22 resultados para Bureaucratic dysfunctions


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The term neurodegeneration defines numerous conditions that modify neuron’s normal functions in the human brain where is possible to observe a progressive and consistent neuronal loss. The mechanisms involved in neurodegenerative chronic and acute diseases evolution are not completely understood yet, however they share common characteristics such as misfolded proteins, oxidative stress, inflammation, excitotoxicity, and neuronal loss. Many studies have shown the frequency to develop neurodegenerative chronic diseases several years after an acute brain injury. In addition, many patients show, after a traumatic brain injury, motor and cognitive manifestations that are close to which are observed in neurodegenerative chronic patients. For this reason it is evident how is fundamental the concept of neuroprotection as a way to modulate the neurodegenerative processes evolution. Neuroinflammation, oxidative stress and the apoptotic process may be functional targets where operate to this end. Taking into account these considerations, the aim of the present study is to identify potential common pathogenetic pathways in neurodegenerative diseases using an integrated approach of preclinical studies. The goal is to delineate therapeutic strategies for the prevention of neuroinflammation, neurodegeneration and dysfunctions associated to Parkinson’s disease (PD) and cerebral ischemia. In the present study we used a murine model of PD treated with an isothiocyanate, 6-MSITC, able to quench ROS formation, restore the antioxidant GSH system, slow down the apoptotic neuronal death and counteract motor dysfunction induced by 6-OHDA. In the second study we utilized a transgenic mouse model knockout for CD36 receptor to investigate the inflammation involvement in a long term study of MCAo, which shows a better outcome after the damage induced. In conclusion, results in this study allow underlying the connection among these pathologies, and the importance of a neuroprotective strategy able to restore neurons activity where current drugs therapies have shown palliative but not healing abilities.

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The enteric nervous system (ENS) modulates a number of digestive functions including well known ones, i.e. motility, secretion, absorption and blood flow, along with other critically relevant processes, i.e. immune responses of the gastrointestinal (GI) tract, gut microbiota and epithelial barrier . The characterization of the anatomical aspects of the ENS in large mammals and the identification of differences and similarities existing between species may represent a fundamental basis to decipher several digestive GI diseases in humans and animals. In this perspective, the aim of the present thesis is to highlight the ENS anatomical basis and pathological aspects in different mammalian species, such as horses, dogs and humans. Firstly, I designed two anatomical studies in horses:  “Excitatory and inhibitory enteric innervation of horse lower esophageal sphincter”.  “Localization of 5-hydroxytryptamine 4 receptor (5-HT4R) in the equine enteric nervous system”. Then I focused on the enteric dysfunctions, including:  A primary enteric aganglionosis in horses: “Extrinsic innervation of the ileum and pelvic flexure of foals with ileocolonic aganglionosis”.  A diabetic enteric neuropathy in dogs: “Quantification of nitrergic neurons in the myenteric plexus of gastric antrum and ileum of healthy and diabetic dogs”.  An enteric neuropathy in human neurological patients: “Functional and neurochemical abnormalities in patients with Parkinson's disease and chronic constipation”. The physiology of the GI tract is characterized by a high complexity and it is mainly dependent on the control of the intrinsic nervous system. ENS is critical to preserve body homeostasis as reflect by its derangement occurring in pathological conditions that can be lethal or seriously disabling to humans and animals. The knowledge of the anatomy and the pathology of the ENS represents a new important and fascinating topic, which deserves more attention in the veterinary medicine field.

