OBJECTIVES Numerous mechanisms for the formation of intimal hyperplasia have been proposed but none have been proven or accepted. Our research focuses on the potential role of Hypoxia Inducible Factors (HIFs), VEGF, and PDGF as well as the ERK, PI3-K/AKT pathway in hypoxia mediated intimal hyperplasia processes. We hypothesize that HIF and VEGF will be down regulated with supplemental oxygen in our arteriovenous fistula rabbit model. METHODS Rabbits were randomized into different experimental groups with varying oxygen exposure (21% O2 or 30% O2), and receipt of surgery (surgery with fistula formation, no surgery, or sham operation with skin incision only). Plasma samples were collected at designated intervals in which cytokines and smooth muscle cell proliferation were measured. In addition, cell specimens were exposed to hyperoxic, normoxic, and hypoxic environments with cytokines measured at various time points. RESULTS Placement of an arteriovenous fistula resulted in hypoxia induced HIF stabilization with a concurrent increase in VEGF levels. There was a 4.2-fold induction in HIF-1α levels in animals that were placed in normal air following surgery when compared to animals that were exposed to hyperoxic air. Also VEGF significantly increased post-surgery in the normoxic group, reaching a maximum VGEF level of 959 pg/mL. Plasma VEGF levels in the surgery plus supplemental oxygen group were significantly lower than the normoxic surgery group with almost a 45% reduction in plasma VEGF levels (524pg/mL). Activation of VEGF receptors on smooth muscle cells through ERK1 and AKT pathways resulted in significant smooth muscle cell proliferation and migration. These effects are dramatically reduced in animals that are exposed to a hyperoxic environment of 30% oxygen. CONCLUSIONS Our results suggest that short-term administration of supplemental oxygen inhibits HIFs and VEGF signaling to reduce smooth muscle proliferation in the local blood vessel. These results provide strong support for the therapeutic use of supplemental oxygen following arterial surgery to reduce intimal hyperplasia. These findings also provide a nidus for future clinical trials to determine whether this is clinical applicable in humans.

The purpose of this study was to determine whether maternal urinary phthalate metabolite concentrations are associated with the development of higher blood pressure or pregnancy-induced hypertension (PIH). Participants were women without chronic hypertension who enrolled in The Infant Development and the Environment Study, a prospective pregnancy cohort conducted at four U.S. academic medical centers from 2010–2012. Prenatal records were reviewed to obtain blood pressure measurements and diagnoses of PIH (gestational hypertension, preeclampsia, eclampsia, and HELLP syndrome, defined as hemolysis, elevated liver enzymes, and low platelet count). Complete-case analyses used multivariable linear and logistic regression for analysis of blood pressure measurements and PIH diagnoses, respectively. In the final dataset (N = 668), higher concentrations of first-trimester monoethyl phthalate (MEP) and mono-3-carboxypropyl phthalate (MCPP) and third-trimester mono-isobutyl phthalate (MiBP) were significantly associated with a medical chart diagnosis of PIH. First-trimester mono-n-butyl phthalate (MBP) and MEP along with the sum of di-(2-ethylhexyl) phthalate metabolites (∑DEHP) were each associated with increased systolic blood pressure across pregnancy. In conclusion, several phthalate metabolite concentrations were significantly associated with PIH and greater increases in systolic blood pressure across pregnancy.

Introduction/Aims Graduate medical education programs must ensure residents and fellows acquire skills needed for independent practice. Workplace‐based observational assessments are informative but can be time‐ and resource‐intensive. In this study we sought to gather “relations‐to‐other‐variables” validity evidence for scores generated by the Electromyography Direct Observation Tool (EMG‐DOT) to inform its use as a measure of electrodiagnostic skill acquisition. Methods Scores on multiple assessments were compiled by trainees during Clinical Neurophysiology and Electromyography rotations at a large US academic medical center. Relationships between workplace‐based EMG‐DOT scores (n = 298) and scores on a prerequisite simulated patient exercise, patient experience surveys (n = 199), end‐of‐rotation evaluations (n = 301), and an American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) self‐assessment examination were assessed using Pearson correlations. Results Among 23 trainees, EMG‐DOT scores assigned by physician raters correlated positively with end‐of‐rotation evaluations (r = 0.63, P = .001), but EMG‐DOT scores assigned by technician raters did not (r = 0.10, P = .663). When physician and technician ratings were combined, higher EMG‐DOT scores correlated with better patient experience survey scores (r = 0.42, P = .047), but not with simulated patient or AANEM self‐assessment examination scores. Discussion End‐of‐rotation evaluations can provide valid assessments of trainee performance when completed by individuals with ample opportunities to directly observe trainees. Inclusion of observational assessments by technicians and patients provides a more comprehensive view of trainee performance. Workplace‐ and classroom‐based assessments provide complementary information about trainee performance, reflecting underlying differences in types of skills measured.

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