Implementation of a Novel Residency-Based Electrocardiogram Curriculum Based on Free Open Access Content.

BACKGROUND: Interpretation of the electrocardiogram (ECG) is fundamental in the practice and teaching of emergency medicine. Previous studies have shown that providers of all levels have expressed interest in additional education with ECGs. Asynchronous learning has been shown to be beneficial for improving residents' ability to recognize findings of acute myocardial ischemia. OBJECTIVES: The goal of the study was to know whether a new format based on free, online content would improve residents' ability to interpret ECGs. METHODS: In this 1-year educational pilot study at a single urban teaching hospital, resident physicians participated in a longitudinal curriculum based on free, online content, which was delivered to them electronically on a weekly basis. The study was conducted during the 2016-2017 academic year. Prior to and after the study period, their subjective attitudes toward ECG interpretation, and their objective ability to interpret them successfully, were assessed. RESULTS: Of 42 residents, 25 (59.5%) completed the pre- and post-ECG testing. During the study period, trainees demonstrated improvement in both their subjective attitude toward ECG interpretation and their objective ability to interpret various abnormalities. CONCLUSIONS: Despite some important limitations, we believe this study represents an essential step in the development of training methods for the modern emergency medicine trainee.

Novel, abundant Drosha isoforms are deficient in miRNA processing in cancer cells.

MicroRNAs (miRNAs) are a class of small noncoding RNAs about 22-nucleotide (nt) in length that collectively regulate more than 60% of coding genes. Aberrant miRNA expression is associated with numerous diseases, including cancer. miRNA biogenesis is licenced by the ribonuclease (RNase) III enzyme Drosha, the regulation of which is critical in determining miRNA levels. We and others have previously revealed that alternative splicing regulates the subcellular localization of Drosha. To further investigate the alternative splicing landscape of Drosha transcripts, we performed PacBio sequencing in different human cell lines. We identified two novel isoforms resulting from partial intron-retention in the region encoding the Drosha catalytic domain. One isoform (AS27a) generates a truncated protein that is unstable in cells. The other (AS32a) produces a full-length Drosha with a 14 amino acid insertion in the RIIID domain. By taking advantage of Drosha knockout cells in combination with a previously established reporter assay, we demonstrated that Drosha-AS32a lacks cleavage activity. Furthermore, neither Drosha-27a nor Drosha-32a were able to rescue miRNA expression in the Drosha knockout cells. Interestingly, both isoforms were abundantly detected in a wide range of cancer cell lines (up to 15% of all Drosha isoforms). Analysis of the RNA-seq data from over 1000 breast cancer patient samples revealed that the AS32a is relatively more abundant in tumours than in normal tissue, suggesting that AS32a may play a role in cancer development.

Rabies Vaccination Compliance and Reasons for Incompletion.

INTRODUCTION: Rabies is a fatal disease with a 91% mortality rate in the United States. Current treatment of rabies consists of post-exposure prophylaxis treatment involving a complicated vaccination regimen. Studies conducted in other countries have found that patients do not complete their rabies vaccination treatment due to forgetting about their treatment, lack of time for visits, and the financial burden of treatment. However, little is known about why patients do not complete the rabies series in the US. The objective of this study was to determine the reasons why patients in the US do not complete rabies treatment. METHODS: We performed a retrospective study to evaluate rabies post-exposure prophylaxis completion in the emergency department of an academic suburban hospital between June 2014- July 2017. Further review was performed for patients who received inadequate vaccination to determine the cause of treatment incompletion. We conducted additional follow-up by phone survey for those patients who did not complete their rabies treatment but had no explanation for discontinuation available in the medical chart review. RESULTS: Results indicated 198 patients received rabies post-exposure treatment during the inclusion period. Of these, 145 patients completed the rabies vaccination regimen. Reasons for treatment incompletion were found for 29 patients, and 24 patients were lost to follow-up. Of the 29 patients for which discontinuation was assessed, 23 patients (79.3%) stopped treatment due to appropriate reasons - either the animal involved tested negative for the rabies virus or the patient had prior rabies treatment and only required two booster shots. Reasons for not completing the series when medically indicated included the patient deciding to not return for treatment, lack of awareness of the full vaccination regimen, and the patient declining initiation of rabies vaccination. CONCLUSION: Most patients in the US discontinue their rabies vaccination treatment for appropriate reasons; however, there is a proportion of patients who discontinue rabies vaccination when further treatment is medically indicated. This subset of patients is particularly at risk of rabies-related mortality, and additional measures need to be taken to ensure increased treatment compliance.

