Development of an Ex Vivo Organ Culture Technique to Evaluate Probiotic Utilization in IBD

The consistent technical and conceptual progress in the study of the microbiota has led novel impulse to the research for therapeutical application of probiotic bacteria in human pathologies, such as inflammatory bowel disease (IBD). Considering the heterogenous results of probiotics in clinical studies, the model of translational medicine may lead to a more specific and efficacious utilization of probiotic bacteria in IBD. In this regard, the selection and utilization of appropriate experimental models may drive the transition from pure in vitro systems to practical clinical application. We developed a simple and reproducible ex vivo organ culture method with potential utilization for the evaluation of probiotic bacteria efficacy in IBD patients

Endoscopic scores for inflammatory bowel disease in the era of 'mucosal healing'. old problem, new perspectives

The importance of the endoscopic evaluation in inflammatory bowel disease (IBD) management has been recognized for many years. However, the modalities for reporting endoscopic activity represent an ongoing challenge. To address this, several endoscopic scores have been proposed. Very few have been properly validated, and the use of such tools remains sub-optimal and is mainly restricted to clinical trials. In recent years, a growing emphasis of the concept of 'mucosal healing' as a prognostic marker and therapeutic goal has increased the need for a more accurate definition of endoscopic activity in both ulcerative colitis (UC) and Crohn's Disease (CD). In the present review, the evolution of the challenges related to endoscopic scores in IBD has been analyzed, with particular attention paid to the renewed relevance of endoscopic activity in recent years. Currently, despite the growing relevance of endoscopic activity, evaluating this activity in IBD is still a challenge. The implementation of efficacious endoscopic scores and a better definition of the absence of activity (mucosal healing) are needed.The importance of the endoscopic evaluation in inflammatory bowel disease (IBD) management has been recognized for many years. However, the modalities for reporting endoscopic activity represent an ongoing challenge. To address this, several endoscopic scores have been proposed. Very few have been properly validated, and the use of such tools remains sub-optimal and is mainly restricted to clinical trials. In recent years, a growing emphasis of the concept of 'mucosal healing' as a prognostic marker and therapeutic goal has increased the need for a more accurate definition of endoscopic activity in both ulcerative colitis (UC) and Crohn's Disease (CD). In the present review, the evolution of the challenges related to endoscopic scores in IBD has been analyzed, with particular attention paid to the renewed relevance of endoscopic activity in recent years. Currently, despite the growing relevance of endoscopic activity, evaluating this activity in IBD is still a challenge. The implementation of efficacious endoscopic scores and a better definition of the absence of activity (mucosal healing) are needed

Detection of bovine papillomavirus type 2 in the peripheral blood of cattle with urinary bladder tumours: possible biological role

Bovine papillomavirus type 2 (BPV-2) infection has been associated with urinary bladder tumours in adult cattle grazing on bracken fern-infested land. In this study, we investigated the simultaneous presence of BPV-2 in whole blood and urinary bladder tumours of adult cattle in an attempt to better understand the biological role of circulating BPV-2. Peripheral blood samples were collected from 78 cattle clinically suffering from a severe chronic enzootic haematuria. Circulating BPV-2 DNA was detected in 61 of them and in two blood samples from healthy cows. Fifty of the affected animals were slaughtered at public slaughterhouses and neoplastic proliferations in the urinary bladder were detected in all of them. BPV-2 DNA was amplified and sequenced in 78% of urinary bladder tumour samples and in 38.9% of normal samples as a control. Circulating episomal BPV-2 DNA was detected in 78.2% of the blood samples. Simultaneous presence of BPV-2 DNA in neoplastic bladder and blood samples was detected in 37 animals. Specific viral E5 mRNA and E5 oncoprotein were also detected in blood by RT-PCR and Western blot/immunocytochemistry, respectively. It is likely that BPV-2 can persist and be maintained in an active status in the bloodstream, in particular in the lymphocytes, as a reservoir of viral infection that, in the presence of co-carcinogens, may cause the development of urinary bladder tumours

VIV regimes and simplified solutions by the spectral model description

The present paper discusses technical aspects of the vortex-induced vibrations (VIVs) of structures excited by the wind in the framework of the spectral model, which is applied by many codes and guidelines for civil engineering verifications. Quantitative thresholds related to Scruton number domains, where the structural response can be considered in \u201cforced vibration\u201d or \u201clock-in\u201d regime, are proposed. In this way, the type of VIV response and its evaluation can be assessed with simple calculations that use the parameters already present in codes and guidelines. An analytical solution of the original model allows straightforward evaluations inclusive of operative criteria to properly consider structural and flow conditions concerning the coefficients governing the VIV response in the spectral description, leaving out some assumptions that are commonly adopted. Extensive numerical applications, limited here to circular cylinders and including a real full-scale chimney, allow to identify the most significant parameters of the model and the criticalities connected with their choice

