Sapienza University of Rome

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    Towards an efficient and sustainable technique: A review on the preparation and synthesis of sorbents for in-tube solid-phase microextraction

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    Microextraction techniques are increasingly valued for their low sample requirements and consistency with green chemistry principles. Over time, several formats have been developed, enabling faster and automated analytical workflows. Among them, in tube-solid phase microextraction (IT-SPME) stands out as a powerful sample preparation technique, offering direct online coupling with chromatographic systems, automation, and reduced solvent use. This review critically examines the main strategies for IT-SPME sorbent fabrication, including fiber-filled, monolithic, coated, and particle-packed capillaries. Emphasis is set on the underlying chemistry of sorbent synthesis, radical polymerization, sol-gel processes, hydrothermal reactions, and click chemistry, while assessing efficiency, scalability, and environmental impact. Challenges such as complex syntheses, hazardous reagents, and artisanal protocols are discussed. The review offers the analytical community a practical guide to reproducible and sustainable strategies for developing IT-SPME devices that are well-suited to automated workflows

    Existence and Approximation Results for Quasi Variational Inequalities with Linear Coupling Constraints

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    We consider quasi variational inequality problems in which the feasible point-to-set mapping is defined by linear coupling constraints. We provide existence conditions easy to verify in practice. We analyze inexact solutions for different reformulations based on gap functions to obtain approximate solutions for the quasi variational inequality

    Investigating neuropsychiatric disorders through environmental and genetic animal models: exploring the role of the endocannabinoid system

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    Autism Spectrum disorders (ASD) are a complex group of neurodevelopmental disorders (NDDs) characterized by impairments in social interaction and communication, alongside stereotyped and repetitive behaviors. Psychotic disorders involve neurodevelopmental alterations and may occur as comorbid conditions in individuals with ASD, contributing to their onset and clinical manifestations. Together, these conditions represent a major global health challenge, accounting for a substantial proportion of disability and reduced quality of life. Emerging evidence highlights the involvement of the endocannabinoid system (ECS) in the regulation of neurodevelopmental processes, suggesting its potential as a therapeutic target in these disorders. Moreover, converging studies indicate that both redox imbalance and gut-brain axis dysfunction act as key contributors to the pathophysiology of these disorders. However, the mechanisms through which pharmacological modulation of the ECS influences neurotransmission, oxidative stress and the gut-brain communication remain poorly understood. This PhD thesis investigated the effects of pharmacological ECS modulation on behavioral, neurochemical and biomolecular alterations characterizing two preclinical models of the above mentioned neuropsychiatric disorders, i.e. the BTBR T+Itpr3tf/J (BTBR) mouse model of idiopathic ASD and the post-weaning social isolation (PSWI) rat model of psychosis. The results presented in the first part of this PhD thesis showed that the BTBR mouse model exhibited ASD-like core behaviors, including reduced sociability, increased repetitive behaviors and hyperlocomotion, associated with neurochemical alterations across key brain areas, including prefrontal cortex, hippocampus, amygdala and hypothalamus. Among these regions, amygdala displayed the most pronounced alterations, indicating its central role in ASD-like behaviors. Multiple pathogenic mechanisms have been proposed to underlie ASD-like behaviors, among which redox imbalance has emerged as a key contributor. In particular, the findings included in this PhD thesis showed that in BTBR mice oxidative stress was associated with impaired antioxidant defenses and elevated Reactive Oxygen Species (ROS) production in the hippocampus, a region critical for behavioral regulation. This ROS overproduction was mediated by NOX2, an isoform of the NADPH oxidase enzyme family that catalyzes the transfer of electrons from NADPH to molecular oxygen. Further, in the same animal model, β-caryophyllene (BCP), a naturally occurring sesquiterpene and selective CB2 receptor agonist, was administered due to its ability to downregulate proinflammatory cytokines and reduce gut inflammation, preventing disruption of gut-brain communication. The obtained findings showed that BCP administration improved social behaviors and hyperlocomotion and partially reduced repetitive behaviors in BTBR mice. These effects were accompanied by normalization of colonic serotonin and kynurenine levels and reduction of sympathetic hyperactivity, indicating that peripheral CB2 receptor activation could regulate enteric neurotransmission and tryptophan metabolism, which in turn may have influenced central ASD-like behaviors through the gut-brain axis. These findings underscored the critical role of gut-brain communication in ASD-like phenotypes and suggested that BCP, through CB2-mediated ECS modulation, represents a potential therapeutic strategy. In the second part of this PhD thesis, the PWSI model was employed to investigate the development of psychotic-like symptoms induced by the exposure to an early-life stressor, i.e social isolation, and its underlying mechanisms. The obtained results showed that isolated rats exhibited increased reactivity to environmental and social stimuli. Neurochemical profiling demonstrated alterations in monoaminergic and glutamatergic systems in prefrontal cortex, a brain area crucially involved in executive function and emotion regulation. Redox imbalance was observed in the same region, characterized by elevated ROS levels and a compensatory upregulation of SOD1, an endogenous antioxidant enzyme. Treatment with PF-3845, a selective inhibitor of fatty acid amide hydrolase (FAAH) that elevates endocannabinoid levels, partially normalized behavioral hypereactivity, attenuated monoaminergic alterations and reduced oxidative stress, without affecting glutamatergic alterations. These findings supported a homeostatic and neuroprotective role of ECS and highlighted a complex and dynamic interplay between neurotransmitter systems, oxidative stress and ECS signaling in psychosis-like alterations. Collectively, the findings obtained from the two considered animal models provide mechanistic insights into the role of the ECS in neurodevelopmental and psychosis-related disorders, highlighting its capacity to modulate both central and peripheral pathways. Moreover, they point towards the ECS as a promising therapeutic target for future preclinical and translational studies in ASD and psychosis-related conditions

