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Exome variants influencing LDL cholesterol in early-onset myocardial infarction
No full textBackground: Low-density lipoprotein cholesterol (LDL-C) causes atherosclerotic cardiovascular diseases, including myocardial infarction (MI). The aim of the Italian Genetic Study on Early-onset MI was to evaluate the effect of the rare exome variants influencing LDL-C on the risk of recurrent ischemic events after a MI occurring before the age of 45 years.
Methods: The study population consisted of 2,000 patients hospitalised because of a first early-onset MI, who were followed up for a median of 19.9 years for the occurrence of the primary endpoints of cardiovascular death, non-fatal MI or non-fatal stroke. Whole-exome sequencing led to the annotation of deleterious variants of 17 genes known to have a significant impact on LDL-C.
Results: One hundred patients had exome variants influencing hypercholesterolemia (HYPER); 60 had variants influencing hypocholesterolemia (HYPO); and 1,840 had no variants (NV). At the time of the index event, the median plasma LDL-C level was 190 mg/dL (interquartile range [IQR] 136-251) in the HYPER group, 114 mg/dL (IQR 86-131) in the HYPO group, and 140 mg/dL (IQR 112-168) in the NV group (p for trend <0.001). During the long-term follow-up the progression of coronary atherosclerosis and the cumulative incidence of primary endpoints was significantly different among the groups, and trend analysis showed that the incremental risk was HYPO<NV<HYPER (p for trend <0.01 and <0.004, respectively).
Conclusion: Exome variants influencing LDL-C have a measurable impact on coronary atherosclerosis progression and the probability of recurrent ischemic events after early-onset MI
Personality functioning, developmental trajectories, and developmental challenges in adolescence
No full textL’adolescenza è un periodo dello sviluppo individuale particolarmente delicato e costellato di profondi cambiamenti, che scardinano vecchi equilibri dando forma a nuove configurazioni e opportunità di crescita. Questa fase dello sviluppo rappresenta un crocevia tra la sedimentazione di esperienze passate e nuove prospettive future. Il presente lavoro intende approfondire alcuni aspetti centrali dello sviluppo adolescenziale, facendo particolare riferimento al funzionamento di personalità come predittore di possibili esiti disadattativi. Specificamente, la presenza di configurazioni fragili di personalità, che deviano dalle traiettorie di sviluppo tipico, potrebbe rendere più difficile il superamento delle crisi adolescenziali e aumentare, nel contempo, i rischi di sviluppo patologico in età adulta. Questo lavoro utilizza i dati relativi a un campione di 383 adolescenti, raccolti mediante un'apposita indagine, per stimare gli effetti predittivi che il funzionamento di personalità potrebbe esercitare su una serie di variabili rilevanti per il benessere e l’adattamento in adolescenza: la sensibilità interpersonale, le strategie di coping, il supporto sociale percepito, la dipendenza dai social media e l’uso dei selfie.Adolescence is a particularly sensitive period of individual development, marked by profound changes that upset old equilibria while creating new configurations and opportunities for growth. This stage of development represents a crossroads between the sedimentation of past experiences and new perspectives for the future. This work aims to explore some key aspects of adolescent development, with particular reference to personality functioning as a predictor of possible maladaptive outcomes. Specifically, the presence of fragile personality configurations that deviate from typical developmental trajectories could make it more difficult to overcome adolescent crises while increasing the risk of pathological development in adulthood. This work uses data from a sample of 383 adolescents, collected through a dedicated survey, to estimate the predictive effects that personality functioning might have on a number of variables relevant to well-being and adaptation in adolescence: interpersonal sensitivity, coping strategies, perceived social support, social media addiction, and selfie use
Brain and creativity : the neural and molecular basis of the creative process and its alterations in mental disorders and brain lesions
