702 research outputs found
Sort by
Cryoablation of para-Hisian and mid-septal accessory pathways: long-term outcome of a specific cryoablation protocol
No full textmissin
Hyaluronan: a new player in the modulation of adaptive changes to neuromuscular damage in the gastrointestinal tract
Full text linkPathological conditions of the gastrointestinal tract, such as chronic inflammatory states or intestinal ischemia/reperfusion (I/R) injury, have severe consequences on different cell types constituting the enteric microenvironment. In particular, myenteric neurons are especially sensitive, and can be irreversibly damaged, resulting in structural and functional changes of the enteric circuitries. Such changes may be, at least in part, due to the interplay among different cell populations of enteric microenvironment. Hyaluronan (HA) represents an important molecule of the extracellular matrix (ECM), which provides an significant framework for that microenvironment. In this context, the aim of my thesis was to evaluate possible changes of HA homeostasis in myenteric ganglia after an experimentally induced colitis and an in vivo-induced ischemia/reperfusion (I/R) damage in rats. Results showed that myenteric neurons synthesize HA to form a well-structured perineuronal net, which undergoes derangement when myenteric ganglia homeostasis is perturbed, i.e. during the inflammatory state in the experimentally-induced colitis. In addition, data indicated that in the neuromuscular compartment of the rat small intestine, an I/R injury increases HA levels, and that HA may influence both the excitatory and inhibitory components of the peristaltic reflex. Overall, this study provides evidence that HA deposition within myenteric ganglia may have a homeostatic role, contributing to the control of myenteric neuron structure and function and supporting the efficiency of the gastrointestinal transit. Hence, modulation of HA deposition within myenteric ganglia may ameliorate intestinal motility patterns related to these disease states
The Peptide Transporters of teleost fish, an emerging model in translational research: functional characterization and comparative study of SLC15A1a (PepT1a) and SLC15A1b (PepT1b) transporters
No full textTranslational research is the process that applies knowledge from basic biology to techniques and devices to solve critical medical issues. The aim of basic and translational research is to identify specific cellular and animal models for every single process, physiological or pathological, under study. To find out the adequate animal model, one of the best approaches is to study the orthologues of human genes in different species. The increase in the number of fully sequenced genomes offers important advances in comparative genomics and in translational research. The finding that in zebrafish genome there are orthologues for most human genes is particularly important. In fact, zebrafish are for many aspects an outstanding model organism for high throughput phenotyping and modeling human disease and disorders. The aim of the research work of this thesis is to understand and compare the function of proteins belonging to the SoLute Carrier family 15 member A1 (PepT1) in different fish orthologues. The intestinal transporter PepT1 represents a major route of peptides and drug intake. Besides the important role of PepT1 in the nutrient uptake and sensing, the study of the functional properties of this transporter is of great importance not only for the involvement in pathological states, but also for its double role in therapeutic approaches. Recently, PepT1 has become an attractive target for potential therapeutic models for developing and enhancing drug-delivery systems
Parkinson’s disease and mitochondrial disfunctions: exploring the effect of PARK2 mutations in human skin fibroblasts
No full textParkinson’s disease is a complex and multifactorial neurodegenerative disease whose etiology has not been totally clarified yet. Strong evidences suggest that a complex interplay between environmental and genetic factors are involved in PD pathogenesis. Many of the molecular pathways implicated in PD etiology converge on mitochondria, resulting in their dysfunction. Mutations in PARK2 gene are the most frequent cause of familial forms of PD. This gene encodes Parkin, an E3 ubiquitin ligase involved in the mitophagy process. Parkin loss-of-function is responsible for the cellular accumulation of damaged mitochondria. Given the importance of mitochondrial dysfunctions and mitophagy impairment in PD pathogenesis, PARK2-mutated primary skin fibroblasts were used as a cellular model to explore the effects of PARK2 mutations both on the mitochondrial function and morphology and on the total and mitochondrial proteome. The first part of this thesis investigates the impact of Parkin impairment on mitochondrial function and network in primary skin fibroblasts of five PARK2 patients and five control subjects. The second part of this project is focused on the characterization of the mitochondrial and the total proteome alterations that characterize patients carrying PARK2 mutations. In conclusion, the present work highlighted new molecular factors and pathways altered by PARK2 mutations, which will unravel possible biochemical pathways altered in the sporadic form of the disease. The Peptide Transporters of teleost fish, an emerging model in translational research: functional characterization and comparative study of SLC15A1a (PepT1a) and SLC15A1b (PepT1b) transporters
Health-related outcomes of educational mismatch: evidence from the Russian Federation
No full textThis PhD Dissertation aims at contributing to the existing literature on health outcomes of educational mismatch and contains a set of studies which raise the question whether different types of educational mismatch affect objective and subjective measures of health and adverse health behaviors represented by drinking habits. The analysis is applied to the context a LMIC country - the Russian Federation - and conducted on the basis of the Russia Longitudinal Monitoring Survey (RLMS-HSE).