    Tracing the path from OCEAN to autonomic balance: The mediating role of cognitive reserve

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    Aging trajectories vary widely. The Big Five – Neuroticism, Openness, Extraversion, Agreeableness, and Conscientiousness – describe individual differences in behavioral, emotional, and physiological patterns influencing health. Heart rate variability (HRV), index of autonomic dynamics, is linked to longevity and cognitive decline in older adults, making it a potential personality-related marker of pathological aging. Inconsistencies in the HRV-personality relationship prompt researchers to consider mediating factors. Cognitive reserve (CR) offers insights, as it is shaped by personality and linked to brain regions underlying HRV. This study investigated the personality-HRV relationship, highlighting CR as a potential mediator. We hypothesized that lower CR would be associated to a higher LF/HF ratio, indicating sympathetic dominance and previously linked to poorer cognition, and that personality would contribute to this pattern through CR. Eighty-nine participants over 50 years underwent HRV recording, the CR Index questionnaire, and the Big Five Inventory administration. As expected, higher LF/HF ratio was associated with lower Openness and CR; CR mediated the relationship between Openness and Neuroticism and LF/HF ratio, suggesting that personality could influence physiological and cognitive health through cognitively stimulating activities. These findings underscore the role of life experiences and individual differences in shaping health, offering insights for prevention and intervention strategies

    Che cosa si può fare (e che cosa assolutamente no) ad lucernam

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    Lo studio verte sulla qualificazione del termine latino 'lucerna' come 'sordido'. Si analizzano in particolare gli usi della locuzione 'ad lucernam'.The essay focuses on the classification of the Latin term “lucerna” as “sordid”. In particular, it analyses the uses of the phrase “ad lucernam”

    Bisphenol A triggers adipocyte dysfunction, thereby fostering triple-negative breast cancer aggressiveness

