Investigation of novel imaging methods using therapeutic ion beams

Imaging techniques play an increasingly important role for treatment planning and in-situ monitoring in ion beam therapy. In this thesis, two novel methods were studied. For real-time in-vivo range verification, FLUKA Monte Carlo simulations were performed to address the detection of prompt gammas, emitted during irradiation of homogeneous and heterogeneous targets, using an ideal detector, highlighting main signal and background features relevant for clinical application. For range monitoring prior to or in-between treatment, a dedicated detector prototype based on a stack of 61 ionization chambers was assembled and its applicability to ion-based transmission imaging was investigated experimentally. Characterization of the set-up in terms of beam parameters and settings of the read-out electronics underlined the potential of heavy ion radiography and tomography as an attractive low dose imaging modality. Possible sources of image artifacts were analyzed and an original method to improve the nominal resolution of the used detector set-up was proposed. The resulting images, expressed directly in water equivalent thickness and path length, of different phantoms of increasing complexity provided a promising proof of principle of ion-based planar and volumetric imaging. Overall, the findings of this thesis strongly support the large potential of the investigated imaging techniques for future clinical use

Disturbi del sonno negli studenti di Infermieristica italiani: uno studio pilota.

INTRODUZIONE: La professione infemrieristica è particolarmente esposta a disturbi del sonno a causa dell’alterazione dei ritmi circadiani, delle frequenti variazioni della turnistica e del lavoro straordinario, con riduzione delle ore dedicate a dormire ed aumentato rischio di errori nell’assistenza. I disturbi del sonno, tuttavia, sembrano iniziare già durante la formazione universitaria: l’elevato carico didattico e l’alternanza fra teoria, esami e tirocinio possono infatti essere fonte di stress e di ansia, portando a questo genere di disturbi. Questo studio si è quindi proposto di indagare l’incidenza dei disturbi del sonno ed i fattori ad essi associati fra gli studenti di infermieristica in Italia METODI: E’ stato condotto uno studio trasversale sul web da gennaio ad agosto 2022, somministrando la versione italiana del Pittsburgh Sleep Quality Index (PSQI). La normalità della distribuzione è stata valutata attraverso il test di Kolmogorov-Smirnov. È stata eseguita un'analisi di regressione logistica binaria. RISULTATI: la survey è stata completata da 4898 studenti. Il test di Kolmogorov-Smirnov ha riscontrato che i punteggi seguissero una distribuzione normale. Le analisi hanno rilevato che essere di sesso femminile, soffrire di una malattia, essere uno studente lavoratore, consumare regolarmente tè o alcol e percepire che i disturbi del sonno hanno un impatto sul rendimento accademico, sono fattori che influenzano l'insorgenza dei disturbi del sonno. CONCLUSIONI: I risultati di questo studio suggeriscono l’attuazione di strategie volte ad agevolare il percorso degli studenti di infermieristica e ridurre il rischio di errori nell’assistenza. I risultati di questo studio pilota dovrebbero essere confermati da studi ufficiali.  BACKGROUND: The nursing profession is particularly susceptible to sleep disturbances due to altered circadian rhythms, frequent changes in shift patterns, and overtime work, resulting in fewer hours devoted to sleep and an increased risk of errors in care. Sleep disorders, however, seem to start as early as during undergraduate training: in fact, it has been found that the high teaching load and the sudden alternation between theory, exams, and internship can be a source of stress and anxiety, leading to these kinds of disorders even during basic training. This study, therefore, set out to investigate the incidence of sleep disorders and examine the factors associated with them among nursing students in Italy. METHODS: A cross-sectional web-based study was conducted from January to August 2022, administering the Italian version of the Pittsburgh Sleep Quality Index (PSQI) was administered. The normality of the distribution was assessed using the Kolmogorov-Smirnov test. A binary logistic regression analysis was performed. RESULTS: The survey was completed by 4898 students. The Kolmogorov-Smirnov test stated that the scores followed a normal distribution. The logistic regression found that being female, suffering from a disease, being a working student, regularly consuming tea or alcohol, and perceiving that sleep disorders impact academic performance are factors influencing the occurrence of sleep disorders.CONCLUSIONS: Our results suggest nurse educators to implement strategies to facilitate the path of nursing students and reduce the risk of errors in nursing. Official studies of individual universities should confirm this pilot study's results

The hypoxic transcription factor KlMga2 mediates the response to oxidative stress and influences longevity in the yeast Kluyveromyces lactis

