RGS10 shapes the hemostatic response to injury through its differential effects on intracellular signaling by platelet agonists.

Platelets express ≥2 members of the regulators of G protein signaling (RGS) family. Here, we have focused on the most abundant, RGS10, examining its impact on the hemostatic response in vivo and the mechanisms involved. We have previously shown that the hemostatic thrombi formed in response to penetrating injuries consist of a core of fully activated densely packed platelets overlaid by a shell of less-activated platelets responding to adenosine 5\u27-diphosphate (ADP) and thromboxane A2 (TxA2). Hemostatic thrombi formed in RGS10-/- mice were larger than in controls, with the increase due to expansion of the shell but not the core. Clot retraction was slower, and average packing density was reduced. Deleting RGS10 had agonist-specific effects on signaling. There was a leftward shift in the dose/response curve for the thrombin receptor (PAR4) agonist peptide AYPGKF but no increase in the maximum response. This contrasted with ADP and TxA2, both of which evoked considerably greater maximum responses in RGS10-/- platelets with enhanced Gq- and Gi-mediated signaling. Shape change, which is G13-mediated, was unaffected. Finally, we found that free RGS10 levels in platelets are actively regulated. In resting platelets, RGS10 was bound to 2 scaffold proteins: spinophilin and 14-3-3γ. Platelet activation caused an increase in free RGS10, as did the endothelium-derived platelet antagonist prostacyclin. Collectively, these observations show that RGS10 serves as an actively regulated node on the platelet signaling network, helping to produce smaller and more densely packed hemostatic thrombi with a greater proportion of fully activated platelets

Design of an air-flow microchamber for microparticles detec

This paper was presented at the 4th Micro and Nano Flows Conference (MNF2014), which was held at University College, London, UK. The conference was organised by Brunel University and supported by the Italian Union of Thermofluiddynamics, IPEM, the Process Intensification Network, the Institution of Mechanical Engineers, the Heat Transfer Society, HEXAG - the Heat Exchange Action Group, and the Energy Institute, ASME Press, LCN London Centre for Nanotechnology, UCL University College London, UCL Engineering, the International NanoScience Community, www.nanopaprika.eu.A novel device, able to funnel a suspension of micrometric particles in air into a microchamber equipped with a capacitive sensor, has been designed for the detection and characterization of particulate matter (PM) in air. Numerical simulations have been performed to predict the trajectory of the microparticles through the PDMS microchamber where the sensor is located. The feasibility of detecting single PM10 particles has been demonstrated by our experiments, where sequences of single industrial talc particles (average diameter of 8 μm) have been detected and counted by a capacitive sensor. Our results indicate that radical miniaturization of air quality monitors is possible and, therefore, pervasive monitoring of air pollution will be soon feasible

6-channel CMOS-based instrument for optical absorption spectroscopy and chemical identification

A multichannel portable instrument for on-chip optical absorption spectroscopy is presented. The system can house photonic chips having up to 6 sensing sites operating in parallel, allowing real-time simultaneous detection of multiple chemicals. A 6-channel CMOS lock-in front-end performs the amplification and demodulation of the signals from the integrated light detectors, while an FPGA is chosen for signal acquisition and analysis. A digital real-time ratiometric processing cancels out the effect of laser power fluctuations to achieve high sensitivity in monitoring the presence of the analytes, as demonstrated with the detection of an acetone sample. Compact size for portability, real-time parallel detection and flexible FPGA processing make this system suitable for environmental investigations on many different pollutants, both in the near- and mid-infrared wavelength range

GTE. A new software for gravitational terrain effect computation: theory and performances

The computation of the vertical attraction due to the topographic masses, the so-called Terrain Correction, is a fundamental step in geodetic and geophysical applications: it is required in high-precision geoid estimation by means of the remove–restore technique and it is used to isolate the gravitational effect of anomalous masses in geophysical exploration. The increasing resolution of recently developed digital terrain models, the increasing number of observation points due to extensive use of airborne gravimetry in geophysical exploration and the increasing accuracy of gravity data represents nowadays major issues for the terrain correction computation. Classical methods such as prism or point masses approximations are indeed too slow while Fourier based techniques are usually too approximate for the required accuracy. In this work a new software, called Gravity Terrain Effects (GTE), developed to guarantee high accuracy and fast computation of terrain corrections is presented. GTE has been thought expressly for geophysical applications allowing the computation not only of the effect of topographic and bathymetric masses but also those due to sedimentary layers or to the Earth crust-mantle discontinuity (the so-called Moho). In the present contribution, after recalling the main classical algorithms for the computation of the terrain correction we summarize the basic theory of the software and its practical implementation. Some tests to prove its performances are also described showing GTE capability to compute high accurate terrain corrections in a very short time: results obtained for a real airborne survey with GTE ranges between few hours and few minutes, according to the GTE profile used, with differences with respect to both planar and spherical computations (performed by prism and tesseroid respectively) of the order of 0.02 mGal even when using fastest profiles

Proteomics Profiling of Heterozygous and Homozygous Patients with ABCA1 Gene Mutation: A Tangier Disease Molecular Map

