Chemokines and their receptors in the metastatic behaviour of human pancreatic ductal adenocarcinoma.

The aim of this thesis was to investigate the role of chemokines and their receptors in human pancreatic adenocarcinoma and to explore whether chemokine receptors and their ligands are involved in tumor dissemination. The repertoire of chemokine receptors expressed in 11 pancreatic adenocarcinoma cell lines tested included CXCR4 and CX3CR1. Their significance was therefore further investigated. Expression of CXCR4 was higher in lines derived from metastases. The chemokine CXCL12 induced chemotaxis in CXCR4-positive cell lines, which was inhibited by an anti-CXCR4 specific antibody and by the antagonist AMD3100. Transendothelial migration, Matrigel invasion and activation of matrix metalloproteases were also enhanced by CXCL12. Proliferation was stimulated by CXCL12 in CXCR4-positive cell lines and partially inhibited by the inhibitor AMD3100, indicating an autocrine loop. The addition of exogenous CXCL12 inhibited apoptosis induced by serum starvation. These data demonstrate that autocrine or paracrine loops centred on the CXCR4/CXCL12 axis promote pancreatic cancer cell migration, matrix degradation and invasion, proliferation and survival. The function of the chemokine receptor CX3CR1 was investigated in the context of the peculiar propensity o f pancreatic cancer to disseminate and grow along nerve fibers, as its chemokine ligand Fractalkine/Neurotactin/CX3CLl is expressed by neuronal structures. CX3CR1-positive tumour cells migrated in a dose-dependent manner to CX3CL1 and this effect was blocked by specific anti-CX3CRl antibodies. CX3CR1-positive tumour cells adhered to endothelial and neuronal cells stimulated with TNFa/IFNy, known to induce Fractalkine expression. Neuronal derived Fractalkine elicited migration of CX3CR1-positive pancreatic tumour cells. The CX3CL1 chemokine was detected in vivo in surgical sections of pancreatic cancer nerve metastasis. These results suggest that the CX3CR1/Fractalkine axis could be involved in the dissemination of pancreatic tumour cells via nerve structures. In conclusion, the data presented here support the hypothesis that a selected set of chemokine receptors are expressed in carcinoma of the pancreas and are involved in tumour cell migration and invasion. For CXCR4, promotion o f cell survival and proliferation was observed. For CX3CR1, a role in perineural tropism is suggested

IL-10 and Macrophages Orchestrate Gut Homeostasis

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Constraining the UV emissivity of AGN throughout cosmic time via X-ray surveys

The cosmological process of hydrogen (H i) reionization in the intergalactic medium is thought to be driven by UV photons emitted by star-forming galaxies and ionizing active galactic nuclei (AGN). The contribution of quasars (QSOs) to H i reionization at z > 4 has been traditionally believed to be quite modest. However, this view has been recently challenged by new estimates of a higher faint-end UV luminosity function (LF). To set firmer constraints on the emissivity of AGN at z < 6, we here make use of complete X-ray-selected samples including deep Chandra and new Cosmic Evolution Survey data, capable to efficiently measure the 1 Ryd comoving AGN emissivity up to z ∼ 5–6 and down to 5 mag fainter than probed by current optical surveys, without any luminosity extrapolation. We find good agreement between the logNH ≲ 21-22 cm−2 X-ray LF and the optically selected QSO LF at all redshifts for M1450 ≤ −23. The full range of the logNH ≲ 21-22 cm−2 LF (M1450 ≤ −17) was then used to quantify the contribution of AGN to the critical value of photon budget needed to keep the Universe ionized. We find that the contribution of ionizing AGN at z = 6 is as small as 1–7 per cent, and very unlikely to be greater than 30 per cent, thus excluding an AGN-dominated reionization scenario

Understanding of the Nutri-Score front-of-pack label by Italian Medical Professionals and its effect on food choices: a web-based study on knowledge, attitudes and practices

A growing number of European Countries have adopted front-of-pack nutrition labels (FPNL) in order to assist costumers' alimentary choices, and particularly Nutri-Score. While its acceptance in Italy has been slowed by ongoing debates, we assessed corresponding knowledge, attitudes and practices of a sample of Italian Medical Professionals (MP)

Hair analysis to monitor abuse of analgesic combinations containing butalbital and propyphenazone

