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1.
Singapore Med J ; 2021 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-34617684

RESUMO

INTRODUCTION: A previous prospective, randomized controlled trial showed that animated videos shown to children before their magnetic resonance imaging (MRI) scan reduced the proportion of children needing repeated MRI sequences and improved confidence of staying still for at least 30 minutes. Children preferred the interactive video. We hypothesize that the interactive video is non-inferior to showing two videos (regular and interactive) in improving children's cooperativeness during MRI scans. METHODS: In this Institutional Review Board-approved prospective, randomized, non-inferiority trial, 558 children aged 3 to 20 scheduled for elective MRI scan from June 2017 to March 2019 were randomized into interactive video only and combined (regular and interactive) videos groups. Children were shown the videos before their scan. Repeated MRI sequences, general anesthesia (GA) requirement, and improvement in confidence of staying still for at least 30 minutes were assessed. RESULTS: In the interactive video group (n = 277), 86 (31.0%) children needed repeated MRI sequences, 2 (0.7%) needed GA, and the proportion of children who had confidence in staying still for greater than 30 minutes increased by 22.1% after the video. In the combined videos group (n = 281), 102 (36.3%) children needed repeated MRI sequences, 6 (2.1%) needed GA, and the proportion of children who had confidence in staying still for greater than 30 minutes increased by 23.2% after videos, not significantly different from the interactive video group. CONCLUSION: The interactive video group demonstrated non-inferiority to the combined videos group.

2.
Proc Natl Acad Sci U S A ; 117(12): 6792-6800, 2020 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-32152097

RESUMO

Intestinal bile acids are known to modulate the germination and growth of Clostridioides difficile Here we describe a role for intestinal bile acids in directly binding and neutralizing TcdB toxin, the primary determinant of C. difficile disease. We show that individual primary and secondary bile acids reversibly bind and inhibit TcdB to varying degrees through a mechanism that requires the combined oligopeptide repeats region to which no function has previously been ascribed. We find that bile acids induce TcdB into a compact "balled up" conformation that is no longer able to bind cell surface receptors. Lastly, through a high-throughput screen designed to identify bile acid mimetics we uncovered nonsteroidal small molecule scaffolds that bind and inhibit TcdB through a bile acid-like mechanism. In addition to suggesting a role for bile acids in C. difficile pathogenesis, these findings provide a framework for development of a mechanistic class of C. difficile antitoxins.


Assuntos
Toxinas Bacterianas/química , Toxinas Bacterianas/metabolismo , Ácidos e Sais Biliares/metabolismo , Clostridioides difficile/metabolismo , Intestinos/fisiologia , Receptores de Superfície Celular/metabolismo , Células CACO-2 , Clostridioides difficile/crescimento & desenvolvimento , Infecções por Clostridium/microbiologia , Células HCT116 , Humanos
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