No full textIl presente lavoro di tesi indaga la relazione esistente tra psicopatologia e creatività, suggerita per molto tempo dalla diade inseparabile di genio e follia, nonostante i dati empirici a supporto siano scarsi. Inizialmente si affronta la complessa definizione del costrutto di creatività e i test psicometrici che sono stati sviluppati al fine di una sua corretta operazionalizzazione, basati soprattutto sul pensiero divergente. Si analizzano le sue basi neurali, con un’attenzione particolare alla corteccia prefrontale e ai tre principali network cerebrali ad essa connessi: Default mode network, Executive control network e Salience network. Successivamente viene considerato l’impatto che i danni cerebrali ad entrambi gli emisferi hanno sull’arte visiva, più nello specifico sulla creatività dei pazienti, considerando anche alcuni casi di artisti affermati. Si prosegue con l’analisi della relazione tra malattie neurodegenerative e creatività, in particolare la Demenza fronto-temporale, in cui è stata spesso osservata una facilitazione funzionale paradossale che porta ad un aumento della creatività, il Parkinson, nel quale la terapia farmacologica, soprattutto gli agonisti dopaminergici, ha un forte impatto positivo sulla creatività e l’Alzheimer, che causa un progressivo deterioramento di quest’ultima a seguito della compromissione del pensiero divergente. Infine, si affronta il rapporto esistente tra creatività e disturbi mentali. Nel dettaglio si tratta la schizofrenia, che potrebbe portare ad un aumento dell’originalità ma anche ad una inferiore capacità di selezionare le idee più utili e svilupparle in qualcosa di innovativo e il disturbo bipolare caratterizzato dall’alternanza di episodi depressivi, in cui la creatività diminuisce, ed episodi maniacali contraddistinti da un aumento della velocità dei pensieri che potrebbe contribuire alla produzione creativa. In ultima analisi si osservano le conseguenze sulla creatività degli psicofarmaci, con particolare riguardo agli stabilizzatori dell’umore (ad esempio il litio) e le sostanze psicoattive, soprattutto quelle psichedeliche come la psilocibina e l’LSD. This thesis paper investigates the existing relationship between psychopathology and creativity, long suggested by the inseparable dyad of genius and madness, although supporting empirical data are scarce. At first we address the complex definition of the creativity construct and the psychometric tests that have been developed in order to properly operationalize it, based mainly on divergent thinking. Its neural basis is analyzed, with a focus on the prefrontal cortex and the three main brain networks connected to it: Default mode network, Executive control network and Salience network. Next, the impact that brain damage to both hemispheres has on visual art, more specifically on patients' creativity, is considered, including some cases of successful artists. It continues with an analysis of the relationship between neurodegenerative diseases and creativity, in particular Fronto-temporal Dementia, in which paradoxical functional facilitation leading to an increase of creativity has often been observed, Parkinson's disease, in which drug therapy, especially dopaminergic agonists, has a strong positive impact on creativity, and Alzheimer's disease, which causes progressive deterioration of the latter as a result of impaired divergent thinking. Finally, the relationship between creativity and mental disorders is addressed. In detail, it deals with schizophrenia, which could lead to increased originality but also to a lower ability to select the most useful ideas and develop them into something innovative, and bipolar disorder characterized by alternating depressive episodes, in which creativity decreases, and manic episodes marked by an increased speed of thoughts that could contribute to creative production. In the end, the possible impact of psychotropic drugs on creativity is considered, with emphasis on mood stabilizers (e.g., lithium) and psychoactive substances, especially psychedelic substances such as psilocybin and LSD
Ruolo differenziale di aree connettivamente definite della corteccia prefrontale ventrolaterale della scimmia durante un compito visuo-motorio
No full textStudi recenti hanno mostrato come la corteccia prefrontale laterale (LPFC) sembri essere funzionalmente caratterizzata da un’inomogeneità in senso rostro-caudale. Nello specifico, è stata suggerita l’esistenza di un’organizzazione gerarchica che segue l’asse antero-posteriore, secondo la quale la parte posteriore tende ad essere più selettiva per gli stimoli processati mentre la regione anteriore sembra essere coinvolta maggiormente in operazioni di tipo astratto (Koechlin et al., 2003; Riley et al., 2016). Un’organizzazione della LPFC di tipo rostro-caudale è stata osservata anche in relazione agli effettori coinvolti in differenti tipologie di comportamento: considerando i due terzi posteriori della LPFC, tipicamente si osservano risposte oculomotorie nelle regioni più caudali, e risposte legate ai movimenti all’arto anteriore più rostralmente (Boch & Goldberg, 1989; Hoshi et al., 1998).