Butalbital, a barbiturate, is present in analgesic combinations used by headache sufferers. Overuse/abuse of these combinations may cause dependence, chronic migraine, and medication-overuse headache (MOH). MOH is difficult to manage: it improves interrupting analgesic overuse, but requires monitoring, because relapses are frequent. A gas chromatography-mass spectrometry (GC–MS) method for hair analysis has been developed and validated to document abuse of an analgesic combination containing butalbital and propyphenazone by a patient with MOH. For over ten years the patient managed her headache using eight suppositories/day of an analgesic combination containing butalbital 150 mg, caffeine 75 mg, and propyphenazone 375 mg per suppository. An outpatient detoxification treatment was carried out. After three weeks, the patient reduced the consumption to one suppository/day. At the first control visit, after three months from the beginning of detoxification, the patient increased the use of the combination to four suppositories/day and at the second control visit, after seven months from the beginning of detoxification, she was back to eight suppositories/day. At the two control visits, a hair sample was taken for determination of butalbital and propyphenazone. Moreover blood and urine samples for determination of butalbital were drawn at the beginning of detoxification treatment and at the two control visits. With the segmental analysis of two hair samples the medication history of ten months could be estimated. In the first hair sample, collected at the first control visit, in the distal segment, butalbital and propyphenazone concentrations were, respectively, 17.5 ng/mg and 56.0 ng/mg, confirming the prolonged abuse; in the proximal segment, concurrently with the detoxification treatment, butalbital and propyphenazone concentrations had reduced respectively to 5.45 ng/mg and 11.1 ng/mg. The second hair sample, collected at the second control visit, proved the fair course of the detoxification treatment in the distal segment and signalled relapse in the abuse of the analgesic combination in the proximal segment. In the clinical context, hair analysis can be advantageously used to monitor the abuse of analgesic combinations with butalbital, common among headache patients. The validation data showed that GC–MS method developed for determination of butalbital and propyphenazone was rapid, highly sensitive, specific and selective

The Marcus Caelius Project: a transmedial approach to support cultural communication and educational activities at the Civical Archaeological Museum of Bologna

[EN] The project “Marcus Caelius – the Value of Memory” is a 8 minute short animation movie located in the Roman Bologna at the Augustan Age. It originated with the Civical Archaeological Museum of Bologna in collaboration with Cineca VisIT-Lab. The project emploies a well known historical fact (the Battle of Teutoburg) to enable a philological approach within an emotional/narrative process. New philologically accurate reconstructions (i.e archaeological finds hedged in the Museum’s collection) are integrated with 3D historical sets caming form previous Cineca projects. Mixed movie-making techniques, such as Blender rendering, Chroma key and Machinima animation, implemented an ad hoc production pipeline in order to define times and costs which could be supported by a small production.[ES] El proyecto de "Marcus Caelius, el valor de la memoria" es una breve película de animación de 8 minutos ambientada en la Bolonia romana (Bononia) durante el periodo del emperador Augusto, que surge de una iniciativa del Museo Arqueológico de Bolonia, en colaboración con Cineca. Este proyecto, basado en un famoso hecho histórico (la batalla de Teutoburgo), quiere proponer un enfoque filológico dentro de un proceso emocional/narrativo, definiendo una pipeline de producción apropiada (que incluye renderizado de Blender, Chroma key y animación Machinima) para definir tiempo y costes que puedan ser cubiertos por un pequeña producción. Nuevas reconstrucciones filológicamente adecuadas (restos arqueológicos en la Colección del Museo), se integran dentro de sets en 3D que proceden deproyectos anteriores de Cineca.The research leading to these results is partly funded by the EU Community's FP7 ICT under the V-MusT.net Project (Grant Agreement 270404). The publication reflects only the author’s views and the Community is not liable for any use that may be made of the information contained therein. Neither the V-MusT.net consortium as a whole, nor a certain participant of the V-MusT.net consortium, warrant that the information contained in this document is capable of use, nor that use of the information is free from risk, and accepts no liability for loss or damage suffered by any person using this information.Bentini, L.; De Luca, D.; Donati, C.; Giovetti, P.; Guidazzoli, A.; Guidi, F.; Marchesi, M.... (2012). The Marcus Caelius Project: a transmedial approach to support cultural communication and educational activities at the Civical Archaeological Museum of Bologna. Virtual Archaeology Review. 3(7):82-85. https://doi.org/10.4995/var.2012.4393OJS828537ANTINUCCI, F. (2010): Comunicare nel museo. Con DVD. Percorsi Laterza. Laterza.BORGATTI, C. et al. (2004): "Databases and virtual environments: a good match for communicating complex cultural sites". in ACM SIGGRAPH 2004 Educators program (New York, NY, USA, 2004), SIGGRAPH '04, ACM. http://dx.doi.org/10.1145/1186107.1186143DELLI PONTI, Francesca et al. (2011): "A Blender open pipeline for a 3D animated historical short film", in Proceeding of the 12th International Symposium on Virtual Reality, Archaeology and Cultural Heritage - Short and Project Papers, VAST 2011.JUNG, Y. et al. (2011): "X3DOM AS CARRIER OF THE VIRTUAL HERITAGE", International Workshop 3D-ARCH, 4, 2011, Trento.O'REILLY, T. (2003): "The Architecture of Participation", [online] http:// www.oreillynet.com/lpt/wlg/3017 [Consult: 14-04-2012]

