Smoking-related cue reactivity in a virtual reality setting: association between craving and EEG measures

BACKGROUND: Cue-reactivity is the array of responses that smokers exhibit when exposed to conditioned and contextual stimuli previously associated to substance use. The difficulty to experimentally recreate the complexity of smokers' spatial experience and context requires more ecological models. Virtual reality (VR) creates a state of immersion close to reality allowing controlled assessments of behavioral responses. To date, no studies investigated brain activation associated to smoking cue-reactivity in VR using electroencephalography (EEG).AIMS: To investigate whether a VR cue-reactivity paradigm (a) may increase smoking craving, (b) is feasible with EEG recording, and (c) induces craving levels associated to EEG desynchronization.METHODS: Smokers (N=20) and non-smokers (N=20) were exposed to neutral and smoking-related VR scenarios, without and with smoking conditioned stimuli, respectively. EEG was recorded from occipital and parietal leads throughout the sessions to assess alpha band desynchronization. Smoking and food craving and presence visual analogue scales (VAS) were assessed during the session.RESULTS: To be smoker, but not non-smoker, significantly influenced smoking craving VAS induced by smoking cue VR but not by neutral VR. No significant food craving changes was observed during the VR sessions. The new finding was that EEG alpha band power in posterior leads was significantly increased by the smoking context scenario only in smokers, and that the degree of smoking (i.e., heavy vs. light) was significantly associated to this neurophysiological measure.CONCLUSIONS: This study demonstrated, for the first time, the feasibility of EEG recording in a VR setting, suggesting that EEG desynchronization may be a neurophysiological marker of smoking cue-reactivity

Maths Anxiety and cognitive state monitoring for neuroadaptive learning systems using electroencephalography

Mathematical competence is important to acquire for everyday and professional purposes, but often represents a considerable hurdle for students, who may associate it with unpleasant experiences. Our goal is to use neuroscience and neural engineering to support students to improve their math- ematical understanding. More specifically, we are interested in the development of a non-invasive electroencephalogram (EEG)- based neuroadaptive Brain-Computer Interface (BCI) learning environment that optimizes learning outcomes by adapting the learning content provided according to the cognitive load of the learner. In this paper, we investigate what cognitive states occur when students with and without Math Anxiety learn to solve a math problem presented in the form of a novel computer puzzle. Results of an offline analysis of data recorded from 10 study participants suggest that different cognitive states occur, each with specific features that a BCI could potentially detect

3-D Fibrin Scaffold Improves Stemness of Human Peripheral Blood Endothelial Progenitor Cells

Aims Fibrin is a natural biopolymer appealing for cell-based regenerative therapies, because it can support growth, migration and differentiation of different cell types. Endothelial progenitor cells (EPC) represent a very interesting alternative cell source for mature endothelial cells; the fact that can easily isolated from the peripheral blood, thereby eliminating donor morbidity, makes them ideal in applications in the field of regenerative medicine. We have demonstrated that fibrin can support EPC viability and growth. Aim of this study was to evaluate if fibrin can affect EPC differentiation and stem cell markers expression. Methods Fibrin was prepared mixing commercially available (Kedrion S.p.A. Lucca, Italy) fibrinogen (9 mg/ml) and thrombin (25 U/ml). Clot ultrastructure was investigated by scanning electron microscopy (SEM) and cryogenic SEM (CRYO-SEM) to measure fibre diameter and density. Clot elasticity was evaluated by atomic force microscopy (AFM), measuring the tip-sample force by cantilever displacement. EPC were obtained from peripheral blood and cultured on fibrin at the concentration of 1x106cell/cm2. Fibronectin coating was used as a control. Metabolic activity was assessed after 7 and 14 days by WST1 assay and viability by confocal microscopy (calcein incorporation). The expression of both endothelial (CD31, KDR, vWF, Ve-Cadherin) and stem cell markers (nanog, oct-4) was assessed by flow cytometry, confocal microscopy and Real Time RT-PCR. Results SEM analysis revealed a nanometric fibrous structure, with mean fiber diameter of 165?4 nm and mean density of 95.9?0.2 %. CRYO-SEM suggested a reticulate structure with mesh-size up to 10 ?m. Fibrin clot elasticity was 1.78 MPa, as in literature. WST1 assay showed that fibrin increased EPC metabolic activity as compared to fibronectin (fibrin: 0.606?0.056 a.u. vs. fibronectin: 0.311?0.067). Calcein staining demonstrated that EPC were still viable at 14 days. Flow cytometry showed the expression of endothelial markers (CD31=41.8?8.4%; vWF=32.3?3.0%; KDR=89.3?3.7%; VE-Cadherin=41.2?3.8%), confirmed also by confocal microscopy and Real Time RT-PCR. Interestingly, nanog and oct-4 (embryonic stem cell markers) expression was significantly greater on fibrin (p<0.001) as compared to fibronectin. Conclusions These findings suggest that fibrin it is not only a suitable scaffold for EPC growth and viability but also induces EPC differentiation. The observation that Nanog, known as the most important marker of stemness, is maintained longer than on fibronectin, may offer a surplus value to stem cell-based therapies

