Just Pop It: Early AROM After Cervical Ripening Reduces the Time to Delivery.

In pregnant patients at term undergoing induction of labor, early time-based artificial rupture of membranes (AROM) within 1 hour of Foley bulb expulsion results in a shorter duration of labor by nearly 9 hours with no significant difference in cesarean delivery rates or maternal or neonatal adverse outcomes..

An intersectional examination of the opportunity gap in science: A critical quantitative approach to latent class analysis.

This study employs a critical quantitative lens to model intersectionality in quantitative analysis and examine how inequities are perpetuated in U.S. schools.

Selectivity, ligand deconstruction, and cellular activity analysis of a BPTF bromodomain inhibitor.

Bromodomain and PHD finger containing protein transcription factor (BPTF) is an epigenetic protein involved in chromatin remodelling and is a potential anticancer target. The BPTF bromodomain has one reported small molecule inhibitor (AU1, rac-1). Here, advances made on the structure-activity relationship of a BPTF bromodomain ligand are reported using a combination of experimental and molecular dynamics simulations leading to the active enatiomer (S)-1.

HNF4A Regulates the Formation of Hepatic Progenitor Cells from Human iPSC-Derived Endoderm by Facilitating Efficient Recruitment of RNA Pol II.

Elucidating the molecular basis of cell differentiation will advance our understanding of organ development and disease. We have previously established a protocol that efficiently produces cells with hepatocyte characteristics from human induced pluripotent stem cells. We previously used this cell differentiation model to identify the transcription factor hepatocyte nuclear factor 4 α (HNF4A) as being essential during the transition of the endoderm to a hepatic fate.

A Drug Screen using Human iPSC-Derived Hepatocyte-like Cells Reveals Cardiac Glycosides as a Potential Treatment for Hypercholesterolemia.

Efforts to identify pharmaceuticals to treat heritable metabolic liver diseases have been hampered by the lack of models. However, cells with hepatocyte characteristics can be produced from induced pluripotent stem cells (iPSCs). Here, we have used hepatocyte-like cells generated from homozygous familial hypercholesterolemia (hoFH) iPSCs to identify drugs that can potentially be repurposed to lower serum LDL-C.

Protein-Observed Fluorine NMR Is a Complementary Ligand Discovery Method to H CPMG Ligand-Observed NMR.

To evaluate its potential as a ligand discovery tool, we compare a newly developed 1D protein-observed fluorine NMR (PrOF NMR) screening method with the well-characterized ligand-observed H CPMG NMR screen. We selected the first bromodomain of Brd4 as a model system to benchmark PrOF NMR because of the high ligandability of Brd4 and the need for small molecule inhibitors of related epigenetic regulatory proteins. We compare the two methods' hit sensitivity, triaging ability, experiment speed, material consumption, and the potential for false positives and negatives.

Protein-observed (19)F-NMR for fragment screening, affinity quantification and druggability assessment.

NMR spectroscopy can be used to quantify the binding affinity between proteins and low-complexity molecules, termed 'fragments'; this versatile screening approach allows researchers to assess the druggability of new protein targets. Protein-observed (19)F-NMR (PrOF NMR) using (19)F-labeled amino acids generates relatively simple spectra that are able to provide dynamic structural information toward understanding protein folding and function. Changes in these spectra upon the addition of fragment molecules can be observed and quantified.

Prediction of (19)F NMR Chemical Shifts in Labeled Proteins: Computational Protocol and Case Study.

The structural analysis of ligand complexation in biomolecular systems is important in the design of new medicinal therapeutic agents; however, monitoring subtle structural changes in a protein's microenvironment is a challenging and complex problem. In this regard, the use of protein-based (19)F NMR for screening low-molecular-weight molecules (i.e.

Paramagnetic relaxation enhancement for protein-observed F NMR as an enabling approach for efficient fragment screening.

