In this work we report the ongoing characterization of the Sos Enattos former mine (Sardinia, Italy), one of the two candidate sites for the Einstein Telescope (ET), the European third-generation ...underground interferometric detector of Gravitational Waves. The Sos Enattos site lies on a crystalline basement, made of rocks with good geomechanical properties, characterized by negligible groundwater. In addition, the site has a very low seismic background noise due to the absence of active tectonics involving Sardinia. Finally, the area has a low population density, resulting in a reduced anthropic noise even at the ground level. This location was already studied in 2012-2014 as a promising site for an underground detector. More recently, in March 2019, we deployed a new network of surface and underground seismometers at the site, that is currently monitoring the local seismic noise. Most of the energy carried by the seismic waves is due to the microseisms below 1 Hz, showing a significant correlation with the waves of the west Mediterranean sea. Above 1 Hz the seismic noise in the underground levels of the mine approaches the Peterson's low noise model. Exploiting mine blasting works into the former mine, we were also able to perform active seismic measurements to evaluate the seismic waves propagation across the area. In conclusion we also give a first assessment about the acoustic and magnetic noise in this underground site.
Background
Several classes of drugs are effective in prevention and treatment of migraine, although they may differ among each other in their mode of action and in indications. One such class is ...represented by antiepileptics. Lacosamide is an approved antiepileptic drug that also shows antinociceptive activity in animal models, including analgesic efficacy in central and trigeminal pain. Calcitonin gene‐related peptide (CGRP) is considered the main neuro‐mediator of trigeminal signalling, playing an essential role in headache, migraine in particular. Here, we investigated the effects of lacosamide on CGRP signalling in both in vitro and ex vivo/vitro models in the rat.
Methods
We assessed: (1) CGRP released from brainstem explants at baseline or after pharmacological challenges; and (2) CGRP levels in brain areas after in vivo treatments with test drugs.
Results
We found that: (1) lacosamide inhibits CGRP release from brainstem explants under basal conditions as well as after stimulation by 56 mM KCl, 10 μM veratridine or 1 μM capsaicin; and (2) the i.p. administration of nitroglycerine produces an increase in CGRP levels in the brainstem and trigeminal ganglia, which is inhibited by a pre‐treatment with lacosamide.
Conclusions
These findings provide preliminary evidence suggesting that lacosamide is able to control pain transmission under conditions affecting the trigeminal system, such as migraine.
In this study we tested the hypothesis that tapentadol inhibits GGRP release from the rat brainstem through a mechanism mediated by the inhibition of NA reuptake; as a second alternative hypothesis, ...we investigated whether tapentadol inhibits GGRP release via the inhibition of 5-HT reuptake.
Rat brainstems were explanted and incubated in short-term experiments. CGRP released in the incubation medium was taken as a marker of CGRP release from the central terminals of trigeminal neurons within the brainstem. CGRP levels were measured by radioimmunoassay under basal conditions or in the presence of tapentadol; NA, 5-HT, clonidine, yohimbine and ondansetron were used as pharmacological tools to investigate the action mechanism of tapentadol.
The α2-antagonist yohimbine failed to counteract the effects of tapentadol. Moreover, neither NA nor the α2-agonist clonidine per se inhibited K+−stimulated CGRP release, thereby indicating that the effects of tapentadol are nor mediated through the block of NA reuptake. Further experiments showed that 5-HT and tramadol, which inhibits both NA and 5-HT reuptake, significantly reduced K+-stimulated CGRP release. Moreover, the 5-HT3 antagonist ondansetron was able to counteract the effects of tapentadol in this system.
This study provided pharmacological evidence that tapentadol inhibits stimulated CGRP release from the rat brainstem in vitro through a mechanism involving an increase in 5-HT levels in the system and the subsequent activation of 5-HT3 receptors.
Abstract Congenital heart disease (CHD) is the most common birth defect, affecting about 0.8% of live births. Advances in recent decades have allowed >85% of children with CHD to survive to ...adulthood, creating a growing population of adults with CHD. Little information exists regarding survival, demographics, late outcomes, and comorbidities in this emerging group, and multiple barriers impede research in adult CHD. The National Heart, Lung, and Blood Institute and the Adult Congenital Heart Association convened a multidisciplinary working group to identify high-impact research questions in adult CHD. This report summarizes the meeting discussions in the broad areas of CHD-related heart failure, vascular disease, and multisystem complications. High-priority subtopics identified included heart failure in tetralogy of Fallot, mechanical circulatory support/transplantation, sudden cardiac death, vascular outcomes in coarctation of the aorta, late outcomes in single-ventricle disease, cognitive and psychiatric issues, and pregnancy.
ESGE/EASL recommend that, as the primary diagnostic modality for PSC, magnetic resonance cholangiography (MRC) should be preferred over endoscopic retrograde cholangiopancreatography (ERCP).Moderate ...quality evidence, strong recommendation.
ESGE/EASL suggest that ERCP can be considered if MRC plus liver biopsy is equivocal or contraindicated in patients with persisting clinical suspicion of PSC. The risks of ERCP have to be weighed against the potential benefit with regard to surveillance and treatment recommendations.Low quality evidence, weak recommendation.
ESGE/EASL suggest that, in patients with an established diagnosis of PSC, MRC should be considered before therapeutic ERCP.Weak recommendation, low quality evidence.
ESGE/EASL suggest performing endoscopic treatment with concomitant ductal sampling (brush cytology, endobiliary biopsies) of suspected significant strictures identified at MRC in PSC patients who present with symptoms likely to improve following endoscopic treatment.Strong recommendation, low quality evidence.