Hybrid molecular brushes with chitosan backbone: facile synthesis and surface grafting.

We developed a facile route toward amphiphilic hybrid molecular brushes (HMB) with chitosan backbone and concurrently grafted chains of poly(acrylamide) and polystyrene. The grafting occurs through amino groups of chitosan; no extra modification of chitosan is required. The kinetic and molecular weight characteristics of the primary molecular brush CHI-graft-PAAm are studied. The second step is grafting of PS by emulsion polymerization. The resulting HMB CHI-graft-PAAm-graft-PS form very stable emulsions. We attached the HMB on solid substrates using chitosan backbone by the "grafting to" approach. Thin films of the immobilized HMB of 3-11 nm thickness completely cover the surface. Being amphiphilic by nature, the immobilized HMB reveal the ability to adapt to the medium, which results in shifting of the hydrophobic/hydrophilic balance over a wide range.

TGF-beta blockade controls ascites by preventing abnormalization of lymphatic vessels in orthotopic human ovarian carcinoma models.

PURPOSE: Ovarian cancer patients with malignant ascites have poor prognosis. The accumulation of ascites is caused by an imbalance between fluid extravasation from the blood vessels and reabsorption by lymphatic vessels. Whereas, the role of TGF-ß in tumor progression has been well studied, the role of TGF-ß in lymphatic vessel function is far from understood. Here, we sought to dissect the role of TGF-ß blockade in the formation of ascites. EXPERIMENTAL DESIGN: We used soluble TGF-ß Receptor II (sTßRII) to block TGF-ß signaling in two orthotopic human ovarian carcinoma models: SKOV3ip1 and Hey-A8. We measured tumor proliferation, apoptosis, lymphangiogenesis, and angiogenesis by immunohistochemical staining, and examined diaphragm lymphatic vessel network by intraperitoneal injection of a fluorescent dye. Diaphragm lymphatic vessel function was assessed by tracking fluorescent beads in the diaphragm and measuring their drainage rate. RESULTS: TGF-ß blockade impaired tumor growth in both models, accompanied by a decreased tumor cell proliferation and angiogenesis. More strikingly, TGF-ß blockade almost completely abolished ascites formation. TGF-ß blockade significantly inhibited the expression of VEGF, which is the major contributor to ascites formation. At the same time, TGF-ß blockade prevent 'abnormalization' of diaphragm lymphatic vessels and improved ascites drainage. CONCLUSIONS: TGF-ß blockade decreased ascites by both inhibiting ascites formation and improving ascites drainage. Based on our finding, it is reasonable to consider the use of TGF-ß blockade as a palliative treatment for symptomatic ascites.

PDGF-D improves drug delivery and efficacy via vascular normalization, but promotes lymphatic metastasis by activating CXCR4 in breast cancer.

PURPOSE: Unlike platelet-derived growth factor-B (PDGF-B), the role of PDGF-D in tumor progression or treatment is largely unknown. To this end, we determined the role of PDGF-D in breast cancer progression, metastasis, and response to chemotherapy. EXPERIMENTAL DESIGN: We first examined PDGF-D expression in human breast carcinomas by immunohistochemical (IHC) staining. To mimic high PDGF-D expressing tumors, we stably transfected the breast cancer cell lines MDA-MB-231 and 4T1 with pdgf-d cDNA, and implanted these tumor cells orthtopically into nude mice. We monitored tumor growth by caliper measurement and bioluminescence imaging. We also used short hairpin RNA interference (shRNAi) and imatinib to block PDGF-D/PDGFRß signaling. Finally, we studied the effect of PDGF-D on doxorubicin delivery and efficacy. RESULTS: Human breast cancers express high levels of PDGF-D. Overexpression of PDGF-D promoted tumor growth and lymph node metastasis through increased proliferation, decreased apoptosis, and induction of CXCR4 expression. Blockade of CXCR4 signaling abolished PDGF-D-induced lymph node metastasis. Furthermore, overexpression of PDGF-D increased perivascular cell coverage and normalized tumor blood vessels. As a result, PDGF-D overexpression facilitated tissue penetration of doxorubicin and enhanced its treatment efficacy. CONCLUSIONS: PDGF-D is highly expressed in human breast cancer and facilitates tumor growth and lymph node metastasis, making it a potential target in breast cancer. At the same time, PDGF-D increases drug delivery and hence improves the efficacy of chemotherapy through vessel normalization. Therefore, judicious use of PDGF-D/PDGFRß blockers would be necessary to minimize the adverse effects on concomitantly administered cytotoxic therapies.