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1.
Pharmacol Ther ; 248: 108437, 2023 08.
Article in English | MEDLINE | ID: mdl-37201738

ABSTRACT

Docosahexaenoic acid (DHA, 22:6n-3) accretion in brain phospholipids is critical for maintaining the structural fluidity that permits proper assembly of protein complexes for signaling. Furthermore, membrane DHA can be released by phospholipase A2 and act as a substrate for the synthesis of bioactive metabolites that regulate synaptogenesis, neurogenesis, inflammation, and oxidative stress. Thus, brain DHA is consumed through multiple pathways including mitochondrial ß-oxidation, autoxidation to neuroprostanes, as well as enzymatic synthesis of bioactive metabolites including oxylipins, synaptamide, fatty-acid amides, and epoxides. By using models developed by Rapoport and colleagues, brain DHA loss has been estimated to be 0.07-0.26 µmol DHA/g brain/d. Since ß-oxidation of DHA in the brain is relatively low, a large portion of brain DHA loss may be attributed to the synthesis of autoxidative and bioactive metabolites. In recent years, we have developed a novel application of compound specific isotope analysis to trace DHA metabolism. By the use of natural abundance in 13C-DHA in the food supply, we are able to trace brain phospholipid DHA loss in free-living mice with estimates ranging from 0.11 to 0.38 µmol DHA/g brain/d, in reasonable agreement with previous methods. This novel fatty acid metabolic tracing methodology should improve our understanding of the factors that regulate brain DHA metabolism.


Subject(s)
Brain , Docosahexaenoic Acids , Mice , Animals , Docosahexaenoic Acids/chemistry , Docosahexaenoic Acids/metabolism , Brain/metabolism , Inflammation/metabolism , Signal Transduction , Oxidative Stress
2.
J Pediatr Surg ; 58(5): 822-827, 2023 May.
Article in English | MEDLINE | ID: mdl-36788057

ABSTRACT

PURPOSE: We implemented and evaluated an Enhanced Recovery after Surgery (ERAS) protocol for Nuss procedures consisting of patient education, bowel management, pre/post-operative transitional pain service involvement, serratus anterior plane blocks and intercostal nerve cryoablation. METHODS: A 5-point ERAS protocol was implemented using multiple plan-do-study-act (PDSA) cycles. Data was collected prospectively for patients in the full ERAS protocol and retrospectively for previous patients. The primary outcome was length of stay (LOS). Secondary outcomes were opioid consumption, pain scores, protocol compliance and patient satisfaction. The impact of PDSA cycles and the ERAS protocol was quantified using statistical process control charts and Mann Whitney U test. RESULTS: A total of 53 patients were identified, 13 within the ERAS protocol and 40 prior to introduction. There was no difference in age, sex, or Haller index between the two cohorts. The median LOS was decreased by 3 days in the ERAS cohort (P = 0.00001). There was decreased opioid consumption on post-operative day 1 (1.47 vs 1.96 MME/kg, p = 0.009) and overall (3.12 vs 6.35 MME/kg, p = 0.0042) in the ERAS cohort. Median pain scores did not differ between cohorts. ERAS bundle element compliance was: education 92%, bowel management 100%, transitional pain involvement 100%, serratus block 100% and cryoablation 100%. The 1-month survey revealed that 92% of patients were satisfied with their experience. CONCLUSION: Our results demonstrate significant reduction in LOS and a trend to decreasing opioid consumption in hospital following ERAS protocol implementation and support the further application of ERAS protocols in pediatrics. LEVEL OF EVIDENCE: III - Retrospective comparative study.


Subject(s)
Analgesics, Opioid , Funnel Chest , Humans , Child , Retrospective Studies , Analgesics, Opioid/therapeutic use , Funnel Chest/surgery , Pain, Postoperative/drug therapy , Pain, Postoperative/prevention & control , Length of Stay
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