Stem Cells as a therapy for myocardial infarction in animal models

Advances in stem cell biology have challenged the notion that infarcted myocardium is irreparable. The pluripotent ability of stem cells to differentiate into specialized cell lines began to garner intense interest within cardiology when it was shown in animal models that intramyocardial injection of bone marrow stem cells (MSCs), or the mobilization of bone marrow stem cells with spontaneous homing to myocardium, could improve cardiac function and survival after induced myocardial infarction (MI) [1, 2]. Furthermore, the existence of stem cells in myocardium has been identified in animal heart [3, 4], and intense research is under way in an attempt to clarify their potential clinical application for patients with myocardial infarction. To date, in order to identify the best one, different kinds of stem cells have been studied; these have been derived from embryo or adult tissues (i.e. bone marrow, heart, peripheral blood etc.). Currently, three different biologic therapies for cardiovascular diseases are under investigation: cell therapy, gene therapy and the more recent “tissue-engineering” therapy . During my Ph.D. course, first I focalised my study on the isolation and characterization of Cardiac Stem Cells (CSCs) in wild-type and transgenic mice and for this purpose I attended, for more than one year, the Cardiovascular Research Institute of the New York Medical College, in Valhalla (NY, USA) under the direction of Doctor Piero Anversa. During this period I learnt different Immunohistochemical and Biomolecular techniques, useful for investigating the regenerative potential of stem cells. Then, during the next two years, I studied the new approach of cardiac regenerative medicine based on “tissue-engineering” in order to investigate a new strategy to regenerate the infracted myocardium. Tissue-engineering is a promising approach that makes possible the creation of new functional tissue to replace lost or failing tissue. This new discipline combines isolated functioning cells and biodegradable 3-dimensional (3D) polymeric scaffolds. The scaffold temporarily provides the biomechanical support for the cells until they produce their own extracellular matrix. Because tissue-engineering constructs contain living cells, they may have the potential for growth and cellular self-repair and remodeling. In the present study, I examined whether the tissue-engineering strategy within hyaluron-based scaffolds would result in the formation of alternative cardiac tissue that could replace the scar and improve cardiac function after MI in syngeneic heterotopic rat hearts. Rat hearts were explanted, subjected to left coronary descending artery occlusion, and then grafted into the abdomen (aorta-aorta anastomosis) of receiving syngeneic rat. After 2 weeks, a pouch of 3 mm2 was made in the thickness of the ventricular wall at the level of the post-infarction scar. The hyaluronic scaffold, previously engineered for 3 weeks with rat MSCs, was introduced into the pouch and the myocardial edges sutured with few stitches. Two weeks later we evaluated the cardiac function by M-Mode echocardiography and the myocardial morphology by microscope analysis. We chose bone marrow-derived mensenchymal stem cells (MSCs) because they have shown great signaling and regenerative properties when delivered to heart tissue following a myocardial infarction (MI). However, while the object of cell transplantation is to improve ventricular function, cardiac cell transplantation has had limited success because of poor graft viability and low cell retention, that’s why we decided to combine MSCs with a biopolimeric scaffold. At the end of the experiments we observed that the hyaluronan fibres had not been substantially degraded 2 weeks after heart-transplantation. Most MSCs had migrated to the surrounding infarcted area where they were especially found close to small-sized vessels. Scar tissue was moderated in the engrafted region and the thickness of the corresponding ventricular wall was comparable to that of the non-infarcted remote area. Also, the left ventricular shortening fraction, evaluated by M-Mode echocardiography, was found a little bit increased when compared to that measured just before construct transplantation. Therefore, this study suggests that post-infarction myocardial remodelling can be favourably affected by the grafting of MSCs delivered through a hyaluron-based scaffold

Transcriptional regulation of human mu-opioid receptor gene: functional characterization of activating and inhibitory transcription factors

