A New In Vivo Model System to Assess the Toxicity of Semiconductor Nanocrystals

In the emerging area of nanotechnology, a key issue is related to the potential impacts of the novel nanomaterials on the environment and human health, so that this technology can be used with minimal risk. Specifically designed to combine on a single structure multipurpose tags and properties, smart nanomaterials need a comprehensive characterization of both chemicophysical properties and adequate toxicological evaluation, which is a challenging endeavour; the in vitro toxicity assays that are often employed for nanotoxicity assessments do not accurately predict in vivo response. To overcome these limitations and to evaluate toxicity characteristics of cadmium telluride quantum dots in relation to surface coatings, we have employed the freshwater polyp Hydra vulgaris as a model system. We assessed in vivo acute and sublethal toxicity by scoring for alteration of morphological traits, population growth rates, and influence on the regenerative capabilities providing new investigation clues for nanotoxicology purposes

Assessment of Skeletal Muscle Mass in Older People: Comparison Between 2 Anthropometry-Based Methods and Dual-Energy X-ray Absorptiometry

Sarcopenia is a common geriatric syndrome, whose diagnosis implies the assessment of muscle mass. Dual-energy x-ray absorptiometry (DXA) is the reference method for clinical practice, but it is not universally available. We compared DXA with 2 anthropometry-based methods to assess muscle mass in older adults

STUDIO DELLE COLONIZZAZIONI/INFEZIONI DA GERMI MULTIRESISTENTI IN UN'AZIENDA OSPEDALIERA DI ALTA SPECIALIZZAZIONE E RUOLO DEL DIRIGENTE NELLA GESTIONE DEI PAZIENTI

Il presente elaborato di tesi si propone di fornire uno spaccato sullo stato di colonizzazione/infezione da batteri multiresistenti, fenomeno di importante rilevanza attuale. all'interno dell'Azienda Ospedaliera Pisana, e nello specifico in ambito neurologico. Quantificare lo stato del fenomeno rappresenta la base per l'attuazione di quelle che sono le attuali condotte più sicure nei per la tutela dei pazienti e degli operatori stessi. La prima parte dell'eleborato si concentra sul fornire dati aggiornati e concetti generali per la comprensione del fenomeno. La parte centrale dell'elaborato si focalizza sulla descrizione del progetto di tesi e del contesto in cui questo si attua assieme ad un'analisi delle critica riscontrate negli esami obiettivi diretti effettuati. L'intervista ai responsabili del processo ha permesso la restrizione delle proposte di miglioramento sulla baste dei costi e dei vincoli dettati dalle direttive aziendali. In conclusione, oltre alle proposte sono state esposte le responsabilità del dirigente in merito all'attuazione delle misure preventive adeguate

Prognostic value of exercise cardiac tomography performed late after percutaneous coronary intervention in symptomatic and symptom-free patients

The long-term prognostic value of single-photon emission computed tomography (SPECT) performed late after percutaneous coronary intervention (PCI) has not been extensively evaluated. Moreover, the role of myocardial ischemia at SPECT in symptom-free patients after PCI is not clear. This study was designed to determine the long-term prognostic value of SPECT in predicting cardiac events after PCI in symptomatic and symptom-free patients. Exercise technetium-99m sestamibi SPECT was performed in 206 patients between 12 and 18 months after PCI. All patients were followed for a mean period of 37 +/- 16 months. Cardiac death, nonfatal myocardial infarction, and late revascularization procedures were considered to be events. Myocardial ischemia at SPECT was detectable in 44 patients. During follow-up, 24 patients experienced events (cardiac death in 4 patients, myocardial infarction in 10, and late revascularization in 10). At univariate analysis, the summed stress score (p <0.05) and summed difference score (p <0.001) were significant predictors of cardiac events. Event-free survival curves showed a higher event rate in patients with than without ischemia (p <0.001). The occurrence of cardiac events was higher in the presence of ischemia at SPECT in symptomatic and symptom-free patients (both p <0.001). The results of this study demonstrate that the extent and severity of myocardial ischemia at exercise SPECT performed between 12 and 18 months after PCI predicts cardiac events during long-term follow-up in symptomatic and symptom-free patients

