The BiliCare(TM) demonstrated good performance with positive bias for the screening of jaundice in healthy late preterm or term infants. However, if adopted, proper cut-off levels should be chosen because of sub-optimal device precision.

We carried out a "pathway" screen of 50,000 small molecules to identify novel modulators of cAMP signaling. One class of compounds, the 2-(acylamino)-3-thiophenecarboxylates, strongly suppressed cAMP and cGMP in multiple cell lines in response to different agonists acting on G-protein-coupled receptors, adenylyl cyclase, and guanylyl cyclase. The best compounds from structure-activity analysis of 124 analogs, including several synthesized chiral analogs, had and IC 50 of Ͻ5 M for suppression of agonist-induced cAMP and cGMP elevation.

G-protein-coupled receptors (GPCRs) such as the vasopressin-2 receptor (V 2 R) are an important class of drug targets. We developed an efficient screen for GPCR-induced cAMP elevation using as read-out cAMP activation of cystic fibrosis transmembrane conductance regulator (CFTR) Cl Ϫ channels. Fischer rat thyroid cells expressing CFTR and a halide-sensing yellow fluorescent protein (H148Q/I152L) were transfected with V 2 R. Increased cell Cl Ϫ conductance after agonist-induced cAMP elevation was assayed using a plate reader from cell fluorescence after solution I Ϫ addition. The ZЈ factor for the assay was ϳ0.7 with the V 2 R agonist [deamino-Cys1, Val4, D-Arg8]-vasopressin (1 nM) as positive control. Primary screening of 50,000 small molecules yielded a novel, 5-aryl-4-benzoyl-3-hydroxy-1-(2-arylethyl)-2H-pyrrol-2-one class of V 2 R antagonists that are unrelated structurally to known V 2 R antagonists. The most potent compound, V 2 R inh -02, which was identified by screening 35 structural analogs, competitively inhibited V 2 R-induced cAMP elevation with K i value of ϳ70 nM and fully displaced radiolabeled vasopressin in binding experiments. V 2 R inh -02 did not inhibit forskolin or ␤ 2 -adrenergic receptor-induced cAMP production and was more than 50 times more potent for V 2 R than for V 1a R. The favorable in vitro properties of the pyrrol-2-one antagonists suggests their potential usefulness in aquaretic applications. The CFTR-linked cAMP assay developed here is applicable for efficient, high-throughput identification of modulators of cAMP-coupled GPCRs.

Due to the small sample size and potential bias accrued through random allocation of higher birthweight infants to the PEEP-5 group, the results did not confirm differences in outcomes between the groups, despite evidence favoring postnatal ventilation with PEEP. A further randomized, controlled clinical trial with a larger sample size is warranted to determine the utility and safety of PEEP during the resuscitation of premature infants immediately after birth.