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Gym in a dish: exploring the impacts of statins and CoQ10 depletion on myotubes in a simulated exercise environment.
No full textL'attività fisica regolare contrasta e previene un'ampia varietà di condizioni fisiopatologiche avverse. Tuttavia, quando l'intensità o la durata dell'esercizio superano livelli ottimali, aumenta il rischio di overtraining, una condizione caratterizzata da un grave squilibrio ossidativo che può comportare rischi per la salute. Se da una parte i comuni antiossidanti hanno mostrato risultati incoerenti nel contrastare questi effetti dannosi, dall'altra il Coenzima Q10 (CoQ10), noto per il suo ruolo antiossidante e bioenergetico, rappresenta un'alternativa promettente.
L'obiettivo di questo progetto è stato quello di sviluppare un sistema di Stimolazione Elettrica Pulsata (EPS) in vitro per simulare un esercizio fisico esaustivo (overtraining), testandolo poi su un modello di miotubi murini deprivati di CoQ (C2C12). È stata inoltre testata la supplementazione con ubiquinolo (la forma ridotta del CoQ10) sul modello EPS accoppiato al modello deprivato. I risultati mostrano un'ottimizzazione del protocollo di overtraining e del modello deprivato di CoQ, evidenziando una diminuzione della vitalità e della durata
della contrazione dei miotubi, oltre a significative alterazioni morfologiche. Diversamente dalle ipotesi iniziali, la supplementazione con ubiquinolo non sembra aver prevenuto il danno cellulare, probabilmente a causa dell'elevata variabilità biologica osservata.Regular physical activity has been shown to counteract and prevent a variety of adverse
health conditions, including non-communicable diseases, along with slowing down the aging
process. However, when exercise intensity or duration exceeds optimal levels, the risk of
overtraining increases, a condition characterized by a severe oxidative imbalance that
results in oxidative damage. Antioxidants have been demonstrated inconsistent results in
counteracting these detrimental effects, Coenzyme Q10 (CoQ10), known for its antioxidant and bioenergetic role, presents a promising alternative. In this context, the aim of this project was to develop an in vitro Electrical Pulse Stimulation (EPS) system to simulate an overtraining physical exercise, testing it on a CoQ-deprived model of murine myotubes cells (C2C12). Exogenous ubiquinol supplementation on the models coupled (EPS+CoQdeprived) was also tested. The results show the fine-tuning of the high-intensity exercise protocol and CoQ-deprived model have been achieved in terms of decreased viability and myotubes contraction duration with significant morphological alterations. Despite of the assumptions, ubiquinol supplementation did not seem to prevent the cellular oxidative alterations, probably due to the high biological variability observed
Innovative multifunctional finish for the improvement of Indoor Air Quality: Performance at laboratory and pilot scale
Get PDFIn this study, the impact of an innovative multifunctional finish on the Indoor Air Quality (IAQ) in terms of temperature (T), relative humidity (RH), and volatile organic compounds (VOCs) was compared to that of a commercial finish for the same application as reference. The two finishes were applied on the same commercial substrate and tested both at laboratory and pilot scale. At laboratory scale, the water vapour permeability, the moisture buffering capacity and the depolluting activity by adsorption of the innovative finish was 15 %, 100 % and more than 200 % higher than those of the commercial one on the same substrate, respectively. At pilot scale, the innovative finish was more effective than the commercial finish in buffering humidity variations (RH increases 53 % slower compared to the commercial solution), temperature variations (-1.5 °C), and decreasing VOCs concentration (from 14 % up to 63 %, depending to the test conditions). Therefore, the innovative multifunctional indoor finish has proven to be more effective than the commercial one in improving IAQ not only in laboratory but also at pilot scale
On the user-based assessments of virtual reality for public safety training in urban open spaces depending on immersion levels
Get PDFThe increasing use of VR (Virtual Reality) training tools in safety-related fields has prompted the scientific community to explore methods for assessing their effectiveness across different levels of immersion. While numerous studies have been conducted in sectors such as healthcare, transportation, agriculture, aviation, mining, firefighting, and construction, one area that remains underexplored is risk training for general public against natural and man-made disasters in both indoor and outdoor built environments. In this context, the paper aims at validating a prototype for VR multi-risk (heat wave and earthquake) training in urban open spaces that was developed according to a Serious Game (SG) approach. To address insights on its extensive adoption, the VR-SG was tested for comparison of three modes: traditional by video recording, non-immersive by desktop, immersive by headset. Outputs from feedback questionnaires on knowledge gain and transfer to expansive contexts, as well as on user experience, suggest that the effectiveness of knowledge acquisition differs significantly between headset and video, as well as between desktop and video, but shows no significant difference between headset and desktop. Additionally, while headset outperforms desktop in terms of engagement, perceived usefulness, and realism, it falls behind in ease of use. Finally, further analyses on training outcome by age, contents of open-ended answers, in-game errors and administration procedures supported the discussion of key aspects in targeting VR for public safety communication
