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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
Ecological factors affecting the whale shark occurrence in Djibouti and presence of contaminants in the trophic web
No full textDjibouti is an important site where the whale shark (Rhincodon typus Smith 1828) regularly aggregates. Sharks gathering off the Djibouti coast are mostly juvenile males and target dense concentrations of zooplankton. However, only few studies has been carried out, leaving a knowledge gap on the main aspects of the whale shark ecology. Therefore, the main outcome of this study is to determine the environmental factors influencing the presence and distribution of this species in Djibouti. A robust understanding of the spatiotemporal distribution is required for developing successful management strategies for the whale shark protection in this area.
Moreover, whale sharks may be potentially exposed to relatively high levels of contaminants in Djibouti since they aggregate along one of the world busiest shipping route. Although the massive release of pollutants in African marine ecosystems and the deleterious effects on biota and humans, at present almost nothing is known about the contamination status of the Gulf of Aden, including Djibouti. The scarcity of studies includes all trophic levels, therefore, with a bottom-up approach, starting from zooplankton to get to predatory shark species, this study aims to characterize the trophic chain from an ecotoxicology point of view. With global decline in shark numbers, evaluating the extent of contaminant exposure is an urgent aspect since anthropogenic pollution may exasperate the current situation. Furthermore, since elasmobranchs are component of the artisanal fishery in Djibouti, and seafood consumption is as an important source of contamination for humans, this study aims to estimate for the first time the exposure health risks derived from shark consumption
Circulating cell-free DNA: a powerful biomarker for tumor management and a possible monitor tool in other pathological conditions.
No full text‘Liquid biopsy’, i.e. the analysis of cfDNA in blood or body fluids, can give a live, ‘total’ image representing the entire heterogeneity of the system.
The application of high throughput analytical procedures, such NGS or ddPCR, are necessary to obtain reliable data on such a small amount of starting material.
Only few applications have achieved a clinical validation, due to the great variability in preanalytical procedures.
In our work we evaluated cfDNA with three different aims.
• Presence of mutation in a panel of 16 genes of the HR pathway in genomic and cfDNA in patients affected by breast cancer. We observed mutations in 3 out of 6 samples; in one case variant fraction in cfDNA was higer than in genomic DNA, probably due to limited ability to detect clonal heterogeneity in tissue.
• Monitoring tool for determining septic risk in patients undergoing dialysis. We detected in a sample, in accordance with the emoculture, a Staphylococcus strain together with Propionibacterium and Streptococcus strains. The detection of Burkholderia multivorans in another sample raised the possibility to identify those bacteria that take more than the canonical 5 days of emoculture to growth, or that completely do not grow in emoculture conditions.
• Detection of donor-derived cfDNA in transplanted patients. We identified more than 50% of donor derived polymorphisms just after reperfusion, falling down to 10% one day after surgery and then disappearing.
The possibility to cross our data with clinical parameters will help us to better describe the pertinence of our results to the effective status of patients.
In all the three settings, we are collecting other samples to have a broader amount of data that will allow us to perform statistical analysis to effectively validate our procedures
Hyaluronan: a new player in the modulation of adaptive changes to neuromuscular damage in the gastrointestinal tract
No full textPathological 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
Synthesis and applications of chiral catalysts based on heterocyclic units
No full textThe present PhD Thesis was mainly focused on the synthesis and the applications of chiral catalysts based on heterocyclic units.
As an appendix of the manuscript, the work concerning my abroad period spent at the University of Glasgow is reported, whose research topic was the synthesis of benzoxazoles through a one-pot two-step procedure involving the use of first iron(III) and copper(I) catalysis for the second step. The fields of catalysis investigated are the Lewis Base, the Brønsted acid catalysis and finally the catalysis promoted by phosphoramidites.
As a contribution for the stereoselective Lewis Base catalysis, the synthesis and the resolution of TetraPh-Tol-BITIOPO (Chapter 1, 37) was carried out, whose application can be considered a further investigation of the huge potentialities of the 3,3’-bithiophenic enantiopure TetraMe-BITIOPO in Lewis-base catalysed Lewis-acid mediated reactions.
For what concern Brønsted acid catalysis, a new chiral phosphoric acid based on a decahydroquinoxalinic scaffold bearing in the position 2 and 3 two thienylic units (Chapter 2, 19) was synthesized and tested in two preliminary stereoselective organocatalytic transformations. Based on the same decahydroquinoxalinic backbone, we decided to design a new heterocyclic- based diphosphinoxide (Chapter 2, 42).
In Chapter 3, a new heterocyclic phosphoramidite based on a 3,3’-bithiophenic scaffold (L6) was synthesized and employed in combination with a copper salt in some catalytic stereoselective 1,4- additions of diethyl zinc to enones and trisubstituted nitroalkenes
Advances in Quantum Nonlinear Optics: a nonclassical journey from the optimization of silicon photomultipliers for Quantum Optics to quantum second-harmonic generation
No full textIn 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
Cryoablation of para-Hisian and mid-septal accessory pathways: long-term outcome of a specific cryoablation protocol
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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)
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