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The last decades have witnessed the foundation and the ascent of a novel discipline that applies the innovation in nanotechnology and material sciences to medicine and biology: nanomedicine. The current trend in one of the major subfields of nanomedicine is the development of “theranostic” nanosystems, devices designed to be employed both for the diagnosis and the treatment of specific pathologies. Within the context of nanomedicine, this PhD thesis work addressed the clinical need for novel theranostic alternatives and proposed two different designs for hybrid organic-inorganic theranostic nanoplatforms. The first one is centred on superparamagnetic iron oxide nanoparticles (SPIONs) enclosed inside polymeric structures. This nanoplatform was conceived to deliver positive contrast in 1H-MRI and to act as a biocompatible and magnetically guided carrier for drug molecules; in perspective, the medical target will be the treatment of amyotrophic lateral sclerosis, a neurodegenerative disorder. This hybrid nanosystem comprises hydrophobic magnetic nanoparticles that were synthesized with a fast and reproducible method based on thermal decomposition of iron acetylacetonate, supported by microwave heating. These SPIONs were subsequently loaded inside polymeric micelles made by Pluronic F127 (a block copolymer of polyethylene oxide and polypropylene oxide) and polyvinyl alcohol (PVA) using an emulsion-solvent evaporation approach mediated by ultrasonication. The specific polymeric mixture was selected to induce the micellization of Pluronic F127 in a structure comprising a hydrophobic core for SPIONs and drug hosting and a hydrophilic shell for water dispersibility, which is further covered and stabilized externally by PVA. Along with the magnetic nanoparticles, two different types of hydrophobic drug molecules addressing the same pathological target were successfully included within the nanosystem: they were a commercial benzothiazole drug (riluzole) and a novel synthesized triazole-triazine derivative. Both the magnetic nanoparticles and the polymeric nanosystems were analysed exploiting (TEM) for the measurement of the inorganic core size and vibrating sample magnetometry (VSM) for the assessment of their magnetic properties. Moreover, the final nanosystem was studied with nanoparticle tracking analysis (NTA) and dynamic light scattering (DLS) to obtain the hydrodynamic diameters. Finally, thermogravimetric analysis (TGA) was employed to extrapolate the organic content of the nanosystems, while UV-Vis spectra were recorded to assess the drug loading. The second nanosystem addressed in this PhD thesis was devised to provide a nanoplatform intended for the diagnosis and treatment of glioblastoma. This system is based on gold nanoparticles passivated by PEGylated thiol ligands bearing a perfluoropolyether moiety. This unit has a twofold role: it provides a large number of quasi-equivalent fluorine nuclei, thus making the nanosystem a contrast agent for 19F-MRI and forms a fluorophobic layer within the nanoparticle monolayer for drug hosting and release. In this project, we proposed three different ligand structures, starting from two different fluorinated symmetrical moieties bearing hydroxyl or methyl esters groups. We outlined three synthetic strategies for linear and branched ligands, managing to complete the preparation of the linear ligand derived from methyl ester. The characterization of each step of the syntheses for the different structures was carried out by 1D (1H, 13C, 19F), 2D (COSY, HSQC, HMBC) NMR spectroscopy and mass spectroscopy to study their chemical structure and functionalities. Moreover, the gold nanoparticles prepared from one of the fluorinated ligands synthesized were studied with TEM and DLS to obtain respectively the core and the hydrodynamic diameters, with TGA for the organic composition and with NMR to confirm the ligand passivation and calculate the T1 and T2 relaxation times. The last decades have witnessed the foundation and the ascent of a novel discipline that applies the innovation in nanotechnology and material sciences to medicine and biology: nanomedicine. The current trend in one of the major subfields of nanomedicine is the development of “theranostic” nanosystems, devices designed to be employed both for the diagnosis and the treatment of specific pathologies. Within the context of nanomedicine, this PhD thesis work addressed the clinical need for novel theranostic alternatives and proposed two different designs for hybrid organic-inorganic theranostic nanoplatforms. The first one is centred on superparamagnetic iron oxide nanoparticles (SPIONs) enclosed inside polymeric structures. This nanoplatform was conceived to deliver positive contrast in 1H-MRI and to act as a biocompatible and magnetically guided carrier for drug molecules; in perspective, the medical target will be the treatment of amyotrophic lateral sclerosis, a neurodegenerative disorder. This hybrid nanosystem comprises hydrophobic magnetic nanoparticles that were synthesized with a fast and reproducible method based on thermal decomposition of iron acetylacetonate, supported by microwave heating. These SPIONs were subsequently loaded inside polymeric micelles made by Pluronic F127 (a block copolymer of polyethylene oxide and polypropylene oxide) and polyvinyl alcohol (PVA) using an emulsion-solvent evaporation approach mediated by ultrasonication. The specific polymeric mixture was selected to induce the micellization of Pluronic F127 in a structure comprising a hydrophobic core for SPIONs and drug hosting and a hydrophilic shell for water dispersibility, which is further covered and stabilized externally by PVA. Along with the magnetic nanoparticles, two different types of hydrophobic drug molecules addressing the same pathological target were successfully included within the nanosystem: they were a commercial benzothiazole drug (riluzole) and a novel synthesized triazole-triazine derivative. Both the magnetic nanoparticles and the polymeric nanosystems were analysed exploiting (TEM) for the measurement of the inorganic core size and vibrating sample magnetometry (VSM) for the assessment of their magnetic properties. Moreover, the final nanosystem was studied with nanoparticle tracking analysis (NTA) and dynamic light scattering (DLS) to obtain the hydrodynamic diameters. Finally, thermogravimetric analysis (TGA) was employed to extrapolate the organic content of the nanosystems, while UV-Vis spectra were recorded to assess the drug loading. The second nanosystem addressed in this PhD thesis was devised to provide a nanoplatform intended for the diagnosis and treatment of glioblastoma. This system is based on gold nanoparticles passivated by PEGylated thiol ligands bearing a perfluoropolyether moiety. This unit has a twofold role: it provides a large number of quasi-equivalent fluorine nuclei, thus making the nanosystem a contrast agent for 19F-MRI and forms a fluorophobic layer within the nanoparticle monolayer for drug hosting and release. In this project, we proposed three different ligand structures, starting from two different fluorinated symmetrical moieties bearing hydroxyl or methyl esters groups. We outlined three synthetic strategies for linear and branched ligands, managing to complete the preparation of the linear ligand derived from methyl ester. The characterization of each step of the syntheses for the different structures was carried out by 1D (1H, 13C, 19F), 2D (COSY, HSQC, HMBC) NMR spectroscopy and mass spectroscopy to study their chemical structure and functionalities. Moreover, the gold nanoparticles prepared from one of the fluorinated ligands synthesized were studied with TEM and DLS to obtain respectively the core and the hydrodynamic diameters, with TGA for the organic composition and with NMR to confirm the ligand passivation and calculate the T1 and T2 relaxation times.

