Stimulus-Evoked Activity Modulation of In Vitro Engineered Cortical and Hippocampal Networks

The delivery of electrical stimuli is crucial to shape the electrophysiological activity of neuronal populations and to appreciate the response of the different brain circuits involved. In the present work, we used dissociated cortical and hippocampal networks coupled to Micro-Electrode Arrays (MEAs) to investigate the features of their evoked response when a low-frequency (0.2 Hz) electrical stimulation protocol is delivered. In particular, cortical and hippocampal neurons were topologically organized to recreate interconnected sub-populations with a polydimethylsiloxane (PDMS) mask, which guaranteed the segregation of the cell bodies and the connections among the sub-regions through microchannels. We found that cortical assemblies were more reactive than hippocampal ones. Despite both configurations exhibiting a fast (<35 ms) response, this did not uniformly distribute over the MEA in the hippocampal networks. Moreover, the propagation of the stimuli-evoked activity within the networks showed a late (35-500 ms) response only in the cortical assemblies. The achieved results suggest the importance of the neuronal target when electrical stimulation experiments are performed. Not all neuronal types display the same response, and in light of transferring stimulation protocols to in vivo applications, it becomes fundamental to design realistic in vitro brain-on-a-chip devices to investigate the dynamical properties of complex neuronal circuits

Comparative cytotoxicity evaluation of eight root canal sealers

The aim of the present study is to evaluate and compare the cytotoxic effects of eight root canal sealers (BioRoot RCS, TotalFill BC Sealer, MTA Fillapex, Sealapex, AH Plus, EasySeal, Pulp Canal Sealer, N2) on immortalized human gingival fibroblasts over a period of 24, 48 and 72 hours. Immortalized human gingival fibroblast-1 HGF-1 (ATCC CRL-2014) were incubated. Root canal sealers were then placed into sterile, cylindrical Teflon moulds. The extraction was made eluting the sealers in cell culture medium. Cells (1 × 104) were seeded in each well of a 96-well plate and incubated for 24 h at 37°C. Cultures were then exposed to 100 ?L of the extracts medium. The percentage of viable cells in each well was calculated relative to control cells set to 100%. BioRoot RCS and TotalFill BC Sealer extracted for 24h showed no cytotoxic effect, while it was mild by using 48 and 72 h extracts. No cytotoxic effect was measured by using AH Plus medium eluted for 24 h, while it was moderate after 48 h and severe after 72 h. Pulp Canal Sealer, Sealapex and N2 showed moderately cytotoxic activity for all the extraction times. EasySeal and MTA Fillapex remained severely or borderline mildly cytotoxic for all the extraction times. In the present study only BioRoot RCS, TotalFill BC Sealer and AH Plus showed no cytotoxic effects at least in the first 24h. All the other sealers revealed moderately or severely cytotoxic activity during all the extraction times

Modularity and neuronal heterogeneity: Two properties that influence in vitro neuropharmacological experiments

IntroductionThe goal of this work is to prove the relevance of the experimental model (in vitro neuronal networks in this study) when drug-delivery testing is performed. MethodsWe used dissociated cortical and hippocampal neurons coupled to Micro-Electrode Arrays (MEAs) arranged in different configurations characterized by modularity (i.e., the presence of interconnected sub-networks) and heterogeneity (i.e., the co-existence of neurons coming from brain districts). We delivered increasing concentrations of bicuculline (BIC), a neuromodulator acting on the GABAergic system, and we extracted the IC50 values (i.e., the effective concentration yielding a reduction in the response by 50%) of the mean firing rate for each configuration. ResultsWe found significant lower values of the IC50 computed for modular cortical-hippocampal ensembles than isolated cortical or hippocampal ones. DiscussionAlthough tested with a specific neuromodulator, this work aims at proving the relevance of ad hoc experimental models to perform neuropharmacological experiments to avoid errors of overestimation/underestimation leading to biased information in the characterization of the effects of a drug on neuronal networks

