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Gender inequality exists in advanced faculty and leadership positions at academic medical centers; however, despite growing awareness, how to best approach and rectify the issue is unknown. To energize the conversation on gender inequality at one academic medical center, chairs and women faculty were surveyed to identify barriers faced by women navigating their careers. A symposium with short talks to increase awareness, a panel with University leaders to discuss issues and successful strategies to overcome gaps, and focus groups to delve further into key areas that underlie inequity through an active café style format were planned and implemented. This multifaceted approach resulted in a wealth of knowledge. The symposium and panel highlighted important relevant issues and offered personal strategies for successful career advancement, while the focus group discussions further identified barriers and inspired ongoing efforts across departments and novel approaches to overcome three key issues (work-life integration, deliberate promotion of mentor/sponsor relationships, and overcoming unconscious bias) identified through the initial surveys. Compiled data were then disseminated to participants and University leaders to enhance awareness of available programs and prompt action in critical areas lacking support. Overall, the approach indicated that securing support from leaders and the academic community alike are pertinent to emphasize actions needed to overcome issues affecting women in academic medicine. Moreover, bringing leaders and faculty together for an informational session and brainstorming appears to energize the conversation. Such efforts can ultimately instill change and establish an inclusive environment where all members of the academic medicine community can thrive.

Background: Wound healing is impaired in diabetes due to dysregulated inflammation. Previous studies by our group and others have demonstrated that inflammatory mediators are significantly increased in diabetic wounds, however, the mechanisms behind this hyper-inflammatory response remain largely unknown. As there is known to be high levels of endotoxin in type 2 diabetic (T2D) wounds, we aimed to assess the role of high fat diet (HFD) on Toll-Like Receptor 4 (TLR4) expression. We hypothesized that HFD/T2D would alter histone methylation, leading to increased receptor expression and enhanced inflammation. Methods: C57/BL6 mice were subjected to either normal or HFD for 12-16 weeks to induce the diet-induced obese (DIO) model of physiologic T2D. 4mm hindlimb wounds were created and healing was monitored daily using NIH ImageJ software. Bone marrow-derived macrophages (BMDM) were cultured and TLR4 expression measured by qPCR. Myeloid TLR4 protein expression was assessed in peripheral blood and wound cell isolates by analytical flow cytometry. Macrophages (NK1.1-/Ly6G-/CD11b+) were isolated using magnetic sorting and inflammatory cytokine expression determined with qPCR and bioplex. Chromatin Immunoprecipitation (ChIP) analysis at the NF-kB binding site on the TLR4 promoter was performed using antibodies to trimethylated Histone 3 Lysine 4 (H3K4me3). (N=~5 mice per group for all studies). Results: DIO mice demonstrated significantly delayed wound healing as compared to littermate controls and BMDM isolated from these mice revealed increased TLR4 gene expression. Correspondingly, peripheral blood and wound monocyte/macrophages showed increased TLR4 receptor levels by flow cytometry. ChIP analysis at the TLR4 promoter revealed significantly increased H3K4me3, a gene activating mark, in the HFD BMDM. Finally, macrophage wound isolates from DIO mice had elevated levels of inflammatory gene expression and cytokines. Conclusion: Enhanced H3K4me3 at the TLR4 promoter in diabetic macrophages may increase receptor expression and contribute to the hyper-inflammatory response seen in T2D. Further mechanistic studies are needed in order to examine the role of TLR4 in wound healing.

To describe the clinical course, resource use, and mortality of patients with leukemia admitted to the pediatric intensive care unit with sepsis and nonsepsis diagnoses over a 10-yr period.Retrospective analysis.Tertiary medical-surgical pediatric intensive care unit at C.S. Mott Children's Hospital, University of Michigan.All patients with leukemia admitted to the pediatric intensive care unit from January 1, 1998, to December 31, 2008.None; chart review.Clinical course was characterized by demographics, leukemia diagnosis, phase of therapy, leukocyte count on admission, presence of sepsis, steroid administration, intensity of care, and Pediatric Risk of Mortality score on admission to the pediatric intensive care unit. The primary outcome was survival to pediatric intensive care unit discharge. Among 68 single admissions to the pediatric intensive care unit with leukemia during the study period, 33 (48.5%) were admitted with sepsis. Admission to the pediatric intensive care unit for sepsis was associated with greater compromise of hemodynamic and renal function and use of stress dose steroids (p = .016), inotropic and/or vasopressor drugs (p = .01), and renal replacement therapy (p = .028) than nonsepsis admission. There was higher mortality among children with sepsis than other diagnoses (52% vs. 17%, p = .004). Also, mortality among children with sepsis was higher among those with acute lymphoblastic leukemia (60% vs. 44%) compared with acute myelogenous leukemia. Administration of stress dose steroids was associated with higher mortality (50% vs. 17%, p = .005) and neutropenia. Patients with acute lymphoblastic leukemia and sepsis showed the greatest mortality and resource use.Patients with acute leukemia and sepsis had a much higher mortality rate compared with previously described sepsis mortality rates for the general pediatric intensive care unit patient populations. Patients who received steroids had an increased mortality rate, but given the retrospective nature of this study, we maintain a position of equipoise with regard to this association. Variation in mortality and resource use by leukemia type suggests further research is needed to develop targeted intervention strategies to enhance patient outcomes.

Proinflammatory adipose tissue macrophages (ATMs) contribute to obesity-associated disease morbidity. We will provide an update of the current state of knowledge regarding the phenotypic and functional diversity of ATMs in lean and obese mice and humans.The phenotypic diversity of ATMs is now known to include more than two types requiring an expansion of the simple concept of an M2 to M1 shift with obesity. Potential functions for ATMs now include the regulation of fibrosis and response to acute lipolysis in states of caloric restriction. Novel pathways that can potentiate ATM action have been identified, which include inflammasome activation and the response to lipodystrophic adipose tissue. Studies provide a new appreciation for the ability of ATMs to respond dynamically to the adipose tissue microenvironment.ATMs play a key role in shaping the inflammatory milieu within adipose tissue, and it is now apparent that ATM heterogeneity is acutely shaped by the adipose tissue environment. To account for the new findings, we propose a new nomenclature for ATM subtypes that takes into account their diversity.