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Inibitori PCSK-9 e infiammazione in pazienti ad alto richio cardiovascolare
Full text linkInibitori PCSK-9 e infiammazione in pazienti ad alto rischio cardiovascolare Inflammation plays an important role in atherosclerosis both in the early stage and in its progression.
PCSK-9 is a newly discovered serine protease playing a key role in destroying LDL receptors in liver and thereby controlling the level of LDL in plasma. New monoclonal antibodies capable of binding to PCSK 9 and blocking their interaction with hepatic receptors for LDL were therefore developed.
NETs are one of the most recent inflammatory markers used for atherosclerotic vasal damage.
The aim of this study is to evaluate the inflammatory response of dyslipidemic patients at high nontarget cardiovascular risk which have been treated with PCSK9 inhibitors in association with statin and compared it to the inflammatory response of a group of patients treated with statin therapy only.
The data of our research is taken from a group of 19 patients with high-risk cardio-vascular dyslipidemia. Among these, 13 patients had non-target LDL levels with the highest tolerated statin dose and were treated with statin and PCSK9; while 6 patients had target LDL values with statin
therapy alone.
Anthropometric measurements such as blood chemistry tests, quantification of NETs formation in neutrophil and its correlation with the elastase release and detecting of some cytokines (IL8 IL10 IL17 IL-1beta and TNFalfa) were determined in all patients.
In conclusion in patients already treated with maximal statin doses, it seems that the addition of PCSK9i did not affect the ability of neutrophils to release NETs nor the trend over time of the inflammatory cytokines evaluated. We assume that the inflammatory pattern may have already been intensively modified by statin therapy at high dosages
Towards circular economy in developing cities: an integrated approach for planning international cooperation projects
Full text linkSolid waste management (SWM) issues are an environmental and social burden, which affect mainly the population of low-middle income countries worldwide, as well as the global environment. The application of the circular economy (CE) principles (reuse of waste materials) is considered the main solution spreading the economy of the waste and therefore reducing environmental impacts.
This research is focused on the analysis and application of integrated approaches for planning sustainable SWM systems in developing big cities, demonstrating the importance of the inclusion of the informal recycling and drafting international cooperation projects for introducing new appropriate technologies and awareness campaigns. The case study of this research is La Paz (Bolivia), low-middle income city where international support is required for the sustainable development.
The results allow suggesting that the inclusion of informal recyclers can be considered the most useful option in terms of technical and financial issues, exploiting a CE system just in place. Moreover, the cooperation with local and international stakeholders allows writing and submitting two international cooperation projects.
The research demonstrates that the cooperation among various international and local actors, such as Universities, non-governmental organizations and local Government, in parallel with the use of technical knowledge and methodologies can support the sustainable development in low-middle countries, driving low-middle income cities towards the CE
Research on a bright light source: optics, technology and effects on humans
No full textThere are countless reasons why the Sun is essential: one of these is daylight. This light, that comprises both the component diffused by the atmosphere and the transmitted one, is the reference for a naturally lit scene, also being the main synchronizer of our circadian rhythms.
I carried out my research in the framework of two European projects (COELUX and SKYCOAT), coordinated by the University of Insubria, which were related to the reconstruction of natural light indoors.
In such a context, in collaboration with the consortium partners but mainly with the spin off CoeLux Srl, my research dealt with the bright light source used to artificially recreate the sun, regarding the optical design, the technological implementation and the effects produced on humans.
The approach is interdisciplinary, involving different branches of science as well as technology, psychology and business perspectives. These aspects were analyzed, insofar as relevant, in order to design, optimize, and realize the prototypes.
The actions that were carried out and are reported in this work comprise: the definition of the requirements for creating a valid light source, a review of the state of the art related to the areas of interest, the development of a solution meeting all the requirements and the characterization and testing of the prototypes.
