Gluten-Free Diet

In the last few years, an increasing number of individuals have adopted a gluten free diet (GFD). A significant proportion of that includes patients affected by celiac disease (CD), who have to follow a strict GFD for medical purposes. However, a high number of individuals are currently following a GFD without medical counseling and without a specific diagnosis needing a gluten withdrawal from the diet. This is due to the frequently incorrect information diffused on the Internet and mass media on the topic of GFD. For these reasons, research on the GFD and its clinical use and biological effects is urgently needed

An axiomatization of verdict equivalence over regular monitors

Monitors are a key tool in the field of runtime verification, where they are used to check for system properties by analysing execution traces generated by processes. Work on runtime monitoring carried out in a series of papers by Aceto et al. has specified monitors using a variation on the regular fragment of Milner's CCS and studied two trace-based notions of equivalence over monitors, namely verdict and $\omega$-verdict equivalence. This article is devoted to the study of the equational logic of monitors modulo those two notions of equivalence. It presents complete equational axiomatizations of verdict and $\omega$-verdict equivalence for closed and open terms over recursion-free monitors.Comment: Preprint submitted to Journal of logical and algebraic methods in programing 202

Complexity results for modal logic with recursion via translations and tableaux

This paper studies the complexity of classical modal logics and of their extension with fixed-point operators, using translations to transfer results across logics. In particular, we show several complexity results for multi-agent logics via translations to and from the $\mu$-calculus and modal logic, which allow us to transfer known upper and lower bounds. We also use these translations to introduce a terminating tableau system for the logics we study, based on Kozen's tableau for the $\mu$-calculus, and the one of Fitting and Massacci for modal logic. Finally, we show how to encode the tableaux we introduced into $\mu$-calculus formulas. This encoding provides upper bounds for the satisfiability checking of the few logics we previously did not have algorithms for.Comment: 43 pages. arXiv admin note: substantial text overlap with arXiv:2209.1037

Isolation and culture of fibroblasts from endoscopic duodenal biopsies of celiac patients

BACKGROUND: Fibroblasts are actually considered pivotal in inflammation and tissue remodelling process and for these reasons they are involved in the pathogenesis of autoimmune disorders such as celiac disease. Investigations to define the role of fibroblasts in celiac diseases are obstructed by the absence of specific models. Our objective is to isolate and culture primary fibroblasts from endoscopic duodenal biopsies of celiac and non-celiac subjects, to analyze their growth patterns and the morphometric characteristics. METHODS: 60 duodenal bioptic specimens from 20 celiac patients and 114 from 38 non-celiac subjects were mechanically chopped and enzymatically digested in order to obtain primary cell cultures. Growth patterns, karyotype (Q-banding analysis), expression of typing proteins (fibroblast surface protein and cytokeratin 20) and morphometric parameters (diameters and their ratio, perimeter, area and perimeter/area ratio at computerised image analysis) were investigated on cultured cells. RESULTS: Primary cells were successfully cultured in 78% of the collected duodenal biopsies. Cultured cells, expressing the fibroblast surface protein, were negative for cytokeratine 20 and maintained a normal kariotype. Cells grew slowly without differences between the celiac and the non celiac group. Morphometric analysis of celiac fibroblasts revealed significantly increased dimensions, with a preserved diameters ratio, and a reduced perimeter/area ratio. CONCLUSION: For the first time this study demonstrates the feasibility of culturing primary fibroblast cell from endoscopic duodenal biopsies in celiac and non-celiac subjects, opening a new window of opportunity in studies intended to establish the role of fibroblasts as a possible partaker in the pathogenesis of the celiac mucosal damage

Changes in protein expression in two cholangiocarcinoma cell lines undergoing formation of multicellular tumor spheroids In vitro

Epithelial-to-Mesenchymal Transition (EMT) is relevant in malignant growth and frequently correlates with worsening disease progression due to its implications in metastases and re- sistance to therapeutic interventions. Although EMT is known to occur in several types of solid tumors, the information concerning tumors arising from the epithelia of the bile tract is still limited. In order to approach the problem of EMT in cholangiocarcinoma, we decided to investigate the changes in protein expression occurring in two cell lines under conditions leading to growth as adherent monolayers or to formation of multicellular tumor spheroids (MCTS), which are considered culture models that better mimic the growth characteristics of in-vivo solid tumors. In our system, changes in phenotypes occur with only a decrease in transmembrane E-cadherin and vimentin expression, minor changes in the transglutami- nase protein/activity but with significant differences in the proteome profiles, with declining and increasing expression in 6 and in 16 proteins identified by mass spectrometry. The aris- ing protein patterns were analyzed based on canonical pathways and network analysis. These results suggest that significant metabolic rearrangements occur during the conver- sion of cholangiocarcinomas cells to the MCTS phenotype, which most likely affect the car- bohydrate metabolism, protein folding, cytoskeletal activity, and tissue sensitivity to oxygen

A Retrospective Study on Dietary FODMAP Intake in Celiac Patients Following a Gluten-Free Diet