I dati sulla connettività, in accordo con queste osservazioni di tipo funzionale, indicano che la LPFC può essere suddivisa rostro-caudalmente in almeno tre strisce verticali: una striscia più caudale, essenzialmente connessa con le aree fronto-parietali e i centri subcorticali coinvolti nel controllo dei movimenti oculari (Gerbella et al., 2017); una striscia intermedia, connessa con le aree parieto-premotorie e le strutture sottocorticali coinvolte nei movimenti di raggiungimento e afferramento (Gerbella et al., 2017); una striscia più rostrale, che mostra essenzialmente connessioni intra-prefrontali (Gerbella et al., 2017).
Questa suddivisione basata sulla connettività coinvolge anche la parte ventrale della LPFC (VLPFC), all’interno della quale Rozzi e collaboratori (Simone et al., 2015; Rozzi et al., 2023) hanno dimostrato, durante l’esecuzione di un compito visuo-motorio di tipo Go-NoGo, la presenza di neuroni legati all’azione di raggiungimento e varie classi di cellule che sembrano legare insieme regole astratte, caratteristiche degli oggetti e comportamento istruito. Tuttavia, questi studi sono stati condotti trattando la VLPFC come una regione indivisa, senza dunque prendere in considerazione le sue possibili suddivisioni. Un simile approccio, sebbene possa essere utile per identificare il ruolo funzionale generale della VLPFC (ad esempio, quali sono le fasi principali e le regole del compito codificate in tutte le zone registrate), non consente tuttavia di raccogliere abbastanza informazioni in merito a come questi aspetti funzionali possano distribuirsi diversamente sui vari territori registrati.
Per affrontare questa problematica, nella presente tesi la popolazione di neuroni studiata precedentemente da Rozzi e collaboratori (2023) è stata nuovamente analizzata tenendo in considerazione una parcellazione della VLPFC basata sulla connettività, identificata a partire da precedenti investigazioni neuroanatomiche (Gerbella et al. 2012; 2013; Borra et al. 2011). Attraverso questo approccio, è stato possibile definire delle suddivisioni utili a delineare gruppi di neuroni successivamente studiati attraverso analisi di popolazione. In particolare, è stato possibile valutare come alcuni aspetti peculiari delle varie epoche del compito siano codificati in modo preferenziale entro le specifiche suddivisioni. Per esempio, i risultati hanno mostrato che il controllo online dell’esecuzione del movimento e il monitoraggio del raggiungimento dello scopo dell’azione sono principalmente rappresentati nel settore intermedio dell’area 46v, in linea con la sua robusta connettività con i circuiti parieto-premotori coinvolti nel controllo di azioni brachio-manuali.Recent studies showed that lateral prefrontal cortex (LPFC) seems to be functionally characterized by a rostro-caudal inhomogeneity. In particular it has been suggested the presence of a hierarchical organization, following an antero-posterior axis, in which the posterior part tends to be more selective for the type of stimuli processed while the anterior region appears to be involved in more abstract operations (Koechlin et al., 2003; Riley et al., 2016). A rostro-caudal organization of the LPFC was also observed in relation to the effectors involved in different types of overt behaviours: within the posterior two-thirds of LPFC, oculomotor responses are typically found in more caudal regions while responses relate to forelimb movements are typically found more rostrally (Boch & Goldberg, 1989; Hoshi et al., 1998).
Connectional evidence, in agreement with these functional observations, indicate that LPFC can be subdivided rostro-caudally into at least three vertical strips: a caudal-most strip, essentially connected with the parietal and frontal areas and subcortical centres involved in control of eye movements (Gerbella et al., 2017); an intermediate strip, connected with parietal and premotor areas and subcortical structures involved in grasping and reaching movements (Gerbella et al., 2017); a rostral-most strip, essentially showing intrinsic prefrontal connections (Gerbella et al., 2017).
This connectional subdivision involved also the ventral part of the LPFC in which Rozzi and coworkers (Simone et al., 2015; Rozzi et al., 2023) demonstrated, during the execution of a Go-NoGo visuo-motor task, the presence of grasping related neurons and various class of cells linking abstract rules, object features, and the instructed behaviour. However, these studies have been carried out considering the VLPFC as a whole, without taking into account its possible subdivisions. This approach although useful to identify the general functional role of this VLPFC territory (for example, which are the main phases and rules of task encoded in all the recorded zones) did not allow to achieve enough information about whether and how these functional features are differentially distributed over the various recorded territories.