ESGE/EASL recommend weighing the anticipated benefits of biliary papillotomy/sphincterotomy against its risks on a case-by-case basis.Strong recommendation, moderate quality evidence.Biliary papillotomy/sphincterotomy should be considered especially after difficult cannulation.Strong recommendation, low quality evidence.
ESGE/EASL suggest routine administration of prophylactic antibiotics before ERCP in patients with PSC.Strong recommendation, low quality evidence.
EASL/ESGE recommend that cholangiocarcinoma (CCA) should be suspected in any patient with worsening cholestasis, weight loss, raised serum CA19-9, and/or new or progressive dominant stricture, particularly with an associated enhancing mass lesion.Strong recommendation, moderate quality evidence.
ESGE/EASL recommend ductal sampling (brush cytology, endobiliary biopsies) as part of the initial investigation for the diagnosis and staging of suspected CCA in patients with PSC.Strong recommendation, high quality evidence.
•We studied the effects of tapentadol on CGRP release from isolated rat brainstem.•Tapentadol did not modify CGRP release in basal condition.•Tapentadol inhibited both K+- and capsaicin-evoked CGRP ...release.•The effects of tapentadol were compared to those morphine and reboxetine.•Tapentadol fully mimicked the effects of reboxetine in this paradigm.
We have previously developed an in vitro model of rat brainstem explants. The latter release sizable amounts of calcitonin gene-related peptide (CGRP); basal release can be stimulated by such secretagogues as high KCl concentrations, veratridine or capsaicine. In this paradigm we investigated the activity of the analgesic agent tapentadol; the effects of tapentadol were compared to those of a classical opioid receptor agonist, morphine, and the selective noradrenaline reuptake inhibitor reboxetine. Morphine inhibited basal CGRP release, with statistical significance from 1nM onward and maximal (−44%) inhibition at 100μM. Morphine also inhibited K+-stimulated peptide release, with a significant effect from 1μM and maximal (−39%) decrease at 100μM, but failed to inhibit release stimulated by 10μM capsaicin. At variance, reboxetine had no effect on baseline CGRP outflow, but was able to inhibit both K+-stimulated significant inhibition from 1μM onward and maximal (−37%) decrease at 100μM, and capsaicin-stimulated release significant effect from 1μM and maximal (−31%) decrease at 100μM. Likewise, tapentadol had no effect on baseline CGRP release up to 100μM, but decreased secretion stimulated by 56mM KCl or capsaicin, with significant effects from 0.1 and 1μM respectively; maximal inhibition over 56mM KCl and capsaicin stimuli was −29% and −31%, respectively. Naloxone antagonized the effect of morphine, but not those of reboxetine and tapentadol, on K+-stimulated CGRP secretion. In conclusion the present study provides consistent pharmacological evidence that tapentadol acts as a noradrenaline reuptake inhibitor agent in this experimental model.
The aim of this study was to cross-sectionally explore the association of obesity with spinal posture and mobility, commonly associated with musculoskeletal problems, by comparing the spinal ...parameters between 90 obese and 109 normal-weight children and adolescents. A non-invasive electromechanical device, the Idiag M360 (Idiag, Fehraltorf, Switzerland), was used to measure the spinal parameters. An age-and-sex-adjusted two-way analysis of variance (ANOVA) was used to determine postural and mobility differences between the two groups. Children and adolescents with obesity had significantly greater thoracic kyphosis difference between groups (Δ) = 13.0
, 95% CI 10.1
-15.8
, p < 0.0001 and thoracic extension (Δ = 6.5
, 95% CI 2.9
-11.6
, p = 0.005), as well as smaller mobility in thoracic flexion (Δ = 5.0
, 95% CI 1.2
-8.8
, p = 0.01), thoracic lateral flexion (Δ = 17.7
, 95% CI 11.6
-23.8
, p < 0.0001), lumbar flexion (Δ = 12.1
, 95% CI 8.7
-15.5
, p < 0.0001), lumbar extension (Δ = 7.1
, 95% CI 3.1
-12.2
, p = 0.003) and lumbar lateral flexion (Δ = 9.1
, 95% CI 5.5
-12.8
, p < 0.0001) compared to the normal-weight children and adolescents. These findings provide important information about the characteristics of the spine in children and adolescents with obesity and unique insights into obesity-related mechanical challenges that the spine has to withstand and strategies designed to improve spinal mobility in this young population.
Summary of the long term data taking, related to one of the proposed next generation ground-based gravitational detector’s location is presented here. Results of seismic and infrasound noise, ...electromagnetic attenuation and cosmic muon radiation measurements are reported in the underground Matra Gravitational and Geophysical Laboratory near Gyöngyösoroszi, Hungary. The collected seismic data of more than two years is evaluated from the point of view of the Einstein Telescope, a proposed third generation underground gravitational wave observatory. Applying our results for the site selection will significantly improve the signal to noise ratio of the multi-messenger astrophysics era, especially at the low frequency regime.
We report on flexible photovoltaic cell fabricated on polymeric substrate optimized for indoor energy harvesting. We have fabricated small area modules (up to 30cm2) obtained by monolithic ...integration of a-Si:H p-i-n solar cells deposited by PECVD at low temperature with excellent mechanical strength, high ability of folding and very good stability. The photovoltaic thin film module is optimized for indoor light generated by indoor lamps and has efficiency as high as 9.1% on aperture area even at less than 100lx of light intensity (under F12 fluorescent lamp spectrum). The optimized system can be used to energize thin film batteries and can be assembled in a flexible system associated with a wireless sensor network or other electronic devices.
•a-Si:H low temperature process for flexible photovoltaic modules.•~9% power conversion efficiency at indoor conditions.•Excellent module mechanical properties.•a-Si:H/contacts interface electrical characterization.
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