MUC-FIRE: Study protocol for a randomized multicenter open-label controlled trial to show that MUCous FIstula REfeeding reduces the time from enterostomy closure to full enteral feeds.

Background: After enterostomy creation, the distal bowel to the ostomy is excluded from the physiologic passage of stool, nutrient uptake, and growth of this intestinal section. Those infants frequently require long-term parenteral nutrition, continued after enterostomy reversal due to the notable diameter discrepancy of the proximal and distal bowel. Previous studies have shown that mucous fistula refeeding (MFR) results in faster weight gain in infants. The aim of the randomized multicenter open-label controlled MUCous FIstula REfeeding ("MUC-FIRE") trial is to demonstrate that MFR between enterostomy creation and reversal reduces the time to full enteral feeds after enterostomy closure compared to controls, resulting in shorter hospital stay and less adverse effects of parenteral nutrition. Methods/Design: A total of 120 infants will be included in the MUC-FIRE trial. Following enterostomy creation, infants will be randomized to either an intervention or a non-intervention group.In the intervention group, perioperative MFR between enterostomy creation and reversal will be performed. The control group receives standard care without MFR.The primary efficacy endpoint of the study is the time to full enteral feeds. Secondary endpoints include first postoperative bowel movement after stoma reversal, postoperative weight gain, and days of postoperative parenteral nutrition. In addition adverse events will be analyzed. Discussion: The MUC-FIRE trial will be the first prospective randomized trial to investigate the benefits and disadvantages of MFR in infants. The results of the trial are expected to provide an evidence-based foundation for guidelines in pediatric surgical centers worldwide. Trial registration: The trial has been registered at clinicaltrials.gov (number: NCT03469609, date of registration: March 19, 2018; last update: January 20, 2023, https://clinicaltrials.gov/ct2/show/NCT03469609?term=NCT03469609&draw=2&rank=1).

Total Synthesis of a Partial Structure from Arabinogalactan and Its Application for Allergy Prevention.

Arabinogalactan, a microheterogeneous polysaccharide occurring in plants, is known for its allergy-protective activity, which could potentially be used for preventive allergy treatment. New treatment options are highly desirable, especially in a preventive manner, due to the constant rise of atopic diseases worldwide. The structural origin of the allergy-protective activity of arabinogalactan is, however, still unclear and isolation of the polysaccharide is not feasible for pharmaceutical applications due to a variation of the activity of the natural product and contaminations with endotoxins. Therefore, a pentasaccharide partial structure was selected for total synthesis and subsequently coupled to a carrier protein to form a neoglycoconjugate. The allergy-protective activity of arabinogalactan could be reproduced with the partial structure in subsequent in vivo experiments. This is the first example of a successful simplification of arabinogalactan with a single partial structure while retaining its allergy-preventive potential.

Zinc supplementation induces regulatory T cells by inhibition of Sirt-1 deacetylase in mixed lymphocyte cultures.

SCOPE: Zinc is an essential trace element, regulating immune function. Its deficiency results in immune dysfunction and transplant rejection. In here, a benefit of zinc supplementation for the induction of tolerance was investigated, focusing on the TH 1-dominated allogeneic immune reaction. METHODS AND RESULTS: Allogeneic immune reaction was modeled by mixed lymphocyte culture (MLC). The effect of zinc supplementation was monitored via expression of cytokines and surface lineage markers using ELISA and flow cytometry. Epigenetic analyses were performed to investigate mechanisms underlying zinc-induced changes in regulatory T cell (Treg) activation. Results reveal that Tregs are induced when MLCs are treated with 50 µM zinc causing a decrease in IFNγ production. IL-2 and IL-10 expression were not affected. The teleology of this effect includes the inhibition of histone deacetylase Sirt-1-mediated Foxp3 deacetylation, resulting in its decreased degradation. CONCLUSION: In conclusion, zinc should be considered to prevent graft-versus-host disease (GVHD) as it is capable of stabilizing iTregs, resulting in increased numbers of this cell type while not suppressing the immune system.