Impact of a 50-Year Premedical Postbaccalaureate Program in Graduating Physicians for Practice in Primary Care and Underserved Areas.

PURPOSE: To evaluate the effectiveness of Wayne State University School of Medicine's (WSUSOM's) 50-year premedical postbaccalaureate program (PBP)-the first and oldest in the United States-in achieving its goals, as measured by medical school matriculation and graduation, primary care specialization, and current practice location. METHOD: A retrospective study of a complete comparative dataset of 9,856 WSUSOM MD graduates (1979-2017) was performed in July-August 2018. This included 539 graduates who were admitted to the PBP between 1969 and 2012. Data collected included PBP students' sociodemographics, postgraduate specialization, residence location at time of admission to the PBP, and current medicine practice location. Health professional shortage areas (HPSAs) and medically underserved areas/populations (MUA/Ps) were determined for residence at admission to the PBP and current medicine practice location. RESULTS: Of the 539 PBP students, 463/539 (85.9%) successfully completed the PBP and matriculated to WSUSOM. Of those, 401/463 (86.6%) obtained an MD, and of those, 233/401 (58.1%) were female and 277/401 (69.1%) were African American. Average investment per PBP student was approximately $52,000 and for an MD graduate was approximately $77,000. The majority of PBP MD graduates with current practice information resided in HPSAs or MUA/Ps at admission to PBP (204/283, 72.1%) and were currently practicing in HPSAs or MUA/Ps (232/283, 82.0%), and 139/283 (49.1%) became primary care physicians (PCPs). Comparison of WSUSOM PBP and non-PBP MD graduates showed PBP physicians become PCPs and practice in HPSAs or MUA/Ps at higher rates than non-PBP physicians (P < .001). CONCLUSIONS: The PBP was successful in graduating a large proportion of physicians from socioeconomically disadvantaged and diverse backgrounds, who practice as PCPs and who practice in HPSAs and MUA/Ps, thereby accomplishing the PBP's goals of helping to address the broad health care needs of all people in the United States.

A conserved hydrolase responsible for the cleavage of aminoacylphosphatidylglycerol in the membrane of Enterococcus faecium.

Aminoacylphosphatidylglycerol synthases (aaPGSs) are enzymes that transfer amino acids from aminoacyl-tRNAs (aa-tRNAs) to phosphatidylglycerol (PG) to form aa-PG in the cytoplasmic membrane of bacteria. aa-PGs provide bacteria with resistance to a range of antimicrobial compounds and stress conditions. Enterococcus faecium encodes a triple-specific aaPGS (RakPGS) that utilizes arginine, alanine, and lysine as substrates. Here we identify a novel hydrolase (AhyD), encoded immediately adjacent to rakPGS in E. faecium, which is responsible for the hydrolysis of aa-PG. The genetic synteny of aaPGS and ahyD is conserved in >60 different bacterial species. Deletion of ahyD in E. faecium resulted in increased formation of Ala-PG and Lys-PG and increased sensitivity to bacitracin. Our results suggest that AhyD and RakPGS act together to maintain optimal levels of aa-PG in the bacterial membrane to confer resistance to certain antimicrobial compounds and stress conditions.

Coronary x-ray angiographic reconstruction and image orientation.

We have developed an interactive geometric method for 3D reconstruction of the coronary arteries using multiple single-plane angiographic views with arbitrary orientations. Epipolar planes and epipolar lines are employed to trace corresponding vessel segments on these views. These points are utilized to reconstruct 3D vessel centerlines. The accuracy of the reconstruction is assessed using: (1) near-intersection distances of the rays that connect x-ray sources with projected points, (2) distances between traced and projected centerlines. These same two measures enter into a fitness function for a genetic search algorithm (GA) employed to orient the angiographic image planes automatically in 3D avoiding local minima in the search for optimized parameters. Furthermore, the GA utilizes traced vessel shapes (as opposed to isolated anchor points) to assist the optimization process. Differences between two-view and multiview reconstructions are evaluated. Vessel radii are measured and used to render the coronary tree in 3D as a surface. Reconstruction fidelity is demonstrated via (1) virtual phantom, (2) real phantom, and (3) patient data sets, the latter two of which utilize the GA. These simulated and measured angiograms illustrate that the vessel center-lines are reconstructed in 3D with accuracy below 1 mm. The reconstruction method is thus accurate compared to typical vessel dimensions of 1-3 mm. The methods presented should enable a combined interpretation of the severity of coronary artery stenoses and the hemodynamic impact on myocardial perfusion in patients with coronary artery disease.

Privileged structure-based quinazolinone natural product-templated libraries: identification of novel tubulin polymerization inhibitors.

A focused quinazolinone natural product-templated library was designed and synthesized. Compounds from this privileged structure-based library were identified as antimitotic agents acting through destabilization of tubulin polymerization. The results suggested that 2 could be a privileged substructure.

Novel one-pot total syntheses of deoxyvasicinone, mackinazolinone, isaindigotone, and their derivatives promoted by microwave irradiation.

[reaction: see text]. Total syntheses of deoxyvasicinone (1), mackinazolinone (2), and 8-hydroxydeoxyvasicinone (3) via novel microwave-assisted domino reactions, as well as a novel three-component one-pot total synthesis of isaindigotone (5) promoted by microwave irradiation, are reported. The efficient reaction process enabled us to rapidly access related natural product derivatives and to identify a new class of cytotoxic agents.