Role of saliva, gingival crevicular fluid and oral microbiota in gastrointestinal diseases

The aim of this dissertation was the evaluation of the role of saliva, gingival crevicular fluid and oral microbiota in two gastrointestinal conditions: colorectal cancer and Helicobacter pylori gastritis. In the first study two specific sub-gingival bacteria, Fusobacterium nucleatum and Porphyromonas gingivalis, pathogens typical of periodontal disease, were analysed in order to detect possible correlations with the tumoral changes leading to colorectal cancer development. In particular, Fusobacterium nucleatum load was found different on the intestinal mucosa of patients with a diagnosis of colorectal cancer and adenoma, compared to the healty control group; on the other hand Phorpyromonas gingivalis, although non directly related with carcinogenesis, might promote the development of the first bacterium. In the second study the relatioship between the presence of Helicobacter pylori in the stomach and in the oral cavity of patients with and without gastric infection was evaluated. Data suggested that periodontal pockets could represent a favourable enviroment where the microrganism is able to replicate, slipping away from human immune system surveillance, and spread within saliva, reaching the stomach during swallowing and possibly contributing to gastric disease recrudescence. In the end, a total number of 212 patients were recruited in this experimental work and each study contributed to better understand the relevant role of oral microbiota in gastrointestinal diseases and the importance of a proper oral hygene mantainance in order to reduce the risk of developing dangerous extra-oral illnesses

Il corpo e l’immaginario politico nella società contemporanea

Thought, word, hermeneutics and imaginary - understood as a social product suspended between the spiritual/virtual and real/material dimensions - which we categorize as "performative saying", construct, influence and modify in the individual, social and therefore political sense, the life of bodies. There are different concepts of corporeity, because each society has its own performative saying, and what unites the performative saying of each society is precisely what binds it to the body, and the power of the performative saying lies in its imaginative dimension that produces real effect, effects that act on the body intended as the foundation of politics. Considering that all social, economic, legal etc. practices are deeply influenced by the imaginary and performative saying that a society has about human body, the political meaning that this concept has in itself becomes clear: the scientific performative saying, the religious performative saying or the tribal one, ecc., determine the structures and the political organization of a society, in a continuous relationship of co-construction with the imaginary. Influencing and influenced by the complex network of relationships built through performative saying, the body is now more than ever a political saying itself, expression of the imaginary and therefore it is the field of experimentation and continuous changes

Atrofia Muscolare Spinale: presentazione clinica, quadri radiologici, nuovi trattamenti e biomarcatori

Spinal Muscular Atrophy is an autosomal recessive disorder affecting 1:100,000 live births, in which survival motor neuron (SMN) protein deficiency leads to motor neuron degeneration and progressive muscle atrophy, weakness,and early mortality. Most of SMA patients harbor homozygous SMN1 deletions while SMN2 copy number predicts the clinical subtype (SMA-I, -II, -III-IV). Few (3-5%) SMA patients display small mutations point mutations on the second allele. The behavior of point mutations in SMN1/SMN2 is heterogenous and requires proper validation. In recent years the discovery of effective therapies has marked the history of Spinal Muscular Atrophy(SMA). The only currently approved drug is Nusinersen, which is an antisense oligonucleotide that binds to the SMN2 pre-mRNA downstream of exon 7,leading to the translation of a fully functional SMN protein. The treatment has opened up a new scenario with the creation of a new phenotypic spectrum. We have studied prospectively patients treated with nusinersen, by planning serial evaluations : neurological exam, muscle strength (MRC), motor functional scales, timed tests, muscle MRI, CMAP and MUNE. Monitoring long-term outcome measures will allow us to characterize the new phenotypes of the disease and to define the efficacy spectrum of Nusinersen in patients with different ages and degrees of motor impairment. Neurofilament chains (Nf) are sensitive, liquor-based marker that can identify patients with neurodegenerative diseases, aid in the prediction of their long-term outcomes, and be used for assessing effects of treatment. At present, little is known about serum Nf levels in patients with SMA. To that purpose, we have measured the levels of Nf during the treatment with Nusinersen

Inibitori PCSK-9 e infiammazione in pazienti ad alto richio cardiovascolare

Inibitori 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

Correlazione tra markers infiammatori e trattamento con antipsicotici atipici in pazienti affetti da disturbo bipolare