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The role of non-neuronal brain cells, called astrocytes, is emerging as crucial in brain function and dysfunction, encompassing the neurocentric concept that was envisioning glia as passive components. Ion and water channels and calcium signalling, expressed in functional micro and nano domains, underpin astrocytes’ homeostatic function, synaptic transmission, neurovascular coupling acting either locally and globally. In this respect, a major issue arises on the mechanism through which astrocytes can control processes across scales. Finally, astrocytes can sense and react to extracellular stimuli such as chemical, physical, mechanical, electrical, photonic ones at the nanoscale. Given their emerging importance and their sensing properties, my PhD research program had the general goal to validate nanomaterials, interfaces and devices approaches that were developed ad-hoc to study astrocytes. The results achieved are reported in the form of collection of papers. Specifically, we demonstrated that i) electrospun nanofibers made of polycaprolactone and polyaniline conductive composites can shape primary astrocytes’ morphology, without affecting their function ii) gold coated silicon nanowires devices enable extracellular recording of unprecedented slow wave in primary differentiated astrocytes iii) colloidal hydrotalcites films allow to get insight in cell volume regulation process in differentiated astrocytes and to describe novel cytoskeletal actin dynamics iv) gold nanoclusters represent nanoprobe to trigger astrocytes structure and function v) nanopillars of photoexcitable organic polymer are potential tool to achieve nanoscale photostimulation of astrocytes. The results were achieved by a multidisciplinary team working with national and international collaborators that are listed and acknowledged in the text. Collectively, the results showed that astrocytes represent a novel opportunity and target for Nanoscience, and that Nanoglial interface might help to unveil clues on brain function or represent novel therapeutic approach to treat brain dysfunctions.

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Alpha oscillations are linked to visual awareness and to the periodical sampling of visual information, suggesting that alpha rhythm reflect an index of the functionality of the posterior cortices, and hence of the visual system. Therefore, the present work described a series of studies investigating alpha oscillations as a biomarker of the functionality and the plastic modifications of the visual system in response to lesions to the visual cortices or to external stimulations. The studies presented in chapter 5 and 6 showed that posterior lesions alter alpha oscillations in hemianopic patients, with reduced alpha reactivity at the eyes opening and decreased alpha functional connectivity, especially in right-lesioned hemianopics, with concurrent dysfunctions in the theta range, suggesting a specialization of the right hemisphere in orchestrating alpha oscillations and coordinating complex interplays among different brain rhythms. The study presented in chapter 7 investigated a mechanism of rhythmical attentional sampling of visual information in healthy participants, showing that perceptual performance is influenced by a rhythmical mechanism of attentional allocation, occurring at lower-alpha frequencies (i.e., 7 Hz), when a single spatial location is monitored, and at lower frequencies (i.e., 5 Hz), when attention is allocated to two spatial locations. Moreover, the right hemisphere seemed to have a dominance in this rhythmical attentional sampling, distributing attentional resources to the entire visual field. Finally, the study presented in chapter 8 showed that prolonged visual entrainment induce long-term modulations of resting-state alpha activity in healthy participants, suggesting that persistent modifications in the functionality of the visual system are possible. Altogheter, these findings show that functional processes and plastic changes of the visual system are reflected in alpha oscillatory patterns. Therefore, investigating and promoting alpha oscillations may contribute to the development of rehabilitative protocols to ameliorate the functionality of the visual system, in brain lesioned patients.

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Lo spazio pubblico urbano potrebbe essere visto come una scenografia mutevole in cui la società rappresenta sé stessa. Soprattutto nei centri storici della città, si perde l’identità di luoghi specifici, così come la coscienza dei cittadini, che porta ad un uso improprio dello spazio causato principalmente dall’assenza di una cultura architettonica. In questo senso, l’obiettivo finale dell’architettura è quello di essere educativa nello spiegare il motivo per cui è stata concepita. La tesi di ricerca tenta di studiare la dimensione educativa e la forza che l’architettura ha nell’influenzare comportamenti spontanei e non spontanei. L’obiettivo è trovare metodi di progettazione e legali in grado di migliorare gli spazi pubblici in termini di qualità della vita dei suoi utenti. Il riconoscimento e la trasmissione dell’architettura, attraverso l’uso dell’architettura stessa, tenta di arginare un’assenza di cultura architettonica e un uso sempre più improprio dei suoi spazi. La domanda a cui, dunque, si tenta di rispondere è: Può la dimensione evocativa dell’architettura stimolare processi di rigenerazione urbana? La tesi si sviluppa in tre parti: la prima presenta alcune riflessioni teoriche sulla progettazione dello spazio pubblico alle quali fanno riferimento altrettanti progetti portati avanti nei mesi di ricerca Dai workshops realizzati sono emerse diverse problematiche riguardo l’effettiva realizzazione di tali progetti evidenziando soprattutto una carenza di tipo normativo che fa “cadere” gli entusiasmi legati al completamento delle opere per la comunità e di conseguenza decade il valore teorico dei progetti. Per questo motivo, nella seconda parte, si tenta di approfondire il tema legislativo per trovare soluzioni alternative agli arresti burocratici che sovente disincentivano le azioni corali della cittadinanza. La terza parte si concentrerà su un progetto per un’area di Bologna da riqualificare, i Prati di Caprara, per i quali si sfrutteranno tutte le conoscenze teoriche precedentemente esposte.