The organization of the nervous and immune systems is characterized by obvious differences and striking parallels. Both systems need to relay information across very short and very long distances. The nervous system communicates over both long and short ranges primarily by means of more or less hardwired intercellular connections, consisting of axons, dendrites, and synapses. Longrange communication in the immune system occurs mainly via the ordered and guided migration of immune cells and systemically acting soluble factors such as antibodies, cytokines, and chemokines. Its short-range communication either is mediated by locally acting soluble factors or transpires during direct cell–cell contact across specialized areas called “immunological synapses” (Kirschensteiner et al., 2003). These parallels in intercellular communication are complemented by a complex array of factors that induce cell growth and differentiation: these factors in the immune system are called cytokines; in the nervous system, they are called neurotrophic factors. Neither the cytokines nor the neurotrophic factors appear to be completely exclusive to either system (Neumann et al., 2002). In particular, mounting evidence indicates that some of the most potent members of the neurotrophin family, for example, nerve growth factor (NGF) and brainderived neurotrophic factor (BDNF), act on or are produced by immune cells (Kerschensteiner et al., 1999) There are, however, other neurotrophic factors, for example the insulin-like growth factor-1 (IGF-1), that can behave similarly (Kermer et al., 2000). These factors may allow the two systems to “cross-talk” and eventually may provide a molecular explanation for the reports that inflammation after central nervous system (CNS) injury has beneficial effects (Moalem et al., 1999). In order to shed some more light on such a cross-talk, therefore, transcription factors modulating mu-opioid receptor (MOPr) expression in neurons and immune cells are here investigated. More precisely, I focused my attention on IGF-I modulation of MOPr in neurons and T-cell receptor induction of MOPr expression in T-lymphocytes. Three different opioid receptors [mu (MOPr), delta (DOPr), and kappa (KOPr)] belonging to the G-protein coupled receptor super-family have been cloned. They are activated by structurallyrelated exogenous opioids or endogenous opioid peptides, and contribute to the regulation of several functions including pain transmission, respiration, cardiac and gastrointestinal functions, and immune response (Zollner and Stein 2007). MOPr is expressed mainly in the central nervous system where it regulates morphine-induced analgesia, tolerance and dependence (Mayer and Hollt 2006). Recently, induction of MOPr expression in different immune cells induced by cytokines has been reported (Kraus et al., 2001; Kraus et al., 2003). The human mu-opioid receptor gene (OPRM1) promoter is of the TATA-less type and has clusters of potential binding sites for different transcription factors (Law et al. 2004). Several studies, primarily focused on the upstream region of the OPRM1 promoter, have investigated transcriptional regulation of MOPr expression. Presently, however, it is still not completely clear how positive and negative transcription regulators cooperatively coordinate cellor tissue-specific transcription of the OPRM1 gene, and how specific growth factors influence its expression. IGF-I and its receptors are widely distributed throughout the nervous system during development, and their involvement in neurogenesis has been extensively investigated (Arsenijevic et al. 1998; van Golen and Feldman 2000). As previously mentioned, such neurotrophic factors can be also produced and/or act on immune cells (Kerschenseteiner et al., 2003). Most of the physiologic effects of IGF-I are mediated by the type I IGF surface receptor which, after ligand binding-induced autophosphorylation, associates with specific adaptor proteins and activates different second messengers (Bondy and Cheng 2004). These include: phosphatidylinositol 3-kinase, mitogen-activated