Preliminary outcomes of the Lake Erie College of Osteopathic Medicine's 3-year Primary Care Scholar Pathway in osteopathic predoctoral education.

CONTEXT: In 2007, the Lake Erie College of Osteopathic Medicine initiated its Primary Care Scholar Pathway (PCSP), a 3-year osteopathic predoctoral education curriculum. OBJECTIVE: To assess preliminary outcomes of the PCSP curriculum. METHODS: Scores for the Comprehensive Osteopathic Medical Licensing Examination (COMLEX-USA) Levels 1 and 2-Cognitive Evaluation (CE) and pass rates for Level 2-Performance Evaluation (PE) were obtained for individuals who graduated from the PCSP program in 2010, 2011, and 2012. Scores for Levels 1 and 2-CE were compared with national mean scores. Acceptance rates for residency programs were also recorded. RESULTS: Nineteen PCSP graduates were included in the study: 3 graduated in 2010, 6 graduated in 2011, and 10 graduated in 2012. Scores for PCSP students were not significantly different than national average scores for COMLEX-USA Levels 1 and 2-CE (P>.05). All 19 PCSP graduates passed the COMLEX-USA Level 2-PE on the first attempt, and all graduates were accepted into primary care residency programs. CONCLUSION: The COMLEX-USA scores of PCSP graduates were similar to national mean scores, suggesting that it is possible for osteopathic medical students to attain the same level of education as students of 4-year programs in less time. A 3-year osteopathic predoctoral education curriculum would allow students to complete their education at a reduced cost. This potential reduction in debt burden could encourage more students to pursue a primary care career and thus could help address the shortage of primary care physicians in the United States.

The impact of pharmacy students' remediation status on NAPLEX first-time pass rates.

OBJECTIVE: To determine whether there is a difference in pass rates on the North American Pharmacist Licensure Examination (NAPLEX) between students who did and did not require remediation for deficient course grades. METHODS: Student-specific data were collected regarding course grade deficiencies and completion of a comprehensive examination or course for remediation. Student-specific first-time NAPLEX performance data for the graduating classes of 2008, 2009, and 2011were provided by the National Association of Boards of Pharmacy (NABP). RESULTS: A significant difference was found in first-time NAPLEX mean pass rates between students who did not need to undergo remediation versus those who did ( 97% vs 70%). CONCLUSION: Students requiring remediation for deficient course grades had a lower pass rate on the NAPLEX compared with those who did not require remediation. The difference can be attributed to several factors and therefore further study is needed.

Synthesis of cell-permeable stapled peptide dual inhibitors of the p53-Mdm2/Mdmx interactions via photoinduced cycloaddition.

We report the first application of a photoinduced 1,3-dipolar cycloaddition reaction to 'staple' a peptide dual inhibitor of the p53-Mdm2/Mdmx interactions. A series of stapled peptide inhibitors were efficiently synthesized and showed excellent dual inhibitory activity in ELISA assay. Furthermore, the positively charged, stapled peptides showed enhanced cellular uptake along with modest in vivo activity.

A bioorthogonal chemistry strategy for probing protein lipidation in live cells.

We report a chemical lipidation model for the study of protein lipidations in vitro and in live mammalian cells based on a bioorthogonal, photoinduced tetrazole-alkene cycloaddition reaction.

Facile synthesis of stapled, structurally reinforced peptide helices via a photoinduced intramolecular 1,3-dipolar cycloaddition reaction.

We report the first use of a photoinduced 1,3-dipolar cycloaddition reaction in "stapling" peptide sidechains to reinforce a model peptide helical structure with moderate to excellent yields; the resulting pyrazoline "staplers" exhibit unique fluorescence useful in a cell permeability study.

Substrate properties of ubiquitin carboxyl-terminally derived peptide probes for protein ubiquitination.

Protein ubiquitination is a widespread protein posttranslational modification in eukaryotes that regulates essentially every aspect of cellular processes. The attachment of ubiquitin to a protein substrate is accomplished through an enzymatic cascade involving the actions of an activating enzyme (E1), a conjugating enzyme (E2), and a ligase (E3). There are more than 600 E3 ligases estimated to exist in the human genome that regulate the targeting specificity of protein ubiquitination. To understand the dynamic role of protein ubiquitination in biological processes, robust tools need to be developed which can be employed to establish the substrate specificity of each of these E3 ligases. In this report, we show that the ubiquitin carboxyl-terminally derived peptide probes can serve as modest ubiquitin surrogates for the ubiquitination pathway. In the E1-catalyzed probe adenylation assay, peptide probe 3 with a RLRGG recognition sequence exhibited the highest activity, with the k cat/ K 1/2 determined to be 1.1 x 10 (4) M (-1) s (-1), roughly 470-fold lower than that of ubiquitin. The rate of transfer from the E1 peptide probe thioesters to E2 showed clear sequence dependency, with peptide probe 4 with an LRLRGG recognition sequence showed the fastest rate ( t 1/2 = 0.9 min), essentially identical to that of ubiquitin ( t 1/2 = 0.8 min) under our assay conditions. Furthermore, peptide probes 4 and 8 also exhibited the selective, parkin-mediated labeling of tubulins in a semipurified tubulin-parkin complex. Finally, these carboxyl-terminally derived peptide probes were shown to label the ubiquitination substrates in fraction II of the rabbit reticulocyte lysate with an efficiency parallel to their substrate properties. The selective use of these ubiquitin carboxyl-terminally derived peptide probes by the ubiquitination pathway suggests that perhaps more potent peptide ubiquitination probes based on the ubiquitin C-terminal scaffold can be developed through additional structural optimization.