Persistence of Nonceliac Wheat Sensitivity, Based on Long-term Follow-up

We investigated how many patients with a diagnosis of nonceliac wheat sensitivity (NCWS) still experienced wheat sensitivity after a median follow-up time of 99 months. We collected data from 200 participants from a previous study of NCWS, performed between July and December 2016 in Italy; 148 of these individuals were still on a strict wheat- free diet. In total, 175 patients (88%) improved (had fewer symptoms) after a diagnosis of NCWS; 145 of 148 patients who adhered strictly to a gluten-free diet (98%) had reduced symptoms, compared with 30 of 52 patients who did not adhere to a gluten-free diet (58%) (P < .0001). Of the 22 patients who repeated the double-blind, placebo- controlled challenge, 20 reacted to wheat. We conclude that NCWS is a persistent condition. Clinicaltrials.gov registration number: NCT02823522

Diagnostic efficacy of the ELISA test for the detection of deamidated anti-gliadin peptide antibodies in the diagnosis and monitoring of celiac disease

Volcano plot of differential gene expression in IZE_Suc vs IZE, ZE_5w vs IZE_Suc and SE_5w vs IZE. (DOCX 256 kb

Gliadin, zonulin and gut permeability: effects on celiac and non-celiac intestinal mucosa and intestinal cell lines.

OBJECTIVE: Little is known about the interaction of gliadin with intestinal epithelial cells and the mechanism(s) through which gliadin crosses the intestinal epithelial barrier. We investigated whether gliadin has any immediate effect on zonulin release and signaling. MATERIAL AND METHODS: Both ex vivo human small intestines and intestinal cell monolayers were exposed to gliadin, and zonulin release and changes in paracellular permeability were monitored in the presence and absence of zonulin antagonism. Zonulin binding, cytoskeletal rearrangement, and zonula occludens-1 (ZO-1) redistribution were evaluated by immunofluorescence microscopy. Tight junction occludin and ZO-1 gene expression was evaluated by real-time polymerase chain reaction (PCR). RESULTS: When exposed to gliadin, zonulin receptor-positive IEC6 and Caco2 cells released zonulin in the cell medium with subsequent zonulin binding to the cell surface, rearrangement of the cell cytoskeleton, loss of occludin-ZO1 protein-protein interaction, and increased monolayer permeability. Pretreatment with the zonulin antagonist FZI/0 blocked these changes without affecting zonulin release. When exposed to luminal gliadin, intestinal biopsies from celiac patients in remission expressed a sustained luminal zonulin release and increase in intestinal permeability that was blocked by FZI/0 pretreatment. Conversely, biopsies from non-celiac patients demonstrated a limited, transient zonulin release which was paralleled by an increase in intestinal permeability that never reached the level of permeability seen in celiac disease (CD) tissues. Chronic gliadin exposure caused down-regulation of both ZO-1 and occludin gene expression. CONCLUSIONS: Based on our results, we concluded that gliadin activates zonulin signaling irrespective of the genetic expression of autoimmunity, leading to increased intestinal permeability to macromolecules

Production and characterisation of environmentally relevant microplastic test materials derived from agricultural plastics

Soil environments across the globe, particularly in agricultural settings, have now been shown to be contaminated with microplastics. Agricultural plastics – such as mulching films – are used in close or direct contact with soils and there is growing evidence demonstrating that they represent a potential source of microplastics. There is a demand to undertake fate and effects studies to understand the behaviour and potential long-term ecological risks of this contamination. Yet, there is a lack of test materials available for this purpose. This study describes the manufacture and characterisation of five large (1–40 kg) batches of microplastic test materials derived from agricultural mulching films. Batches were produced from either polyethylene-based conventional mulching films or starch-polybutadiene adipate terephthalate blend mulching films that are certified biodegradable in soil. Challenges encountered and overcome during the micronisation process provide valuable insights into the future of microplastic test material generation from these material types. This includes difficulties in micronising virgin polyethylene film materials. All five batches were subjected to a thorough physical and chemical characterisation - both of the original virgin films and the subsequent microplastic particles generated - including a screening for the presence of chemical additives. This is a critical step to provide essential information for interpreting particle fate or effects in scientific testing. Trade-offs between obtaining preferred particle typologies and time and cost constraints are elucidated. Several recommendations emerging from the experiences gained in this study are put forward to advance the research field towards greater harmonisation and utilisation of environmentally relevant test materials

The Sicilian network of biological therapy in inflammatory bowel disease: preliminary data on efficacy .

Background and aim: The monitoring of appropriateness and costs of biological therapy in Inflammatory bowel disease (IBD) is a relevant need. We aimed to evaluate appropriateness, efficacy and safety of biological therapy in IBD in Sicily through a web based network of prescribing centers. Material and methods: The Sicilian network for the monitoring of biological therapy in IBD is composed by a super Hub coordinator center and five Hub plus ten Spoke centers. From January 2013 all IBD patients starting a biological agent (incident cases) or already on treatment (prevalent cases) were entered in a web based software. Herein we report data on remission and response after twelve weeks of biological therapy, and side effects until the end of follow-up of incident cases. Results: From January 2013 to June 2016, 1475 patients were included. Complete data were available in 1338 cases (983 with Crohn’s disease [CD], 345 with ulcerative colitis [UC], and 10 with unclassified colitis). Incident cases were 956 (673 CD, 274 UC, and 9 unclassified colitis). Considering that 12% of patients experienced more than one line of therapy, a total of 1098 treatments were reported. Adalimumab was used in 543 CD patients, in 69 UC patients, and in 4 with unclassified colitis. Infliximab was prescribed in 221 CD patients (64 biosimilars), in 226 UC patients (41 biosimilars), and in 5 patients with unclassified colitis. Golimumab was prebscribed in 29 UC patients, and in 1 patient with unclassified colitis. After twelve weeks, the rate of response with Adalimumab was 46% and the rate of remission was 38% in CD, while the rate of response with Infliximab originator was 48% and the rate of remission 42% (biosimilars: 37% and 50%, respectively). In UC the rate of response with Adalimumab was 46% and the rate of remission was 38%, the rate of response with Infliximab was 41% and the rate of remission 45% (biosimilars: 25% and 64%, respectively), while the rate of response with Golimumab was 47% and the rate of remission was 27%. Overall, the rate of side effects was 17% (9.2% with Adalimumab, 20% with Infliximab originator, 15% with biosimilars, and 17% with Golimumab). Conclusions: In one of the largest series of IBD patients on biological therapy reported to date, the rates of remission and response after twelve weeks were comparable to data from literature, and similar between the different biologics. Efficacy and safety of biosimilars were analogous to those reported for infliximab originator