protein kinase (Vincent and Feldman 2002; Di Toro et al. 2005) and members of the Janus kinase (JAK)/STAT3 signalling pathway (Zong et al. 2000; Yadav et al. 2005). REST plays a complex role in neuronal cells by differentially repressing target gene expression (Lunyak et al. 2004; Coulson 2005; Ballas and Mandel 2005). REST expression decreases during neurogenesis, but has been detected in the adult rat brain (Palm et al. 1998) and is up-regulated in response to global ischemia (Calderone et al. 2003) and induction of epilepsy (Spencer et al. 2006). Thus, the REST concentration seems to influence its function and the expression of neuronal genes, and may have different effects in embryonic and differentiated neurons (Su et al. 2004; Sun et al. 2005). In a previous study, REST was elevated during the early stages of neural induction by IGF-I in neuroblastoma cells. REST may contribute to the down-regulation of genes not yet required by the differentiation program, but its expression decreases after five days of treatment to allow for the acquisition of neural phenotypes. Di Toro et al. proposed a model in which the extent of neurite outgrowth in differentiating neuroblastoma cells was affected by the disappearance of REST (Di Toro et al. 2005). The human mu-opioid receptor gene (OPRM1) promoter contains a DNA sequence binding the repressor element 1 silencing transcription factor (REST) that is implicated in transcriptional repression. Therefore, in the fist part of this thesis, I investigated whether insulin-like growth factor I (IGF-I), which affects various aspects of neuronal induction and maturation, regulates OPRM1 transcription in neuronal cells in the context of the potential influence of REST. A series of OPRM1-luciferase promoter/reporter constructs were transfected into two neuronal cell models, neuroblastoma-derived SH-SY5Y cells and PC12 cells. In the former, endogenous levels of human mu-opioid receptor (hMOPr) mRNA were evaluated by real-time PCR. IGF-I upregulated OPRM1 transcription in: PC12 cells lacking REST, in SH-SY5Y cells transfected with constructs deficient in the REST DNA binding element, or when REST was down-regulated in retinoic acid-differentiated cells. IGF-I activates the signal transducer and activator of transcription-3 (STAT3) signaling pathway and this transcription factor, binding to the STAT1/3 DNA element located in the promoter, increases OPRM1 transcription. T-cell receptor (TCR) recognizes peptide antigens displayed in the context of the major histocompatibility complex (MHC) and gives rise to a potent as well as branched intracellular signalling that convert naïve T-cells in mature effectors, thus significantly contributing to the genesis of a specific immune response. In the second part of my work I exposed wild type Jurkat CD4+ T-cells to a mixture of CD3 and CD28 antigens in order to fully activate TCR and study whether its signalling influence OPRM1 expression. Results were that TCR engagement determined a significant induction of OPRM1 expression through the activation of transcription factors AP-1, NF-kB and NFAT. Eventually, I investigated MOPr turnover once it has been expressed on T-cells outer membrane. It turned out that DAMGO induced MOPr internalisation and recycling, whereas morphine did not. Overall, from the data collected in this thesis we can conclude that that a reduction in REST is a critical switch enabling IGF-I to up-regulate human MOPr, helping these findings clarify how human MOPr expression is regulated in neuronal cells, and that TCR engagement up-regulates OPRM1 transcription in T-cells. My results that neurotrophic factors a and TCR engagement, as well as it is reported for cytokines, seem to up-regulate OPRM1 in both neurons and immune cells suggest an important role for MOPr as a molecular bridge between neurons and immune cells; therefore, MOPr could play a key role in the cross-talk between immune system and nervous system and in particular in the balance between pro-inflammatory and pro-nociceptive stimuli and analgesic and neuroprotective effects.