Tangier Disease (TD) is a rare inherited disorder with approximately 100 worldwide identified cases. Alpha-lipoprotein deficiency is the main characteristic of this disease, associated with a virtual absence of High Density Lipoproteins (HDL) in blood. Additional symptoms are mild hypertriglyceridemia, neuropathy and enlarged, orange-colored tonsils. Genetically TD is caused by mutations in the ABCA1 gene, which prevent the release of cholesterol and phospholipids from cells, leading to the accumulation of lipids within cells and body tissues. In this work a TD patient and his parental heterozygous were examined from a proteomics point of view. Plasma as well as proteome and secretome of circulating monocytes were analyzed. Plasma proteins underlined in TD the imbalance of lipid trafficking and metabolism, associated with the stimulation of pro-inflammatory pathways. Proteome and secretome of monocytes highlighted an extensive down regulation of mitochondrial enzymes and vesicular trafficking agents along with a substantial cytoskeletal rearrangement, suggesting a reduced activation state of monocytes from TD homozygous patient. This work is the first proteomics profiling of heterozygous and homozygous TD phenotypes and it suggests a TD case as a model to understand general mechanisms of lipid transport and metabolism and their linkage to inflammatory processes

Towards a greener endoscopy: considerations on the strategies to improve sustainability

Climate crisis is dramatically changing life on earth. Environmental sustainability and waste management are rapidly gaining centrality in quality improvement strategies of healthcare, especially in procedure- dominant fields such as gastroenterology and digestive endoscopy. Therefore, healthcare interventions and endoscopic procedures must be evaluated through the ‘triple bottom line’ of financial, social, and environmental impact. The purpose of the paper is to provide information on the carbon footprint of gas- troenterology and digestive endoscopy and outline a set of measures that the sector can take to reduce the emission of greenhouse gases while improving patient outcomes. Scientific societies, hospital execu- tives, single endoscopic units can structure health policies and investment to build a “green endoscopy”. The AIGO study group reinforces the role of gastrointestinal endoscopy professionals as advocates of sus- tainability in digestive endoscopy. The “green endoscopy” can shape a more sustainable health service and lead to an equitable, climate-smart, and healthier future.info:eu-repo/semantics/publishedVersio

P132 Uncovering blood biomarkers of Inflammatory Bowel Diseases by Raman spectroscopy and FAP dosage: toward a noninvasive triage of patients in first care diagnostic

Abstract Background Currently, a major point of concern in the management of Inflammatory Bowel Diseases (IBD) is the absence of accurate and specific circulating biomarkers able to drive diagnosis in a timely and noninvasive manner. Aim of the present study was to explore blood biomarkers of IBD by coupling the targeted detection of circulating fibroblast activation protein (FAP), a recognized valuable marker of bowel lesion in IBD, and Raman spectroscopy (RS), a quick and label-free metabolomic technique that provides a real-time biochemical characterization of plasma samples without any previously known target. Methods Blood samples were collected from over 140 patients with IBD and 170 control subjects matched for gender and age. Isolated plasma was analysed by enzyme-linked immunosorbent assay for quantitative detection of circulating form of FAP. RS was performed on dry droplets of plasma, with the aim to decipher specific fingerprint of IBD in peripheral blood. A predictive model was built on FAP and Raman data separately, to determine specificity, sensitivity and accuracy of the two approaches in patients classification. Supervised multivariate model was applied on a subset of 203 patients to discriminate IBD and control subjects based on combined datasets. Results FAP levels were reduced in patients with IBD as compared to controls (p<0.0001). The sensitivity and specificity of FAP were 70% and 84% based on the optimal cutoff (57.6 ng mL-1, AUC=0.78). Raman spectra of IBD plasma revealed significant differences in peaks corresponding to carotenoids, proteins with β-sheet secondary structure, lipids and aromatic amino-acids. A machine learning model was applied on a subset of patients reaching an accuracy of 85% in classifying IBD and control subjects. No statistically significant differences were observed so far between the discriminative performance of the sole RS or the combination of RS and FAP. Conclusion RS and FAP dosage enable new discoveries in the biological fingerprint of IBD plasma and provide novel candidate biomarkers of IBD. Our preliminary results strongly suggest that novel blood-based approaches could represent a fast noninvasive way to triage patents with suspected IBD in first care diagnostic, to be applied prior to further specific evaluation

An accelerated access pathway for innovative high-risk medical devices under the new European Union Medical Devices and health technology assessment regulations?:Analysis and recommendations

Introduction: The new European Union (EU) Regulations for medical devices (MDs) and health technology assessment (HTA) are welcome developments that will hopefully increase the quality of clinical evidence for MDs and reduce fragmentation in the EU market access process. To fully exploit anticipated benefits, their respective assessment processes should be closely coordinated, particularly for promising, highly innovative MDs. Accelerated approval is worth exploring for certain categories of high-risk MDs to keep the EU regulatory process competitive compared to ad-hoc accelerated MD approval processes elsewhere (e.g., US). Areas covered: Problems observed in worldwide accelerated drug and MD regulatory approval programs are reviewed, including greater uncertainty in pre-market clinical evidence generation and lack of oversight for post-approval evidence requirements. Implications for MD approval, HTA and coverage are explored. Expert opinion: Through analysis of two decades of drug and MD accelerated approval programs worldwide, recommendations for an Accelerated Access Pathway for select innovative, high-risk MDs are proposed that can fit the EU context, leverage the two new regulations, increase opportunities for Expert Panels to provide timely advice regarding manufacturers’ evidence generation plans along the MD lifecycle (pre-, post-market), and safely speed patient access while promoting increased collaboration among Member States on coverage decisions.</p