Publications by authors named "Joshua Makhoul"

Elevated endogenous estrogens stimulate human uterine artery endothelial cell (hUAEC) hydrogen sulfide (H2S) production by selectively upregulating the expression of H2S synthesizing enzyme cystathionine β-synthase (CBS), but the underlying mechanisms are underdetermined. We hypothesized that CBS transcription mediates estrogen-stimulated pregnancy-dependent hUAEC H2S production. Estradiol-17β (E2β) stimulated CBS but not cystathionine γ-lyase (CSE) expression in pregnant human uterine artery ex vivo, which was attenuated by the estrogen receptor (ER) antagonist ICI 182,780.

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Objectives: The aim of the study is to evaluate how current management of Category II fetal heart rate tracings compares with that suggested by a published algorithm and whether these differences lead to disparate neonatal outcomes.

Study Design: This is a retrospective observational study from the resident service at an academic-community tertiary care center from 2013 to 2018. We reviewed archived fetal heart rate tracings from patients with cesarean delivery performed for nonreassuring fetal heart rate tracing and interpreted tracings against the algorithm.

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To identify maternal and/or fetal characteristics associated with delivery within seven days for patients who present with vaginal bleeding in the antepartum period. This is a retrospective chart review performed at a community-academic tertiary care center. Three hundred and twenty-two consecutive charts associated with admission for vaginal bleeding during pregnancy between January 2015 and May 2020 were reviewed.

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Objective: To estimate alcohol, tobacco, and recreational drug use during pregnancy among nulliparous women.

Methods: In a cohort of nulliparous women followed through pregnancy from the first-trimester nuMoM2b (Nulliparous Outcomes in Pregnancy: Monitoring Mothers to be) study, self-reported use of alcohol, tobacco, and drugs was chronicled longitudinally at four study visits in this secondary analysis. Rates of use before pregnancy, in each trimester (visit 1, visit 2, visit 3, approximating each trimester), and at the time of delivery (visit 4) were recorded.

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While it is evident that the carboxyl-terminal region of natural peptide ligands bind to the amino-terminal domain of class B GPCRs, how their biologically critical amino-terminal regions dock to the receptor is unclear. We utilize cysteine trapping to systematically explore spatial approximations among residues in the first five positions of secretin and in every position within the receptor extracellular loops (ECLs). Only Cys(2) and Cys(5) secretin analogues exhibited full activity and retained moderate binding affinity (IC(50): 92±4 and 83±1 nM, respectively).

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Selective blockade of hypoxia-inducible gene expression by designed small molecules would prove valuable in suppressing tumor angiogenesis, metastasis and altered energy metabolism. We report the design, synthesis, and biological evaluation of a dimeric epidithiodiketopiperazine (ETP) small molecule transcriptional antagonist targeting the interaction of the p300/CBP coactivator with the transcription factor HIF-1alpha. Our results indicate that disrupting this interaction results in rapid downregulation of hypoxia-inducible genes critical for cancer progression.

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