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As the AAMC initiates a pilot for the Core Entrustable Professional Activities (EPAs) for Entering Residency, we are seeking baseline data from residency program directors about the readiness of graduates of LCME-accredited US medical schools to perform the 13 Core EPAs without direct supervision upon entry to residency. These EPAs are based on the work of a thirteen-member expert panel informed by the literature and by feedback from the academic medicine community. Your response will be helpful in establishing a baseline against which we can assess impact as some schools implement the Core EPAs for Entering Residency.Your participation in this project is voluntary. All responses are confidential. The data will be reported in aggregate by specialty type for research purposes. No individual respondent or individual program will be identified in any report of these data. This data collection activity has been reviewed according to AAMC policies and procedures and its Institutional Review Board and is considered to be minimal risk. The AAMC has taken extensive measures to ensure the security of the data and the confidentiality of the responses. Nevertheless, if individually identified data were made public, it could prove embarrassing. If you have any questions about your rights as a participant, contact the AAMC Office of Human Subjects Research Protection by email

Macrophage colony stimulating factor (MCSF) is important for formation of osteoclasts. We investigated the ability of 1,25(OH)2D3 to regulate osteoblast production of MCSF. Mouse calvarial osteoblasts were cultured for 2 days +/- 1,25(OH)2D3. Since 1, 25(OH)2D3 decreased osteoblast proliferation by 17.6 +/- 1% at 10 nM and 11 +/- 4% at 1 nM, the effect of growth rate on MCSF secretion was examined. Limiting cell proliferation by serum did not affect MCSF production. 1,25(OH)2D3 (1 nM) increased MCSF production (U/10(5) cells) maximally by 68 +/- 33% (n = 3) with an ED50 for 1, 25(OH)2D3 of 5 x 10(-11) M. To investigate effects of 1,25(OH)2D3 on MCSF gene regulation, RT-PCR primers were designed to identify the mRNA coding for the membrane-bound isoform of MCSF. Simultaneous RT-PCR of glyceraldehyde-phosphate dehydrogenase (GAP) allowed semiquantitative assessment of MCSF mRNA between treatment groups expressed as the MCSF/GAP RT-PCR product ratio; both MCSF and GAP (+) primers were labeled with 32P-ATP for phosphorimage quantitation. The membrane-bound MCSF/GAP PCR product ratio was not affected by proliferative rate when growth was limited by [serum]. The MCSF/GAP RT-PCR product ratio was dose dependently increased by 1,25(OH)2D3, maximally at 1 nM at 2.2 +/- 0.2 = fold (n = 10). 1,25 (OH)2D3 also increased the expression of an RT-PCR MCSF/GAP product ratio which represented the secreted isoform of MCSF. The ability of 1,25(OH)2D3 to pretranslationally regulate expression of membrane-bound osteoblast MCSF may be important in osteoblast:osteoclast interactions.

One of the forces generated during skeletal loading is hydrostatic pressure. In the work presented here, the ability of increased pressure to influence recruitment of osteoclasts was evaluated. Murine marrow cultures, with pO2 and pCO2 kept constant, were subjected to either control (1.0 atm) or elevated (1.37 or 2.0 atm) hydrostatic pressure. As compared to control, cultures pressurized for 6 days at 1.37 atm formed less osteoclast-like cells (OCLC) (71 +/- 6% of control, P < 0.0001). A similar degree of inhibition occurred in cultures exposed to pressure during days 2-4 only (62 +/- 6%), while treatment during days 5-7 failed to inhibit the OCLC number relative to control (99 +/- 5%). Delivery of 2.0 atm pressure on days 2-4 generated 52 +/- 4% OCLC compared to control. Since macrophage colony stimulating factor (MCSF)-dependent proliferation of osteoclast precursors occurs during the pressure-sensitive period, semiquantitative RT-PCR for MCSF mRNA was performed after 3 days in 1.37 atm (days 2-4). As compared to controls, pressure caused a decrease in mRNA coding for the membrane bound form of MCSF (71.2 +/- 4% (n = 25, P < or = 0.05), while the MCSF RT-PCR product representing the secreted form showed no consistent change. This lack of response of the soluble MCSF RT-PCR product was expected, as levels of bioassayable MCSF were not altered by pressure. Extrapolating these data to in vivo conditions suggests that load-bearing will inhibit the formation of osteoclasts.

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