Hypoxia is defined as the decline of oxygen availability, depending on environmental supply and cellular consumption rate. The decrease in O2 results in reduction of available energy in facultative aerobes. The response and/or adaptation to hypoxia and other changing environmental conditions can influence the properties and functions of membranes by modifying lipid composition. In the yeast Kluyveromyces lactis, the KlMga2 gene is a hypoxic regulatory factor for lipid biosynthesis-fatty acids and sterols-and is also involved in glucose signaling, glucose catabolism and is generally important for cellular fitness. In this work we show that, in addition to the above defects, the absence of the KlMGA2 gene caused increased resistance to oxidative stress and extended lifespan of the yeast, associated with increased expression levels of catalase and SOD genes. We propose that KlMga2 might also act as a mediator of the oxidative stress response/adaptation, thus revealing connections among hypoxia, glucose signaling, fatty acid biosynthesis and ROS metabolism in K. lactis

High-Rate Capable Floating Strip Micromegas

We report on the optimization of discharge insensitive floating strip Micromegas (MICRO-MEsh GASeous) detectors, fit for use in high-energy muon spectrometers. The suitability of these detectors for particle tracking is shown in high-background environments and at very high particle fluxes up to 60MHz/cm$^2$. Measurement and simulation of the microscopic discharge behavior have demonstrated the excellent discharge tolerance. A floating strip Micromegas with an active area of 48cm$\times$50cm with 1920 copper anode strips exhibits in 120GeV pion beams a spatial resolution of 50$\mu$m at detection efficiencies above 95%. Pulse height, spatial resolution and detection efficiency are homogeneous over the detector. Reconstruction of particle track inclination in a single detector plane is discussed, optimum angular resolutions below $5^\circ$ are observed. Systematic deviations of this $\mu$TPC-method are fully understood. The reconstruction capabilities for minimum ionizing muons are investigated in a 6.4cm$\times$6.4cm floating strip Micromegas under intense background irradiation of the whole active area with 20MeV protons at a rate of 550kHz. The spatial resolution for muons is not distorted by space charge effects. A 6.4cm$\times$6.4cm floating strip Micromegas doublet with low material budget is investigated in highly ionizing proton and carbon ion beams at particle rates between 2MHz and 2GHz. Stable operation up to the highest rates is observed, spatial resolution, detection efficiencies, the multi-hit and high-rate capability are discussed.Comment: Presented at ICHEP 2014, accepted for publication in Nuclear Physics B Proceedings Supplement

The semi-synthetic peptide Lin-SB056-1 in combination with EDTA exerts strong antimicrobial and antibiofilm activity against pseudomonas aeruginosa in conditions mimicking cystic fibrosis sputum

Pseudomonas aeruginosa is a major cause of chronic lung infections in cystic fibrosis (CF) patients. The ability of the bacterium to form biofilms and the presence of a thick and stagnant mucus in the airways of CF patients largely contribute to antibiotic therapy failure and demand for new antimicrobial agents able to act in the CF environment. The present study investigated the anti-P. aeruginosa activity of lin-SB056-1, a recently described semi-synthetic antimicrobial peptide, used alone and in combination with the cation chelator ethylenediaminetetraacetic acid (EDTA). Bactericidal assays were carried out in standard culture conditions and in an artificial sputum medium (ASM) closely resembling the CF environment. Peptideâ\u80\u99s structure and interaction with large unilamellar vesicles in media with different ionic strengths were also investigated through infrared spectroscopy. Lin-SB056-1 demonstrated fast and strong bactericidal activity against both mucoid and non-mucoid strains of P. aeruginosa in planktonic form and, in combination with EDTA, caused significant reduction of the biomass of P. aeruginosa mature biofilms. In ASM, the peptide/EDTA combination exerted a strong bactericidal effect and inhibited the formation of biofilm-like structures of P. aeruginosa. Overall, the results obtained highlight the potential of the lin-SB056-1/EDTA combination for the treatment of P. aeruginosa lung infections in CF patients

Nano-biocomposite films with modified cellulose nanocrystals and synthesized silver nanoparticles

Ternary nano-biocomposite films based on poly(lactic acid) (PLA) with modified cellulose nanocrystals (s-CNC) and synthesized silver nanoparticles (Ag) have been prepared and characterized. The functionalization of the CNC surface with an acid phosphate ester of ethoxylated nonylphenol favoured its dispersion in the PLA matrix. The positive effects of the addition of cellulose and silver on the PLA barrier properties were confirmed by reductions in the water permeability (WVP) and oxygen transmission rate (OTR) of the films tested. The migration level of all nano-biocomposites in contact with food simulants were below the permitted limits in both non-polar and polar simulants. PLA nano-biocomposites showed a significant antibacterial activity influenced by the Ag content, while composting tests showed that the materials were visibly disintegrated after 15 days with the ternary systems showing the highest rate of disintegration under composting conditions.L.V. would like to acknowledge the financial support from MIUR, PRIN 2010–11 project entitled “Nanomed” (prot.2010FPTBSH 009). M.P. and A.J. acknowledge the financial support from the Spanish Ministry of Economy and Competitiveness (MAT2011-28648-C02-1)