Aldo Rossi, autobiografia scientifica: scrittura come progetto. Indagine critica tra scrittura e progetto di architettura

«In altri termini mi sfuggiva e ancora oggi mi sfugge gran parte del significato dell’evoluzione del tempo; come se il tempo fosse una materia che osservo dall’esterno. Questa mancanza di evoluzione è fonte di alcune mie sventure ma anche mi appartiene con gioia.» Aldo Rossi, Autobiografia scientifica. The temporal dimension underpinning the draft of Autobiografia scientifica by Aldo Rossi may be referred to what Lucien Lévy-Bruhl, the well-known French anthropologist, defines as “primitive mentality” and “prelogical” conscience : the book of life has lost its page numbers, even punctuation. For Lévy-Bruhl, but certainly for Rossi, life or its summing up becomes a continuous account of ellipses, gaps, repetitions that may be read from left to right or viceversa, from head to foot or viceversa without distinction. Rossi’s autobiographical writing seems to accept and support the confusion with which memories have been collected, recording them after the order memory gives them in the mental distillation or simply according to the chronological order in which they have happened. For Rossi, the confusion reflects the melting of memory elements into a composite image which is the result of a fusion. He is aware that the same sap pervades all memories he is going to put in order: each of them has got a common denominator. Differences have diminished, almost faded; the quick glance is prevalent over the distinction of each episode. Rossi’s writing is beyond the categories dependent on time: past and present, before and now. For Rossi, the only repetition – the repetition the text will make possible for an indefinite number of times – gives peculiarity to the event. As Gilles Deleuze knows, “things” may only last as “singleness”: more frequent the repetition is, more singular is the memory phenomenon that recurs, because only what is singular magnifies itself and happens endlessly forever. Rossi understands that “to raise the first time to nth forever”, repetition becomes glorification . It may be an autobiography that, celebrating the originality, enhances the memory event in the repetition; in fact it greatly differs from the biographical reproduction, in which each repetition is but a weaker echo, a duller copy, provided with a smaller an smaller power in comparison with the original. Paradoxically, for Deleuze the repetition asserts the originality and singularity of what is repeated. Rossi seems to share the thought expressed by Kierkegaard in the essay Repetition: «The hope is a graceful maiden slipping through your fingers; the memory of an elderly woman, indeed pretty, but never satisfactory if necessary; the repetition is a loved friend you are never tired of, as it is only the new to make you bored. The old never bores you and its presence makes you happy [...] life is but a repetition [...] here is the beauty of life» . Rossi knows well that repetition hints at the lasting stability of cosmic time. Kierkegaard goes on: «The world exists, and it exists as a repetition» . Rossi devotes himself, on purpose and in all conscience, to collect, to inventory and «to review life», his own life, according to a recovery not from the past but of the past: a search work, the «recherche du temps perdu», as Proust entitled his masterpiece on memory. If you want the past time to be not wasted, you must give it presence. «Memoria e specifico come caratteristiche per riconoscere se stesso e ciò che è estraneo mi sembravano le più chiare condizioni e spiegazioni della realtà. Non esiste uno specifico senza memoria, e una memoria che non provenga da un momento specifico; e solo questa unione permette la conoscenza della propria individualità e del contrario (self e non-self)» . Rossi wants to understand himself, his own character; it is really his own character that requires to be understood, to increase its own introspective ability and intelligence. «Può sembrare strano che Planck e Dante associno la loro ricerca scientifica e autobiografica con la morte; una morte che è in qualche modo continuazione di energia. In realtà, in ogni artista o tecnico, il principio della continuazione dell’energia si mescola con la ricerca della felicità e della morte» . The eschatological incipit of Rossi’s autobiography refers to Freud’s thought in the exact circularity of Dante’s framework and in as much exact circularity of the statement of the principle of the conservation of energy: in fact it was Freud to connect repetition to death. For Freud, the desire of repetition is an instinct rooted in biology. The primary aim of such an instinct would be to restore a previous condition, so that the repeated history represents a part of the past (even if concealed) and, relieving the removal, reduces anguish and tension. So, Freud ask himself, what is the most remote state to which the instinct, through the repetition, wants to go back? It is a pre-vital condition, inorganic of the pure entropy, a not-to-be condition in which doesn’t exist any tension; in other words, Death. Rossi, with the theme of death, introduces the theme of circularity which further on refers to the sense of continuity in transformation or, in the opposite way, the transformation in continuity. «[...] la