See Covering the Cover synopsis on 269. See editorial on page 295. BACKGROUND & AIMS: Exclusive enteral nutrition (EEN) is recommended for children with mild to moderate Crohn's disease (CD), but implementation is challenging. We compared EEN with the CD exclusion diet (CDED), a whole-food diet coupled with partial enteral nutrition (PEN), designed to reduce exposure to dietary components that have adverse effects on the microbiome and intestinal barrier. METHODS: We performed a 12-week prospective trial of children with mild to moderate CD. The children were randomly assigned to a group that received CDED plus 50% of calories from formula (Modulen, Nestlé) for 6 weeks (stage 1) followed by CDED with 25% PEN from weeks 7 to 12 (stage 2) (n ¼ 40, group 1) or a group that received EEN for 6 weeks followed by a free diet with 25% PEN from weeks 7 to 12 (n ¼ 38, group 2). Patients were evaluated at baseline and weeks 3, 6, and 12 and laboratory tests were performed; 16S ribosomal RNA gene (V4V5) sequencing was performed on stool samples. The primary endpoint was dietary tolerance. Secondary endpoints were intention to treat (ITT) remission at week 6 (pediatric CD activity index score below 10) and corticosteroid-free ITT sustained remission at week 12. RESULTS: Four patients withdrew from the study because of intolerance by 48 hours, 74 patients (mean age 14.2 ± 2.7 years) were included for remission analysis. The combination of CDED and PEN was tolerated in 39 children (97.5%), whereas EEN was tolerated by 28 children (73.6%) (P ¼ .002; odds ratio for tolerance of CDED and PEN, 13.92; 95% confidence interval [CI] 1.68-115.14). At week 6, 30 (75%) of 40 children given CDED plus PEN were in corticosteroid-free remission vs 20 (59%) of 34 children given EEN (P ¼ .38). At week 12, 28 (75.6%) of 37 children given CDED plus PEN were in corticosteroid-free remission compared with 14 (45.1%) of 31 children given EEN and then PEN (P ¼ .01; odds ratio for remission in children given CDED and PEN, 3.77; CI 1.34-10.59). In children given CDED plus PEN, corticosteroid-free remission was associated with sustained reductions in inflammation (based on serum level of C-reactive protein and fecal level of calprotectin) and fecal Proteobacteria. CONCLUSION: CDED plus PEN was better tolerated than EEN in
Cell-cell communication, which enables cells to coordinate their activity and is essential for growth, development and function, is usually ascribed a chemical or electrical origin. However, cells can exert forces and respond to environment elasticity and to mechanical deformations created by their neighbours 1-13 . The extent to which this mechanosensing ability facilitates intercellular communication remains unclear. Here we demonstrate mechanical communication between cells directly for the first time, providing evidence for a long-range interaction that induces long-lasting alterations in interacting cells. We show that an isolated cardiac cell can be trained to beat at a given frequency by mechanically stimulating the underlying substrate. Deformations are induced using an oscillatory mechanical probe that mimics the deformations generated by a beating neighbouring cardiac cell. Unlike electrical field stimulation, the probe-induced beating rate is maintained by the cell for an hour after the stimulation stops, implying that long-term modifications occur within the cell. These long-term alterations provide a mechanism for cells that communicate mechanically to be less variable in their electromechanical delay. Mechanical coupling between cells therefore ensures that the final outcome of action potential pacing is synchronized beating. We further show that the contractile machinery is essential for mechanical communication.Here we sought to separate the mechanical component of intercellular communication from indirect effects, such as a change in the amount or type of secreted chemo-attractants. We did so by introducing a 'mechanical cell' . The 'mechanical cell' consists of a probe that mimics the mechanical aspect of a cell by generating substrate deformations identical to the ones induced by a neighbouring beating cell. Previous studies have shown that mechanical stimulation of a quiescent cell or an engineered cardiac construct can induce beating 12,14 . However, in those studies, the magnitude and direction of forces applied were not controlled as to mimic the magnitude and direction of forces applied by cells. In addition, the duration of stimulation was extremely brief and the cells did not synchronize with the probe. These studies therefore did not provide a demonstration or characterization of cellular mechanical communication.Here, we use a 'mechanical cell' to apply deformations identical to those generated by an aligned beating cardiac cell both in magnitude and in directionality. We show that such deformations can synchronize cell beating. This provides clear evidence for mechanical cellular communication. Training of both quiescent and spontaneously beating cells takes up to 10-15 min and the induced beating frequency persists for over an hour after stimulation had stopped. These results demonstrate that mechanical communication is a unique type of interaction that is both long ranged and induces long-lasting alterations in interacting cells. We further demonstrate that mechanical communication...
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