The first Chapter of this Dissertation investigates the impact of the vertical type of educational mismatch – overeducation and undereducation - on hypertension and self-reported health of the Russian labour force. The second Chapter considers the impact of overeducation and undereducation on the physical and psychological components of general health, proxied by pain and anxiety (EQ-5D metrics) and the health-related reporting styles of the Russian employees. Finally, the third Chapter investigates the impact of different types of educational mismatch - overeducation, undereducation and horizontal (field-of-study) mismatch - on alcohol use and alcohol consumption in Russia, along with defining potential channels for transmission of this effect by means of conducting a mediator analysis.
Overall, the results of the studies included in this Dissertation provide evidence that educational mismatch affects the health outcomes, health-related reporting styles and drinking behaviors of the Russian employees. However, the direction and the magnitude of these effects are gender-specific and vary with the types of educational mismatch considered
Statistical analysis of Dynamic Light Scattering data: from the Schätzel formulas to new approaches based on multi−tau Photon Counting Histogram and variance methods
No full textDynamic Light Scattering (DLS) is an optical technique aimed at the determination of the dimensions of small particles in a suspension in a range of diameters from about 1 nm to 1 μm. It consists in the measurement, at a fixed angle, of the scattered intensity radiation that, because of the Brownian motion of the particles, fluctuates stochastically with time. A DLS experiment provides the correlation function of the received intensity which is dependent from the coherence time of the fluctuations, that is related to the hydrodynamical radius of the particles that constitute the sample. In this thesis work, we analyzed the error bars associated to a correlation function and proposed a new approach for the analysis of Dynamic Light Scattering data based on multi-tau Photon Counting Histogram and variance methods. We obtained the following results and future perspectives.
Statistical analysis of Dynamic Light Scattering data
The first goal of this work consists in the analytical determination of the error bars associated to a correlation function. This problem has been analyzed by K. Schätzel in the 1990s. He provided two analytical expressions for the covariance matrix and the variance for the specific case of a Lorentzian spectrum where the correlation function is characterized by a single exponential decay. These formulas do not include the effects due to a triangular averaging and are consequently inaccurate for sampling times higher or similar than the coherence time. In this work, we analyzed these formulas and worked out two exact analytical expressions in which the effects due to the triangular averaging are corrected to all orders. By the use of extensive computer simulations and experimental test carried out on dilute dispersions of calibrated latex spheres, we have shown that the new formula for the variance works quite accurately for sampling times both higher and lower than the coherence time and can be applied well beyond the specific case of a single exponential decay auto-correlation function. We believe that these new covariance and variance formulas would turn out to be a fairly useful tool for the wide community of scientists working in the field of DLS. Nowadays, this technique is ubiquitously based on the use of multi-tau correlators, where, if not properly taken into account, the triangular averaging would introduce huge errors in the estimates of the uncertainties to be associated to the measured correlation function.
Photon Counting Histogram applied for the analysis of Dy- namic Light Scattering data
The second goal of this thesis work consists in the analysis of a second method for performing particle sizing. In this case the coherence time of the intensity fluctuations will not be recovered from a correlation, but from a series of histograms of the photon counts detected over different integration times. It represents, once normalized, the probability distribution to detect a discrete number of photon counts over a given sam- pling time. In my work we applied the Photon Counting Histogram (PCH) technique for the analysis of DLS data and we analyzed, for a monodisperse sample, the combined use of these two techniques and the advantages it gives with respect to a single one. This technique has been developed for the first time by E. Gratton for the analysis of fluorescent data. His theory works when the sampling time is much smaller than the coherence time. By using the PCH method for the analysis of DLS data, because of the raw data has been taken with the multi-tau method, we analyzed different histograms generated with different sampling times which are both higher and lower than the co- herence time. Moreover, we exploited an alternative method to perform particle sizing by recovering the hydrodynamical diameter by fitting not the histograms themselves, but the variances of the photon count distributions recovered stage by stage as a func- tion of the sampling time. We believe that both the PCH method and the variance analysis applied to DLS data may be useful because they provide a different technique to perform particle sizing, which can work independently from the auto- (or cross-) correlation functions. Both these three techniques can work in parallel and, if they provide the same result, it can be a further proof or cross-check for the correctness of the recovered hydrodynamical diameter of the considered sample
Universae Gothorum gentes Romano sese imperio dediderunt. Profili dei rapporti romano-gotici nel IV sec. d.C.
