Electronic Health Record and Parenteral Nutrition Functionality: A Gap Analysis.

Parenteral nutrition (PN) is a complex, high-alert medication that contains up to 40 different ingredients. Surveys have shown that current electronic health record (EHR) systems may lack functionality for safe and optimal delivery of PN. A gap analysis was performed by a multihospital system to identify opportunities to enhance the current PN process using the EHR utilized by the organization.

G-quadruplex deconvolution with physiological mimicry enhances primary screening: Optimizing the FRET Melt2 assay.

Non-B-DNA G-quadruplex (G4) structures have shown promise as molecular targets. Modulating G4 stability for oncogenic transcriptional control is a promising avenue for the development of novel therapeutics. Extracellularly, G4 stabilization can be mediated by alkali cations, modifying water content, or with molecular crowding. Intracellularly, G4 formation is mediated by negative superhelicity and transcriptional activity, and can be stabilized with small molecules or oligonucleotides. Numerous G4-stabilizing compounds have been identified that impact promoter activity in plasmids. These compounds, however, infrequently show activity in cells, are found to have non-G4-mediated mechanisms of action, or do not demonstrate activity in vivo. The G4 field requires enhanced predictive screening methods to identify compounds with G4-mediated in vitro activity and in vivo efficacy. Using the best characterized promoter G4 to date, MYC, we examined the effects of varying annealing conditions (rate of cool down and number of heat/cool cycles), co-solvents (glucose, acetonitrile, polyethylene glycol, dextran sulfate, sucrose, ficoll-70, glycerol) and nucleoplasm on G4 formation and compound screening. We observed a marked decrease in hit rates when shifting from simple buffer conditions to include potassium and glycerol, and utilizing two or more rapid annealing cycles; the difference in hit compounds coincides with previous findings of active, inactive, and non-G4-mediated activity, including NSC338258, Quindoline i, and TMPyP4; with these changes, we describe a modification of the primary FRET Melt screening assay - the FRET Melt2. This understanding of physiological principles governing the above G4 formation will better inform future drug discovery efforts for this and other oncogenic promoters.