To address this issue, in the present thesis the populations of neurons previously studied in Rozzi et al. (2023) have been reanalysed according to a connectional parcellation of the VLPFC, based on previous neuroanatomical investigations (Gerbella et al. 2012; 2013; Borra et al. 2011). Through this approach, it was possible to define subdivisions suitable for delineating groups of neurons subsequently studied through population analysis. In particular, it was possible to assess how some peculiar aspects of the various epochs of the tasks are preferentially encoded within specific subdivisions. For example, the results showed that the online control of movement execution and the monitoring of the action goal achievement are mainly represented in the middle sector of area 46v, in line with its robust connectivity with parieto-premotor circuits involved in the control of brachio-manual actions
Multi-species interacting particle systems: duality, integrability and scaling limits
No full textInteracting particle systems (IPS) are paradigmatic models for non-equilibrium statistical me chanics. Indeed, they allow to keep the computations manageable without losing the fundamen tal features of the systems they aim to reproduce. Usually, two central questions are investigated:
the non-equilibrium stationary probability distribution, that is reached in the long-time horizon,
and the hydrodynamic limit, which allows us to derive macroscopic laws that the IPS satisfies,
once rescaled to the continuum.
In the literature many results and techniques have been developed regarding single species
IPS, which are models where indistinguishable particles move on a discrete geometry occupying
the available vacancies. At the microscopic level, duality and integrability allow to obtain closed
expressions for the non-equilibrium stationary distribution, while, the scaling limits theory has
made rigorous the passage from micro to macro dynamics.
At present, there is a growing interest in systems with multiple conservation laws, therefore,
from the point of view of statistical mechanics, research focuses on multi-species interacting
particles systems. In these IPS, there is the presence of multiple different species (or colours) of
particles which perform the dynamic on a discrete geometry. The difference with respect to the
single species set up is that, now, in addition to the occupation of the available vacancies, the
different species of particles interact with each other, for instance by exchanging their positions
and mutating species. This dynamics, is also reflected in the scaling limits, giving rise to systems
of partial differential equations (PDE’s) describing multi-component transport models. In this
realm, new phenomena may arise, such as multi-component uphill diffusion, which is a situation
where the flux (of mass, particle, energy, charges...) has the same sign as the difference between
boundary densities, causing the current to go uphill and violating the Fick’s law of diffusion.
In this thesis we focus on boundary driven multi-species IPS where each vertex of the discrete
geometry can host at most a finite number of particles, which can be chosen among the different
species. For this reason, these IPS are said to have compact state space. First we analyse
the so-called multi-species stirring process, which consists of a generalization of the symmetric
exclusion process (SEP), when many colours of particles are considered. After describing the
model without boundary interaction, we derive its scaling limits, both the hydrodynamic limit
and the equilibrium fluctuations from it. Then, we put the system out of equilibrium by adding
boundary reservoirs. We describe the non-equilibrium generator via a Lie algebra and we use this
property to find an absorbing duality result. This absorbing duality, allows us to characterized
the non-equilibrium steady state by means of absorption probabilities, which are the probabilities
that dual particles are absorbed at extra-sites. These extra-sites replace, in the dual process, the
original boundary reservoirs. While this duality result is available regardless of the geometry
and maximal occupancy of the process, the complete characterization of the non-equilibrium
steady state is accomplished for the integrable version of multi-species stirring process via the
combination of duality and matrix product ansatz (MPA). This allows us to write a closed formula for the multi-point correlations. Finally, as a still partially open problem, we construct,
for this integrable chain, the so-called mapping of non-equilibrium onto equilibrium by the use
of quantum inverse scattering method.
After having analyzed the stirring process we add a further transition mechanism: the re action. Starting from a system of linear PDE’s showing uphill diffusion for one of the species
(partial uphill), we construct a multi-species reaction-diffusion process with the feature of having
evolution equations for the average occupation variable (thought as a proxy for the true density)
given by the discretization on a finite lattice of the previously introduced linear system of PDE’s.
Then, the hydrodynamic limit is obtained. We observe that at this last level the uphill diffusion
is lost. Furthermore, we prove the absorbing duality for this boundary driven reaction diffusion
model and we derive the equilibrium density fluctuation from its hydrodynamic limit.