No full textThe paper analyzes the particularly problematic political, juridical-legislative and cultural situation of the period between 350 A.D. and 410 AD about, coinciding with the great migrations of the barbarian populations (especially the Gothic ones) within the borders of the Roman Empire and placing as a thematic and temporal center of gravity, the Foedus Gothicum of 382 A.D. In this context, the scientific target pursued is to identify and distinguish, if it’s possible, which legislative provisions and which literary works, produced in conjunction with the aforementioned migrations of peoples, were in causal, direct or indirect relationship, with the same relocations; which imperial constitutions were the expression of the legislative, pro-barbaric or anti-barbaric, policy of the imperial chancelleries (especially under Valente, Theodosius and his direct successors) and which coeval philosophical-literary works, on the other hand, showed the social and cultural perception of this situation and of the consequent imperial Gothic politics
Genetic abnormalities as diagnostic and prognostic markers in B cell lymphomas: role of new molecular technologies in personalized medicine for extranodal diffuse large B cell lymphoma (EN-DLBCL) and follicular lymphoma (FL)
Full text linkA plethora of molecular biomarkers are available nowadays in the field of cancer research. However, it is crucial to understand when and how they can be integrated into the clinical setting, translating experimental results from bench to bedside, with the aim of improving patients’ care.
We decided to investigate the role of some of these biomarkers in two subtypes of non-Hodgkin lymphoma which still represent a challenge for both researchers and clinicians.
We started from diffuse large B cell lymphomas (DLBCLs), investigating a multicentric series of primary extranodal DLBCLs. Overall, data analysis provided strong evidence that the distribution of immunophenotypic, cytogenetic and survival characteristics is site-dependent.
We next moved to follicular lymphoma (FL). The translocation (14;18), leading to BCL2 protein overexpression, is considered the genetic hallmark of FL. We tested the incidence of BCL2 negative FLs in a series of Italian patients from the Insubric region, concluding that BCL2 rearrangement in FL is not as frequent as generally reported and that the genetic landscape of FL is more complex than previously thought.
What we learned is that even within an individual clinical entity, there is considerable heterogeneity with respect to genetic alterations, expression of commonly assayed markers and, most important, outcome. The personalized approach acknowledges this complexity and gives us tools for the continuous improvement of patients’ care
Current perspective on the pathogenesis, predictive features and treatment of Graves’ disease
No full textGraves’ disease is the most common cause of hyperthyroidism in iodine-sufficient areas. Recognized that the ultimate cause of the disease is the production of autoantibodies directed to TSH-receptor, a great deal remains to be discovered on its pathogenesis. Nonetheless, due to the high risk of relapse, the identification of tailored treatment strategy, contemplating both the severity of the disease and the risk of relapse, is mandatory.
Answering these queries, we firstly performed an observational, longitudinal study, involving the University of Pavia, to evaluate the current clinical features of newly diagnosed Graves’ disease patients. An innovative score (Clinical Severity Score) to assess the overall disease severity was developed by grading each component of the Merseburg triad. The predictivity of this score for the risk of persistence/relapsing of the disease was studied. Meantime, comparing newly diagnosed Graves’ disease patients to controls we speculated on a possible role of micronutrients (selenium and vitamin D) into disease pathogenesis and severity. More into-depht approaches on the role of natural killer cells and regulatory T cells in the pathogenesis of the disease were then used. Finally, we developed a randomized clinical trial to test whether the association of the supplementation with vitamin D and selenium to the standard therapy with thionamide would provide a more efficient treatment strategy. The protocol has been regularly registered (EUDRACT number 2017-00505011) and approved by the local Ethical Committee and by Agenzia Italiana del Farmaco (AIFA)
Advances in Quantum Nonlinear Optics: a nonclassical journey from the optimization of silicon photomultipliers for Quantum Optics to quantum second-harmonic generation
Full text linkIn this thesis, we present our experimental and theoretical work on modern and old topics of Nonlinear Quantum Optics. The thesis is structured as follows.
In the first chapter, we provide a general introduction about the basis of this field, in particular about the main concepts and results that will be needed in the following.
In the second and third chapters, we explain our research on the role of silicon photomultipliers in Quantum Optics experiments. After a specific characterization of the sensors, we used them to detect nonclassical states of light. Different strategies for the estimation of experimental quantities are suggested.
In the fourth chapter, we propose our quantum description for the second-harmonic-generation process, based on well-known perturbative methods. After a general introduction on the state of the art, we immediately dive into the problem by explaining the employed methods and showing our analytical results.
Finally, we resume the essence of our achievements and draw our conclusions