Ground motion areas detection (GMA-D): an innovative approach to identify ground deformation areas using the SAR-based displacement time series

Abstract. In this work, an innovative methodology to generate the automatic ground motion areas mapping is presented. The methodology is based on the analysis of the Synthetic Aperture Radar (SAR)-based displacement time series. The procedure includes two modules developed using the ModelBuilder tool (ArcGis). These modules allow to identify the ground motion areas (GMA) using only one dataset and the persistent GMA (PGMA) considering the different monitored periods and datasets. These areas represent clusters of targets characterized by the same displacement time series trend. The procedure was tested using different sensors such as ERS-1/2, ENVISAT, COSMO-SkyMed and Sentinel-1 covering the periods, 1992–2000, 2003–2010, 2012–2016 and 2014–2017, respectively, over an area of about 500 km2 in the Venetian-Friulian coastal Plain (NE Italy). The resulting mapping allows to detect priority areas where to address further in situ investigations such as to verify the presence of localized buried landforms

Il Museo dell'Industria e del Lavoro "Eugenio Battisti": l'anteprima in un CD

Nasce a Brescia il primo museo italiano dedicato alla modernità, alla grande trasformazione divenuta sempre più rapida nel 900, che prosegue oggi e si proietta in un futuro che è già presente. È questo il tema del Museo che sta sorgendo nella città e nella provincia di Brescia e proporrà un itinerario dalla realtà locale all'Italia e all'Europa. L'associazione Museo dell'Industria e del Lavoro "Eugenio Battisti" (Brescia), con il patrocinio del Ministero dell'Istruzione, della Università e della Ricerca, annuncia la realizzazione e la prossima distribuzione di un CD-Rom in cui collezioni e materiali documentari vengono presentati attraverso quattro percorsi tematici, che prefigurano le sezioni espositive della sede centrale del Museo

Biological and physico-chemical properties of new root canal sealers

The purpose of the present study was to compare the biological and the physico-chemical properties of bioceramic-based root canal sealers, calcium hydroxide-based, MTA-based and epoxy resin-based root canal sealers. Two bioceramic-based sealers, one calcium hydroxide-based sealer, one MTA-based sealer and two epoxy resin-based sealers were tested. EasySeal and MTA Fillapex showed severe citotoxic activity, AH Plus and SealapexTM moderate cytotoxicity, BioRoot? RCS and TotalFill BC Sealer were both cytocompatible. Except for TotalFill BC Sealer, all root canal sealers caused inhibition zones when tested with E. faecalis. The highest inhibition zone was observed for EasySeal, followed by AH Plus. BioRoot? RCS, SealapexTM and MTA Fillapex showed the lowest inhibition zone. All the tested materials showed different degree of antibacterial activity by using direct contact test (DCT). The highest values were observed for BioRoot? RCS, TotalFill BC Sealer and EasySeal, followed by MTA Fillapex and SealapexTM. Except for BioRoot RCS and TotalFill BC Sealer, all the root canal sealers fulfilled the requirements of the ISO 6876 standard, demonstrating a weight loss less than 3%. Bioroot RCS, TotalFill BC Sealer and SealapexTM exhibited high alkaline pH with an increase both for BioRoot? RCS and TotalFill BC Sealer after 24 hours. The new bioceramic-based sealers showed acceptable physico-chemical properties, but BioRoot? RCS and TotalFill BC Sealer seems to be too soluble, not respecting ISO 6876 requirements

Modularity and neuronal heterogeneity: Two properties that influence in vitro neuropharmacological experiments