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CDKL5 (cyclin-dependent kinase-like 5) deficiency disorder (CDD) is a rare and severe neurodevelopmental disease that mostly affects girls who are heterozygous for mutations in the X-linked CDKL5 gene. The lack of CDKL5 protein expression or function leads to the appearance of numerous clinical features, including early-onset seizures, marked hypotonia, autistic features, and severe neurodevelopmental impairment. Mouse models of CDD, Cdkl5 KO mice, exhibit several behavioral phenotypes that mimic CDD features, such as impaired learning and memory, social interaction, and motor coordination. CDD symptomatology, along with the high CDKL5 expression levels in the brain, underscores the critical role that CDKL5 plays in proper brain development and function. Nevertheless, the improvement of the clinical overview of CDD in the past few years has defined a more detailed phenotypic spectrum; this includes very common alterations in peripheral organ and tissue function, such as gastrointestinal problems, irregular breathing, hypotonia, and scoliosis, suggesting that CDKL5 deficiency compromises not only CNS function but also that of other organs/tissues. Here we report, for the first time, that a mouse model of CDD, the heterozygous Cdkl5 KO (Cdkl5 +/-) female mouse, exhibits cardiac functional and structural abnormalities. The mice also showed QTc prolongation and increased heart rate. These changes correlate with a marked decrease in parasympathetic activity to the heart and in the expression of the Scn5a and Hcn4 voltage-gated channels. Moreover, the Cdkl5 +/- heart shows typical signs of heart aging, including increased fibrosis, mitochondrial dysfunctions, and increased ROS production. Overall, our study not only contributes to the understanding of the role of CDKL5 in heart structure/function but also documents a novel preclinical phenotype for future therapeutic investigation.

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Fin dalla sua attuazione nel 2012, l'Iniziativa dei cittadini europei (ICE) ha catturato l'attenzione di accademici e politici per il suo apparente potenziale come strumento di democrazia partecipativa in grado di promuovere il coinvolgimento diretto dei cittadini nel processo decisionale dell'UE. Tuttavia, dopo il suo lancio, questo strumento sembra aver deluso le speranze e le aspettative riposte in esso e, invece di fungere da ponte tra i cittadini e le istituzioni dell'UE, sembra essere diventato una chiara prova della leadership burocratica dell'UE a Bruxelles. Con la riforma della sua legislazione di attuazione, le istituzioni europee hanno voluto dare all'ICE un'altra possibilità di raggiungere il suo pieno potenziale di democratizzazione. A tre anni dall'entrata in vigore del nuovo Regolamento 2019/788 e a più di dieci anni dal suo inserimento nell'ordinamento giuridico europeo, riteniamo che sia il momento giusto per valutare il reale impatto dell'ICE nella promozione della democrazia partecipativa nell'UE. Per raggiungere questo obiettivo, la presente tesi di dottorato intraprende un'analisi completa di questa struttura di opportunità per la partecipazione dei cittadini, esplorando le sue origini, il suo quadro normativo, la sua applicazione pratica e le sue implicazioni per la democrazia europea attraverso un approccio interdisciplinare che combina l'uso di metodi sia qualitativi che quantitativi. Questa ricerca mira a fornire una comprensione più profonda e critica dell'ICE e del suo ruolo nella costruzione di un'Europa più partecipativa e più vicina ai cittadini.