"OSSERVATORIO NAZIONALE SULLA SPERIMENTAZIONE CLINICA E REGISTRO DEGLI STUDI OSSERVAZIONALI-AIFA:PROMOZIONE E SUPPORTO NELLE ATTIVITA' DEL COMITATO ETICO PER LA SPERIMENTAZIONE CLINICA DELL' AZIENDA USL 6 DI LIVORNO. PERIODO APRILE 2010- GIUGNO 2013.

Il presente lavoro di tesi si propone di effettuare una revisione completa delle attività del Comitato Etico per la Sperimentazione Clinica dei Farmaci dell’Azienda USL 6 di Livorno, nel percorso di valutazione, approvazione ed avvio di una sperimentazione clinica nel periodo di mandato compreso tra aprile 2010 e giugno 2013

Operability timescale of defect-engineered graphene

Defects in the lattice are of primal importance to tune graphene chemical, thermal and electronic properties. Electron-beam irradiation is an easy method to induce defects in graphene following pre-designed patterns, but no systematic study of the time evolution of the resulting defects is available. In this paper, the change over time of defected sites created in graphene with low-energy ($\leq 20$ keV) electron irradiation is studied both experimentally via micro-Raman spectroscopy for a period of $6\times 10^3$ hours and through molecular dynamics simulations. During the first 10 h, the structural defects are stable at the highest density value. Subsequently, the crystal partially reconstructs, eventually reaching a stable, less defected condition after more than one month. The simulations allow the rationalization of the processes at the atomic level and confirm that the irradiation induces composite clusters of defects of different nature rather than well-defined nanoholes as in the case of high-energy electrons. The presented results identify the timescale of the defects stability, thus establishing the operability timespan of engineerable defect-rich graphene devices with applications in nanoelectronics. Moreover, long-lasting chemical reactivity of the defective graphene is pointed out. This property can be exploited to functionalize graphene for sensing and energy storage applications.Comment: 21 pages, 5 figure

Synthesis of hexafluorovaline-containing di- and tripeptides

A new strategy for the synthesis of peptides incorporating racemic hexafluorovaline (hfVal) is presented. The synthetic pathway relies on the anti-Michael addition of benzyl amine derivatives to ad hoc prepared β-bis-trifluoromethyl-acryloyl-α-amino esters which proceeds in mild condition, high yields, even if with low stereocontrol. The following elaboration of the intermediates, namely deprotection of the benzyl moiety and coupling with α-amino esters allowed us to synthetize the targeted tripeptides in four overall synthetic steps, resulting in a synthetic pathway more favorable respect to those appeared in literature based on the synthesis and isolation of racemic Boc-hfVal-OH (eight synthetic steps)

Dual Antibiotic Approach: Synthesis and Antibacterial Activity of Antibiotic–Antimicrobial Peptide Conjugates

In recent years, bacterial resistance to conventional antibiotics has become a major concern in the medical field. The global misuse of antibiotics in clinics, personal use, and agriculture has accelerated this resistance, making infections increasingly difficult to treat and rendering new antibiotics ineffective more quickly. Finding new antibiotics is challenging due to the complexity of bacterial mechanisms, high costs and low financial incentives for the development of new molecular scaffolds, and stringent regulatory requirements. Additionally, innovation has slowed, with many new antibiotics being modifications of existing drugs rather than entirely new classes. Antimicrobial peptides (AMPs) are a valid alternative to small-molecule antibiotics offering several advantages, including broad-spectrum activity and a lower likelihood of inducing resistance due to their multifaceted mechanisms of action. However, AMPs face challenges such as stability issues in physiological conditions, potential toxicity to human cells, high production costs, and difficulties in large-scale manufacturing. A reliable strategy to overcome the drawbacks associated with the use of small-molecule antibiotics and AMPs is combination therapy, namely the simultaneous co-administration of two or more antibiotics or the synthesis of covalently linked conjugates. This review aims to provide a comprehensive overview of the literature on the development of antibiotic–AMP conjugates, with a particular emphasis on critically analyzing the design and synthetic strategies employed in their creation. In addition to the synthesis, the review will also explore the reported antibacterial activity of these conjugates and, where available, examine any data concerning their cytotoxicit

Load bearing capability of three-units 4Y-TZP monolithic fixed dental prostheses: An innovative model for reliable testing

In this work, three-units monolithic fixed dental prostheses (FDPs) have been analysed and a novel model for reliable testing has been proposed. Such model is based on a new design of the polymeric base of the FDP, realised via additive manufacturing (AM) - a solution that conveys at the same time quick manufacturability, low cost, custom-ability, and design freedom. By means of this new model, the load-bearing capability of three-units monolithic FDPs has been thoroughly tested; in particular, three different analyses were performed: (i) analytical with a beam-like model, (ii) numerical, using non-linear three-dimensional Finite Elements (FE) models and (iii) experimental, by static bending test. The FDPs considered in this work were manufactured using a fourth-generation zirconia, namely 4Y-TZP. The findings demonstrated the undoubted advantages of the new base configuration, which minimized the effect of the base (which as a matter of fact is absent in in-vivo conditions) on the stress state of the connectors in the FDPs, and increased the repeatability and reliability of the experimental bending tests, able to determine the load bearing capability of the 4Y-TZP FDPs

Synthesis of Amphiphilic Hydantoin-based Universal Peptidomimetics as Antibiotic Agents

Three model hydantoin-based universal peptidomimetics are designed and synthetized. Their preferred amphiphilic -turn conformation was assessed by molecular modeling and NMR experiments, and their antibacterial acivity tasted against Gram positive and Gram negative bacteria strains, demostrating that these compounds could be a captivating class of antibiotic to fight emergent drug resistanc

Reliability of Multisensor Armband in Estimating Energy Expenditure According to Degree of Obesity

Resting energy expenditure (REE) represents the amount of calories required by the body to maintain vital bodyfunctions. One of the most commonly used methods for estimating REE is indirect calorimetry. Recent studies ondifferent populations have validated a highly innovative instrument, the SenseWear® Armband (SWA), which evaluatestotal energy expenditure and, when used in resting conditions, could also evaluate REE. The purpose of this study wasto determine the agreement of the SWA in assessing REE in obese subjects and, see how this agreement varies withdifferent obesity degree.89 obese subjects (59 women and 30 men), with an age range from 35-65 years and body mass index (BMI)34.5 4.5 kg/m2 were studied. REE was measured by IC Sensor Medics Vmax (SM-29N) and by SWA. Fat mass(FM) and fat-free mass (FFM) was determined by anthropometry and bio-impedance measurements. No statisticaldifference was found between REE measured by SWA (1693±276) and REE measured by SM-29N (1627±293). Thetwo methods showed similar assessments (r=0.8, p 35 kg/m2), the agreement decreases (r =0.6 p 35