The clinical effectiveness of an integrated multidisciplinary evidence-based program to prevent intraoperative pressure injuries in high-risk children undergoing long-duration surgical procedures: a quality improvement study

The prevention of hospital-acquired pressure injuries (HAPIs) in children undergoing long-duration surgical procedures is of critical importance due to the potential for catastrophic sequelae of these generally preventable injuries for the child and their family. Long-duration surgical procedures in children have the potential to result in high rates of HAPI due to physiological factors and the difficulty or impossibility of repositioning these patients intraoperatively. We developed and implemented a multi-modal, multi-disciplinary translational HAPI prevention quality improvement program at a large European Paediatric University Teaching Hospital. The intervention comprised the establishment of wound prevention teams, modified HAPI risk assessment tools, specific education, and the use of prophylactic dressings and fluidized positioners during long-duration surgical procedures. As part of the evaluation of the effectiveness of the program in reducing intraoperative HAPI, we conducted a prospective cohort study of 200 children undergoing long-duration surgical procedures and compared their outcomes with a matched historical cohort of 200 children who had undergone similar surgery the previous year. The findings demonstrated a reduction in HAPI in the intervention cohort of 80% (p &lt; 0.01) compared to the comparator group when controlling for age, pathology, comorbidity, and surgical duration. We believe that the findings demonstrate that it is possible to significantly decrease HAPI incidence in these highly vulnerable children by using an evidence-based, multi-modal, multidisciplinary HAPI prevention strategy

The ketamine analogue methoxetamine generalizes to ketamine discriminative stimulus in rats

Methoxetamine (MXE) is a chemical analogue of ketamine. Originally proposed as a ketamine-like fast-acting antidepressant, owing to similar N-methyl-D-aspartate blocker properties, it is now scheduled for reports of hallucinations and psychosis similar to ketamine and lysergic acid. As little is known about the addictive properties of MXE, the aim of this study was to investigate the similarity between discriminative stimuli of MXE and ketamine, as well as to provide data and protocols that could be used in the future for the characterization of novel ketamine-like drugs. The paradigm used was a two-lever operant conditioning paradigm in which rats were trained to discriminate ketamine (7.5\u2009mg/kg/ml, intraperitoneal) from vehicle. Generalization tests were performed with MXE (0.0625, 0.125, 0.25, 0.5, or 1.0). We also tested the N-methyl-D-aspartate channel blocker MK-801 (0.005-0.1), lysergic acid (0.025-0.30), a serotonergic drug that had similar hallucinogenic effects as ketamine and methamphetamine (0.15-0.60) a drug with no generalization with ketamine, injected intraperitoneally presession (mg/kg). MXE and MK-801 fully generalized to ketamine. Lysergic acid and methamphetamine partially substituted for the ketamine stimulus, although the highest lysergic acid dose showed a 77.7% generalization. The present findings suggest that investigation of 'ketamine-like compounds' should explore not only substances with chemical analogy and common molecular mechanisms with ketamine, but also with similar psychopharmacological effects

2,5-Diamide-Substituted Five-Membered Heterocycles: Challenging Molecular Synthons

We describe synthetic routes for preparing previously unknown 2,5-diamide-substituted five-membered heterocycles based on the thiophene, pyrrole, and furan ring systems by exploiting Curtius-like rearrangement reactions. Conformation analysis of the 2,5-diamidothiophene derivatives identified a "closed" conformation, in which the two carbonyl O atoms are in close contact with the thiophene S atom

Procoagulant, tissue factor-bearing microparticles in bronchoalveolar lavage of interstitial lung disease patients: an observational study.

Coagulation factor Xa appears involved in the pathogenesis of pulmonary fibrosis. Through its interaction with protease activated receptor-1, this protease signals myofibroblast differentiation in lung fibroblasts. Although fibrogenic stimuli induce factor X synthesis by alveolar cells, the mechanisms of local posttranslational factor X activation are not fully understood. Cell-derived microparticles are submicron vesicles involved in different physiological processes, including blood coagulation; they potentially activate factor X due to the exposure on their outer membrane of both phosphatidylserine and tissue factor. We postulated a role for procoagulant microparticles in the pathogenesis of interstitial lung diseases. Nineteen patients with interstitial lung diseases and 11 controls were studied. All subjects underwent bronchoalveolar lavage; interstitial lung disease patients also underwent pulmonary function tests and high resolution CT scan. Microparticles were enumerated in the bronchoalveolar lavage fluid with a solid-phase assay based on thrombin generation. Microparticles were also tested for tissue factor activity. In vitro shedding of microparticles upon incubation with H₂O₂ was assessed in the human alveolar cell line, A549 and in normal bronchial epithelial cells. Tissue factor synthesis was quantitated by real-time PCR. Total microparticle number and microparticle-associated tissue factor activity were increased in interstitial lung disease patients compared to controls (84±8 vs. 39±3 nM phosphatidylserine; 293±37 vs. 105±21 arbitrary units of tissue factor activity; mean±SEM; p<.05 for both comparisons). Microparticle-bound tissue factor activity was inversely correlated with lung function as assessed by both diffusion capacity and forced vital capacity (r² = .27 and .31, respectively; p<.05 for both correlations). Exposure of lung epithelial cells to H₂O₂ caused an increase in microparticle-bound tissue factor without affecting tissue factor mRNA. Procoagulant microparticles are increased in interstitial lung diseases and correlate with functional impairment. These structures might contribute to the activation of factor X and to the factor Xa-mediated fibrotic response in lung injury