The LED-based light projector that includes the results of this work perfectly suits the CoeLux technology and is a cornerstone in the study of effects on humans
Role of RNASET2 in innate immune response regulation
No full textNumerous studies have highlighted the existence of enzymes that, besides presenting a conserved role, take part in different biological processes acquiring new functions. In particular, the T2 RNase family of enzymes is one of the most investigated group, which is involved not only in RNA regulation, but also performs additional functions, regardless of the catalytic activity. It has been recently observed that, through the continuous cross-talk between the cancer cells and the adjacent microenvironment and the activation of inflammatory response by inducing macrophages activation, the human protein RNASET2 is able to control the ovarian cancer malignancy. However, the details about the mechanisms by which T2 enzymes interact with immune system remain poorly defined. The medicinal leech Hirudo verbana is here proposed as a consolidated invertebrate model to shed light on these aspects. The results presented in this project reveal that both human and leech T2 RNases cause fibroplasia, connective tissue remodeling and macrophage recruitment in leeches. Moreover, in vivo and in vitro experiments proved that HvRNASET2, released by granulocytes after bacterial infection, is a candidate molecule for counteracting pathogens. In particular, it plays a dual role, inducing bacterial clustering to facilitate macrophage phagocytosis and promoting immunocompetent cells recognition. In conclusion, HvRNASET2 acts as an effector of innate immune response, to favore an efficient microbial pathogen elimination and an effective oncosuppressive activity. These studies, related to roles of T2 RNases in tissue remodeling, immune response modulation and antimicrobial activity, could be essential for developing new therapeutic application
Unravelling the physiopathological role of sacsin, the protein mutated in the autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS).
No full textSacsin is a large, multimodular protein encoded by the SACS gene and found only in vertebrates. It is expressed in the central nervous system, especially in Purkinje cells and corticospinal neurons. Bioinformatics’ predictions suggest that sacsin plays a role in protein quality control. However, to date sacsin physiological functions and subcellular localization are still open questions.
Loss of function mutations in SACS gene cause Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS), an early-onset neurodegenerative disorder. Being sacsin function still unknown, the molecular pathogenesis leading to ARSACS has very poorly been investigated. My thesis is focused on exploring sacsin physiopathological role at the cellular level and on dissecting the pathogenesis of ARSACS.
First, we examined how sacsin mutations alter the residual amount of the protein in ARSACS patient cells, since until now it has never been evaluated, leaving a hole in the genotypephenotype correlation in ARSACS.
At the same time, we investigated the effects of the lack of sacsin in different models depleted of its expression (ARSACS patient fibroblasts, SACS KO HeLa cells, Sacs KO mouse embryonic fibroblasts, and primary Purkinje neurons from the Sacs KO mouse model). We found alterations in mitochondrial dynamics, namely mitochondrial hyperfusion and, by dissecting the molecular mechanism, we demonstrated that the mitochondrial fission process was indeed impaired. In line with these results, we showed that mitochondrial hyperfusion has a strong impact on mitochondrial trafficking in primary Purkinje cells that lack sacsin expression. This highlights the importance of this phenotype in the pathogenesis of ARSACS, as Purkinje neurons are the first cells to be affected.
In sacsin-depleted cells, we detected a dramatic remodelling of the cytoskeletal network, particularly of intermediate filaments. Our data supports the hypothesis that sacsin may be involved in intermediate filament remodelling in an indirect manner, such as by regulating their folding. This is also suggested by the predicted chaperone-like activities of certain sacsin domains. An intermediate filament reorganization and/or accumulation could sterically hinder both transport and distribution of mitochondria in Purkinje neurons of Sacs KO mouse. On the other hand, cytoskeletal derangement could be responsible for impairing DRP1 recruitment.
The cellular phenotypes that we have identified in the absence of sacsin are steps forward in understanding the pathogenetic cascade of ARSACS and shed light on potential sacsin functions
Migration and innovation: An analysis based on patent data. Migration et innovation : Une analyse basée sur des données de brevet.