Mechanisms underlying toxicity induced by CdTe quantum dots determined in an invertebrate model organism

A systematic and thorough quantitative analysis of the in vivo effects of inorganic nanoparticles is extremely important for the design of functional nanomaterials for diagnostic and therapeutic applications, better understanding of their non-specificity toward tissues and cell types, and for assessments of their toxicity. This study was undertaken to examine the impact of CdTe quantum dots (QDs) on an invertebrate freshwater model organism, Hydra vulgaris, for assessment of long term toxicity effects. The continuous exposure of living polyps to sub-lethal doses of QDs caused time and dose dependent morphological damages more severe than Cd2+ ions at the same concentrations, impaired both reproductive and regenerative capability, activated biochemical and molecular responses. Of remarkable interest, low QD doses, apparently not effective, caused early changes in the expression of general stress responsive and apoptotic genes. The occurrence of subtle genetic variations, in the absence of morphological damages, indicates the importance of genotoxicity studies for nanoparticle risk assessment. The versatility in morphological, cellular, biochemical and molecular responses renders Hydra a perfect model system for high-throughput screening of toxicological and ecotoxicological impact of nanomaterials on human and environmental health

An Integrated Multilevel Analysis Profiling Biosafety and Toxicity Induced by Indium- and Cadmium-Based Quantum Dots in Vivo

Indium phosphide quantum dots (QDs) have emerged as a new class of fluorescent nanocrystals for manifold applications, from biophotonics to nanomedicine. Recent efforts in improving the photoluminescence quantum yield, the chemical stability and the biocompatibility turned them into a valid alternative to well established Cd-based nanocrystals. In vitro studies provided first evidence for the lower toxicity of In-based QDs. Nonetheless, an urgent need exists for further assessment of the potential toxic effects in vivo. Here we use the freshwater polyp Hydra vulgaris, a well-established model previously adopted to assess the toxicity of CdSe/CdS nanorods and CdTe QDs. A systematic multilevel analysis was carried out in vivo, ex vivo, and in vitro comparing toxicity end points of CdSe- and InP-based QDs, passivated by ZnSe/ZnS shells and surface functionalized with penicillamine. Final results demonstrate that both the chemical composition of the QD core (InP vs CdSe) and the shell play a crucial role for final outcomes. Remarkably, in absence of in vivo alterations, cell and molecular alterations revealed hidden toxicity aspects, highlighting the biosafety of InP-based nanocrystals and outlining the importance of integrated multilevel analyses for proper QDs risk assessment

Clinical Practice Use of Liquid Biopsy to Identify RAS/BRAF Mutations in Patients with Metastatic Colorectal Cancer (mCRC): A Single Institution Experience

Tumor heterogeneity represents a possible cause of error in detecting predictive genetic alterations on tumor tissue and can be overcome by testing alterations in circulating tumor DNA (ctDNA) using liquid biopsy. We assessed 72 consecutive patients with a diagnosis of metastatic colorectal cancer (mCRC) using Idylla&trade; Biocartis, a fully automated platform that evaluates the most frequent mutations of KRAS, NRAS and BRAF genes. We correlated the results of liquid biopsy and standard tissue-based next generation sequencing (NGS) analyses to patient clinical features. The overall agreement was 81.94%. Concordance was 85.71% and 96.15% in treatment-na&iuml;ve patients and in the patient subgroup with liver metastases, respectively. In liver metastases positive, treatment-na&iuml;ve patients, sensitivity, specificity and positive predictive value (PPV) were 92.31%, 100% and 100%, respectively. Circulating mutational fraction (CMF) was significantly higher in patients with liver metastases and high carcinoembryonic antigen (CEA) levels. In a subgroup of patients pre-treated with anti-Epidermal Growth Factor Receptor (EGFR) agents, emerging KRAS mutations were evidenced in 33% of cases. Testing RAS/BRAF mutations on plasma using the Idylla&trade; Biocartis platform is feasible and reliable in mCRC patients in clinical practice