Characterization of applicants for residency training in pathology: Does diversity exist?

CONTEXT: A diverse workforce has been shown to improve productivity and innovation. The level of diversity among pathology residency applicants has not previously been reported. OBJECTIVE: This study aims to characterize the applicants at an academic pathology department to gain a better understanding of diversity among them. DESIGN: Between 2015 and 2017, data from a tertiary care center were analyzed for gender, US and international medical school, USMLE scores, and self-identified racial or ethnic group. For 2017, data was compared to that published by the Association of American Medical Colleges (AAMC). RESULTS: There were 1293 pathology applicants with 48-49% being female. The overall underrepresented minority (URM) applicant pool in pathology represented 12.6%, 9.5%, and 11.1% of our applicants for 2015, 2016, and 2017, respectively. URMs from US medical schools alone represented 4.7%, 3.7%, and 4.5% of our applicants for 2015, 2016, and 2017, respectively. The percentage of 2017 US medical school graduates applying to any US pathology training program was 22.2% versus 38.7% applying to pathology at our center (p ≤0.001). URM applicants for pathology from US medical schools were significantly lower than URM applicants to all AAMC medical specialties (p = 0.035). Among our pathology applicants in 2017, USMLE I scores and number of applicants with any publications were higher for non-URMs compared to URMs (p = 0.048 and p = 0.046, respectively). CONCLUSION: No significant difference related to gender was identified among our applicants while racial/ethnic groups remain underrepresented with significantly fewer URM applicants from US medical schools compared to published AAMC data for all medical specialties.

Ovarian cancer cells, not normal cells, are damaged by Mirk/Dyrk1B kinase inhibition.

Prior studies had shown that the Mirk/dyrk1B gene is amplified/upregulated in about 75% of ovarian cancers, that protein levels of this kinase are elevated in quiescent G0 cells and that Mirk maintains tumor cells in quiescence by initiating rapid degradation of cyclin D isoforms and by phosphorylation of a member of the DREAM complex. Depletion of Mirk/dyrk1B led to increased cyclin D levels, an elevated reactive oxygen species (ROS) content and loss of viability. However, many normal cells in vivo are quiescent, and therefore, targeting a kinase found in quiescent cells might be problematic. In our study, Mirk kinase activity was found to be higher in ovarian cancer cells than in normal cells. Pharmacological inhibition of Mirk/dyrk1B kinase increased cyclin D levels both in quiescent normal diploid cells and in quiescent CDKN2A-negative ovarian cancer cells, but led to more active CDK4/cyclin D complexes in quiescent ovarian cancer cells, allowing them to escape G0/G1 quiescence, enter cycle with high ROS levels and undergo apoptosis. The ROS scavenger N-acetyl cysteine reduced both the amount of cleaved poly(ADP-ribose) polymerase (PARP) and the extent of cancer cell loss. In contrast, normal cells were spared because of their expression of cyclin directed kinase (CDK) inhibitors that blocked unregulated cycling. Quiescent early passage normal ovarian epithelial cells and two strains of quiescent normal diploid fibroblasts remained viable after the inhibition of Mirk/dyrk1B kinase, and the few cells that left G0/G1 quiescence were accumulated in G2+M. Thus, inhibition of Mirk kinase targeted quiescent ovarian cancer cells.

Mild hypothermia inhibits inflammation after experimental stroke and brain inflammation.

BACKGROUND AND PURPOSE: We previously showed that mild hypothermia protects against experimental stroke, even when cooling was delayed by 2 hours. Protection may be due in part to inhibiting inflammation. To clarify, we examined leukocyte infiltration, microglial activation, and adhesion molecule expression in models of stroke and pure brain inflammation. METHODS: Rats underwent 2-hour middle cerebral artery occlusion (MCAO; n=36) or intravenous injection with 5 mg/kg lipopolysaccharide (LPS; n=22). Temperature was lowered to 33 degrees C for 2 hours or kept at 37 degrees C. In MCAO, cooling was applied intraischemically or on reperfusion (delayed). In the LPS model, cooling began after injection. One and 3 days later, brains were assessed for neutrophils, monocytes/microglia, major histocompatibility complex class II antigen, and intercellular adhesion molecule-1 (ICAM-1). RESULTS: One day after MCAO, both intraischemic and delayed hypothermia decreased ICAM-1 (51% and 60%, respectively, versus normothermia; P<0.001), monocytes (63% and 57%; P<0.01), and microglia (55% and 53%; P<0.001). Similar decreases were seen at 3 days for ICAM-1 (91% and 93%; P<0.001), monocytes (62% and 54%; P<0.01), and microglia (55% and 53%; P<0.001). In the LPS model, ED-1-positive cells were not observed in the brain, but hypothermia decreased ICAM-1 (26%; P<0.05), OX6 (56%; P<0.01), and microglia (47%; P<0.01) at 1 day. CONCLUSIONS: Mild hypothermia decreases inflammatory responses in both brain inflammation and stroke, implicating a direct anti-inflammatory effect of cooling. This suggests that hypothermia can attenuate factors contributing to delayed ischemic injury.