descrizione e il rilievo delle forme antiche permettevano una continuità altrimenti irripetibile, permettevano anche una trasformazione, una volta che la vita fosse fermata in forme precise» . Rossi’s attitude seems to hint at the reflection on time and – in a broad sense – at the thought on life and things expressed by T.S. Eliot in Four Quartets: «Time present and time past / Are both perhaps present in time future, / And time future is contained in time past. / I all time is eternally present / All time is unredeemable. / What might have been is an abstraction / Remaining perpetual possibility / Only in a word of speculation. / What might have been and what has been / Point to one end, which is always present. [...]» . Aldo Rossi’s autobiographical story coincides with the description of “things” and the description of himself through the things in the exact parallel with craft or art. He seems to get all things made by man to coincide with the personal or artistic story, with the consequent immediate necessity of formulating a new interpretation: the flow of things has never met a total stop; all that exists nowadays is but a repetition or a variant of something existing some time ago and so on, without any interruption until the early dawnings of human life. Nevertheless, Rossi must operate specific subdivisions inside the continuous connection in time – of his time – even if limited by a present beginning and end of his own existence. This artist, as an “historian” of himself and his own life – as an auto-biographer – enjoys the privilege to be able to decide if and how to operate the cutting in a certain point rather than in another one, without being compelled to justify his choice. In this sense, his story is a matter very ductile and flexible: a good story-teller can choose any moment to start a certain sequence of events. Yet, Rossi is aware that, beyond the mere narration, there is the problem to identify in history - his own personal story – those flakings where a clean cut enables the separation of events of different nature. In order to do it, he has to make not only an inventory of his own “things”, but also to appeal to authority of the Divina Commedia started by Dante when he was 30. «A trent’anni si deve compiere o iniziare qualcosa di definitivo e fare i conti con la propria formazione» . For Rossi, the poet performs his authority not only in the text, but also in his will of setting out on a mystical journey and handing it down through an exact descriptive will. Rossi turns not only to the authority of poetry, but also evokes the authority of science with Max Plank and his Scientific Autobiography, published, in Italian translation, by Einaudi, 1956. Concerning Planck, Rossi resumes an element seemingly secondary in hit account where the German physicist «[...] risale alle scoperte della fisica moderna ritrovando l’impressione che gli fece l’enunciazione del principio di conservazione dell’energia; [...]» . It is again the act of describing that links Rossi to Planck, it is the description of a circularity, the one of conservation of energy, which endorses Rossi’s autobiographical speech looking for both happiness and death. Rossi seems to agree perfectly to the thought of Planck at the opening of his own autobiography: «The decision to devote myself to science was a direct consequence of a discovery which was never ceased to arouse my enthusiasm since my early youth: the laws of human thought coincide with the ones governing the sequences of the impressions we receive from the world surrounding us, so that the mere logic can enable us to penetrate into the latter one’s mechanism. It is essential that the outer world is something independent of man, something absolute. The search of the laws dealing with this absolute seems to me the highest scientific aim in life» . For Rossi the survey of his own life represents a way to change the events into experiences, to concentrate the emotion and group them in meaningful plots: «It seems, as one becomes older. / That the past has another pattern, and ceases to be a mere sequence [...]» Eliot wrote in Four Quartet, which are a meditation on time, old age and memory . And he goes on: «We had the experience but missed the meaning, / And approach to the meaning restores the experience / In a different form, beyond any meaning [...]» . Rossi restores in his autobiography – but not only in it – the most ancient sense of memory, aware that for at least 15 centuries the Latin word memoria was used to show the activity of bringing back images to mind: the psychology of memory, which starts with Aristotele (De Anima), used to consider such a faculty totally essential to mind. Keith Basso writes: «The thought materializes in the form of “images”» . Rossi knows well – as Aristotele said – that if you do not have a collection of mental images to remember – imagination – there is no thought at all. According to this psychological tradition, what today we conventionally call “memory” is but a way of imagining created by time. Rossi, entering consciously this stream of thought, passing through the Renaissance ars memoriae to reach us gives a great importance to the word and assumes it as a real place, much more than a recollection, even more than a production and an emotional elaboration of images.

