Publications

Community efforts and peer support programs are needed in addition to provider-initiated and opt-out HIV testing in adolescents, Sheri Weiser and colleagues discuss.

To characterize susceptibility to HIV infection, we phenotyped infected tonsillar T cells by single-cell mass cytometry and created comprehensive maps to identify which subsets of CD4+ T cells support HIV fusion and productive infection. By comparing HIV-fused and HIV-infected cells through dimensionality reduction, clustering, and statistical approaches to account for viral perturbations, we identified a subset of memory CD4+ T cells that support HIV entry but not viral gene expression. These cells express high levels of CD127, the IL-7 receptor, and are believed to be long-lived lymphocytes. In HIV-infected patients, CD127-expressing cells preferentially localize to extrafollicular lymphoid regions with limited viral replication. Thus, CyTOF-based phenotyping, combined with analytical approaches to distinguish between selective infection and receptor modulation by viruses, can be used as a discovery tool.

Since the 1990s it has been known that B and T lymphocytes exhibit low-level, constitutive signaling in the basal state (tonic signaling). These lymphocytes display a range of affinity for self, which in turn generates a range of tonic signaling. Surprisingly, what signaling pathways are active in the basal state and the functional relevance of the observed tonic signaling heterogeneity remain open questions today. Here we summarize what is known about the mechanistic and functional details of tonic signaling. We highlight recent advances that have increased our understanding of how the amount of tonic signal impacts immune function, describing novel tools that have moved the field forward and toward a molecular understanding of tonic signaling.

The androgen receptor (AR) has context-dependent roles in breast cancer growth and progression. Overall, high tumor AR levels predict a favorable patient outcome, but several studies have established a tumor promotional role for AR, particularly in supporting the growth of estrogen receptor positive (ER-positive) breast cancers after endocrine therapy. Our previous studies have demonstrated that obesity promotes mammary tumor progression after ovariectomy (OVX) in a rat model of postmenopausal breast cancer. Here, we investigated a potential role for AR in obesity-associated post-OVX mammary tumor progression following ovarian estrogen loss. In this model, we found that obese but not lean rats had nuclear localized AR in tumors that progressed 3 weeks after OVX, compared to those that regressed. AR nuclear localization is consistent with activation of AR-dependent transcription. Longer-term studies (8 weeks post-OVX) showed that AR nuclear localization and expression were maintained in tumors that had progressed, but AR expression was nearly lost in tumors that were regressing. The anti-androgen enzalutamide effectively blocked tumor progression in obese rats by promoting tumor necrosis and also prevented the formation of new tumors after OVX. Neither circulating nor mammary adipose tissue levels of the AR ligand testosterone were elevated in obese compared to lean rats; however, IL-6, which we previously reported to be higher in plasma from obese versus lean rats, sensitized breast cancer cells to low levels of testosterone. Our study demonstrates that, in the context of obesity, AR plays a role in driving ER-positive mammary tumor progression in an environment of low estrogen availability, and that circulating factors unique to the obese host, including IL-6, may influence how cancer cells respond to steroid hormones.

OBJECTIVE

Assess effects of a bedside interpreter-phone intervention on hospital discharge preparedness among patients with limited English proficiency (LEP).

METHODS

Mixed-methods study compared patient-reported discharge preparedness and knowledge of medications and follow-up appointments among 189 Chinese- and Spanish-speakers before (n=94) and after (n=95) bedside interpreter-phone implementation, and examined nurse and resident-physician interpreter-phone utilization through focus groups.

RESULTS

Pre-post discharge preparedness (Care Transitions Measure mean 77.2 vs. 78.5; p=0.62) and patient-reported knowledge of follow-up appointments, discharge medication administration and side effects did not differ significantly. Pre-post knowledge of medication purpose increased in bivariate (88% vs. 97%, p=0.02) and propensity score adjusted analyses [aOR (adjusted odds ratio), 4.49; 95% CI, 1.09-18.4]. Nurses and physicians reported using interpreter-phones infrequently for discharge communication, preferring in-person interpreters for complex discharges and direct communication with family for routine discharges. Post-implementation patients reported continued use of ad-hoc family interpreters (43%) or no interpretation at all (22%).

CONCLUSION

Implementation of a bedside interpreter-phone systems intervention did not consistently improve patient-reported measures of discharge preparedness, possibly due to limited uptake during discharges.

PRACTICE IMPLICATIONS

Hospital systems must better understand clinician preferences for discharge communication to successfully increase professional interpretation and shift culture away from using family members as interpreters.

Consumption of non- or low-fat dairy products is recommended as a strategy to lower the risk of childhood obesity. However, recent evidence suggests that consumption of whole fat dairy products may, in fact, be protective against obesity. Our objective was to determine the association between milk fat consumption and severe obesity among three-year-old Latino children, a population with a disproportionate burden of obesity and severe obesity. 24-hour-dietary recalls were conducted to determine child intake in San Francisco based cohort recruited in 2006-7. Mother-child dyads were weighed and measured. The 24-hour recall data was analyzed to determine participants' consumption of whole milk, 2% milk, and 1% milk. The milk consumption data was used to calculate grams of milk fat consumed. The cross-sectional association between milk fat intake and severe obesity (BMI ≥ 99th percentile) was determined using multivariable logistic regression. Data were available for 145 children, of whom 17% were severely obese. Severely obese children had a lower mean intake of milk fat (5.3 g vs. 8.9 g) and fewer drank any milk (79% versus 95% for not severely obese children (p < 0.01)). Among the potential confounders assessed, maternal BMI and maternal marital status were associated with severe obesity and were included in a multivariate model. In the multivariate model, higher milk fat consumption was associated with lower odds of severe obesity (OR 0.88 CI 0.80-0.97). Higher milk fat consumption is associated with lower odds of severe obesity among Latino preschoolers. These results call into question recommendations that promote consumption of lower fat milk.