No full textThis thesis investigates the migration of inventors by studying their contribution to the innovation at both destination and in their home country, after controlling for individual characteristics such as gender, education, experience, company mobility and others. In addition, we decompose the flows of migrants by entry channel in the destination country, such as the education channel, the multinational channel or when the inventors change of company and investigate the selection of migrants and the productivity gap between natives and migrants. Also, in the analysis, we decompose the cohort of entry in the destination country to compare the productivity differences among migrants themselves. Finally, we study whether return migrants are more productive than their non-migrants’ colleagues in origin countries, as a function of their experiences abroad. Cette thèse a pour but d’analyser la migration des inventeurs en étudiant leur contribution à l’innovation de leur pays de destination ainsi que leur pays d’origine, en contrôlant par leurs caractéristiques individuelles telles que leur genre, éducation, expérience, mobilité interentreprise et d’autres. De plus, nous décomposons les flux de migrants par canaux d’entrer dans le pays de destination, tel que le canal de l’éducation, multinational ou si l’inventeur change d’entreprise, et analysons la sélection des migrants et le gap de productivité entre les natifs et les migrants. Aussi, dans cette analyse, nous décomposons les cohortes d’entrées dans le pays de destination en comparant la productivité entre les migrants eux-mêmes. Finalement, nous étudions si les migrants de retour sont plus productifs que leurs collègues non migrants dans leur pays d’origine en fonction de leur expérience acquise à l’étranger
Monitoring air pollution effects on sleep-disordered breathing in children for supporting Public Health Policy
No full textThe so called “Sleep Disordered Breathing” (SDB) are breathing disorders which appear while the baby is sleeping. They rappresent a variety of pathologics mainly characterized by an airways change with snooring and/or a breathing effort caused by an increased resistance of the high airways and pharingeal collapse. Ethipatogenetic has been mainly understood and there are some risk factors like adenotonsillar hypertrophy, obesity and cranium-facial anomalies. There are also some other factors which can determine pathology like e.g. enviromental and genetic factors.
In literature there are some studies that show how environmental pollution (outdoor and indoor) represents the main cause of SDB in a child.
The aim of this ecological study is to analize the geografical distribution of SDB in the italian province of Varese, by using the data collected in the Pediatrics.
In order to put in evidence the possible associations between SDB and the enriromental pollution, we have compared these results with NO2 distribution spatial scheme.
NO2 can be considered the most important marker of enviromental pollution because it is the main component of gas emission and it’s correlated with other combustion products.
Data were collected from 2010–2014 and focused on children who resided in Varese, were over 1 year of age, with SDB.
The total number of children analyzed was 754: 476 males (63,13%) and 278 females (36,87%). Snooring occurs in 284 cases ((37,67%), mild OSAS in 259 (34,35%), moderate OSAS in 150 (19,89%) and severe OSAS in 61 (8,09%).
For each patient, we gathered information about the child’s municipality of residence, sex, and the value of the apnea-hypopnea index (AHI). AHI is based on polysomnographic recordings conducted overnight by means of Embla’s Embletta Gold sleep system, a recording system that can discriminate the SDB severity level. All of the children were diagnosed with respect to SDB based on their AHI index.
AHI mean is 3,48, value that doesn’t differ from the AHI in F and M (3,58 vs 3,42)
With the available data was made a map representing the geography of the SDB.
The results reported have to be considered preliminary and exploratory note abouve.
The positive association we observed between SDB in children and the fact that they were living in an area characterized by a high density of traffic-related pollutants should be more carefully examined, as airway inflammation is a potential mechanism connected with the effect of air pollution and SDB exacerbations—such effect can be due to the oxidative stress related to the incomplete combustion of fossil fuels that produces high levels of polyaromatic hydrocarbons.