Body ares networks for human motor assessment

Healthcare, Human Computer Interfaces (HCI), Security and Biometry are the most promising application scenario directly involved in the Body Area Networks (BANs) evolution. Both wearable devices and sensors directly integrated in garments envision a word in which each of us is supervised by an invisible assistant monitoring our health and daily-life activities. New opportunities are enabled because improvements in sensors miniaturization and transmission efficiency of the wireless protocols, that achieved the integration of high computational power aboard independent, energy-autonomous, small form factor devices. Application’s purposes are various: (I) data collection to achieve off-line knowledge discovery; (II) user notification of his/her activities or in case a danger occurs; (III) biofeedback rehabilitation; (IV) remote alarm activation in case the subject need assistance; (V) introduction of a more natural interaction with the surrounding computerized environment; (VI) users identification by physiological or behavioral characteristics. Telemedicine and mHealth [1] are two of the leading concepts directly related to healthcare. The capability to borne unobtrusiveness objects supports users’ autonomy. A new sense of freedom is shown to the user, not only supported by a psychological help but a real safety improvement. Furthermore, medical community aims the introduction of new devices to innovate patient treatments. In particular, the extension of the ambulatory analysis in the real life scenario by proving continuous acquisition. The wide diffusion of emerging wellness portable equipment extended the usability of wearable devices also for fitness and training by monitoring user performance on the working task. The learning of the right execution techniques related to work, sport, music can be supported by an electronic trainer furnishing the adequate aid. HCIs made real the concept of Ubiquitous, Pervasive Computing and Calm Technology introduced in the 1988 by Marc Weiser and John Seeley Brown. They promotes the creation of pervasive environments, enhancing the human experience. Context aware, adaptive and proactive environments serve and help people by becoming sensitive and reactive to their presence, since electronics is ubiquitous and deployed everywhere. In this thesis we pay attention to the integration of all the aspects involved in a BAN development. Starting from the choice of sensors we design the node, configure the radio network, implement real-time data analysis and provide a feedback to the user. We present algorithms to be implemented in wearable assistant for posture and gait analysis and to provide assistance on different walking conditions, preventing falls. Our aim, expressed by the idea to contribute at the development of a non proprietary solutions, driven us to integrate commercial and standard solutions in our devices. We use sensors available on the market and avoided to design specialized sensors in ASIC technologies. We employ standard radio protocol and open source projects when it was achieved. The specific contributions of the PhD research activities are presented and discussed in the following. • We have designed and build several wireless sensor node providing both sensing and actuator capability making the focus on the flexibility, small form factor and low power consumption. The key idea was to develop a simple and general purpose architecture for rapid analysis, prototyping and deployment of BAN solutions. Two different sensing units are integrated: kinematic (3D accelerometer and 3D gyroscopes) and kinetic (foot-floor contact pressure forces). Two kind of feedbacks were implemented: audio and vibrotactile. • Since the system built is a suitable platform for testing and measuring the features and the constraints of a sensor network (radio communication, network protocols, power consumption and autonomy), we made a comparison between Bluetooth and ZigBee performance in terms of throughput and energy efficiency. Test in the field evaluate the usability in the fall detection scenario. • To prove the flexibility of the architecture designed, we have implemented a wearable system for human posture rehabilitation. The application was developed in conjunction with biomedical engineers who provided the audio-algorithms to furnish a biofeedback to the user about his/her stability. • We explored off-line gait analysis of collected data, developing an algorithm to detect foot inclination in the sagittal plane, during walk. • In collaboration with the Wearable Lab – ETH, Zurich, we developed an algorithm to monitor the user during several walking condition where the user carry a load. The remainder of the thesis is organized as follows. Chapter I gives an overview about Body Area Networks (BANs), illustrating the relevant features of this technology and the key challenges still open. It concludes with a short list of the real solutions and prototypes proposed by academic research and manufacturers. The domain of the posture and gait analysis, the methodologies, and the technologies used to provide real-time feedback on detected events, are illustrated in Chapter II. The Chapter III and IV, respectively, shown BANs developed with the purpose to detect fall and monitor the gait taking advantage by two inertial measurement unit and baropodometric insoles. Chapter V reports an audio-biofeedback system to improve balance on the information provided by the use centre of mass. A walking assistant based on the KNN classifier to detect walking alteration on load carriage, is described in Chapter VI.