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    Bisphenol A (BPA) is an organic compound widely used in the production of polycarbonate plastics and epoxy resins. As a pervasive environmental pollutant, BPA accumulates in adipose tissue (AT) due to its lipophilic properties. AT, an endocrine organ central to homeostasis, constitutes the main component of breast stroma and plays a pivotal role in the microenvironment of breast cancer, including triple-negative breast cancer (TNBC). This study investigated how BPA disrupts adipocyte differentiation and metabolism, and the subsequent effects on the crosstalk between adipocytes and TNBC cells. We induced adipogenic differentiation of preadipocytes in the presence of BPA and evaluated alterations in differentiation and cytokine secretion. TNBC cells were cultured in homotypic and heterotypic organoids, exposing them to BPA either directly or indirectly, through a conditioned medium of BPA-treated adipocytes. BPA exposure altered adipocyte differentiation, reducing lipid accumulation and perturbing cytokines release, leading to the upregulation of molecules involved in cell migration and invasiveness. TNBC cells exposed to conditioned medium of BPA-treated adipocytes exhibited enhanced growth, migration and invasiveness, whereas direct BPA treatment did not induce significant changes. These indirect effects were, at least in part, mediated by SDF1α and GAS1. Moreover, TNBC organoids showed increased infiltrative capacity when co-cultured with BPA-conditioned adipocytes. These findings highlight the profound impact of environmental pollution on cancer progression. BPA perturbates adipose differentiation, creating a dysfunctional adipocyte that fosters cancer growth and invasiveness in TNBC. This study underscores the impact of environmental pollutants on tumour progression by revealing the importance of BPA perturbation on tissue homeostasis and how this could promote cancer

    Lo strumento della collaborazione a tutela dell'interesse ambientale

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    Il proposito del presente lavoro di ricerca è quello di verificare se sia possibile concepire all’interno del nostro ordinamento un altro modo di “amministrare” fondato sulla collaborazione tra cittadini e pubbliche amministrazioni per la tutela dell’interesse ambientale, nella sua qualità di interesse diffuso, generale ed intergenerazionale. Ed inoltre, se questa modalità di intervento possa essere la più idonea e adeguata a favorire soluzioni specifiche di tutela, al fine di risolvere nel miglior modo possibile le problematiche ambientali che investono gli ecosistemi urbani ed extraurbani. Ci si chiede, pertanto, se i tempi siano finalmente maturi per immaginare una nuova centralità dello strumento collaborativo nel sistema del diritto amministrativo contemporaneo, in accordo con la più recente lettura costituzionale del principio di sussidiarietà orizzontale di cui all’art. 118, comma 4, Cost., che si basa sulla valorizzazione e sulla promozione attiva delle iniziative di interesse generale da parte delle pubbliche amministrazioni

    Smoking and alcohol during pregnancy: effects on fetal and child health. The role of oxidative stress and possible dysregulation of neurotrophins

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    Introduction: the aim of this study was to evaluate fetal and neonatal effects induced by smoking and alcohol during pregnancy. The role of oxidative stress and possible dysregulation of neurotrophins were also investigated. Material and methods: after written informed consent, we recruited full-term pregnant patients. Exclusion criteria: age ˂20 or ˃40 years; gestational age ˂37+0 or >42+0; multiple pregnancies; placental pathologies; medically assisted procreation; maternal psychiatric, neurological and/or autoimmune diseases. Questionnaires were used to investigate smoking and alcohol habits. Ultrasound was performed to evaluate fetal weight, amniotic fluid index, and maternal-fetal Doppler velocimetry. At the time of delivery, we collected a tuft of maternal hair (nicotine, cotinine, ethyl glucuronide-EtG), maternal venous blood and cord blood (reactive oxygen species-ROS, neurotrophins). Placental weight and neonatal data were also collected. Phase I: determination of nicotine, cotinine and EtG on maternal keratin matrix with the gas chromatography-mass spectrometry technique. Positive test for nicotine if > 0.16 ng/mg, cotinine if > 0.07 ng/mg and EtG if > 20 pg/mg. Phase II: Free Oxygen Radicals Test (FORT) and Free Oxygen Radical Defense (FORD) test were used to asses circulating ROS. A condition of oxidative stress was indicated by FORT > 330 Fort Unit and FORD test < 1.08 Trolox equivalents. Neurotrophins were evaluated on maternal venous blood and cord blood using ELISA. The descriptive statistical analyses were performed using ANOVA software. Results: 119 pregnant patients were enrolled (n=62 were tested for smoking and n=57 for alcohol). Twenty-six patients (42%) out of 62 were active smokers, 18 (29%) were passive smokers, and the remaining 18 (29%) were non-smokers. Three patients (5%) out of 57 resulted alcoholic consumers. The mean neonatal weight was on the 51^ percentile for non-smoker patients, on the 49^ percentile for passive smokers and on the 8^ percentile for active smokers. Comparing active smokers and non-smokers, mean neonatal weight and mean placental weight were significantly lower for active smokers (p=0.0001 and p=0.0060, respectively). The neonatal weight was on the 1^-2^ percentile for alcohol abusers. Considering two subgroups (n=10 non-smokers and n=10 active smokers) for ROS determination, Student’s-t test (95% CI, p<0.05) showed a statistically significant higher oxidative stress in the blood of smoking patients (FORT p<0.0001; FORD p=0.0156). In cord blood the differences were not statistically significant with a condition of oxidative defense, probably induced by the mother. Moreover, active smoking mothers exhibited significantly lower BDNF levels compared to non-smokers (p = 0.001), whereas their children had significantly higher BDNF levels (p = 0.001). Conclusions: fetal growth restriction was confirmed in the group of active smokers and in patients with alcohol abuse. Oxidative stress is higher in smoking patients than in non-smokers. However, in cord blood FORT and FORD were negative in all cases, suggesting a protective mechanism in utero. Higher BDNF levels in the offspring of smoking mothers also suggested potential compensatory mechanisms