Further research is necessary to clarify the role of air pollutants on SDB and on respiratory diseases in children. This additional work would allow the wider acquisition of knowledge about potentially modifiable contributors to the risk of developing SDB during childhood, which could then be the basis for improving children’s pulmonary health
Proteomics and network analysis identify common and specific pathways of neurodegeneration
Full text linkNeurodegenerative disorders, such as Parkinson's disease (PD), Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS) are multi-factorial in nature, involving several genetic mutations (in coding or regulatory regions) and epigenetic and environmental factors. The main clinical manifestation (movement disorders, cognitive impairment and/or psychiatric disturbances) depends on the neuron population being primarily affected. Complex and multifactorial neurodegenerative diseases can be investigated using a holistic approach that can give a global view about the pathogenetic process and shed light on specific and generic pathways of neurodegeneration. Proteomics offers a global molecular snapshot of proteins and consequently of processes that may influence neuronal death. The proteome in fact provides a dynamic view of what is happening in the system under investigation, because the expression of proteins, their abundance, their localization in tissues or cells, the type and amount of their post-translational changes depend from the environment and from the cellular physiological state. Therefore, all the projects presented in this thesis, by combining bioinformatics tools with proteomics, aimed at highlighting biochemical processes shared by different neurodegenerative diseases and diseasespecific pathways, which may justify the degeneration of dopaminergic neurons in PD. Finally, a focus on the mitochondrial interactome and proteome intended to elucidate important specific steps of the degenerative process in PD
Sustainability in passenger transport: the relevance of punctuality in rail and modal choice in commuting
Full text linkThe overall purpose of this PhD research is the analysis of the sustainable passenger mobility, both on long and short-distance trips. Mobility plays a central role in the social system and it is a key driving force for socio-economic, global and local development, but it produces also negative externalities on the territory. The thesis has the aim to explain the main elements of sustainable mobility from a theoretical point of view and, successively, to apply these concepts to two empirical cases with the use of Italian real data. These empirical analyses can help in underling the importance of sustainable mobility and of the efforts to improve it, influencing the transport modal choices of the commuter journeys. The first case regards the most sustainable mode of transport for medium-long distance trips, the train, and particularly the problem of delay that strongly affects the performance of the train, influencing the modal choices of commuters. The analysis is based on data collected in the period 2013-2016 on the railway line from Milano to Genoa. The second case concerns medium-short trips, focusing on the issue of home-work commuting of a medium Italian university located in two different cities (Varese and Como) in the north of Italy. The data come from a survey performed in November 2017. Finally, the last chapter draws some conclusions and mentions some upcoming evolutions of mobility that could give a strong contribution in achieving sustainability
A comprehensive multi-scale modeling of defective CdSe colloidal nanocrystals through advanced X-ray scattering techniques
Full text linkThe dissertation includes a comprehensive multi-scale modeling of defective CdSe colloidal nanocrystals through advanced X-ray scattering techniques.
Chapter 1 introduces the reader to the entire work of the Ph. D. thesis and to its main topic of research, which is focused on structural and microstructural characterization of colloidal quantum-dots. The following Chapter is dedicated to the description of conventional and unconventional characterization methods at the nanoscale, discussing their limits and potentiality in characterizing real nano-systems. Chapter 3 serves as a mathematical description of the DSE, and its implementation in the DebUsSy suite for the characterization of real ensembles of nanosized samples. Therein, the data collection and reduction procedures are also reported, together with a brief section in which the DSE to PDF approaches are compared. The need of introducing strains and defects in the complex atomistic model of CdSe nanocrystals makes it necessary to describe these defects, with a brief state of the art of their characterization methods (Chapter 4). Chapter 5 is completely dedicated to describing the computational model used for the characterization of cQDs and its use as a part of the overall data analysis strategy. The final Chapters focus on the application of the model to real systems in which its potentiality and sensitivity are tested on different materials, disclosing new size-dependent fault driven relaxation and faceting features in CdSe cQDs. An additional section presents an alternative method for the characterization of metallic NPs with larger sizes, but (much) lower stacking fault probabilities