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Background:
Inflammatory bowel disease (IBD) represents a dysregulation of the mucosal immune system. The pathogenesis of Crohn’s disease (CD) and ulcerative colitis (UC) is linked to the loss of intestinal tolerance and barrier function. The healthy mucosal immune system has previously been shown to be inert against food antigens. Since the small intestine is the main contact surface for antigens and therefore the immunological response, the present study served to analyse food-antigen-specific T cells in the peripheral blood of IBD patients.
Methods:
Peripheral blood mononuclear cells of CD, with an affected small intestine, and UC (colitis) patients, either active or in remission, were stimulated with the following food antigens: gluten, soybean, peanut and ovalbumin. Healthy controls and celiac disease patients were included as controls. Antigen-activated CD4+ T cells in the peripheral blood were analysed by a magnetic enrichment of CD154+ effector T cells and a cytometric antigen-reactive T-cell analysis (‘ARTE’ technology) followed by characterisation of the ef- fector response.
Results:
The effector T-cell response of antigen-specific T cells were compared between CD with small intestinal inflammation and UC where inflammation was restricted to the colon. Among all tested food antigens, the highest frequency of antigen-specific T cells (CD4+CD154+) was found for gluten. Celiac disease patients were included as control, since gluten has been identified as the disease- causing antigen. The highest frequency of gluten antigen-specific T cells was revealed in active CD when compared with UC, celiac disease on a gluten-free diet (GFD) and healthy controls. Ovalbuminspecific T cells were almost undetectable, whereas the reaction to soybean and peanut was slightly higher. But again, the strong- est reaction was observed in CD with small intestinal involvement compared with UC. Remarkably, in celiac disease on a GFD only
antigen-specific cells for gluten were detected. These gluten-specific T cells were characterised by up-regulation of the pro-inflammatory cytokines IFN-γ, IL-17A and TNF-α. IFN-g was exclusively elevated in CD patients with active disease. Gluten-specific T-cells expressing IL-17A were increased in all IBD patients. Furthermore, T cells of CD patients, independent of disease activity, revealed a high expression of the pro-inflammatory cytokine TNF-α.
Conclusion:
The ‘ARTE’-technique allows to analyse and quantify food antigen specific T cells in the peripheral blood of IBD patients indicating a potential therapeutic insight. These data provide evidence that small intestinal inflammation in CD is key for the development of a systemic pro-inflammatory effector T-cell response driven by food antigens.
Acute ankle sprain leads in 40% of all cases to chronic ankle instability (CAI). CAI is related to a variety of motor adaptations at the lower extremities. Previous investigations identified increased muscle activities while landing in CAI compared to healthy control participants. However, it remains unclear whether muscular alterations at the knee muscles are limited to the involved (unstable) ankle or are also present at the uninvolved leg. The latter might potentially indicate a risk of ankle sprain or future injury on the uninvolved leg. Purpose: To assess if there is a difference of knee muscle activities between the involved and uninvolved leg in participants with CAI during perturbed walking. Method: 10 participants (6 females; 4 males; 26±4 years; 169±9 cm; 65±7 kg) with unilateral CAI walked on a split-belt treadmill (1m/s) for 5 minutes of baseline walking and 6 minutes of perturbed walking (left and right side, each 10 perturbations). Electromyography (EMG) measurements were performed at biceps femoris (BF) and rectus femoris (RF). EMG amplitude (RMS; normalized to MVIC) were analyzed for 200ms pre-heel contact (Pre200), 100ms post heel contact (Post100) and 200ms after perturbation (Pert200). Data was analyzed by paired t-test/Wilcoxon test based on presence or absence of normal distribution (Bonferroni adjusted α level p≤ 0.0125). Results: No statistical difference was found between involved and uninvolved leg for RF (Pre200: 4±2% and 11± 22%, respectively, p= 0.878; Post100: 10± 5 and 18±31%, p=0.959; Pert200: 6±3% and 13±24%, p=0.721) as well as for BF (Pre200: 12±7% and 11±6, p=0.576; Post100: 10±7% and 9±7%, p=0.732; Pert200: 7±4 and 7±7%, p=0.386). Discussion: No side differences in muscle activity could be revealed for assessed feedforward and feedback responses (perturbed and unperturbed) in unilateral CAI. Reduced inter-individual variability of muscular activities at the involved leg might indicate a rather stereotypical response pattern. It remains to be investigated, whether muscular control at the knee is not affected by CAI, or whether both sides adapted in a similar style to the chronic condition at the ankle.
History without borders
(2020)
PURPOSE: To determine the feasibility of upright compared to supine MRI measurements to determine characteristics of the lumbar spine in AA with spondylolisthesis.
METHODS: Ten AA (n=10; m/f: 4/6; 14.5±1.7y; 163±7cm; 52±8kg) from various sports, diagnosed with spondylolisthesis grade I-II Meyerding confirmed by x-ray in standing lateral view, were included. Open low-field MRI images (0.25 Tesla) in upright (82°) and supine (0°) position were evaluated by two observers. Medical imaging software was used to measure the anterior translation (AT, mm), lumbosacral joint angle (LSJA, °) and lordosis angle (LA, °). Reliability was analyzed by the intra-rater correlation coefficient (ICC) and standard error of measurements (SEM).
RESULTS: Due to motion artifacts during upright position, measures of three participants had to be excluded. Between observers, AT ranged from 4.2±2.7mm to 5.5±1.9mm (ICC=0.94, SEM=0.6mm) in upright and from 4.9±2.4mm to 5.9±3.0mm (ICC=0.89, SEM=0.9mm) in supine position. LSJA varied from 5.1±2.2° to 7.3±1.5° (ICC=0.54, SEM=1.5°) in upright and from 9.8±2.5° to 10±2.4° (ICC=0.73, SEM=1.1°) in supine position. LA differed from 58.8±14.6° to 61.9±6° (ICC=0.94, SEM=1.19°) in upright and from 51.9±11.7° to 52.6±11.1° (ICC=0.98, SEM=1.59°) in supine position.
CONCLUSIONS: Determination of AT and LA showed good to excellent reliability in both, upright and supine position. In contrast, reliability of LSJA had only moderate to good correlation
between observers and should therefore be interpreted with caution. However, motion artifacts should be taken into consideration during upright imaging procedures.
Climate change entails an intensification of extreme weather events that can potentially trigger socioeconomic and energy system disruptions. As we approach 1 degrees C of global warming we should start learning from historical extremes and explicitly incorporate such events in integrated climate-economy and energy systems models.