Educational Studies Examining Knowledge of Substance Use Disorders and Career Aspirations Among Medical Trainees in an Inner-City Hospital.

OBJECTIVES: Gaps in addiction medicine training are a reason for poor substance use care in North America. Hospital addiction medicine consult services (AMCS) provide critical medical services, including screening and treatment of substance use disorders. Although these programs often feature an educational component for medical learners, the impact of AMCS teaching on objective knowledge and career aspirations in addiction medicine has not been well described. METHODS: The authors report findings from two sequential studies conducted at a large academic hospital in Vancouver, Canada. The first study assessed the impact of an AMCS clinical rotation on medical trainee addiction medicine objective knowledge using an online survey of 6 true/false questions before and after the rotation. The second study examined the impact of an AMCS rotation on career aspirations using 4 seven-point Likert-type questions. One-sample t tests on mean differences (MD) with Benjamini-Hochberg adjustment for multiple comparisons were employed for statistical analyses. RESULTS: Between May 2017 and June 2018, knowledge scores were significantly higher postrotation (MD = 4.78, standard deviation [SD] = 19.5, P = 0.034) among 115 medical trainees. Between July 2018 and July 2019, aspirations to practice addiction medicine were significantly more favorable postrotation (MD = 3.48, SD = 3.15, P < 0.001) among 101 medical trainees. CONCLUSIONS: AMCS rotations appear to improve addiction medicine knowledge and aspirations to practice addiction medicine among medical trainees. Larger-scale evaluations and outcomes research on integrating substance use disorders teaching in these settings will help move the discipline forward.

Targeting Semaphorin 3C in Prostate Cancer With Small Molecules.

Despite the amenability of early-stage prostate cancer to surgery and radiation therapy, locally advanced and metastatic prostate cancer is clinically problematic. Chemical castration is often used as a first-line therapy for advanced disease, but progression to the castration-resistant prostate cancer phase occurs with dependable frequency, largely through mutations to the androgen receptor (AR), aberrant AR signaling, and AR-independent mechanisms, among other causes. Semaphorin 3C (SEMA3C) is a secreted signaling protein that is essential for cardiac and neuronal development and has been shown to be regulated by the AR, to drive epithelial-to-mesenchymal transition and stem features in prostate cells, to activate receptor tyrosine kinases, and to promote cancer progression. Given that SEMA3C is linked to several key aspects of prostate cancer progression, we set out to explore SEMA3C inhibition by small molecules as a prospective cancer therapy. A homology-based SEMA3C protein structure was created, and its interaction with the neuropilin (NRP)-1 receptor was modeled to guide the development of the corresponding disrupting compounds. Experimental screening of 146 in silico‒identified molecules from the National Cancer Institute library led to the discovery of four promising candidates that effectively bind to SEMA3C, inhibit its association with NRP1, and attenuate prostate cancer growth. These findings provide proof of concept for the feasibility of inhibiting SEMA3C with small molecules as a therapeutic approach for prostate cancer.

Altered DNA methylation and expression of PLAGL1 in cord blood from assisted reproductive technology pregnancies compared with natural conceptions.

OBJECTIVE: To investigate DNA methylation and expression of imprinted genes and an imprinted gene network (IGN) in neonates conceived via assisted reproductive technology (ART). DESIGN: Case control. SETTING: Research institution. PATIENT(S): Two hundred sixty-four cases of cord blood and/or placental villi from neonates (101 IVF, 81 ICSI, 82 naturally conceived). INTERVENTION(S): Placentas were obtained at birth for biopsy and cord blood extraction. MAIN OUTCOME MEASURE(S): DNA methylation and expression of imprinted genes. RESULT(S): DNA methylation at the PLAGL1 differentially methylated region (DMR) was significantly higher in IVF cord blood (48.0%) compared with controls (46.0%). No differences were found in DNA methylation between conception modes for KvDMR1 and LINE-1 in cord blood and placenta as well as PLAGL1 and PEG10 in placenta villi. PLAGL1 expression was lower in both IVF and ICSI cord blood groups than in controls (relative quantification of 0.65, 0.74, 0.89, respectively). Analyzing the expression of 3 genes in a PLAGL1 regulated IGN revealed different expression between conception modes and a significant correlation to PLAGL1 expression in only one (KCNQ1OT1). CONCLUSION(S): Our results suggest a stability of DNA methylation at imprinted DMRs; however, we show PLAGL1 methylation/expression to be altered after ART. As PLAGL1 expression correlated with only one of the three IGN genes in cord blood, we propose there is a more complex mechanism of regulating the IGN that may involve other genes and epigenetic modifications in this tissue. Further research investigating IGN-implicated genes in various neonatal tissues is warranted to elucidate the full effects ART-induced alterations to PLAGL1 and the IGN may have on fetal growth/development.