MD-PhD Program Graduates' Engagement in Research: Results of a National Study.

PURPOSE: To determine if specialty, among other professional development and demographic variables, predicted MD-PhD program graduates' research engagement. METHOD: The authors merged the 2015 Association of American Medical Colleges (AAMC) National MD-PhD Program Outcomes Survey database with selected data from the AAMC Student Records System, Graduation Questionnaire, and Graduate Medical Education (GME) Track Resident Survey. At the person level, they tested variables of interest for independent associations with MD-PhD graduates' research engagement using chi-square, Pearson correlations, and analysis of variance tests and logistic and linear regressions. RESULTS: Of 3,297 MD-PhD graduates from 1991-2010 who were no longer in GME training in 2015, 78.0% (2,572/3,297) reported research engagement. In models controlling for several variables, a neurology (vs internal medicine; adjusted odds ratio [AOR]: 2.48; 95% confidence interval [CI]: 1.60-3.86) or pathology (vs internal medicine; AOR: 1.89; 95% CI: 1.33-2.68) specialty, full-time faculty/research scientist career intention at graduation (vs all other career intentions; AOR: 3.04; 95% CI: 2.16-4.28), and ≥ 1 year of GME research (vs no GME research year[s]; AOR: 2.45; 95% CI: 1.96-3.06) predicted a greater likelihood of research engagement. Among graduates engaged in research, the mean percentage of research time was 49.9% (standard deviation 30.1%). Participation in ≥ 1 year of GME research (beta [ß] coefficient: 7.99, P < .001) predicted a higher percentage of research time, whereas a radiation oncology (ß: -28.70), diagnostic radiology (ß: -32.92), or surgery (ß: -29.61) specialty, among others, predicted a lower percentage of research time (each P < .001 vs internal medicine). CONCLUSIONS: Most MD-PhD graduates were engaged in research, but the extent of their engagement varied substantially among specialties. Across specialties, participation in research during GME may be one factor that sustains MD-PhD graduates' subsequent early- to midcareer research engagement.

Is conflict of interest becoming a challenge for institution-based institutional review boards?

Expansion of business relationships between academic institutions and their leaders and industry have become a reality, whereas media attention regarding conflict of interest (COI) at academic institutions has raised concerns about possible erosion of public trust. The Institutional Review Board (IRB) should collaborate with institutional COI committees to ensure that research with human subjects is in compliance with various applicable federal regulations. The IRB and COI committee should take additional independent action as necessary under their separate mandates to protect the welfare, safety, and rights of human subjects and to include limits on protocols affected by significant financial interests of the institution or its decision makers. If unable to review research due to an intrainstitutional conflict, the local IRB should consider transferring the study review and oversight to an external unaffiliated institutional or central IRB. A process for involvement of an executive institutional IRB is proposed.

Converting GLX2-1 into an active glyoxalase II.

Arabidopsis thaliana glyoxalase 2-1 (GLX2-1) exhibits extensive sequence similarity with GLX2 enzymes but is catalytically inactive with SLG, the GLX2 substrate. In an effort to identify residues essential for GLX2 activity, amino acid residues were altered at positions 219, 246, 248, 325, and 328 in GLX2-1 to be the same as those in catalytically active human GLX2. The resulting enzymes were overexpressed, purified, and characterized using metal analyses, fluorescence spectroscopy, and steady-state kinetics to evaluate how these residues affect metal binding, structure, and catalysis. The R246H/N248Y double mutant exhibited low level S-lactoylglutathione hydrolase activity, while the R246H/N248Y/Q325R/R328K mutant exhibited a 1.5-2-fold increase in k(cat) and a decrease in K(m) as compared to the values exhibited by the double mutant. In contrast, the R246H mutant of GLX2-1 did not exhibit glyoxalase 2 activity. Zn(II)-loaded R246H GLX2-1 enzyme bound 2 equiv of Zn(II), and (1)H NMR spectra of the Co(II)-substituted analogue of this enzyme strongly suggest that the introduced histidine binds to Co(II). EPR studies indicate the presence of significant amounts a dinuclear metal ion-containing center. Therefore, an active GLX2 enzyme requires both the presence of a properly positioned metal center and significant nonmetal, enzyme-substrate contacts, with tyrosine 255 being particularly important.