Synthesis and application of new ion-tagged ligands and organocatalysts

We report the synthesis and application of some ion-tagged catalysts in organometallic catalysis and organocatalysis. With the installation of an ionic group on the backbone of a known catalyst, two main effects are generally obtained. i) a modification of the solubility of the catalyst: if judicious choice of the ion pair is made, the ion-tag can confer to the catalyst a solubility profile suitable for catalyst recycling. ii) the ionic group can play a non-innocent role in the process considered: if stabilizing interaction between the ionic group and the developing charges in the transition state are established, the reaction can speed up. We describe the use of ion-tagged diphenylprolinol as Zn ligand. The chiral ligand grafted onto an ionic liquid (IL) was recycled 10 times with no loss of reactivity and selectivity, when it was employed in the first example of enantioselective addition of ZnEt2 to aldehydes in ILs. An ammonium-tagged phosphine displayed the capability to stabilize Pd catalysts for the Suzuki reaction in ILs. The ionic phase was recycled 6 times with no detectable loss of activity and very low Pd leaching in the organic phase. This catalytic system was also employed for the functionalization of the challenging substrate 5,11-dibromotetracene. In the field of organocatalysis, we prepared two ion-tagged derivatives of the McMillan imidazolidinone. The results of the asymmetric Diels-Alder reaction between trans-cinnamaldehyde and cyclopentadiene exhibited great dependence on the position and nature of the ionic group. Finally, when O-TMS-diphenylprolinol was tagged with an imidazolium ion, exploiting a silyl ether linker, an efficient catalyst for the asymmetric addition of aldehydes to nitroolefins was achieved. The catalyst displayed enhanced reactivity and the same high level of selectivity of the untagged parent catalyst and it could be employed in a wide range of reaction conditions, included use of water as solvent.

Riccardo Lombardi nel socialismo italiano (1947-1964)

Il primo capitolo della tesi verte sull’ultimo anno di vita del Partito d’Azione, sulle modalità di partecipazione di Lombardi allo scontro elettorale del 1948 nelle liste del Fronte democratico popolare, e sul breve periodo di direzione ‘centrista’ del Psi a cavallo tra il 1948 e il 1949, quando Lombardi, appena entratovi, fu magna pars nel gruppo dirigente del partito. Il secondo capitolo abbraccia il periodo in cui Lombardi agì all’interno del Psi ‘morandiano’, o frontista: si è cercato di dare ragione sia dell’inserimento di Lombardi nelle logiche del frontismo socialista, sia della peculiarità di quell’inserimento negli ambiti privilegiati della politica economica e della politica estera. Oggetto del terzo capitolo è il ruolo giocato da Lombardi nella definizione delle linee guida dell’autonomismo socialista, un ruolo fattosi via via più pregnante a partire dal 1956, che ebbe la sua massima consacrazione col XXXIV Congresso del Psi, celebrato a Milano nel 1961: centrale in questo periodo la riflessione lombardiana sulle «riforme di struttura», un argomento che ci si è sforzati di inquadrare storicamente, sfuggendo dai luoghi comuni storiografici di cui spesso – con lodevoli eccezioni – è caduto vittima. Tali «riforme di struttura» Lombardi avrebbe voluto alla base dei governi di centro-sinistra. La tesi si chiude con un ultimo capitolo dedicato ad illustrare l’apporto di Lombardi al quarto Governo Fanfani e al primo Governo Moro, il ruolo da lui giocato nella loro nascita e il suo progressivo allontanamento da quell’esperimento che era stato, in gran parte, sua creatura.

