Creatine synthesis in neonates demands high amounts of its precursors, arginine and methionine. Parenteral nutrition (PN) is typically marginal in these amino acids and devoid in creatine. The present study investigated the effectiveness of creatine supplementation of PN compared to supplementation with arginine, methionine and the unmethylated intermediate guanidinoacetic acid (GAA). The goal of this study was to determine if PN supplementation with creatine or GAA can spare methionine and/or arginine for other functions. Yucatan miniature‐piglets (6–10 d old; n=31) were fed 1 of 5 elemental PN diets: 1) low arginine and low methionine (Low Arg&Met), 2) low arginine and methionine plus GAA, 3) low arginine and methionine plus creatine, 4) high arginine and high methionine (High Arg&Met), or 5) low arginine with high methionine plus GAA (Met&GAA). After 7 d of feeding, a primed, constant infusion of [3H‐methyl]‐methionine was intravenously infused for 4 h and label incorporation in transmethylation products (creatine, phosphatidylcholine, DNA) and protein were measured. Both High Arg&Met and Met&GAA pigs had greater daily weight gain compared to GAA‐ and creatine‐supplemented pigs (p < 0.05), indicating methionine was deficient in low methionine groups. Moreover, 72‐h nitrogen retention was significantly greater in High Met&Arg and Met&GAA pigs compared to GAA (p < 0.05). These results suggest that because methionine is heavily transmethylated in the neonatal piglet, excess methionine is needed to promote protein synthesis and increase growth. As expected, plasma methionine and arginine concentrations were significantly higher in High Met&Arg compared to Low Arg&Met, GAA and creatine treatments (p < 0.05). Plasma levels of ornithine were significantly higher and glutamine levels were significantly lower in High Met&Arg compared to all other treatments (p < 0.05) suggesting urea cycle metabolism was limited in the low arginine groups. Hepatic fractional synthetic rate of creatine was ~30–40% higher in High Met&Arg and Met&GAA pigs, suggesting creatine synthesis was limited by precursor availability. These results also suggest that PN supplementation of GAA requires excess levels of methionine to facilitate transmethylation to creatine. These results suggest that arginine or GAA is needed to adequately synthesize creatine in PN‐fed piglets, but only when sufficient methionine is fed to provide methyl groups. Moreover, it is clear that the methionine and arginine requirements during PN feeding need to accommodate creatine synthesis.Support or Funding InformationSupported by Canadian Institutes of Health Research and the Janeway Research Foundation
Objective: The objective of this paper is to outline key principles required for a knowledge translation (KT) strategy on concussion education for medical trainees and physicians to promote knowledge retention and practice change. Design: Qualitative review of the literature on concussion education for medical trainees and physicians utilizing the Canadian Institute of Health Research (CIHR) Knowledge to Action (KTA) Cycle as a framework. Results: Medical education on concussion appears to be increasing, but many knowledge gaps persist. Although many concussion guidelines and standardized assessments have been developed, many physicians are either not aware of them, do not use them, or provide inaccurate or inconsistent discharge instructions. Focused, interactive concussion education sessions, education outreach by trained facilitators, and adoption of a spiral curriculum are preferred modalities. To facilitate concussion education, medical professionals must recognize the importance of concussion in their practice. Interventions should deliver high-yield information and be integrated into existing programs such as academic half days (AHD) and the Maintenance of Certification Program (MOC). Many KT tools and interventions have been developed, such as the Concussion Awareness Training Tool (CATT) for Medical Professionals, but evidence of their utilization and effectiveness is limited. Existing tools should be reviewed, updated, implemented, and evaluated for their effectiveness of improving both conceptual and instrumental knowledge. Conclusion: KT strategies for concussion medical education should utilize the CIHR KTA Cycle principles outlined in this review as a guide to design interventions that improve the concussion knowledge of medical trainees and physicians.
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