The MS. Darmstadt, Universitäts- und Landesbibliothek, misc. gr. 2773 (14th century) preserves a short quotation from Nikephoros Blemmydes which has usually been taken as not genuine. In this paper, the source of the quotation is identified as coming from the Epitome physica, Chapter 17 concerning the doctrine of winds. The wind-rose that follows the quotation comes from the same chapter as well., Parekbolai. An Electronic Journal for Byzantine Literature, Vol 8 (2018)

AIM: The aim of this work was to validate the Italian version of GAI (GAI-It) and its short form (GAI-It SF) in an over 65-population. METHODS: In 3 recruitment areas across Italy, two raters reciprocally blind to results assessed eligible subjects; a semi-structured diagnostic clinical interview was performed by a psychiatrist. RESULTS: Among the 76 enrolled subjects (mean age 72.7±6.8 years), anxiety symptoms were very common: 69.7% (moderate/ severe HADS-Anxiety), 76.3% (moderate/severe STAI-state), 71.0% (moderate/severe STAI-trait), 61.8% (GAI), 55.3% (GAI-SF). Sensitivity, specificity and positive predictive value of GAI confirmed a good reliability of the Italian version, with Cronbach's Alpha equal to 0.93 for GAI-It and to 0.77 for GAI-It SF, indicating a very good and good construct validity, respectively, of the scales. The Pearson correlation index demonstrated a moderately positive correlation among GAI, GAI-SF and STAI. CONCLUSIONS: Our data confirm the validity of GAI-It as a valuable instrument to assess anxiety in an elderly population, for clinical and research purposes.

Corneal ectasia is a serious vision-threatening complication of laser in situ keratomileusis (LASIK). It is associated with progressive corneal steepening, an increase in myopia and astigmatism, and decrease in uncorrected visual acuity. Before LASIK presence of risk factors (corneal thickness, refractive error, presence of clinical and subclinical corneal pathologies) should be studied so patients should be risk-stratified. Forme fruste keratoconus or marginal pellucid degeneration should be investigated before LASIK in order to inform the patients of the possibility to develop a corneal complication. Management of post-LASIK ectasia enlists crosslinking, INTACTS, contact lenses and, in the most serious cases, lamellar keratoplasty and corneal transplantation. Crosslinking is a technique to treat and even prevent post-LASIK corneal ectasia. LASIK is a technique that reduces the corneal strength and stability. Crosslinking increases the number of collagen interfibrillar covalent bonds, using ultraviolet A and riboflavin. This result increases stability in corneal strength, reducing the risk to develop corneal ectasia (if performed simultaneously with LASIK) or it treats ectasia (if performed after LASIK keratectasia). How to cite this article Spadea L, Verboschi F, Valente S, Vingolo EM. Corneal Collagen Crosslinking for Keratectasia after Laser in situ Keratomileusis: A Review of the Literature. J Kerat Ect Cor Dis 2013;2(3):113-120.