IntroductionThe goal of this work is to prove the relevance of the experimental model (in vitro neuronal networks in this study) when drug-delivery testing is performed.MethodsWe used dissociated cortical and hippocampal neurons coupled to Micro-Electrode Arrays (MEAs) arranged in different configurations characterized by modularity (i.e., the presence of interconnected sub-networks) and heterogeneity (i.e., the co-existence of neurons coming from brain districts). We delivered increasing concentrations of bicuculline (BIC), a neuromodulator acting on the GABAergic system, and we extracted the IC50 values (i.e., the effective concentration yielding a reduction in the response by 50%) of the mean firing rate for each configuration.ResultsWe found significant lower values of the IC50 computed for modular cortical-hippocampal ensembles than isolated cortical or hippocampal ones.DiscussionAlthough tested with a specific neuromodulator, this work aims at proving the relevance of ad hoc experimental models to perform neuropharmacological experiments to avoid errors of overestimation/underestimation leading to biased information in the characterization of the effects of a drug on neuronal networks

Biomarkers in Coronary Artery Bypass Surgery: Ready for Prime Time and Outcome Prediction?

Coronary artery bypass surgery (CABG) is still one of the most frequently performed surgical procedures all over the world. The results of this procedure have been constantly improved over the years with low perioperative mortality rates, with relatively low complication rates. To further improve these outstanding results, the clinicians focused their attention at biomarkers as outcome predictors. Although biological testing for disease prediction has already been discussed many times, the role of biomarkers in outcome prediction after CABG is still controversial. In this article, we reviewed the current knowledge regarding the role of genetic and dynamic biomarkers and their possible association with the occurrence of adverse clinical outcomes after CABG. We also took into consideration that the molecular pathway activation and the possible imbalance may affect hard outcomes and graft patency. We analyzed biomarkers classified in two different categories depending on their possibility to change over time: genetic markers and dynamic markers. Moreover, we evaluated these markers by dividing them, into sub-categories, such as inflammation, hemostasis, renin-angiotensin, endothelial function, and other pathways. We showed that biomarkers might be associated with unfavorable outcomes after surgery, and in some cases improved outcome prediction. However, the identification of a specific panel of biomarkers or of some algorithms including biomarkers is still in an early developmental phase. Finally, larger studies are needed to analyze broad panel of biomarkers with the specific aim to evaluate the prediction of hard outcomes and graft patency

Economic Evaluation of Different Organizational Models for the Management of Patients with Hepatitis C

BACKGROUND: Access to Directly Acting Antivirals (DAAs) for Hepatitis C Virus (HCV) treatment in Italy was initially restricted to severe patients. In 2017, AIFA expanded access to all patients, to achieve elimination by 2030.AIM: To investigate the impact of different hospitals’ organizational models on elimination timing, treatment capacity and direct costs.METHODS: Most Regional healthcare systems in Italy deploy a Center of Excellence (CoE) organizational model, where patients are referred to a single major hospital in the area, which is the only one that can prescribe and deliver DAAs. The study was conducted at Bergamo’s (Lombardy, Italy) Papa Giovanni XXIII hospital (PG-23), which deploys a Hub&Spoke model: the Hub (PG-23) prescribes and delivers DAAs while Spokes (four smaller hospitals) can only prescribe them. The study compares the two models (CoE vs. H&S). Patient journey and workloads were mapped and quantified through interviews with hospital stakeholders. Cost data were collected through the hospital’s IT system; the sample comprised 2,277 HCV patients, over one year.RESULTS: The study calculated the average cost to treat HCV patients (~ € 1,470 per patient). Key cost drivers are lab tests (60%) and specialist visits (30%). Over one year, H&S can treat 68% more patients than CoE. As deferred patients absorb up to 40% of total costs, the “Optimized” model was designed by streamlining specialists’ visits and involving general practitioners during follow-up. “Optimized” model increases treatment capacity and reduces costs of deferred patients by 72% vs CoE.CONCLUSION: The study demonstrates the importance of organizational models in efficiently achieving 2030 elimination

Efficacy and Safety of Bempedoic Acid in Patients With Hypercholesterolemia: Systematic Review and Meta‐Analysis of Randomized Controlled Trials

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