Why Are There So Few Women Medical School Deans? Debunking the Myth That Shorter Tenures Drive Disparities.

PURPOSE: Gender disparities among the senior echelons of academic medicine are striking and persistent. The role of medical school dean has been particularly immune to gender diversity, and limited prior research identified women's shorter decanal tenures as a potential driver. The authors assessed gender differences in tenure length of deanships in the current era to elucidate this finding. METHOD: From October 2020 to June 2021, the authors collected information about medical school deanships that were held from January 1, 2006, to June 30, 2020. All schools were members of the Association of American Medical Colleges (AAMC). The authors collected data from online public records and augmented their findings via direct outreach to medical schools. They used time-to-event analyses before and after adjustment for interim vs permanent status of the initial appointment, school ownership (public/private), and school size to assess for gender differences in length of deanship tenure during the study period. The unit of analysis was deanships, and the primary outcome was length of deanships measured in years. RESULTS: Authors included data on 528 deanships. Women held 91 (17%) of these terms. Men held the majority of permanent deanships (n = 352 [85%]). A greater percentage of the deanships held by women were interim only (n = 27 [30%]) compared with men (n = 85 [20%]). In unadjusted and adjusted analyses, there were no significant gender differences in length of deanship tenures. CONCLUSIONS: Analysis of appointments of AAMC-member medical school deans from 2006 to 2020 revealed that women have remained in their deanships as long as their male counterparts. The myth about women deans' shorter longevity should no longer be promulgated. Academic medicine should consider novel solutions to addressing women's persistent underrepresentation in the dean role, including employing the gender proportionality principle used in the business and legal communities.

Licensing delineates helper and effector NK cell subsets during viral infection.

Natural killer (NK) cells can be divided into phenotypic subsets based on expression of receptors that bind self-MHC-I molecules, a concept termed licensing or education. Here we show NK cell subsets with different migratory, effector, and immunoregulatory functions in dendritic cell and antigen (ag)-specific CD8+ T cell responses during influenza and murine cytomegalovirus infections. Shortly after infection, unlicensed NK cells localized in draining lymph nodes and produced GM-CSF, which correlated with the expansion and activation of dendritic cells, and resulted in greater and sustained ag-specific T cell responses. In contrast, licensed NK cells preferentially migrated to infected tissues and produced IFN-γ. Importantly, human NK cell subsets exhibited similar phenotypic characteristics. Collectively, our studies demonstrate a critical demarcation between the functions of licensed and unlicensed NK cell subsets, with the former functioning as the classical effector subset and the latter as the stimulator of adaptive immunity helping to prime immune responses.

The office of student wellness: innovating to improve student mental health.

OBJECTIVE: Despite increasing mental health needs among medical students, few models for effective preventive student wellness programs exist. METHODS: This paper describes a novel approach developed at the University of California (UC) Davis School of Medicine: the Office of Student Wellness (OSW). RESULTS: Improved access and mental health service utilization have been documented, with over half of all students receiving support and clinical care. UC Davis student satisfaction mean scores on the Association of American Medical Colleges Graduation Questionnaire wellness questions have reached or exceeded national average over the last 4 years, since the OSW was founded. CONCLUSIONS: This program may serve as a blueprint for other medical schools in developing effective student wellness programs.

A transparent oversight policy for human anatomical specimen management: the University of California, Davis experience.

The authors describe the development and implementation of a University of California (UC) system of oversight, education, tracking, and accountability for human anatomical specimen use in education and research activities. This program was created and initially implemented at UC Davis in 2005. Several incidents arising out of the handling of human anatomical specimens at UC campuses revealed significant challenges in the system for maintaining control of human anatomical specimens used in education and research. These events combined to undermine the public perception for research and educational endeavors involving anatomical materials at public institutions. Risks associated with the acquisition, maintenance, and disposal of these specimens were not fully understood by the faculty, staff, and students who used them. Laws governing sources of specimens are grouped with those that govern organ procurement and tissue banking, and sometimes are found in cemetery and funeral regulations. These variables complicate interpretations and may hinder compliance. To regain confidence in the system, the need to set appropriate and realistic guidelines that mitigate risk and facilitate an institution's research and educational mission was identified. This article chronicles a multiyear process in which diverse stakeholders developed (1) a regulatory policy for oversight, (2) a policy education program, (3) procedures for tracking and accountability, and (4) a reporting and enforcement mechanism for appropriate and ethical use of human anatomical specimens in university education and research.

Murine NK-cell licensing is reflective of donor MHC-I following allogeneic hematopoietic stem cell transplantation in murine cytomegalovirus responses.

