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Background: Women are underrepresented within internal medicine (IM). Whether women leaders attract women trainees is not well explored. Objective: To characterize leader and trainee gender across US academic IM and to investigate the association of leader gender with trainee gender. Design: Cross-sectional study. Participants: Leaders (chairs, chiefs, program directors (PDs)) in 2018 and trainees (residents, fellows) in 2012–2016 at medical school-affiliated IM and seven IM fellowship programs. Exposure: Leadership (chair/chief and program director; and, for resident analyses, fellow) gender. Main Measures: Our primary outcome was percent women trainees (IM residents and, separately, subspecialty fellows). We used standard statistics to describe leadership and trainee gender. We created separate multivariable linear regressions to evaluate associations of leader gender and percent women fellows with percent women IM residents. We then created separate multivariable multilevel models (site as a random effect) to evaluate associations of leader gender with percent women subspecialty fellows. Key Results: Our cohort consisted of 940 programs. Women were 13.4% of IM chairs and <25% of chiefs in each fellowship subspecialty (cardiology: 2.6%; gastroenterology: 6.6%; pulmonary and critical care: 10.7%; nephrology: 14.4%; endocrinology: 20.6%; hematology-oncology: 23.2%; infectious diseases: 24.3%). IM PDs were 39.7% women; fellowship PDs ranged from nearly 25% (cardiology and gastroenterology) to nearly 50% (endocrinology and infectious disease) women. Having more women fellows (but not chairs or PDs) was associated with having more women residents (0.3% (95% CI: 0.2–0.5%) increase per 1% fellow increase, p<0.001); this association remained after adjustment (0.3% (0.1%, 0.4%), p=0.001). In unadjusted analyses, having a woman PD (increase of 7.7% (4.7%, 10.6%), p<0.001) or chief (increase of 8.9% (4.6%, 13.1%), p<0.001) was associated with an increase in women fellows; after adjustment, these associations were lost. Conclusions: Women held a minority of leadership positions in academic IM. Having women leaders was not independently associated with having more women trainees. [ABSTRACT FROM AUTHOR]

Considerable interest has been generated from the results of recent clinical trials using smoothened (SMO) antagonists to inhibit the growth of hedgehog (HH) signaling-dependent tumors. This interest is tempered by the discovery of SMO mutations mediating resistance, underscoring the rationale for developing therapeutic strategies that interrupt HH signaling at levels distinct from those inhibiting SMO function. Here, we demonstrate that HH-dependent non-small cell lung carcinoma (NSCLC) growth is sensitive to blockade of the HH pathway upstream of SMO, at the level of HH ligand processing. Individually, the use of different lentivirally delivered shRNA constructs targeting two functionally distinct HH-processing proteins, skinny hedgehog (SKN) or dispatched-1 (DISP-1), in NSCLC cell lines produced similar decreases in cell proliferation and increased cell death. Further, providing either an exogenous source of processed HH or a SMO agonist reverses these effects. The attenuation of HH processing, by knocking down either of these gene products, also abrogated tumor growth in mouse xenografts. Finally, we extended these findings to primary clinical specimens, showing that SKN is frequently overexpressed in NSCLC and that higher DISP-1 expression is associated with an unfavorable clinical outcome. Our results show a critical role for HH processing in HH-dependent tumors, identifies two potential druggable targets in the HH pathway, and suggest that similar therapeutic strategies could be explored to treat patients harboring HH ligand-dependent cancers. [ABSTRACT FROM AUTHOR]

Cells derived from the endothelium of human iliac arteries were cultured in vivo. The cells were isolated, grown, and subcultured in HEPES buffered Medium 199 supplemented with 20% heat inactivated human whole blood serum, human alpha-thrombin, and commercial endothelial cell growth supplement derived from bovine brain. The cells were viable in culture for 8 to 10 passages at a split ratio of 1:3. After the 10th passage, the cells began to enlarge and their growth rate was reduced. No cultures were viable after the 12th passage. The cells were determined to be of endothelial origin by their morphology at confluence; their ultrastructural characteristics, including the presence of Weibel-Palade bodies; the production and release of factor VIII-related antigen; and by their maintenance of a surface that prevented platelet attachment. The cultured arterial endothelial cells released prostacyclin in response to challenge with thrombin and protamine sulfate but not in response to bradykinin or the platelet-derived growth factor. Although the cultures described in this report were derived from patients with varying degrees of atherosclerotic disease, there were no significant differences in morphological or physiological parameters among these cultures or in comparison with commonly studied cells derived from human umbilical veins. [ABSTRACT FROM AUTHOR]