Women writing Ireland, 1798 – 1921: il popular novel tra identità nazionale e immaginario religioso nelle autrici cattoliche e protestanti.

La presente tesi si concentra sul romanzo popolare irlandese scritto da donne, nel periodo compreso tra il 1798 e il 1921. Quattro sono le autrici prese in considerazione: Charlotte Elizabeth Tonna, Sydney Owenson (meglio conosciuta come Lady Morgan), Edith Somerville e Katharine Tynan, le cui vite e opere coprono un periodo storico fondamentale per l’uscita dell’Irlanda dal dominio coloniale britannico e la formazione della nazione irlandese nel sud del paese. L’interesse principale è quello di analizzare il modo in cui nei loro testi prende forma la nazione, e in particolare attraverso quali immagini e riferimenti religiosi. Il senso è quello, dunque, di rileggere tali testi prestando maggiore attenzione alla religione, uno dei principali collanti tra autrici e pubblico: all’epoca in cui l’Irlanda stava acquisendo i confini che oggi ancora mantiene, esisteva un terreno d’incontro tra discorso politico e letterario, quello della nazione, e tale terreno veniva attraversato anche dal messaggio religioso. Il fine ultimo è quello di dimostrare che la letteratura popolare non è “seconda” ad altre quanto a valori che è in grado di trasmettere e a messaggi che è in grado di veicolare: trascurarla significa non capire i meccanismi attraverso i quali una società si sviluppa e si modifica.

Studio sull'applicazione della piattaforma ForcetriadTM con sistema LigasureTM nella chirurgia oncologica e dei tessuti molli nel cane

Questo studio prospettico valuta l’efficacia e i vantaggi del sistema LigasureTM rispetto alle tecniche chirurgiche tradizionali, in quattro differenti procedure eseguite su 77 cani. I soggetti sono stati suddivisi in 4 gruppi, a seconda della chirurgia eseguita: Gruppo 1, 25 pazienti sottoposti a Splenectomia “aperta” semplice; Gruppo 2, 15 pazienti sottoposti a Splenectomia “aperta” complessa; Gruppo 3, 22 pazienti sottoposti ad Ovariectomia “aperta”. Gruppo 4: 18 pazienti sottoposti a Linfoadenectomia. Ciascun gruppo è stato a sua volta suddiviso in due sottogruppi: a (LigasureTM) e b (Tradizionale), a seconda della metodica utilizzata. Sono stati analizzati: il segnalamento, i parametri ematologici, le condizioni cliniche, le informazioni riguardanti l’intervento chirurgico e l’outcome. In tutti i gruppi il ricorso all’utilizzo di garze nonché dei fili da sutura sono risultati statisticamente inferiori nei pazienti operati con il sistema a radiofrequenza (Gruppo 1, P < 0.0001; Gruppo 2, P < 0,0014; Gruppo 3, P = 0,0001; Gruppo 4, P = 0,0148). Anche i tempi per la rimozione dell’organo sono significativamente ridotti in tutti i gruppi in cui è stato utilizzato il sistema LigasureTM (Gruppo 1 P < 0.0001; Gruppo 2 P < 0,0014; Gruppo 3 P = 0,0009; Gruppo 4 P = 0,0008), come i tempi chirurgici nei gruppi 1, 2 e 3 (P = 0,0287; P = 0,0064; e P = 0,0124) ed anestesiologici nei gruppi 1a e 2a (P = 0,0176; P = 0,0043). Tra le variabili analizzate, l’utilizzo del sistema di sintesi vascolare a radiofrequenza, è l’unico ad influenzare i tempi necessari per l’esecuzione della procedura. Questo studio dimostra, quindi, come il sistema LigasureTM sia sicuro ed efficace per le procedure chirurgiche esaminate, riducendo i tempi della chirurgia e limitando, quindi, i rischi per il paziente, indipendentemente dall’operatore, dall’esecuzione di altre procedure contemporanee e dalla natura della patologia splenica o linfonodale.