Localization effects in micropolar laminated composites with imperfect contact conditions
Get PDFWithin the framework of three-dimensional linear micropolar media, the Asymptotic Homogenization Method (AHM) has been recently applied to obtain the effective engineering moduli for a laminated composite with imperfect contact between the layers. The imperfect contact is prescribed by using a micropolar spring-type interface model, and the interface parameters enter the engineering constants related to the stiffness and torque. In this work, we obtain the concentration tensors linking the macroscopic averaged quantities (stress/couple-stress and strain/curvature) with their microscopic counterparts. A numerical example is proposed to illustrate the influence of the phases volume fraction and of the interface parameters on the strain/curvature and stress/couple-stress concentrations
Application of hydrokinetic turbines in microtidal rivers: The Misa River test site
Get PDFThe present study focuses on the potential application of Archimedes screw turbines in microtidal rivers. The Misa River, a 48-km long Italian course flowing into the Adriatic Sea, is taken as the reference test. Since hydrokinetic turbines operate with low discharges and require little engineering facilities, an Archimedes turbine was recently tested both in laboratory and numerically, showing performance coefficients up to 23.8%. To investigate its functioning within the Misa River, observed river stages are statistically analyzed and then used at the upstream boundary of a hydraulic model. The flow results are analyzed to evaluate the potential energy production of turbine configurations built upon a range of: (i) potential installation zones along the river, (ii) turbine radii, (iii) streamwise inclinations of the turbine axis. The energetic analysis of each configuration is performed accounting for one or more turbines installed along selected river cross-sections. A direct dependence is found between generated power and turbine size, especially for the inclined configurations. The optimal size and number of devices to be deployed at specific cross-sections are identified. The total annual energy for the best configurations is around 1MWh, which may find application to supply energy to community buildings, like schools or kindergarten
Metabolism and Pharmacological Characterization at μ-, κ-, and δ- Opioid Receptors Using a Novel Non-Radioactive Assay of Nitazenes and Methadone-like Synthetic Opioids
No full textI nuovi oppioidi sintetici (NSO), inclusi i nitazeni e i derivati della difenilmetilpiperidina, rappresentano sfide significative per la salute pubblica a causa della loro elevata potenza, rapida diffusione e limitata caratterizzazione. Questo studio mira a migliorare la comprensione del loro metabolismo e della loro attività farmacologica, fornendo strumenti essenziali per il rilevamento e la valutazione del rischio. Utilizzando epatociti primari umani e microsomi epatici umani e analisi LC-HRMS/MS, abbiamo caratterizzato il metabolismo in vitro e in vivo di etonitazepipne, dipianone, protonitazepine e metonitazepine. Un’analisi approfondita dei dati, supportata da software predittivi, ha permesso l’identificazione delle principali vie metaboliche e biomarcatori.
La caratterizzazione farmacologica di questi composti si è concentrata sulla loro attivazione dei recettori oppioidi μ-, κ- e δ- (MOR, KOR e DOR). È stato sviluppato e ottimizzato un saggio ad alta capacità basato su HTRF® per il legame del GTP Gi, per valutarne la potenza e l’efficacia. Come previsto, etonitazepipne, protonitazepine e metonitazepine hanno condiviso, come principali trasformazioni metaboliche, l’O-dealchilazione, l’idrossilazione e l’apertura del gruppo pirrolidinico o piperidinico in acido butanoico. Il dipianone ha mostrato un profilo metabolico unico, con metaboliti principali generati dopo l’apertura del pirrolidinico in butanolo e acido butanoico, seguita da ciclizzazione.
Grazie al saggio HTRF® basato sul legame GTP Gi, il protonitazepine è risultato il più potente ed efficace agonista del MOR, con una potenza circa 6 volte superiore al fentanyl, seguita da etonitazepipne, metonitazepine e dipianone. Questa ricerca fornisce informazioni fondamentali sul metabolismo e sulla farmacologia degli NSO, proponendo biomarcatori unici di consumo e un nuovo saggio HTRF® rapido e semplice per lo studio dell’attività dei recettori.Novel Synthetic Opioids (NSOs), including nitazenes and diphenylmethylpiperidine derivatives, pose significant challenges to public health due to their high potency, rapid emergence, and limited characterization. This study aims to advance the understanding of their metabolism and pharmacological activity, providing essential tools for detection and risk assessment. Using cryopreserved primary human hepatocytes, Pooled Human Liver Microsomes and LC-HRMS/MS analysis, we characterized the in vitro and in vivo metabolism of etonitazepipne, dipyanone, protonitazepyne, and metonitazepyne. Comprehensive data mining supported by predictive software enabled the identification of key metabolic pathways and biomarkers. The pharmacological characterization of these compounds focused on their activation of the μ-, κ-, and δ-opioid receptors (MOR, KOR, and DOR). A high-throughput HTRF®-based GTP Gi binding assay was developed and optimized to assess their potency and efficacy.