Finally, we report two perspective for future research. The first concerns the study of
multi-species processes with non-compact state space, i.e. having the possibility of hosting
an unbounded number of particles at each site. In this context we introduce the multi-species
independent random walker where, exploiting the lack of interaction we manage to completely
characterize the non-equilibrium steady state via duality. We then introduce the multi-species
harmonic process and the multi-species simple inclusion process. For both we define the genera tor with boundary driving and we find the reversible (equilibrium) measure. This is the starting
point for the proof of absorbing duality, an goal of future research.
As a second perspective we report a result regarding a single species asymmetric energy trans port model with boundary driving. The reservoirs have been designed to maintain the absorbing
duality property. Furthermore, using this duality it is possible to characterize the exponential
current in the non-equilibrium steady state. We believe that this single species result can be
a starting point for the generalization of this bulk-boundary driven model to the multi-species
set-up. Moreover, the scaling limits of this bulk-boundary driven process could also be used to
describe the macroscopic equations of multi-component transport models with drift
Key factors for university well-being : promoting mental health and preventing burnout
No full textLa seguente tesi di ricerca si è proposta di esplorare e valutare il benessere degli studenti universitari ponendo l’accento su un costrutto ancora poco riconosciuto in ambito accademico, ovvero la sindrome di burnout. Per perseguire tale scopo si è indagato in che misura specifici fattori di rischio (stress accademico, sensibilità interpersonale) e protettivi (senso di appartenenza e supporto sociale) vadano ad influenzare il benessere e di conseguenza come questi possano contribuire o meno allo sviluppo di sintomi legati al burnout. Utilizzando le categorie del modello Mental Health Continuum (Keyes 2002, 2005, 2007) si è osservato se fosse possibile distinguere in modo significativo i livelli di stress accademico, sensibilità interpersonale, supporto sociale, senso di appartenenza e burnout. Successivamente sono stati costruiti i modelli predettivi di benessere e burnout per stimare se i fattori presi in considerazione esercitassero un effetto significativo sui livelli dei due costrutti. Hanno partecipato allo studio 464 studenti e studentesse appartenenti all’Università di Parma. I dati raccolti sono stati elaborati utilizzando analisi descrittive, correlazionali e modelli di regressione multipla. I risultati hanno messo in luce che il modello di Keyes permette di osservare livelli significativamente differenti dei fattori presi in esame sulla base della classificazione di benessere proposta. Nello specifico, i modelli predittivi hanno confermato come siano fattori protettivi del benessere universitario sia il supporto sociale che il senso di appartenenza e invece come lo stress e la sensibilità interpersonale siano fattori di rischio. Per il burnout lo stress ha esercitato l’effetto significativo maggiore, mentre il supporto sociale non è risultato particolarmente rilevante. Inoltre, è stata evidenziata una differenza significativa nei livelli di burnout tra chi frequenta una laurea triennale e una magistrale a ciclo unico. Tali evidenze hanno permesso di acquisire informazioni importanti circa lo stato di benessere degli studenti dell’Università di Parma e potrebbero essere utili per progettare azioni da parte del servizio di Counseling Psicologico d’Ateneo. This research thesis aims to evaluate the well-being of college students by focusing on burnout syndrome, a construct that is still under-recognized in academia. To achieve this goal, was investigated the extent to which certain risk factors, such as academic stress and interpersonal sensitivity, and protective factors, such as a sense of belonging and social support, influence well-being and contribute to the development of burnout-related symptoms. The study aimed to determine if the levels of academic stress, interpersonal sensitivity, social support, sense of belonging, and burnout could be distinguished using the categories of the Mental Health Continuum model (Keyes 2002, 2005, 2007). Predictive models were then constructed to estimate the impact of these factors on well-being and burnout. A total of 464 male and female students from the University of Parma participated in the study. Descriptive, correlational analyses, and multiple regression models were used to process the collected data. The results showed that Keyes' model enables the observation of significantly different levels of the examined factors based on the proposed well-being classification. The predictive models confirmed that social support and a sense of belonging are protective factors for university well-being, while stress and interpersonal sensitivity are risk factors. Stress had the largest significant effect on burnout, while social support was not particularly significant. Furthermore, a significant difference in burnout levels was found between those attending a bachelor's degree and a single-cycle master's degree. This evidence provides important information about the well-being of students at the University of Parma. It could be useful for designing actions by the University Psychological Counseling service.
