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Objective: Self‐management interventions may enhance health‐related quality of life (HRQoL) in epilepsy. However, several barriers often impair their implementation in the real world. Digital interventions may help to overcome some of these barriers. Considering this, the Helpilepsy Plus Prototype was developed as a prototype smartphone‐delivered self‐care treatment program for adults with epilepsy. Methods: The 12‐week Helpilepsy Plus Prototype was evaluated through a randomized controlled feasibility trial with a waiting‐list control (WLC) group. Outcome measurement at baseline and at 12 weeks assessed adherence to the prototype intervention and changes in epilepsy‐related outcomes. The primary endpoint was patient autonomy measured with EASE, and secondary endpoints included HRQoL measured with QOLIE‐31, health literacy measured with HLQ, anxiety, and depression symptoms measured with HADS. Semi‐structured interviews were conducted with a heterogeneous sample of participants to assess user‐friendliness and usefulness. The prototype program was delivered through the Neuroventis Platform (Neuroventis, BV, Overijse, Belgium), a certified medical device (under EU/MDD Class I, and EU/MDR grace period). Results: Ninety‐two patients were included (46 in the intervention group, 46 in WLC). Most participants (63%, 58/92 women, median age 30 years) had pharmacoresistant epilepsy (61%, 56/92). Only 22% of participants (10/46) in the intervention group completed at least half of all intervention sessions. No significant differences between the intervention group and WLC were observed. Although there was a larger proportion of patients in the intervention group with meaningful improvements in HRQoL compared to WLC (19/46 versus 11/46), the difference was not significant (p = 0.119). Qualitative feedback showed that participants would appreciate more personalization, such as adaptation of the content to their current epilepsy knowledge level, a more interactive interface, shorter text sections, and interaction through reminders and notifications. Significance: Digital interventions should allow sufficient scope for personalization and interaction to increase patient engagement and enable benefits from self‐care apps. Feedback loops allow the participatory development of tailored interventions. Plain Language Summary: In this study, we investigated the effectiveness of an app‐based self‐help intervention. Study participants were either randomly assigned to a group that had access to the app or a group that received access to the app after the end of the study. Although a larger proportion of participants in the intervention group showed a relevant improvement in quality of life, the difference between the two groups was not statistically significant. Less than one‐fifth of participants in the intervention group attended at least half of all intervention sessions; patient feedback showed that patients required more personalization and interactive options. [ABSTRACT FROM AUTHOR]

Background: A complex interplay between a failing intestinal barrier and low‐grade inflammation leading to sensorimotor disturbances is an often‐cited mechanism in the pathogenesis of functional gastrointestinal disorders (FGID). However, the cause‐consequence relationship between these features has not been clearly established. We previously described jejunal alterations in the normoglycemic BB‐rat (BBDP‐N) model proposing this model as a suitable animal model to study FGID pathophysiology. The current study explores colonic permeability, inflammation, and sensitivity of the BB‐rat. Methods: Colonic tissue of BBDP‐N and control (BBDR) rats at 50, 90, 110, 160, and 220 days (n ≥ 7 per group) was used to assess intestinal permeability in Ussing chambers and inflammation, including infiltration by eosinophils, mast cells, and eosinophil peroxidase (EPO) activity. Anxiety‐like symptoms were evaluated at 50, 90, and 220 days and colonic sensitivity at 160 and 220 days by measuring the visceromotor response (VMR) to isobaric colorectal distensions. Keys results: Lamina propria eosinophil and mast cell infiltration and increased EPO activity were demonstrated from 90 days onward. Increased permeability and myenteric ganglionitis were observed in the oldest BBDP‐N rats. At 220 days, the VMR was significantly increased suggesting colonic hypersensitivity. At the same age, increased anxiety‐like behavior was observed. Conclusion and inferences: We demonstrated a lamina propria eosinophil and mast cell infiltration preceding visceral hypersensitivity in the colon of the BBDP‐N rat, reminiscent of patients with FGID. These findings help elucidating pathogenetic pathways in FGID and further validate the BBDP‐N rat as an attractive model to study pathophysiology and therapy of FGID. [ABSTRACT FROM AUTHOR]

Background Among the different mechanisms involved in irritable bowel syndrome ( IBS) physiopathology, visceral hypersensitivity seems to play a key role. It involves sensitization of the colonic primary afferent fibers, especially through an overexpression of ion channels. The aims of this translational study were to investigate the colonic expression of Cav3.2 calcium channels and their involvement in an animal model of colonic hypersensitivity, and to assess their expression in the colonic mucosa of symptomatic IBS patients. Methods This bench-to-bed study combined a preclinical experimental study on mice and a case-control clinical study. Preclinical studies were performed on wild-type and Cav3.2- KO mice. Colonic sensitivity and Cav3.2 expression were studied after a low-dose treatment of dextran sodium sulfate ( DSS 0.5%). Regarding the clinical study, colonic biopsies were performed in 14 IBS patients and 16 controls during a colonoscopy to analyze the mucosal Cav3.2 expression. Key results Wild-type, but not Cav3.2- KO, mice developed visceral hypersensitivity without colonic inflammation, after 0.5% DSS treatment. A significant increase of Cav3.2 mRNA ( p = 0.04) was found in the colon of low-dose DSS-treated wild-type ( WT) mice compared to their controls. In human colonic biopsies, the Cav3.2 mRNA level was significantly higher in the IBS group compared to the control group ( p = 0.01). The immunofluorescence staining revealed their protein expression in colonic mucosa, particularly in nerve fibers. Conclusions & inferences This translational study supports the involvement of the calcium channels Cav3.2 in abdominal pain, as observed in IBS patients. It opens new therapeutic perspectives based on molecules specifically blocking these channels. [ABSTRACT FROM AUTHOR]

Background Irritable bowel syndrome ( IBS) is a functional gastrointestinal disorder associated with idiopathic colonic hypersensitivity ( CHS). However, recent studies suggest that low-grade inflammation could underlie CHS in IBS. The pro-inflammatory mediator nerve growth factor ( NGF) plays a key role in the sensitization of peripheral pain pathways and several studies have reported its contribution to visceral pain development. NGF modulates the expression of Acid-Sensing Ion Channels ( ASICs), which are proton sensors involved in sensory neurons sensitization. This study examined the peripheral contribution of NGF and ASICs to IBS-like CHS induced by butyrate enemas in the rat colon. Methods Colorectal distension and immunohistochemical staining of sensory neurons were used to evaluate NGF and ASICs contribution to the development of butyrate-induced CHS. Key Results Systemic injection of anti- NGF antibodies or the ASICs inhibitor amiloride prevented the development of butyrate-induced CHS. A significant increase in NGF and ASIC1a protein expression levels was observed in sensory neurons of rats displaying butyrate-induced CHS. This increase was specific of small- and medium-diameter L1 + S1 sensory neurons, where ASIC1a was co-expressed with NGF or trkA in CGRP-immunoreactive somas. ASIC1a was also overexpressed in retrogradely labeled colon sensory neurons. Interestingly, anti- NGF antibody administration prevented ASIC1a overexpression in sensory neurons of butyrate-treated rats. Conclusions & Inferences Our data suggest that peripheral NGF and ASIC1a concomitantly contribute to the development of butyrate-induced CHS NGF- ASIC1a interplay may have a pivotal role in the sensitization of colonic sensory neurons and as such, could be considered as a potential new therapeutic target for IBS treatment. [ABSTRACT FROM AUTHOR]