Our aim was to evaluate the intake of foods containing fermentable oligo/di/mono-saccharides and polyols (FODMAP) as a possible factor that induces gastrointestinal symptoms in treated celiac disease (CD) patients. We collected seven-day weighed food records for 104 CD patients and 91 healthy volunteers. All evaluated food items were from sources with high and low content of FODMAP, which were divided into cereals and sweets, sweeteners and soft drinks, fruits, dried fruits, and vegetables. Nutrient intake was calculated using the food database of the European Institute of Oncology. The symptoms reported were assessed by a Rome IV Irritable bowel syndrome (IBS) diagnostic questionnaire and by specific questions for the evaluation of functional gastrointestinal disorders (FGIDs). The 12% of CD patients met IBS symptoms criteria as opposed to 6% of controls (p = 0.09) and 27% of patients reported FGIDs symptoms vs. 22% of healthy controls (p = 0.42). The intake by CD patients was significantly higher than healthy volunteers for: sweeteners and sugars with low content of FODMAP (p = 0.0007), fruits, dried fruits, and vegetables high in FODMAP (p = 0.003) and low in FODMAP (p = 0.04) when compared to controls. CD patients had a lower intake of cereals and sweets with a high content of FODMAP (p = 0.00001). Healthy volunteers consumed significantly higher alcoholic beverages and fats high in FODMAP (both p < 0.044). The mean daily intake of other food categories did not differ between both groups. Even though CD patients had a low intake of gluten-free cereals high in FODMAP, they still consumed a significant amount of fruits and vegetables high in FODMAP. The clinical effect of a concomitant gluten-free diet and low-FODMAP diet should be prospectively evaluated as a supportive therapy in CD patients

Capsule enteroscopy versus small-bowel ultrasonography for the detection and differential diagnosis of intestinal diseases

Background/Aims Capsule enteroscopy (CE) and intestinal ultrasonography (IUS) are techniques that are currently used for investigating small-bowel (SB) diseases. The aim of this study was to compare the main imaging findings and the lesion detection rate (LDR) of CE and IUS in different clinical scenarios involving the SB. Methods We retrospectively enrolled patients who underwent CE and IUS for obscure gastrointestinal bleeding (OGIB), complicated celiac disease (CeD), and suspected or known inflammatory bowel disease (IBD). We evaluated the LDR of both techniques. The accuracy of IUS was determined using CE as the reference standard. Results A total of 159 patients (113 female; mean age, 49±19 years) were enrolled. The LDR was 55% and 33% for CE and IUS (p<0.05), respectively. Subgroup analysis showed that the LDR of CE was significantly higher than that of IUS in patients with OGIB (62% vs. 14%, p<0.05) and CeD (55% vs. 35%, p<0.05). IUS showed a similar LDR to CE in patients with suspected or known IBD (51% vs. 46%, p=0.83). Conclusions CE should be preferred in cases of OGIB and CeD, whereas IUS should be considered an early step in the diagnosis and follow-up of IBD even in patients with a proximal SB localization of the disease

Quality performance measures for small capsule endoscopy: Are the ESGE quality standards met?

Background and study aims The European Society of Gastrointestinal Endoscopy (ESGE) recently issued a quality performance measures document for small bowel capsule endoscopy (SBCE). The aim of this nationwide survey was to explore SBCE practice with ESGE quality measures as a benchmark. Patients and methods A dedicated per-center semiquantitative questionnaire based on ESGE performance measures for SBCE was created by a group of SBCE experts. One-hundred-eighty-one centers were invited to participate and were asked to calculate performance measures for SBCE performed in 2018. Data were compared with 10 ESGE quality standards for both key and minor performance measures. Results Ninety-one centers (50.3 %) participated in the data collection. Overall in the last 5 years (2014–2018), 26,615 SBCEs were performed, 5917 of which were done in 2018. Eighty percent or more of the participating centers reached the minimum standard established by the ESGE Small Bowel Working Group (ESBWG) for four performance measures (indications for SBCE, complete small bowel evaluation, diagnostic yield and retention rate). Conversely, compliance with six minimum standards established by ESBWG concerning adequate bowel preparation, patient selection, timing of SBCE in overt bleeding, appropriate reporting, reading protocols and referral to device-assisted enteroscopy was met by only 15.5%, 10.9%, 31.1%, 67.7%, 53.4%, and 32.2% of centers, respectively. Conclusions The present survey shows significant variability across SBCE centers; only four (4/10: 40 %) SBCE procedural minimum standards were met by a relevant proportion of the centers ( ≥ 80 %). Our data should help in identifying target areas for quality improvement programs in SBCE

Integrated Genomic, Functional, and Prognostic Characterization of Atypical Chronic Myeloid Leukemia

Atypical chronic myeloid leukemia (aCML) is a BCR-ABL1-negative clonal disorder, which belongs to the myelodysplastic/myeloproliferative group. This disease is characterized by recurrent somatic mutations in SETBP1, ASXL1 and ETNK1 genes, as well as high genetic heterogeneity, thus posing a great therapeutic challenge. To provide a comprehensive genomic characterization of aCML we applied a high-throughput sequencing strategy to 43 aCML samples, including both whole-exome and RNA-sequencing data. Our dataset identifies ASXL1, SETBP1, and ETNK1 as the most frequently mutated genes with a total of 43.2%, 29.7 and 16.2%, respectively. We characterized the clonal architecture of 7 aCML patients by means of colony assays and targeted resequencing. The results indicate that ETNK1 variants occur early in the clonal evolution history of aCML, while SETBP1 mutations often represent a late event. The presence of actionable mutations conferred both ex vivo and in vivo sensitivity to specific inhibitors with evidence of strong in vitro synergism in case of multiple targeting. In one patient, a clinical response was obtained. Stratification based on RNA-sequencing identified two different populations in terms of overall survival, and differential gene expression analysis identified 38 significantly overexpressed genes in the worse outcome group. Three genes correctly classified patients for overall survival