The main aim of this study was to give evidences that the drugs used in the treatment of BD patients can have anti-inflammatory properties. We have longitudinally investigated in 50 BD patients the clinical outcome during six week of treatment and the effects of the drug on inflammatory markers such as CRP and ERS. In addition, in 15 patients, on the basis of the recent data of literature showing a typical anti-inflammatory pattern of quetiapine, we have additionally investigated their ability to affects plasma levels of inflammatory cytokines. A cohort of 50 BD patients were consecutively enrolled at the psychiatric unit of the Cantonal Clinic (Ticino, CH). All patients were visited three times: at each visit, all the subjects were evaluated both for clinical conditions by using clinical psychopathological scales and for biochemical parameters with complete blood formula and PRC and ERS levels. In the subgroup of 15 patients enrolled from October 2017 to May 2018 (same inclusion and exclusion criteria), we have additionally evaluated plasma levels of IL-6 and IFN-γ, and IL-10. We found a significant reduction only for CRP. In the group of 15 patients, the levels of IL-6 were dramatically reduced at all visit time and reached the statistical values for the Δ T2-T0. A direct correlation was found between clinical response and CRP plasma levels after 6 weeks of treatment. The main finding of the present study is that, antipsychotic drugs, in addition to the ability to improve clinical outcome in BP patients, are also able to profoundly affect inflammatory markers

Development of nanostructured supported photocatalysts for hydrogen production and inorganic pollutants removal

Semiconductor photocatalysis has emerged as one of the most promising approach to exploit a renewable energy source (i.e. sunlight irradiation) for several environmental purposes such as the production of clean energy (e.g. photocatalytic H2 evolution), the removal of organic and inorganic pollutants in natural water, purification of air and antibacterial activity. In view of these recent trends, the focus of this thesis was directed towards the study of different supported photo(electro)catalytic materials for topical environmental applications: i) Photocatalytic hydrogen gas evolution from aqueous solutions under UV light irradiation (365 nm) over highly ordered TiO2 nanotubes decorated through a sputtering/dewetting approach with a well-defined stacked co-catalyst (a WO3 layer decorated with Pt NPs); ii) Photocatalytic hydrogen gas evolution from aqueous solutions under UV light irradiation (365 nm) over highly ordered TiO2 nanotubes decorated through a sputtering/dewetting approach with dewetted-alloyed NiCu nanoparticles; iii) Photocatalytic reduction/scavenging of inorganic mercury (Hg(II)) from water under solar light irradiation over templated-dewetted Au on TiO2 nanotubes; iv) Photoelectrocatalytic oxidation/abatement of inorganic arsenic (As(III)) over hematite-based photoanodes under solar light irradiation. After a general introduction about photocatalytic processes and materials, each chapter of this dissertation contains the outcomes of the above listed studies

Essays on multidimensional poverty measurement and the dependence among well-being dimensions

Evaluating the welfare of nations is high on the research agenda of the economists, practitioners and policy-makers. The literature contributions of the last decades triggered a multivariate perception of the well-being, which is suggested to go beyond the GDP, and created a need for more complex approaches to evaluate the welfare as well as poverty. The first essay investigates the approaches to multivariate poverty measurement and focuses on the composite index approach and the steps involved in it. An important aspect of the multivariate perspective in well-being is the dependence among the underlying indicators. There is a growing evidence in the literature that well-being dimensions are interrelated. This dependence among attributes matters for multidimensional poverty measurement, since income is no longer the only indicator to be considered. However, the reviewed approaches to multivariate poverty measurement do not commonly capture this interdependence. The second essay suggests a copula function as a flexible tool to estimate the dependence among welfare variables. Moreover, it proposes to incorporate the evaluated dependence in the composite indicator. The trade-off among attributes, which is established via the weighting of dimensions, is identified as a possible channel to include the interdependence in the composite indicator. The third essay of this dissertation defines bivariate and multivariate copula-based measures of dependence and applies them using the recent data from the EU-SILC. The results suggest that key dimensions of well-being, i.e. income, education and health, are positively interdependent. In addition, the strength of pairwise and multivariate dependence reinforced in the post-crises period in some European countries. Finally, the last essay proposes a new class of the copula-based multidimensional poverty indices by innovating over the weighting approach. The weighting scheme proposed in this dissertation incorporates the estimated copula-based dependence and contains necessary normative controls to be chosen by the practitioner. The findings of the last essay suggest that the overall poverty is driven not only by the individual shortfalls, but also I by the degree of interdependence among well-being indicators. Considering the proposed copula-based weighting scheme and the proposal of the new class of copula-based poverty indices, this dissertation contributes to the multivariate poverty measurement by suggesting the channel to enclose the dependence structure in the composite indicators. The proposed copula-based methodology will advance the multidimensional poverty analysis and the poverty-reducing policy, which can be designed to address the problem of interdependence of individual achievements

Fluids at interfaces: Casimir effect, depletion and thermo-osmosis.