    Genuinely multi-dimensional stationarity preserving Finite Volume formulation for nonlinear hyperbolic PDEs

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    Classical Finite Volume methods for multi-dimensional problems include stabilization (e.g. via a Riemann solver), that is derived by considering several one-dimensional problems in different directions. Such methods therefore ignore a possibly existing balance of contributions coming from different directions, such as the one characterizing multi-dimensional stationary states. Instead of being preserved, they are usually diffused away by such methods. Stationarity preserving methods use a better suited stabilization term that vanishes at the stationary state, allowing the method to preserve it. This work presents a general approach to stationarity preserving Finite Volume methods for nonlinear conservation/balance laws. It is based on a multi-dimensional stationarity preserving quadrature strategy that allows to naturally introduce genuinely multi-dimensional numerical fluxes. The new methods are shown to significantly outperform existing ones even if the latter are of higher order of accuracy and even on non-stationary solutions

    Ricostruzione Sequenzializzata Integrata (RSI): sequenzializzare come metodo di auto-osservazione in psicoterapia per un’applicazione efficace delle tecniche

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    L’incremento della capacità di auto-osservazione ha un ruolo centrale in diversi modelli di psicoterapia. Il presente lavoro ha lo scopo di proporre la procedura che abbiamo definito Ricostruzione Sequenzializzata Integrata (RSI), metodo finalizzato allo sviluppo delle capacità di auto-osservazione, come “piattaforma” entro cui integrare le tecniche a disposizione del professionista per l’impostazione del lavoro psicoterapeutico. La RSI mantiene i concetti cardine della Moviola, metodo proposto da Vittorio Guidano (1991) in ambito post-razionalista, tentando una sistematizzazione della procedura e una maggiore focalizzazione su corporeità, aspetti sensoriali, percettivi ed emozionali, che possa permettere un approfondimento del processo di organizzazione dell’esperienza sia top-down che bottom-up. Dopo aver definito la rilevanza di un metodo di auto-osservazione in psicoterapia e aver delineato i principi di base della Moviola, descriveremo nel dettaglio obiettivi e aspetti metodologici specifici delle procedure che caratterizzano la RSI. Successivamente, definiremo le possibilità di integrazioni metodologiche offerte dalla RSI e rileveremo vantaggi e limiti di tale metodo. Pur essendo necessario un progetto di ricerca che permetta di avvalorare i benefici dell’utilizzo della RSI in psicoterapia, riteniamo tale procedura un metodo trasversale, utile a molteplici orientamenti, in grado di favorire un’integrazione metodologica strutturale che permetta di far emergere diverse componenti dell’esperienza umana nella loro complessità al servizio del lavoro psicoterapeutico

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