Seizures of illicit substances for personal use in two Italian provinces: analysis of trends by type and purity from 2008 to 2017

Background: The use of illicit substances represents one of the most difficult problems to confront in the health system. Drug use is a global problem but is not uniform throughout the world, within the same country and changes over time. Therefore, knowing the illicit substances that are used in a territory is essential to better organize health services in that specific geographical area. To this aim, we analysed 4200 samples confiscated from individuals who held them for personal use by police forces in the Italian provinces of Modena and Reggio Emilia from 2008 to 2017. Methods: The suspected samples were screened by gas-chromatography-mass spectrometry (GC-MS) and by liquid chromatography-tandem mass spectrometry (LC-MS/MS); all samples were subsequently analysed by gas chromatography-flame ionization detector (GC-FID) for quantitative analyses. Results: Cannabis was the most seized illicit substance (70.7%). Over the study period, the number of seizures of herb with a high content of \u3949-THC increased. The number of cocaine seizures remained stable (total 16.1%), but the median purity of seized cocaine increased to 75% in 2017. Heroin seizures decreased over time, but the median purity of seized heroin reached 16.8% in 2017. In almost all the years, heroin samples with a purity exceeding the 97.5 percentile were found. Especially from 2014, the range of seized substances increased and started to include synthetic cathinones, phenylethylamines, UR-144, LSD, psilocybe, prescription opioid and hypnotics. In two cases, tramadol together with tropicamide was seized. Most of the seizures involved male subjects and 82% of the seizures were from individuals younger than 35 years of age. Conclusions: The persistence of old illicit drugs and the rapid emergence of new psychoactive substances represented a serious challenge for public health in the studied Italian area. Some useful interventions might be: informing mainly young people about the possible complications of cannabis use; implementing standardized procedures to diagnose and treat cocaine-related emergencies in hospitals; increasing the distribution of naloxone to antagonize possible heroin overdoses; equipping laboratories to be able to identify the new psychoactive substances

The relevance of molecular genotyping to allocate cases in a suspected outbreak of Legionella pneumonia in patients with prolonged immunosuppressive therapy

Three cases of pneumonia caused by Legionella pneumophila serogroup 1 (Lp1) in immunosuppressed patients with repeated hospitalization were suspected as a healthcare-associated cluster. The environmental investigation did not reveal the presence of legionellae in the hospital patient rooms. Water samples collected from the homes of two patients were also negative for Legionella spp. In the absence of environmental strains potentially involved in the infections, we proceeded to genotype environmental Lp1 strains isolated in the hospital during routine water sampling during the decade 2009–2019 and recovered after long-term storage at −20 °C. These 'historical' strains exhibited a high grade of similarity and stability over time, regardless of the disinfection systems. The different molecular profiles shown among the clinical and environmental strains excluded a nosocomial outbreak. The study suggests that the application of molecular typing may be a useful tool to discriminate hospital vs community-acquired cases, mostly for severely immunosuppressed patients in whom the symptomatology could be insidious and the incubation period could be prolonged. Moreover, the genotyping allowed us to exclude any link between the cases. Keywords: Legionnaires' disease, Immunosuppressed patients, Sequence-based typing, Cluster, Environmental strains, Clinical strain

Characterisation of Microbial Community Associated with Different Disinfection Treatments in Hospital hot Water Networks

Many disinfection treatments can be adopted for controlling opportunistic pathogens in hospital water networks in order to reduce infection risk for immunocompromised patients. Each method has limits and strengths and it could determine modifications on bacterial community. The aim of our investigation was to study under real-life conditions the microbial community associated with different chemical (monochloramine, hydrogen peroxide, chlorine dioxide) and non-chemical (hyperthermia) treatments, continuously applied since many years in four hot water networks of the same hospital. Municipal cold water, untreated secondary, and treated hot water were analysed for microbiome characterization by 16S amplicon sequencing. Cold waters had a common microbial profile at genera level. The hot water bacterial profiles differed according to treatment. Our results confirm the effectiveness of disinfection strategies in our hospital for controlling potential pathogens such as Legionella, as the investigated genera containing opportunistic pathogens were absent or had relative abundances ≤1%, except for non-tuberculous mycobacteria, Sphingomonas, Ochrobactrum and Brevundimonas. Monitoring the microbial complexity of healthcare water networks through 16S amplicon sequencing is an innovative and effective approach useful for Public Health purpose in order to verify possible modifications of microbiota associated with disinfection treatments