FRODI IN PRODOTTI DELLA PESCA A BASE DI MOLLUSCHI BIVALVI: IDENTIFICAZIONE MOLECOLARE DI SPECIE DEL GENERE MYTILUS

Introduzione I mitili (genere Mytilus) rappresentano un prodotto molto apprezzato dai consumatori europei. Sebbene la produzione comunitaria sia piuttosto elevata, non è tuttavia in grado di sopperire alla crescente domanda. Per tale motivo vengono importate notevoli quantità di tali prodotti, soprattutto in forma processata, da paesi terzi, primo su tutti il Cile. L’etichettatura di tali prodotti è normata dal Regolamento (UE) 1169/2011, relativo alla fornitura di informazioni sugli alimenti ai consumatori, mentre risultano esclusi dal campo d’applicazione del Regolamento (UE) n. 1379/2013, relativo all'organizzazione comune dei mercati nel settore dei prodotti della pesca e dell'acquacoltura, che stabilisce informazioni obbligatorie per i prodotti della pesca. Infatti, quest’ultimo Regolamento non si applica ai prodotti della pesca trasformati, per i quali riportare tali informazioni sull’etichetta è a discrezione dell’OSA. Lo scopo del presente lavoro di tesi è stato quello di valutare il livello di conformità alla normativa vigente in prodotti trasformati a base di cozze e di identificare la specie attraverso analisi molecolare. Summary Mussels (Mytilus genus) represent a very appreciated product by European consumers. Although EU production is quite high, it is not able to meet the growing demand. For this reason, significant quantities of these products are imported, especially in processed form, from third countries, especially from Chile. The labelling of these products is regulated by Regulation (EU) n. 1169/2011, concerning the supply of food information to consumers, while they are excluded from the field of application of Regulation (EU) n. 1379/2013, on to the common organization of the market in fishery and aquaculture products. In fact, the latter Regulation is not applied to processed fishery products, for which the information on the label are reported at the discretion of the FBO. The aim of this work was to assess the level of compliance with the current regulations in mussel-based processed products and identify the species through molecular analysis. Materiali e Metodi Sono stati analizzati 18 prodotti trasformati del genere Mytilus acquistati presso la GDO e la distribuzione etnica. E’ stato anzitutto valutato il grado di conformità dell’etichettatura alla normativa vigente ed in particolare al Reg. UE n. 1169/2011 e al Reg. UE n. 1379/2013. In quest’ultimo caso è stata valutata la presenza delle informazioni riportate su base volontaria dall’OSA. L’analisi molecolare, effettuata in collaborazione con il Centro specialistico di ittiopatologia dell’Istituto Zooprofilattico Sperimentale delle Venezie, ha previsto l’utilizzo di primer specificamente progettati per l’amplificazione di frammenti di lunghezza variabile del gene nucleare codificante per la Adhesive Foot Protein delle specie di Mytilus di maggior interesse economico. L’eventuale presenza di specie ibride è stata preventivamente valutata attraverso il rilevamento di una doppia banda di amplificazione mediante corsa elettroforetica. I prodotti di PCR sono stati successivamente sequenziati e le sequenze ottenute opportunamente editate e sottoposte ad analisi BLAST su GenBank per l’identificazione tassonomica. Le specie identificate attraverso l’analisi molecolare sono state quindi confrontate con quelle riportate in etichetta (laddove presenti) allo scopo di valutare il livello di mislabelling dei prodotti in esame. Risultati e Discussione Sebbene siano state riscontrate alcune irregolarità in materia di etichettatura ai sensi del Reg. (UE) N.1169/2011, è stato osservato nel complesso un elevato tasso di conformità alla luce della suddetta normativa (78%). Inoltre, gran parte dei prodotti riportavano su base volontaria le informazioni stabilite dal Reg. (UE) 1379/2013. Tutti i campioni sono stati amplificati con successo. La corsa elettroforetica dei prodotti di PCR ha messo in evidenza doppie bande riferibili ad esemplari ibridi in 2 campioni, dai quali non è stato possibile ottenere sequenze sufficientemente informative. Al contrario, l’ottenimento di sequenze leggibili in caso di bande singole, ha confermato le specie riportate in etichetta. Considerando l’ormai ampia diffusione sui mercati di individui ibridi, derivanti principalmente dal contatto tra specie affini appartenenti al Mytilus edulis complex (M. galloprovincialis, M.edulis e M. trossolus) risulta necessario sviluppare metodiche molecolari in grado di differenziare anche tali specie