On the merits of sparse surrogates for global sensitivity analysis of multi-scale nonlinear problems: application to turbulence and fire-spotting model in wildland fire simulators

Many nonlinear phenomena, whose numerical simulation is not straightforward, depend on a set of parameters in a way which is not easy to predict beforehand. Wildland fires in presence of strong winds fall into this category, also due to the occurrence of firespotting. We present a global sensitivity analysis of a new sub-model for turbulence and fire-spotting included in a wildfire spread model based on a stochastic representation of the fireline. To limit the number of model evaluations, fast surrogate models based on generalized Polynomial Chaos (gPC) and Gaussian Process are used to identify the key parameters affecting topology and size of burnt area. This study investigates the application of these surrogates to compute Sobol' sensitivity indices in an idealized test case. The performances of the surrogates for varying size and type of training sets as well as for varying parameterization and choice of algorithms have been compared. In particular, different types of truncation and projection strategies are tested for gPC surrogates. The best performance was achieved using a gPC strategy based on a sparse least-angle regression (LAR) and a low-discrepancy Halton's sequence. Still, the LAR-based gPC surrogate tends to filter out the information coming from parameters with large length-scale, which is not the case of the cleaning-based gPC surrogate. The wind is known to drive the fire propagation. The results show that it is a more general leading factor that governs the generation of secondary fires. Using a sparse surrogate is thus a promising strategy to analyze new models and its dependency on input parameters in wildfire applications.This research is supported by the Basque Government through the BERC 2014–2017 and BERC 2018–2021 programs, by the Spanish Ministry of Economy and Competitiveness MINECO through BCAM Severo Ochoa accreditations SEV-2013-0323 and SEV-2017-0718 and through project MTM2016-76016-R “MIP”, and by the PhD grant “La Caixa2014”. The authors acknowledge EDF R&D for their support on the OpenTURNS library. They also acknowledge Pamphile Roy and Matthias De Lozzo at CERFACS for helpful discussions on batman and scikit-learn tools

Application of clinical indexes in ulcerative colitis patients in regular follow-up visit. correlation with endoscopic 'mucosal healing' and implication for management

OBJECTIVE: Ulcerative Colitis (UC) is a chronic inflammatory disease of the colon of unknown etiology. Several clinical indexes have been proposed for UC disease activity evaluation, but none have been properly validated. Moreover, the reference parameter for the scores and their prognostic value is not clear. Mucosal healing has been recently proposed as an important end-point. Aim of the present study was to evaluate the correlation of four clinical indexes with objective diagnostic tools for UC evaluation, the discriminative ability in identifying patients with endoscopic mucosal healing, and to analyze the possible prognostic indication for disease course in 1 year of follow-up. PATIENTS AND METHODS: We analyzed data of 75 patients recorded in regular follow-up visit in IBD clinic at S. Andrea Hospital, Rome, between 2007-2011. We recorded clinical data and lab tests at the time of the visit, and endoscopic/ histological repor ts performed within 1 month. Clinical indexes (Seo' activity index, Simple Clinical Colitis Activity Index, partial Mayo score and Endoscopic-Clinical Correlation Index) were calculated and correlation to endoscopic and histologic activity, and to C-reactive protein increment, was assessed by mean of Spearman's rank correlation. Discriminative ability of the indexes for patients with and without endoscopic mucosal healing was tested by calculation of area under ROC curve (AUC). Patients with low and high clinical scores were compared for number of flares and increment of therapy during 1 year of follow-up. RESULTS: Clinical indexes had a good correlation with endoscopic activity (mean r = 0.73 ± 0.06), a fair correlation with CRP-increment (mean r = 0.55 ± 0.01) and a poor one with histologic activity (mean r = 0.35 ± 0.01). The discriminatory ability of the indexes for endoscopic mucosal healing was good for all the indexes (mean AUC = 0.87 ± 0.05). Patients with high clinical score had more flares and required more frequently increase of therapy at 1 year of follow up compared with patients with low score. CONCLUSIONS: Clinical indexes have a good correlation with endoscopic activity and can discriminate patients with and without mucosal healing. Patients with low and high score have different risk of disease flare and of need to increase therapy at 1 year. Clinical indexes may represent a useful tool for disease assessment in clinical practice in UC outpatients with mildmoderate disease