Because the signaling eicosanoids, epoxyeicosatrienoic acids (EETs) and HETEs, are esterified to membrane phospholipids, we asked which long-chain acyl-CoA synthetase (ACSL) isoforms would activate ...these molecules and whether the apparent FA substrate preferences of each ACSL isoform might differ depending on whether it was assayed in mammalian cell membranes or as a purified bacterial recombinant protein. We found that all five ACSL isoforms were able to use EETs and HETEs as substrates and showed by LC-MS/MS that ACSLs produce EET-CoAs. We found differences in substrate preference between ACS assays performed in COS7 cell membranes and recombinant purified proteins. Similarly, preferences and Michaelis-Menten kinetics for long-chain FAs were distinctive. Substrate preferences identified for the purified ACSLs did not correspond to those observed in ACSL-deficient mouse models. Taken together, these data support the concept that each ACSL isoform exhibits a distinct substrate preference, but apparent substrate specificities depend upon multiple factors including membrane character, coactivators, inhibitors, protein interactions, and posttranslational modification.
Head and neck cancer (HNC) treatments cause severe toxicities, leading to high rates of emergency department (ED) visits and unplanned hospital admissions (UHAs). .
The study aimed to evaluate a ...quality improvement project to reduce ED visits and UHAs. .
A weekly nurse/nurse practitioner-led symptom management clinic was created for patients with HNC receiving radiation therapy deemed at high risk for an ED visit or UHA. Primary quality metrics were rate of visits or unplanned admissions. Time-to-event actuarial analysis and log-rank tests (two-tailed) were performed to compare observed to historic rates. .
Rates of ED visits and UHAs were 11% and 16%, respectively. Having more symptom management visits marginally correlated with reduction in UHA. The authors estimate six ED visits and four UHAs were prevented, which is a $176,848 cost reduction.
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