Analisi conformazionale guidata dall'NMR: una strategia analitica per la determinazione della struttura di composti farmaceutici
No full textNuclear Magnetic Resonance (NMR) spectroscopy is one of the most powerful techniques for structure elucidation and characterization. Moreover, NMR, coupled with computational chemistry, can be useful for the conformational analysis of free ligands in solution to investigate target-ligand interactions within Structure-Based Drug Design (SBDD) approach. Structure-based drug design, using X-ray crystallography, computational molecular modelling, molecular docking and NMR methods, is a powerful and straightforward approach in drug design process.
Conformational analysis by NMR is based upon the idea of ligand conformational selection, in which the free ligand in solution can be fully pre-organized into the bioactive conformation. Thus, the free ligand can adopt multiple three-dimensional conformations due to rotatable bonds, including the one adopted in the binding pocket of the ligand-target complex. This method includes a detailed analysis of multiple NMR constraints, comprising chemical shifts, through-space distances between pairs of atoms derived from rotating-frame Overhauser spectroscopy (ROESY) or quantitative nuclear Overhauser effect (qNOE), torsion angles derived from J-couplings and dynamic average of orientation of internuclear vectors derived from residual dipolar couplings (RDCs).
In addition, quantum mechanical (QM) calculations to predict some NMR parameters, such as isotropic shielding constants, within a reasonable timeframe can be useful. Chemical shift predictions, which are conformation-dependent, provide important information for the conformational analysis as far as some diagnostic protons are detected. Calculated chemical shifts can also be used to confirm the proposed conformational ensemble derived from NMR-based analysis.
The objective of this project is to set up and validate a protocol with high accuracy and precision, which exploits NMR constraints to obtain structural information from free ligands in solution, combining experimental information with computational chemistry simulations. For this purpose, three active macrocyclic compounds, i.e. Lorlatinib, Pacritinib and Simeprevir were tested. Several approaches such as single or multi-parametric fitting, different solvents and various alignment media were investigated
The effect of mesenchymal stem cell-derived secretome on the coagulation of the blood plasma in species of veterinary interest.
No full textNegli ultimi decenni è stato dimostrato che l’efficacia terapeutica rigenerativa delle cellule staminali mesenchimali (MSC) è dovuta principalmente al loro biosecretoma (MSCs), che è costituito da un elevato numero di molecole bioattive rilasciate nello spazio extracellulare tramite secrezione. Queste sono sia in forma solubile che all’interno di vescicole extracellulari. Basandosi su queste premesse, Bari e colleghi hanno di recente presentato nell’articolo: “Pilot production of mesenchymal stem/stromal freeze-dried secretome for cell-free regenerative nanomedicine: a validated GMP-compliant process (2018). Cells 7.11, p. 190” una procedura innovativa e conforme alle norme GMP (Good Manufacturing Practice) per la produzione su larga scala di un prodotto farmaceutico costituito da MSCs di tessuto adiposo (AT-MSCs), che venendo sottoposto a liofilizzazione, viene denominato ‘Liosecretoma’. Questo prodotto, che può venire riscostituito mediante aggiunta di acqua sterile, è classificabile come un farmaco pronto all’uso, potenzialmente in grado di rimpiazzare le terapie a base di cellule staminali nel campo della medicina rigenerativa.
Poiché il processo coagulativo viene favorito dalla presenza di materiale micro e nano particolato e di sostanze procoagulanti che si trovano all’interno del liosecretoma, nel presente elaborato di tesi è stato verificato, per la prima volta in modo quantitativo, il suo effetto, in vitro, sulla formazione del coagulo di fibrina nelle specie canina ed equina. Lo sviluppo di torbidità causata dal processo coagulativo in funzione del tempo in campioni di plasma deprivato delle particelle endogene (mediante centrifugazione o ultracentrifugazione), è stata valutata attraverso l’aumento dell’assorbanza, sia in assenza che in presenza di quantità crescenti di liosecretoma. Le cinetiche di coagulazione seguono un andamento nel tempo che è descritto da funzioni sigmoidee a tre parametri, dalle quale è possibile valutare la fase di latenza del processo, il tempo in cui si realizza metà della coagulazione (t1/2 ) e, dalla pendenza al flesso, la velocità con cui il processo si realizza. Il valore finale di torbidità consente inoltre di ipotizzare differenti modalità di formazione del coagulo in funzione della velocità del suo processo di formazione.