Natural killer (NK) cells express inhibitory receptors with varied binding affinities to specific major histocompatibility complex class I (MHC-I) haplotypes. NK cells can be classified as licensed or unlicensed based on their ability or inability to bind MHC-I, respectively. The role of donor vs host MHC on their development after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is not known. Following reciprocal MHC-disparate allogeneic transplants and during de novo NK-cell recovery, depletion of the licensed and not unlicensed population of NK cells as determined by the licensing patterns of donor MHC-I haplotypes, resulted in significantly increased susceptibility to murine cytomegalovirus (MCMV) infection. A corresponding expansion of the licensed Ly49H(+) NK cells occurred with greater interferon γ production by these cells than unlicensed NK cells in the context of donor MHC-I. Thus, NK licensing behavior to MCMV corresponds to the donor, and not recipient, MHC haplotype after allo-HSCT in mice.

Contrasting effects of anti-Ly49A due to MHC class I cis binding on NK cell-mediated allogeneic bone marrow cell resistance.

NK subsets have activating and inhibitory receptors that bind MHC-I. Ly49A is a mouse inhibitory receptor that binds with high affinity to H2(d) in both a cis- and trans-manner. Ly49A cis-associations limit trans-interactions with H2(d)-expressing targets as well as mAb binding. We demonstrate that cis-interactions affect mAb effector functions. In vivo administration of anti-Ly49A depleted NK cells in H2(b) but not H2(d) mice. Despite lack of depletion, in vivo treatment with anti-Ly49A reduced NK killing capabilities and inhibited activation, partially due to its agonistic effect. These data explain the previously described in vivo effects on bone marrow allograft rejection observed with anti-Ly49A treatment in H2(d)-haplotype mice. However, prior treatment of mice with poly(I:C) or mouse CMV infection resulted in increased Ly49A expression and Ly49A(+) NK cell depletion in H2(d) mice. These data indicate that, although Ly49 mAbs can exert similar in vivo effects in mice with different MHC haplotypes, these effects are mediated via different mechanisms of action correlating with Ly49A expression levels and can be altered within the same strain contingent on stimuli. This illustrates the marked diversity of mAb effector functions due to the regulation of the level of expression of target Ags and responses by stimulatory incidents such as infection.

Prioritizing health disparities in medical education to improve care.

Despite yearly advances in life-saving and preventive medicine, as well as strategic approaches by governmental and social agencies and groups, significant disparities remain in health, health quality, and access to health care within the United States. The determinants of these disparities include baseline health status, race and ethnicity, culture, gender identity and expression, socioeconomic status, region or geography, sexual orientation, and age. In order to renew the commitment of the medical community to address health disparities, particularly at the medical school level, we must remind ourselves of the roles of doctors and medical schools as the gatekeepers and the value setters for medicine. Within those roles are responsibilities toward the social mission of working to eliminate health disparities. This effort will require partnerships with communities as well as with academic centers to actively develop and to implement diversity and inclusion strategies. Besides improving the diversity of trainees in the pipeline, access to health care can be improved, and awareness can be raised regarding population-based health inequalities.

Murine natural killer cell licensing and regulation by T regulatory cells in viral responses.

Natural killer (NK) cells show differential functionality based on their capability of binding to self-MHC consistent with licensing. Here we show in vivo confirmation of the physiologic effects of licensing with differential effects of NK subsets on anti-murine cytomegalovirus (anti-MCMV) responses after syngeneic hematopoietic stem cell transplantation (HSCT) or regulatory T-cell (Treg) depletion. After HSCT, depletion of licensed NK cells led to far greater viral loads in target organs early after infection compared with nondepleted and unlicensed depleted mice. There was a preferential expansion of licensed, C-type lectin-like activating receptor Ly49H+ NK cells with increased IFNγ production after infection in nondepleted mice post-HSCT and after Treg depletion. Adoptive transfer of licensed NK subsets into immunodeficient hosts provided significantly greater MCMV resistance compared with transfer of total NK populations or unlicensed subsets. In non-HSCT mice, only concurrent depletion of Tregs or TGF-ß neutralization resulted in detection of NK licensing effects. This suggests that licensed NK cells are the initial and rapidly responding population of NK cells to MCMV infection, but are highly regulated by Tregs and TGF-ß.

Murine cytomegalovirus (MCMV) infection upregulates P38 MAP kinase in aortas of Apo E KO mice: a molecular mechanism for MCMV-induced acceleration of atherosclerosis.