Evaluation of the Local Immune Response to Hydatid Cysts in Sheep Liver

In order to characterize the inflammatory phenotype of livers of sheep naturally infected by cystic echinococcosis, 100 sheep livers have been macroscopically assessed for the presence of hydatid cysts and sampled for histopathological and molecular analysis. According to gross and microscopic examination, livers were subsequently classified into three groups: normal liver (Group A), liver with the presence of fertile hydatid cysts (Group B), and liver with the presence of sterile hydatid cysts (Group C). Immunohistochemical analyses were accomplished using primary antibodies anti-Iba1, anti-CD3, anti-CD20, anti-TGF-β, and anti-MMP9. Finally, real-time PCR was performed in order to estimate the concentration levels of tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ), interleukin (IL)-12, IL-10, and TGF-β. Immunohistochemical analysis showed a diffuse immunolabelling of mononuclear cells for Iba-1 and TGF-β and a higher amount of CD20+ B cells compared to CD3+ T cells in both Groups B and C. The expression levels of Th-1-like immune cytokines TNF-α, INF-γ, and IL-12 did not show significant statistical differences. However, we found a significant increase in expression levels of Th-2 immune cytokines TGF-β and IL-10 in Groups B and C compared to Group A. Taken together, our findings suggest that macrophages have a predominant role in the local immune response to cystic echinococcosis. Moreover, we can speculate that Th2 immunity may be dominant, corroborating the idea that B cells are decisively essential in the control of the immune response during parasitic infection and that the immunomodulatory role of IL-10 and TGF-β may ensure the persistence of the parasite within the host

Sleep-related hypermotor epilepsy: Long-term outcome in a large cohort

To assess the long-term outcome of sleep-related hypermotor epilepsy (SHE)

The representation of child–parent relation: validation of the Italian version of the child–parent relationship scale (CPRS-I)

This study proposes a psychometric validation of the Italian version of the Child–Parent Relationship Scale (CPRS) developed by Pianta in 1992. Based on attachment theory, the scale assesses parents’ relationship perceptions with their own child and comprises three scales: Closeness, Conflict, and Dependency. A sample of 501 parents (188 fathers and 313 mothers) completed 30 items of the Italian version of the Child–Parent Relationship Scale (CPRS-I) online, but only 437 answered 85% of the entire protocol; hence, the analyses only focused on 437 participants. The first analysis of the original theoretical model revealed poor fit, item loadings, and internal consistency. Therefore, a follow-up analysis was conducted. Exploratory and confirmatory analyses with a split sample (EFA = 218; CFA = 219) confirmed the original three-factor structure of the Italian sample, although some items were eliminated. The validity and reliability of the Italian version of the CPRS-I were also verified by correlating the above three factors with measures of adult attachment styles and children’s internalizing and externalizing behaviors. The CPRS-I showed significant correlations with all tested constructs, in line with those found by Driscoll and Pianta for the short form of the scale. Our results confirm that the CPRS-I has the same structure as the original scale; therefore, it can be a useful tool for assessing parents’ perceptions of their relationship with their children. The implications for educational and clinical settings are also discussed

PEGylated Liposomes Loaded with Carbamate Inhibitor ANP0903 Trigger Apoptosis by Enhancing ER Stress in HepG2 Cancer Cells

Liver cancer is one of the most common causes of cancer death worldwide. In recent years, substantial progress has been made in the development of systemic therapies, but there is still the need for new drugs and technologies that can increase the survival and quality of life of patients. The present investigation reports the development of a liposomal formulation of a carbamate molecule, reported as ANP0903, previously tested as an inhibitor of HIV-1 protease and now evaluated for its ability to induce cytotoxicity in hepatocellular carcinoma cell lines. PEGylated liposomes were prepared and characterized. Small, oligolamellar vesicles were produced, as demonstrated by light scattering results and TEM images. The physical stability of the vesicles in biological fluids was demonstrated in vitro, alongside the stability during storage. An enhanced cellular uptake was verified in HepG2 cells treated with liposomal ANP0903, resulting in a greater cytotoxicity. Several biological assays were performed to elucidate the molecular mechanisms explaining the proapoptotic effect of ANP0903. Our results allow us to hypothesize that the cytotoxic action in tumor cells is probably due to the inhibition of the proteasome, resulting in an increase in the amount of ubiquitinated proteins within the cells, which in turn triggers activation of autophagy and apoptosis processes, resulting in cell death. The proposed liposomal formulation represents a promising approach to deliver a novel antitumor agent to cancer cells and enhance its activity