Search

Introduction: Virtual interviews (VI) are now a permanent part of pediatric emergency medicine (PEM) recruitment, especially given the cost and equity advantages. Yet inability to visit programs in person can impact decision-making, leading applicants to apply to more programs. Moreover, the cost advantages of VI may encourage applicants to apply to programs farther away than they might otherwise have been willing or able to travel. This could create unnecessary strain on programs. We conducted this study to determine whether PEM fellowship applicants would apply to a larger number of programs and in different geographic patterns with VI (2020 and 2021) as compared to in-person interviews (2018 and 2019)., Methods: We conducted an anonymous national survey of all PEM fellows comparing two cohorts: current fellows who interviewed inperson (applied in 2018/2019) and fellows who underwent VIs in 2020/2021 (current fellows and those recently matched in 2021). The study took place in March-April 2022. Questions focused on geographic considerations during interviews and the match. We used descriptive statistics, chi-square and t -tests for analysis., Results: Overall response rate was 42% (231/550); 32% (n = 74) interviewed in person and 68% (n = 157) virtually. Fellows applied to a median of 4/6 geographic regions (interquartile range 2, 5). Most applied for fellowship both in the same region as residency (216, 93%) and outside (192, 83%). Only the Pacific region saw a statistically significant increase in applicants during VI (59.9% vs 43.2%, P  = 0.02). There was no statistical difference in the number of programs applied to during in-person vs VI (mean difference (95% confidence interval 0.72, -2.8 - 4.2). A majority matched in their preferred state both during VI (60.4%) and in-person interviews (65.7%). The difference was not statistically significant ( P  = 0.45)., Conclusion: While more PEM fellowship applicants applied outside the geographic area where their residency was and to the Pacific region, there was no overall increase in the number of programs or geographic areas PEM applicants applied to during VI as compared to in-person interview seasons. As this was the first two years of VI, ongoing data collection will further identify trends and the impactof VI., Competing Interests: Conflicts of Interest: By the WestJEM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. No author has professional or financial relationships with any companies that are relevant to this study. There are no conflicts of interest or sources of funding to declare.

A series of 63 3-substituted quinoline derivatives has been prepared and tested for inhibition of cell-free platelet derived growth factor receptor tyrosine kinase (PDGF-RTK) activity. The compounds were generally prepared either by a Friedlander condensation between an aryl-acetaldehyde and an o-aminobenzaldehyde or by a palladium-catalyzed coupling between an aryl bromide or triflate and an organostannane or organozinc chloride. The presence of 6,7-dimethoxy groups on the quinoline ring was found to be advantageous although not essential for potent inhibition of PDGF-RTK. A lipophilic group attached to the quinoline 3-position contributed substantially to activity. The lipophilic groups generally consisted of monocyclic aromatics or small alkynyl, alkenyl, and alkyl groups. Optimum activity of ca. < or = 20 nM (IC50) was observed when 6,7-dimethoxyquinoline was substituted in the 3-position with 4-methoxyphenyl (15d), 3-fluoro-4-methoxyphenyl (17m), 3-fluorophenyl (17b), 4-hydroxyphenyl (24), 6-methoxypyridin-3-yl (15o), 5-pyridin-2(1H)-one (23), trans-beta-styryl (15e), thiophene-3-yl (2e), 5-chlorothiophene-2-yl (15f), or cyclopentenyl (17n) groups. Most of the compounds in the series were tested for inhibition of cell-free epidermal growth factor receptor tyrosine kinase activity and found to be inactive.

Tyrphostins are low-molecular-weight synthetic inhibitors of protein tyrosine kinase, which block cell proliferation. Since platelet-derived growth factor (PDGF) is thought to figure prominently in disorders of vascular smooth muscle cells (VSMC), such as atherosclerosis, hypertension, and restenosis, we examined whether tyrphostins would inhibit PDGF-induced mitogenesis in VSMC. In this communication, we demonstrate that tyrphostins with the benzenemalononitrile nucleus inhibited PDGF-dependent growth of VSMC as well as PDGF-dependent DNA synthesis in these cells, with the concentrations for 50% inhibition ranging from 0.04 to 9 microM. Up to 30-fold higher tyrphostin concentrations were required to inhibit serum-stimulated DNA synthesis of VSMC. The effect of the tyrphostins is reversible, since on their removal a normal proliferative response to PDGF was resumed. Tyrphostins also inhibited PDGF-receptor autophosphorylation and PDGF-induced phosphorylation of intracellular substrates, including the phosphorylation of phospholipase C-gamma, with a potency ratio similar to their antimitogenic activity. The expression of c-fos mRNA, a mitogenic nuclear signal, was also reduced in PDGF-stimulated VSMC treated with tyrphostins at concentrations which inhibit PDGF-induced mitogenesis. It is concluded that tyrphostins are potent reversible inhibitors of PDGF-induced mitogenesis which act by inhibiting the tyrosine kinase activity of the PDGF receptor and the subsequent signaling cascade. Tyrphostins may be useful in the study and treatment of VSMC proliferation disorders.

Administration of sodium aurothioglucose (10 mg/kg per day) to female rats for up to 8 weeks resulted in no apparent effects on the kidney. Gold accumulated in kidney, liver, spleen, pancreas, skin and blood. Although plasma and hepatic gold levels increased with time, no remarkable change in either copper, zinc or metallothionein (MT) levels was observed. Gel filtration chromatography of plasma showed binding of gold to albumin, whereas copper was associated with albumin, ceruloplasmin and a protein eluting in the void volume of the Sephadex G-150 column. Almost all of the hepatic gold was bound to proteins other than MT. In the kidney, not only gold but also copper and MT increased rapidly, reached a maximum between 2 and 4 weeks and exhibited insignificant change thereafter. Gold-treated animals showed an increase in binding of copper to the very high molecular weight plasma protein, which may be involved in transport of copper to the kidneys. Urinary gold and MT followed a pattern similar to that in the kidney. Renal zinc also increased but returned to normal by week 8. In renal cytosol 57% and 54% of the gold and copper, respectively, were associated with MT. It appears that the elevated levels of copper and zinc, rather than gold, are responsible for the induction of MT synthesis. This then provides a mechanism by which gold and the inducing metals are retained by the kidney.