In entrambe le specie si è evidenziata, all’aumentare della concentrazione di Liosecretoma, una significativa diminuzione dei t1/2 accompagnata da un altrettanto significativo incremento della velocità di formazione del coagulo (aumento della pendenza al flesso).
Queste variazioni sono risultate maggiori nella specie canina rispetto a quella equina. La coagulazione dei derivati del plasma indotta in tempi definiti dall’aggiunta di opportune quantità di liosecretoma, potrebbe quindi essere sfruttata anche in ambito clinico per la preparazione, ad esempio, di gel prodotti dalla coagulazione di derivati plasmatici pronti all’uso. Questi prodotti, applicati nella sede di danno permetterebbero alle sostanze utili presenti all’interno del Liosecretoma di rimanere localizzate in situ e di agire direttamente sul tessuto danneggiato.In recent decades, it has been demonstrated that the regenerative therapeutic efficacy of mesenchymal stem cells (MSCs) is primarily due to their biosecretome (MSCs), which consists of a high number of bioactive molecules released into the extracellular space by secretion. These molecules are both in soluble form and within extracellular vesicles. According to this, Bari and colleagues recently presented in their article: “Pilot production of mesenchymal stem/stromal freeze-dried secretome for cell-free regenerative nanomedicine: a validated GMP-compliant process (2018). Cells 7.11, p. 190” an innovative procedure, compliant with Good Manufacturing Practice (GMP) standards, for the large-scale production of a liophilized pharmaceutical product consisting of adipose tissue-derived MSCs (AT-MSCs), that has been called 'Lyosecretome'. This product, that is reconstituted by adding sterile water, can be classified as a ready-to-use drug, potentially capable of replacing stem cell-based therapies in the field of regenerative medicine.
As the coagulation process is facilitated by the presence of micro and nano particulate material and pro-coagulant substances that are also main constituents of the lyosecretome, this thesis investigates, for the first time quantitatively, its effect, in vitro, on the formation of fibrin clot in both canine and equine species. The development of turbidity caused by the coagulation process as a function of time in samples of plasma deprived of the endogenous particles (by centrifugation or ultracentrifugation) was evaluated spectrophotometrically as the increase of the absorbance, both in the absence and presence of increasing amounts of lyosecretome.
The coagulation kinetics follow a time course described by three-parameter sigmoid functions, that allow to assess the latency phase of the process, the time required to obtain one half of the coagulation (t1/2 ), and, from the slope at the inflection point, the velocity of the process. The final turbidity value also allows to hypothesize different models of both formation and molecular structure of the fibrin frame within the clot formation as functions of the velocity of the coagulation process. In both animal species, as the concentration of Lyosecretoma increased, a significant decrease of t1/2 was accompanied by an increase of the clot formation velocity (as determined by an increase of the slope at the inflection point). These variations were more pronounced in the canine species compared to the equine. The precise timing of the coagulation process, that is determined by the addition of appropriate quantities of Lyosecrteome, can be of interest for the prompt preparation of ready to use plasma derivatives (as for instance platelet rich and poor plasma gels) suitable for clinical applications in the field of regenerative medicine. Moreover these gels, applied at the site of injury, would allow the beneficial substances present within the Lyosecretoma to remain localized in situ and act directly on the damaged tissue
Peri-natal exposure to endocrine disruptors and socio-emotional development of the 3-month-old child in a cohort of the Life-MILCH project
No full textGli interferenti endocrini (IE) sono sostanze chimiche presenti in modo pervasivo
nell’ambiente e a cui siamo esposti quotidianamente che, anche a basse dosi,
possono interferire con il sistema endocrino influenzando il successivo sviluppo a
diversi livelli. Il presente studio ha l’obiettivo di indagare l’associazione tra
l’esposizione peri-natale a bisfenoli, parabeni e ftalati e lo sviluppo
socioemozionale del bambino a tre mesi di vita. Il campione di riferimento è parte
del progetto Mother and Infant dyads: Lowering the impact of endocrine disrupting
Chemicals in milk for a Healthy Lif (Life-MILCH) e si compone di 25 bambini che
hanno preso parte, insieme alle loro madri, allo studio, di cui sono state analizzate