Multiple studies suggest an association between cytomegalovirus (CMV) infection and atherogenesis; however, the molecular mechanisms by which viral infection might exacerbate atherosclerosis are not well understood. Aortas of MCMV-infected and uninfected Apo E knockout (KO) mice were analyzed for atherosclerotic lesion development and differential gene expression. Lesions in the infected mice were larger and showed more advanced disease compared to the uninfected mice. Sixty percent of the genes in the MAPK pathway were upregulated in the infected mice. p38 and ERK 1/2 MAPK genes were 5.6- and 2.0-fold higher, respectively, in aortas of infected vs. uninfected mice. Levels of VCAM-1, ICAM-1, and MCP-1 were ~2.0-2.6-fold higher in aortas of infected vs. uninfected mice. Inhibition of p38 with SB203580 resulted in lower levels of pro-atherogenic molecules and MCMV viral load in aortas of infected mice. MCMV-induced upregulation of p38 may drive the virus-induced acceleration of atherogenesis observed in our model.

Women's Health Research: Road Map to the Future.

For more than 20 years, the US National Institutes of Health (NIH) Office of Research on Women's Health (ORWH) has promoted the NIH's research agenda on women's health and sex and gender issues. Important biological and behavioral differences between women and men influence health and well-being, affecting normal function as well as the manifestations, epidemiology, and response to treatment of many illnesses. This special issue is dedicated to reaching across the globe to increase awareness of the importance of women's health research and to stimulate consideration of sex and gender differences in research at institutions around the world.

Paradoxical response to prophylactic Didox (N-3, 4 trihydroxybenzamide) treatment in murine cytomegalovirus-infected mice.

BACKGROUND: In this study, we investigated the effect of Didox (DX) on the pathogenicity of and host responses to murine cytomegalovirus (MCMV) infection. METHODS: In vitro efficacy of DX against MCMV was determined using plaque reduction assays. For in vivo studies, mice infected with a sublethal dose (10(4) PFU) of MCMV were treated daily with DX (200 mg/kg) using either a prophylactic or delayed protocol. At predetermined intervals, target organs were removed for histopathology. Cytokine transcription and viral load were performed using real-time PCR. Serum cytokine levels were determined by ELISA, and T-cell markers by real-time PCR. RESULTS: DX (0.5-50 µM) inhibited MCMV plaque formation in vitro. However, in vivo, prophylactic DX treatment did not decrease viral load and prolonged hepatic proinflammatory cytokine transcription at days 3 and 5 post-infection, which corresponded with more severe histopathological changes observed in the liver. Significant CD8(+) T-cell marker suppression was seen, in accordance with DX-induced inhibition of lymphocyte proliferation observed in vitro. DX prolonged the recovery of MCMV-infected mice when given after infection was established. CONCLUSIONS: Despite promising MCMV inhibition in vitro, DX had no beneficial effect on MCMV disease in our model and paradoxically had adverse effects when administered prophylactically. The lack of correlation between in vitro activity and in vivo efficacy emphasizes the importance of selecting appropriate antiviral targets and of using animal models when testing new drugs.

Creating the future biomedical research workforce.

As an NIH task force ponders the future of the U.S. biomedical research workforce, clinical and translational scientists can contribute crucial insights and should share comments by 7 October 2011.

Interleukin-10 repletion suppresses pro-inflammatory cytokines and decreases liver pathology without altering viral replication in murine cytomegalovirus (MCMV)-infected IL-10 knockout mice.

OBJECTIVE AND DESIGN: To determine the role of interleukin-10 (IL-10) in protecting against the deleterious pro-inflammatory cytokine response to murine cytomegalovirus (MCMV), we studied the impact of IL-10 repletion in MCMV-infected IL-10 knockout (KO) mice. MATERIALS AND METHODS: IL-10 KO mice were infected with a sub-lethal dose of MCMV and treated daily with 5 µg of mouse recombinant IL-10 (mrIL-10). Cytokine transcription, viral load, cytokine expression and liver histopathology were assessed in IL-10 treated and untreated mice. RESULTS: mrIL-10 repletion suppressed the exaggerated pro-inflammatory cytokine response observed in IL-10 KO mice (vs. control) both systemically and at the organ level, without affecting viral load. Levels of IFN-γ and TNF-α mRNA in livers of treated mice were ~50-70-fold lower than in untreated mice at day 5 post-infection (p ≤ 0.05). In spleens and sera, levels of IFN-γ and IL-6 were significantly lower in treated mice than in untreated mice at day 5-7 post-infection (p ≤ 0.05). IL-10 blunting of cytokine responses was accompanied by attenuation of inflammation in livers of treated mice. CONCLUSIONS: Repletion of IL-10 modulates the exaggerated pro-inflammatory cytokine responses that characterize IL-10 KO mice and protects against liver damage without altering viral load. IL-10 may be useful to control dysregulated pro-inflammatory cytokines responses during CMV infection.