Faculty Bibliography

BACKGROUND:Most published treatment trials for cocaine use disorders (CUD) have been conducted with samples composed predominantly of White men and underrepresent women and racial/ethnic minorities. Because of the high prevalence of men and White individuals in CUD treatment trials, results from studies that have compared treatment outcomes by gender and race or ethnicity separately may not be representative of women or racial/ethnic minorities. METHODS:With a sample pooled from seven randomized clinical trials of treatment for CUD (n = 629), baseline characteristics and treatment outcome responses were compared with 4 subgroups of individuals created based on the intersection of gender and race (White men, Black men, White women and Black women). RESULTS:At baseline, sociodemographic status, pattern, frequency and severity of cocaine use, psychiatric comorbidities, employment and legal problems significantly differed across groups. Treatment outcome indicators collected during treatment and through follow-up, consistently indicated poorer outcomes among the sample of White women, but were similar for the other groups. CONCLUSIONS:Men and women with CUD from both racial groups enter treatment with different psychosocial issues (e.g., history of violence/trauma, financial problems, co-occurring psychiatric disorders) and substance use problems (e.g. types of substances) that may impact treatment outcomes and indicate a need for culturally-informed care to deliver more effective treatment for CUD. Poorer overall outcomes among White women may reflect the need for a more focused treatment approach for this group; and highlight the importance of evaluating gender and race in treatment trials to better address health disparities.

While much of the social and political attention surrounding the nationwide opioid epidemic has focused on the dramatic increase in overdose deaths among white, middle-class, suburban and rural users, the impact of the epidemic in Black communities has largely been unrecognized. Though rates of opioid use at the national scale are higher for whites than they are for Blacks, rates of increase in opioid deaths have been rising more steeply among Blacks (43%) than whites (22%) over the last five years. Moreover, the rate of opioid overdose deaths among Blacks already exceeds that of whites in several states. The lack of discussion of Black overdose deaths in the national opioid discourse further marginalizes Black people, and is highly consistent with a history of framing the addictions of people of color as deserving of criminal punishment, rather than worthy of medical treatment. This article argues that, because racial inequalities are embedded in American popular and political cultures as well as in medicine, the federal and state governments should develop more culturally targeted programs to benefit Black communities in the opioid crisis. Such programs include the use of faith-based organizations to deliver substance use prevention and treatment services, the inclusion of racial impact assessments in the implementation of drug policy proposals, and the formal consideration of Black people's interaction with the criminal justice system in designing treatment options.

PURPOSE/OBJECTIVE:The transition from medical school to residency is a critical step in the careers of physicians. Because of the standardized application process-wherein schools submit summative Medical Student Performance Evaluations (MSPE's)-it also represents a unique opportunity to assess the possible prevalence of racial and gender disparities, as shown elsewhere in medicine. METHOD/METHODS:The authors conducted textual analysis of MSPE's from 6,000 US students applying to 16 residency programs at a single institution in 2014-15. They used custom software to extract demographic data and keyword frequency from each MSPE. The main outcome measure was the proportion of applicants described using 24 pre-determined words from four thematic categories ("standout traits", "ability", "grindstone habits", and "compassion"). RESULTS:The data showed significant differences based on race and gender. White applicants were more likely to be described using "standout" or "ability" keywords (including "exceptional", "best", and "outstanding") while Black applicants were more likely to be described as "competent". These differences remained significant after controlling for United States Medical Licensing Examination Step 1 scores. Female applicants were more frequently described as "caring", "compassionate", and "empathic" or "empathetic". Women were also more frequently described as "bright" and "organized". CONCLUSIONS:While the MSPE is intended to reflect an objective, summative assessment of students' qualifications, these data demonstrate for the first time systematic differences in how candidates are described based on racial/ethnic and gender group membership. Recognizing possible implicit biases and their potential impact is important for faculty who strive to create a more egalitarian medical community.

Regulatory T cells (Tregs) control autoreactive T cells by inhibiting activation-induced proliferation and cytokine expression. The molecular mechanisms responsible for the inactivation of effector T cells by Tregs remain yet to be fully characterized. We report that T-helper cells stimulated in the presence of Tregs quickly activate NFAT1 and have increased NFAT1-dependent expression of the transcription repressor Ikaros. NFAT1 deficiency or dominant-negative Ikaros compromises Treg-mediated inhibition of T-helper cells in vitro and in vivo. Thus, our results place NFAT-dependent mechanisms as general regulators of T-cell tolerance and show that Treg-mediated suppression of T-helper cells results from the activation of NFAT-regulated gene expression.

AKT3, a member of the serine/threonine kinase AKT family, is involved in a variety of biologic processes. AKT3 is expressed in immune cells and is the major AKT isoform in the CNS representing 30% of the total AKT expressed in spinal cord, and 50% in the brain. Myelin-oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE) is a mouse model in which lymphocytes and monocytes enter the CNS, resulting in inflammation, demyelination, and axonal injury. We hypothesized that during EAE, deletion of AKT3 would negatively affect the CNS of AKT3(-/-) mice, making them more susceptible to CNS damage. During acute EAE, AKT3(-/-)mice were more severely affected than wild type (WT) mice. Evaluation of spinal cords showed that during acute and chronic disease, AKT3(-/-) spinal cords had more demyelination compared with WT spinal cords. Quantitative RT-PCR determined higher levels of IL-2, IL-17, and IFN-γ mRNA in spinal cords from AKT3(-/-) mice than WT. Experiments using bone marrow chimeras demonstrated that AKT3(-/-) mice receiving AKT3-deficient bone marrow cells had elevated clinical scores relative to control WT mice reconstituted with WT cells, indicating that altered function of both CNS cells and bone marrow-derived immune cells contributed to the phenotype. Immunohistochemical analysis revealed decreased numbers of Foxp3(+) regulatory T cells in the spinal cord of AKT3(-/-) mice compared with WT mice, whereas in vitro suppression assays showed that AKT3-deficient Th cells were less susceptible to regulatory T cell-mediated suppression than their WT counterparts. These results indicate that AKT3 signaling contributes to the protection of mice against EAE.