The critical Casimir effect is the long-range interaction between two planar walls in a critical fluid due to the confinement, achieved by the wall interfaces, of the critical density fluctuations. In this Thesis we provide a microscopic description of the critical Casimir force, introducing a novel density functional approximation coupled to the hierarchical reference theory of fluids. The depletion interaction is an effective attractive force arising between colloidal particles immersed in a solvent: The first prediction of this effect dates back to the seminal work by Asakura and Oosawa and has been obtained assuming that the colloidal particles were perfectly smooth spheres immersed in an ideal gas. In this Thesis we address the study of the interaction potential mediated by an ideal gas between two rough colloidal particles, as a function of the geometry, the dimension and the spatial configuration of the corrugations. When a thermal gradient is applied to a fluid at contact with a surface a stationary flow develops. This effect, referred to as thermo-osmosis, has been discovered in the late nineteenth century but successful theoretical descriptions have been up to now devised only when the fluid is a rarefied gas. In this thesis we presents a microscopic theory of thermo-osmosis based on a generalisation of linear response theory to inhomogeneous and anisotropic environments and to thermal disturbances

CDKL5 and neuronal morphological defects: novel perspectives of microtubule related drugs

Mutations in the CDKL5 gene have been found in individuals with a rare neurodevelopmental disorder. CDKL5 is a serine/threonine kinase whose functions are still not fully understood. An aberrant neuronal morphology linked to Cdkl5 has been observed both in Cdkl5--‐silenced primary neurons as well as in Cdkl5--‐null brains strongly suggesting that these defects may underlie the cognitive impairment characterizing both patients and mice devoid of the kinase. The molecular basis of these defects is still far from understood but altered cytoskeletal dynamics are likely to be involved. The identification of IQGAP1 as novel CDKL5 interactor may provide a key to understand such neuronal defects. IQGAP1 promotes microtubule dynamics through its association with Rac1 and CLIP--‐170, whose activity on MTs might play a significant role in the regulation of cytoskeletal dynamics in cycling cells and neurons. Considering how the loss of CDKL5 negatively impacts on cellular and neuronal morphology, we envisaged that this kinase could regulate cytoskeletal dynamics acting directly or indirectly on CLIP--‐170. Indeed, CLIP--‐170 is known to regulate several aspects of neuronal morphology such as axon outgrowth, dendritic arborization and growth cone organization. By bridging the actin cytoskeleton to MTs, CLIP--‐170 coordinates proper cytoskeletal dynamics. In the current study, we analysed the role of CDKL5 in the regulation of CLIP--‐170 activity. Through a FRET analysis on COS7 cells we demonstrated that the loss of CDKL5 causes CLIP--‐170 to be mainly in its closed inactive conformation, thus reducing its interaction with MTs. Furthermore, using Cdkl5--‐ KO primary hippocampal neurons we demonstrated that the loss of CDKL5 is detrimental for the correct progression of several steps of neuronal maturation. Moreover, we demonstrated that such defects can be restored upon treatment with pregnenolone (a neurosteroid which stabilizes the extended conformation of CLIP--‐170, increasing its affinity for MTs and promoting their polymerization) and Pregnenolone--‐Methyl--‐Ether, a synthetic non--‐metabolizable P5 derivative. We speculate that the positive effects of the two compounds are likely to be due to an activation of CLIP--‐ 170 functionality and a concomitant increase in MT dynamics

Integrated multidisciplinary approaches to investigate geochemical anomalies in waters.

Water is a fundamental need for human and environmental benefits, and its inorganic quality is a mandatory standard. Potentially Toxic Elements (PTEs), due to their high toxicity need to be evaluated. Consequently, in case of possibly alarming concentration, the causes (natural or anthropogenic) need to be clarified, to evaluate possible remediation techniques. Integrated multidisciplinary approaches are needed to clearly understand causes of anomalous PTEs concentrations in waters, coupling chemical, hydrogeological and statistical tools, especially in a dynamic comportment as water. In this dissertation integrated approaches will be applied to understand sources of anomalous concentrations of PTEs in waters. Firstly, PTEs sources in an alpine catchment are evaluated through the application multivariate statistics and the analysis of water and sediment to evaluate the natural load of PTEs. Also, hydrogeochemical anomalies caused by a seismic sequence in Central Italy are explained through the application of a temporal trend analysis of hydrogeochemical and seismic variables. In this way, a conceptual model of PTEs release after the shocks is proposed. The collection of these case studies highlights the need of a complete, integrated, and multidisciplinary approach to deal with geochemical data. These approaches still require a good knowledge of lithology and a big data set of chemical variables, but could fit as a first step to create leaching and transport models