As expected, etonitazepipne, protonitazepyne and metonitazepyne shared as main transformation O-dealkylation, hydroxylation and pyrrolidine or piperidine opening to butanoic acid. Dipyanone presented a unique metabolic profile, and the main metabolites were generated after pyrrolidine opening to butanol and butanoic acid followed by cyclisation. As a result of the HTRF®-based GTP Gi binding assay, protonitazepyne was the most potent and efficacious agonist at MOR, resulting around 6 times more potent than fentanyl, followed by etonitazepipne, metonitazepyne and dipyanone. This research provides critical insights into the metabolism and pharmacology of NSOs, proposing unique biomarkers of consumption and a novel, fast and easy HTRF®-based GTP Gi binding assay for receptor activity study
Emotions in conceptual spaces
No full textThe overreliance on verbal models and theories in psychology has been criticized for hindering the development of reliable research programs (Harris, 1976; Yarkoni, 2020). We demonstrate how the conceptual space framework can be used to formalize verbal theories and improve their precision and testability. In the framework, scientific concepts are represented by means of geometric objects. As a case study, we present a formalization of an existing three-dimensional theory of emotion which was developed with a spatial metaphor in mind. Wundt posits that the range of human emotion can be represented along three axes of basic emotions (pleasure/displeasure, excitement/inhibition, tension/relaxation), just as color vision can be represented using three basic colors. We use dimensions to represent basic emotions, points to represent emotional states, and regions to represent broader emotional concepts. We then compare our formalization to an existing structuralist formalization of Wundt’s theory. Further, we discuss the empirical predictions that our formalization generates, such as comparisons of similarity and intensity. We conclude by demonstrating how the tools developed in the conceptual space framework can be used to formulate a theory of emotion based on empirical observation
Art. 160, Ulteriori effetti dell'esercizio dell'opzione - Commento
No full textCommento all'art. 160, TUIR relativo al regime istitutivo ed applicativo della tonnage tax e del sistema di imposizione reddituale di vantaggio per le imprese marittime. Ulteriori effetti dell’esercizio dell’opzione e novità applicative introdotte dal D.Lgs. n. 192/202
Funzione, rilevanza e ragionevolezza della forma del testamento olografo in Domenico Barbero. Un’antesignana «interpretazione a fini applicativi»
No full textLa rilettura di un «classico» contributo di Domenico Barbero offre occasione per riflettere, in una prospettiva di metodo funzionale, sistematica ed assiologica, sul delicato problema della validità del testamento olografo nel caso di incompletezza della datazione
Environmental Impact Assessment of New Sea Fennel-Based Food Products: Spice and Fermented Pickles
Get PDFSea fennel, a halophyte with growing economic importance in the Mediterranean region, offers a rich source of bioactive compounds for diverse applications in various industries, including food, pharmaceuticals, and cosmetics. Recognizing the crucial role of eco-design in promoting sustainable food production, this study aimed to assess the environmental impacts of two novel sea fennel products: dried spice and fermented pickles. The Life Cycle Assessment (LCA) method was used to evaluate the environmental burdens of these new products, from raw material acquisition to packaging end-of-life, to fine-tune the innovation process. Primary data were collected from a company in the Marche region, Italy. The Environmental Footprint 3.1 method was applied to analyze the impacts. From the results obtained, the climate change score for the spice was 6.24 kg CO2 eq./kg spice, while the fermented pickle was 0.89 kg CO2 eq./kg product—net weight. The results also revealed that primary packaging emerged as the primary environmental hotspot for both products, accounting for more than 40% of the total impacts in most of the impact categories. Glass packaging significantly contributed to the environmental impact of the spice, while both glass jars and tin-plated steel lids contributed substantially to the impact of the pickled products. Despite the generally low impact of sea fennel cultivation, the processing and packaging stages significantly increased the overall environmental impacts of both products. This study provides valuable insights for manufacturers seeking to develop and commercialize highly sustainable sea fennel-based products. By identifying key environmental hotspots and implementing eco-design principles during the product development phase, manufacturers can significantly reduce the environmental impact of these novel food products