Modulation of intestinal IL-37 expression and its impact on the epithelial innate immune response and barrier integrity.

Background and Aims: Intestinal epithelial cells separate the luminal flora from lamina propria immune cells and regulate innate immune responses in the gut. An imbalance of the mucosal immune response and disrupted intestinal barrier integrity contribute to the evolution of inflammatory bowel diseases. Interleukin (IL)-37 has broad anti- inflammatory activity and is expressed by the human intestinal epithelium. Mice ectopically expressing human IL-37 show reduced epithelial damage and inflammation after DSS-induced colitis. Here, we investigated the impact of IL-37 on the innate immune response and tight junction protein expression of mouse intestinal organoids and the modulation of IL37 expression in human intestinal organoids. Methods: Murine intestinal organoids were generated from IL-37tg and wildtype mice. Human ileal organoids were generated from healthy young donors. Results: Expression of transgene IL-37 or recombinant IL-37 protein did not significantly reduce overall proinflammatory cytokine mRNA expression in murine intestinal organoids. However, higher IL37 expression correlated with a reduced proinflammatory cytokine response in murine colonic organoids. IL37 mRNA expression in human ileal organoids was modulated by proinflammatory cytokines showing an increased expression upon TNF-α-stimulation and decreased expression upon IFN-gamma stimulation. Transgene IL-37 expression did not rescue TNF-α-induced changes in morphology as well as ZO-1, occludin, claudin-2, and E-cadherin expression patterns of murine jejunal organoids. Conclusions: We speculate that the anti-inflammatory activity of IL-37 in the intestine is mainly mediated by lamina propria immune cells protecting intestinal epithelial integrity.

Maximal and Explosive Muscle Strength During Hip Adduction Squeeze and Hip Abduction Press Test Using A Handheld Dynamometer: An Intra- and Inter-tester Reliability Study.

Background: Hip adduction and abduction muscle function plays an important role for risk of groin pain in athletes. Maximal isometric strength can be obtained clinically using a handheld dynamometer. However, in very strong athletes this is challenging, as external fixation of the dynamometer is needed for reliable measures. An alternative to unilateral testing, is the long-lever hip adduction squeeze test and a novel bilateral hip abduction press test. While promising intra-tester reliability has been found for maximal strength during the long-lever hip adduction squeeze test, inter-tester reliability may be more challenging during both maximal and explosive strength measurements. Hypothesis/purpose: The aim of the present study was to assess intra- and inter-tester reliability of maximal, and explosive strength during the long lever hip adduction squeeze test and the long lever hip abduction press test in healthy adults using a hand-held dynamometer. Study design: Intra- and interrater reliability study. Methods: Forty-nine healthy subjects were included for intra- (n=20) and inter-tester reliability (n=29). Subjects performed the hip adduction long lever squeeze test and the bilateral hip abduction press test in a randomized order. Maximal isometric strength and early (0-100 ms) and late (0-200 ms) phase rate of force development (explosive muscle strength) was obtained using a hand-held dynamometer. Relative reliability for all tests was assessed using ICC2,1 two-way mixed model with absolute agreement, thereby taking bias between testers into account. Results: Maximal isometric strength showed good intra- and inter-tester reliability for adduction (ICC: 0.93-0.97) and abduction (ICC: 0.88-0.92). For 0-200 ms rate of force development, both the squeeze and press test showed good intra-tester reliability (ICC: 0.85-0.87), whereas inter-tester reliability was good for hip adduction squeeze (ICC: 0.75) and moderate for hip abduction press (ICC: 0.71). For 0-100 ms rate of force development, the hip abduction press test showed good intra-tester reliability (ICC: 0.78). Remaining tests for intra- and inter-tester reliability showed moderate reliability (ICC: 0.50-0.71). Conclusion: Assessment of maximal isometric strength in hip adduction squeeze and abduction press test showed good intra- and inter-tester reliability, whereas only 0-200 ms rate of force development demonstrated good intra-tester reliability of both tests. Therefore, rate of force development should preferably be conducted by the same tester, while the long lever squeeze and press test can reliably be used within- and between testers to measure maximal isometric strength. Level of Evidence: 3©The Author(s).

TMS of the occipital face area modulates cross-domain identity priming.

Accumulating evidence suggests that besides its function in early facial feature processing, the role of the right occipital face area (rOFA) extends to higher level, image-independent processing. Recent studies hint at the possibility that the activity of this region can be modulated by semantic information as well. To test whether the OFA is sensitive to semantic information in a functionally relevant way, we implemented a cross-domain, name-face priming paradigm combined with state-dependent transcranial magnetic stimulation, whereby stimulation preferentially facilitates the processing of attributes encoded by less active neural populations. Our volunteers performed a familiarity decision task for target face images preceded by primes that were either the name of the same identity (congruent), a name of a different person (incongruent), or the character string 'XXXXX' (no prime). Stimulating the rOFA at target stimulus onset, we observed the disappearance of the behavioral disadvantage of incongruent primes, compared to the vertex control condition. Performance in the congruent and no prime conditions remained intact. This result suggests the existence of neural populations in the rOFA that take part in the semantic processing of identity, probably in interplay with other nodes in the extended face network.