Protein-observed F (PrOF) NMR is an emerging tool for ligand discovery. To optimize the efficiency of PrOF NMR experiments, paramagnetic relaxation enhancement through the addition of chelated Ni(II) was used to shorten longitudinal relaxation time without causing significant line broadening. Thus enhancing relaxation time leads to shorter experiments without perturbing the binding of low- or high-affinity ligands.

FGF2 mediates hepatic progenitor cell formation during human pluripotent stem cell differentiation by inducing the WNT antagonist NKD1.

Fibroblast growth factors (FGFs) are required to specify hepatic fate within the definitive endoderm through activation of the FGF receptors (FGFRs). While the signaling pathways involved in hepatic specification are well understood, the mechanisms through which FGFs induce hepatic character within the endoderm are ill defined. Here we report the identification of genes whose expression is directly regulated by FGFR activity during the transition from endoderm to hepatic progenitor cell.

Dual Screening of BPTF and Brd4 Using Protein-Observed Fluorine NMR Uncovers New Bromodomain Probe Molecules.

Bromodomain-containing protein dysregulation is linked to cancer, diabetes, and inflammation. Selective inhibition of bromodomain function is a newly proposed therapeutic strategy. We describe a (19)F NMR dual screening method for small molecule discovery using fluorinated tryptophan resonances on two bromodomain-containing proteins.

Fluorinated aromatic amino acids are sensitive 19F NMR probes for bromodomain-ligand interactions.

We describe a (19)F NMR method for detecting bromodomain-ligand interactions using fluorine-labeled aromatic amino acids due to the conservation of aromatic residues in the bromodomain binding site. We test the sensitivity, accuracy, and speed of this method with small molecule ligands (+)-JQ1, BI2536, Dinaciclib, TG101348, and acetaminophen using three bromodomains Brd4, BrdT, and BPTF. Simplified (19)F NMR spectra allowed for simultaneous testing of multiple bromodomains to assess selectivity and identification of a new BPTF ligand.

Embryonic stem cell-derived cardiomyocyte heterogeneity and the isolation of immature and committed cells for cardiac remodeling and regeneration.

Pluripotent stem cells represent one promising source for cell replacement therapy in heart, but differentiating embryonic stem cell-derived cardiomyocytes (ESC-CMs) are highly heterogeneous and show a variety of maturation states. In this study, we employed an ESC clonal line that contains a cardiac-restricted ncx1 promoter-driven puromycin resistance cassette together with a mass culture system to isolate ESC-CMs that display traits characteristic of very immature CMs. The cells display properties of proliferation, CM-restricted markers, reduced mitochondrial mass, and hypoxia-resistance.

Sparfloxacin versus cefaclor in the treatment of patients with community-acquired pneumonia: a randomized, double-masked, comparative, multicenter study.

Community-acquired pneumonia remains an important infectious disease problem, with more than 4 million cases occurring in the United States annually. Although Streptococcus pneumoniae remains the most commonly identified organism, a variety of bacterial and nonbacterial pathogens may be involved. Hospitalization is unnecessary in most cases, and oral antibiotic therapy is common.

Efficacy and tolerability of enalapril and sustained-release verapamil in older patients with mild to moderate essential hypertension.

The study involved 113 patients over age 50 years with mild to moderate essential hypertension, randomly assigned to treatment with enalapril (n = 54) or sustained-release verapamil (n = 59). During an eight-week titration period, doses were adjusted to achieve supine diastolic blood pressures (DBP) below 90 mmHg; patients were then given maintenance doses for eight weeks. Mean blood pressures were reduced significantly from 147.

Comparison of enalapril and hydrochlorothiazide in mild hypertension and changes in plasma lipid concentrations during therapy.

An open, randomized, parallel clinical study comparing the antihypertensive efficacy and tolerability of the angiotensin converting enzyme inhibitor enalapril and the diuretic hydrochlorothiazide was carried out in 40 patients with mild uncomplicated essential hypertension. Changes in plasma lipid profiles were also studied. The results show that the two treatments were equally efficacious in controlling blood pressure and were generally well tolerated.