15 research outputs found

    Augmented Reality to Engage Visitors of Science Museums through Interactive Experiences

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    In the last years, interactive exhibitions based on digital technologies have become widely common, thanks to their flexibility and effectiveness in engaging visitors and creating memorable experiences. One of the topics in which digital technologies can be particularly effective is the communication of abstract concepts that are difficult for the human mind to imagine. An emblematic example is the astronomy discipline, which requires us to imagine and understand phenomena far away from our everyday life. In this paper, the authors present a research project, MARSS, in which digital technologies are used effectively to enhance the Users’ Experience of the Museo Astronomico di Brera located in Milan. Specifically, the MARSS project aims at designing and developing a new digital journey inside the museum to allow different categories of visitors to enjoy the exhibition in an engaging and interactive way. The paper presents the design and development phases of the experience and its evaluation with users. The results of the evaluation indicate that the digital interactive experience is appreciated by users and is successful in translating the content of high scientific value into more engaging and easily understandable elements

    Microbiota-driven gut vascular barrier disruption is a prerequisite for non-alcoholic steatohepatitis development.

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    BACKGROUND & AIMS Fatty liver disease, including non-alcoholic fatty liver (NAFLD) and steatohepatitis (NASH), has been associated with increased intestinal barrier permeability and translocation of bacteria or bacterial products into the blood circulation. In this study, we aimed to unravel the role of both intestinal barrier integrity and microbiota in NAFLD/NASH development. METHODS C57BL/6J mice were fed with high-fat diet (HFD) or methionine-choline-deficient diet for 1 week or longer to recapitulate aspects of NASH (steatosis, inflammation, insulin resistance). Genetic and pharmacological strategies were then used to modulate intestinal barrier integrity. RESULTS We show that disruption of the intestinal epithelial barrier and gut vascular barrier (GVB) are early events in NASH pathogenesis. Mice fed HFD for only 1 week undergo a diet-induced dysbiosis that drives GVB damage and bacterial translocation into the liver. Fecal microbiota transplantation from HFD-fed mice into specific pathogen-free recipients induces GVB damage and epididymal adipose tissue enlargement. GVB disruption depends on interference with the WNT/β-catenin signaling pathway, as shown by genetic intervention driving β-catenin activation only in endothelial cells, preventing GVB disruption and NASH development. The bile acid analogue and farnesoid X receptor agonist obeticholic acid (OCA) drives β-catenin activation in endothelial cells. Accordingly, pharmacologic intervention with OCA protects against GVB disruption, both as a preventive and therapeutic agent. Importantly, we found upregulation of the GVB leakage marker in the colon of patients with NASH. CONCLUSIONS We have identified a new player in NASH development, the GVB, whose damage leads to bacteria or bacterial product translocation into the blood circulation. Treatment aimed at restoring β-catenin activation in endothelial cells, such as administration of OCA, protects against GVB damage and NASH development. LAY SUMMARY The incidence of fatty liver disease is reaching epidemic levels in the USA, with more than 30% of adults having NAFLD (non-alcoholic fatty liver disease), which can progress to more severe non-alcoholic steatohepatitis (NASH). Herein, we show that disruption of the intestinal epithelial barrier and gut vascular barrier are early events in the development of NASH. We show that the drug obeticholic acid protects against barrier disruption and thereby prevents the development of NASH, providing further evidence for its use in the prevention or treatment of NASH

    Il riallestimento del Museo Astronomico di Brera

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    Grazie a uno stanziamento della Regione Lombardia ottenuto tramite il bando “Progetti di valorizzazione e promozione di Istituti, Luoghi della cultura, siti UNESCO, itinerari culturali e di catalogazione del patrimonio culturale - ambito museo 2019” tra il maggio e il dicembre 2020 è stato realizzato il nuovo allestimento della galleria del MusAB. Il MusAB ha in questa nuova esposizione l’ambizione di rispondere alla domanda “Cosa fa l’astronoma/o”? “Osservare, scoprire, misurare, rappresentare, sono queste le operazioni che compiono gli astronomi; noi cercheremo di illustrarle con l’aiuto degli antichi strumenti della Specola di Brera.” Così si legge nella rinnovata pannellistica del Museo mentre il telescopio Gualtieri, il Magnetometro, Boscovich e Napoleone ci guidano in prima persona alla scoperta di questa straordinaria disciplina. Van Gogh, Shakespeare, Tomasi di Lampedusa fanno da cornice alla visita e ci conducono fino a Marte dove il ricco patrimonio archivistico dell’INAF – Osservatorio Astronomico di Brera viene illustrato grazie alle riproduzioni digitali

    Serum IgG against Simian Virus 40 antigens are hampered by high levels of sHLA-G in patients affected by inflammatory neurological diseases, as multiple sclerosis

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    Background: Many investigators detected the simian polyomavirus SV40 footprints in human brain tumors and neurologic diseases and recently it has been indicated that SV40 seems to be associated with multiple sclerosis (MS) disease. Interestingly, SV40 interacts with human leukocyte antigen (HLA) class I molecules for cell entry. HLA class I antigens, in particular non-classical HLA-G molecules, characterized by an immune-regulatory function, are involved in MS disease, and the levels of these molecules are modified according with the disease status. Objective: We investigated in serum samples, from Italian patients affected by MS, other inflammatory diseases (OIND), non-inflammatory neurological diseases (NIND) and healthy subjects (HS), SV40-antibody and soluble sHLA-G and the association between SV40-prevalence and sHLA-G levels. Methods: ELISA tests were used for SV40-antibodies detection and sHLA-G quantitation in serum samples. Results: The presence of SV40 antibodies was observed in 6 % of patients affected by MS (N = 4/63), 10 % of OIND (N = 8/77) and 15 % of NIND (N = 9/59), which is suggestive of a lower prevalence in respect to HS (22 %, N = 18/83). MS patients are characterized by higher sHLA-G serum levels (13.9 \ub1 0.9 ng/ml; mean \ub1 St. Error) in comparison with OIND (6.7 \ub1 0.8 ng/ml), NIND (2.9 \ub1 0.4 ng/ml) and HS (2.6 \ub1 0.7 ng/ml) subjects. Interestingly, we observed an inverse correlation between SV40 antibody prevalence and sHLA-G serum levels in MS patients. Conclusion: The data obtained showed a low prevalence of SV40 antibodies in MS patients. These results seems to be due to a generalized status of inability to counteract SV40 infection via antibody production. In particular, we hypothesize that SV40 immune-inhibitory direct effect and the presence of high levels of the immune-inhibitory HLA-G molecules could co-operate in impairing B lymphocyte activation towards SV40 specific peptides

    Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

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    IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

    Gene expression profile of endothelial cells during perturbation of the gut vascular barrier

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    It has been widely demonstrated that tolerance against gut microbiota is compartmentalized to mucosal sites where microbes mostly reside. How the commensal bacteria are excluded from the entrance into the blood stream via intestinal capillaries that are located beneath the gut epithelium was not clear. We recently described the existence of a new anatomical structure, the ‘gut vascular barrier’ (GVB), both in murine and human intestines that plays a fundamental role in avoiding indiscriminate trafficking of bacteria from the gut into the blood circulation. The vascular barrier integrity could be altered by Salmonella typhimurium, a pathogen capable of systemic dissemination, through the modulation of the Wnt/β-catenin signaling pathway. Here we have analyzed the differences in gut endothelial gene expression profiles during Salmonella infection and have identified some interesting characteristics of endothelial to mesenchymal transition. These findings add new insights in the gut-liver axis

    FXR modulates the gut-vascular barrier by regulating the entry sites for bacterial translocation in experimental cirrhosis.

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    BACKGROUND & AIMS Pathological bacterial translocation (PBT) in cirrhosis is the hallmark of spontaneous bacterial infections, increasing mortality several-fold. Increased intestinal permeability is known to contribute to PBT in cirrhosis, although the role of the mucus layer has not been addressed in detail. A clear route of translocation for luminal intestinal bacteria is yet to be defined, but we hypothesize that the recently described gut-vascular barrier (GVB) is impaired in experimental portal hypertension, leading to increased accessibility of the vascular compartment for translocating bacteria. MATERIALS Cirrhosis was induced in mouse models using bile-duct ligation (BDL) and CCl4. Pre-hepatic portal-hypertension was induced by partial portal vein ligation (PPVL). Intestinal permeability was compared in these mice after GFP-Escherichia coli or different sized FITC-dextrans were injected into the intestine. RESULTS Healthy and pre-hepatic portal-hypertensive (PPVL) mice lack translocation of FITC-dextran and GFP-E. coli from the small intestine to the liver, whereas BDL and CCl4-induced cirrhotic mice demonstrate pathological translocation, which is not altered by prior thoracic-duct ligation. The mucus layer is reduced in thickness, with loss of goblet cells and Muc2-staining and expression in cirrhotic but not PPVL mice. These changes are associated with bacterial overgrowth in the inner mucus layer and pathological translocation of GFP-E. coli through the ileal epithelium. GVB is profoundly altered in BDL and CCl4-mice with Ileal extravasation of large-sized 150 kDa-FITC-dextran, but only slightly altered in PPVL mice. This pathological endothelial permeability and accessibility in cirrhotic mice is associated with augmented expression of PV1 in intestinal vessels. OCA but not fexaramine stabilizes the GVB, whereas both FXR-agonists ameliorate gut to liver translocation of GFP-E. coli. CONCLUSIONS Cirrhosis, but not portal hypertension per se, grossly impairs the endothelial and muco-epithelial barriers, promoting PBT to the portal-venous circulation. Both barriers appear to be FXR-modulated, with FXR-agonists reducing PBT via the portal-venous route. LAY SUMMARY For intestinal bacteria to enter the systemic circulation, they must cross the mucus and epithelial layer, as well as the gut-vascular barrier. Cirrhosis disrupts all 3 of these barriers, giving bacteria access to the portal-venous circulation and thus, the gut-liver axis. Diminished luminal bile acid availability, cirrhosis and the associated reduction in farnesoid x receptor (FXR) signaling seem, at least partly, to mediate these changes, as FXR-agonists reduce bacterial translocation via the portal-venous route to the liver in cirrhosis

    Biomimetic superabsorbent hydrogel acts as a gut protective dynamic exoskeleton improving metabolic parameters and expanding A. muciniphila

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    The rising prevalence of obesity and metabolic disorders worldwide highlights the urgent need to find new long-term and clinically meaningful weight-loss therapies. Here, we evaluate the therapeutic potential and the mechanism of action of a biomimetic cellulose-based oral superabsorbent hydrogel (OSH). Treatment with OSH exerts effects on intestinal tissue and gut microbiota composition, functioning like a protective dynamic exoskeleton. It protects from gut barrier permeability disruption and induces rapid and consistent changes in the gut microbiota composition, specifically fostering Akkermansia muciniphila expansion. The mechanobiological, physical, and chemical structures of the gel are required for A. muciniphila growth. OSH treatment induces weight loss and reduces fat accumulation, in both preventative and therapeutic settings. OSH usage also prevents liver steatosis, immune infiltration, and fibrosis, limiting the progression of non-alcoholic fatty liver disease. Our work shows the potential of using OSH as a non-systemic mechano-biological approach to treat metabolic syndrome and its comorbidities
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