm in group 1 vs. 83.7\ub123 bpm in Group 2, respectively (p < ns). In group 2, overall image quality was high and comparable with that of group 1 (Likert scale =3.2 \ub1 1.4 vs. 3.3 \ub1 1.2, p = ns, in group 1 and 2, respectively). Coronary interpretability was high and similar between the two groups (97.5% and 97.1% in group 1 and 2, p = ns, respectively). Mean ED was significantly higher in group 1 than in group 2 (5.3 \ub1 1.8 mSv vs. 2.7 \ub1 0.7 mSv, p < 0.001). Conclusion: The novel whole-heart coverage CT scanner allows to perform CCTA with a single-acquisition protocol with high image quality and low radiation exposure in AF patients

Deliverable 2.3 - Research needs in terms of statistical methodologies and new data

The MAKSWELL project was set up to help strengthening the use of evidence and information on well-being and sustainability for policy-making in the EU, as also the political attention to well-being and sustainability indicators has been increasing in recent years. Traditionally sample surveys are the data source used for measurement frameworks for well-being and sustainability. Over the last decades more and more new, alternative data sources become available. Examples are administrative data like tax registers, or other large data sets - so called big data - that are generated as a by-product of processes not directly related to statistical production purposes. In Deliverables 2.1, 2.2 as well as 3.1, 4.1 and 4.3 it is discussed in detail how these new data sources can be used in the production of official statistics and measurement frameworks for well-being and sustainability indicators. This Deliverable extends on the experiences obtained in these preceding deliverables by pointing out the needs for new data sources and methods in this context

CT Perfusion Versus Coronary CT Angiography in Patients With Suspected In-Stent Restenosis or CAD Progression

Objectives: The goal of this study was to assess the diagnostic performance of coronary computed tomography angiography (CTA) alone, adenosine-stress myocardial perfusion assessed by computed tomography (CTP) alone, and coronary CTA + CTP by using a 16-cm Z-axis coverage scanner versus invasive coronary angiography (ICA) and fractional flow reserve (FFR) as the clinical standard. Background: Diagnostic performance of coronary CTA for in-stent restenosis detection is still challenging. Recently, CTP showed additional diagnostic power over coronary CTA in patients with suspected coronary artery disease. However, few data are available on CTP performance in patients with previous stent implantation. Methods: Consecutive stable patients with previous coronary stenting referred for ICA were enrolled. All patients underwent stress myocardial CTP and rest CTP + coronary CTA. Invasive FFR was performed during ICA when clinically indicated. The diagnostic rate and diagnostic accuracy of coronary CTA, CTP, and coronary CTA + CTP were evaluated in stent-, territory-, and patient-based analyses. Results: In the 150 enrolled patients (132 men; mean age 65.1 \ub1 9.1 years), the CTP diagnostic rate was significantly higher than that of coronary CTA in all analyses (territory based [96.7% vs. 91.1%; p < 0.0001] and patient based [96% vs. 68%; p < 0.0001]). When ICA was used as gold standard, CTP diagnostic accuracy was significantly higher than that of coronary CTA in all analyses (territory based [92.1% vs. 85.5%, p < 0.03] and patient based [86.7% vs. 76.7%, p < 0.03]). The concordant coronary CTA + CTP assessment exhibited the highest diagnostic accuracy values versus ICA (95.8% in the territory-based analysis). The diagnostic accuracy of CTP was significantly higher than that of coronary CTA (75% vs. 30.5%; p < 0.001). The radiation exposure of coronary CTA + CTP was 4.15 \ub1 1.5 mSv. Conclusions: In patients with coronary stents, CTP significantly improved the diagnostic rate and accuracy of coronary CTA alone compared with both ICA and invasive FFR as gold standard