le concentrazioni di bisfenoli, parabeni e ftalati nelle urine raccolte alla nascita e a
un mese di vita del bambino. Lo sviluppo socioemozionale è stato osservato
attraverso il paradigma Face-to-Face-Still-Face (FFSF) in termini di emozionalità
negativa mostrata dal bambino durante la procedura. Le associazioni tra
concentrazioni di IE e punteggi di emozionalità negativa sono state analizzate
utilizzando l’analisi della varianza per gruppi indipendenti (ANOVA a una via). I
risultati indicano potenziali associazioni tra le concentrazioni perinatali di bisfenoli,
parabeni e ftalati e la regolazione emotiva durante la procedura FFSF. In particolare,
le concentrazioni di bisfenoli alla nascita sono risultate associate a un aumento
dell'emozionalità negativa, mentre le concentrazioni di parabeni e ftalati a un mese
hanno mostrato associazioni con lo sviluppo socioemozionale del bambino, ma
nella direzione opposta. Tali risultati evidenziano la complessità delle relazioni tra
esposizione a tali IE e sviluppo socioemozionale nei bambini, sottolineando la
necessità di condurre ulteriori studi per chiarie meglio l’associazione tra IE e
sviluppo socioemozionale del bambino e i potenziali meccanismi, nonché i fattori
moderatori o modulatori, sottostanti.Endocrine disruptors (EDs) are chemicals that are ubiquitously present in the
environment and to which we are exposed daily. Even at low doses, they can
interfere with the endocrine system, affecting subsequent development at various
levels. This study aims to investigate the relationship between perinatal exposure to
bisphenols, parabens, and phthalates, and the socio-emotional development of
infants at three months of age. The reference sample is part of the Mother and Infant
Dyads: Lowering the Impact of Endocrine Disrupting Chemicals in Milk for a
Healthy Life (Life-MILCH) project, consisting of 25 infants who, together with
their mothers, participated in the study. The concentrations of bisphenols, parabens,
and phthalates were analyzed in urine samples collected at birth and one month after
birth. The socio-emotional development was assessed using the Face-to-Face Still-
Face (FFSF) paradigm, with a particular focus on the negative emotionality
exhibited by the infants during the procedure. Associations between ED
concentrations and negative emotionality scores were analyzed using one-way
analysis of variance (ANOVA) for independent groups. The findings suggest the
existence of potential correlations between the perinatal concentrations of
bisphenols, parabens, and phthalates and the capacity for emotional regulation
during the FFSF procedure. Specifically, bisphenol concentrations at birth were
associated with increased negative emotionality, whereas concentrations of
parabens and phthalates at one month were linked to socio-emotional development,
but in the opposite direction. These findings highlight the intricate nature of the
relationships between exposure to these EDs and socio-emotional development in
infants, underscoring the necessity for further research to elucidate the associations
between EDs and infant socio-emotional development, as well as the potential
underlying mechanisms, including moderating or mediating factors
Applications of laser light: Scribing of Solar Cells and treatment of Ocular diseases
No full textLasers play a crucial role in many scientific experiments and research studies due to their ability to deliver highly precise and focused light beams. This research is organized into two principal projects. The first part investigates laser scribing of thin-film solar cells (TFSC), conducted through a collaborative effort between the Department of Engineering and Architecture at the University of Parma and the IMEM-CNR, Institute of Materials for Electronics and Magnetism. Thin-film solar cells are a promising technology for both terrestrial and astronomical photovoltaic (PV) applications, offering considerable flexibility in design and manufacturing. A variety of substrates—such as flexible, rigid, metallic, and insulating types—can be used to deposit multiple functional layers, including contacts, absorbers, and reflectors.
Additionally, laser light application in ophthalmology is widely recognized, thanks to the high precision and control offered by different laser types. These specialized lasers are engineered and optimized specifically for various ocular treatments. Another part of this thesis investigates evaluating a fiber laser designed for treating ocular diseases. A model of a dysprosium-doped fiber laser was established, with physical and numerical parameters observed to evaluate the efficiency of the laser output