Publications

For nearly 100 years, growth hormone (GH) has been known to affect insulin sensitivity and risk of diabetes. However, the tissue governing the effects of GH signaling on insulin and glucose homeostasis remains unknown. Excess GH reduces fat mass and insulin sensitivity. Conversely, GH insensitivity (GHI) is associated with increased adiposity, augmented insulin sensitivity, and protection from diabetes. Here, we induce adipocyte-specific GHI through conditional deletion of (JAK2A), an obligate transducer of GH signaling. Similar to whole-body GHI, JAK2A mice had increased adiposity and extreme insulin sensitivity. Loss of adipocyte augmented hepatic insulin sensitivity and conferred resistance to diet-induced metabolic stress without overt changes in circulating fatty acids. While GH injections induced hepatic insulin resistance in control mice, the diabetogenic action was absent in JAK2A mice. Adipocyte GH signaling directly impinged on both adipose and hepatic insulin signal transduction. Collectively, our results show that adipose tissue governs the effects of GH on insulin and glucose homeostasis. Further, we show that JAK2 mediates liver insulin sensitivity via an extrahepatic, adipose tissue-dependent mechanism.

BACKGROUND

Language barriers disrupt communication and impede informed consent for patients with limited English proficiency (LEP) undergoing healthcare procedures. Effective interventions for this disparity remain unclear.

OBJECTIVE

Assess the impact of a bedside interpreter phone system intervention on informed consent for patients with LEP and compare outcomes to those of English speakers.

DESIGN

Prospective, pre-post intervention implementation study using propensity analysis.

SUBJECTS

Hospitalized patients undergoing invasive procedures on the cardiovascular, general surgery or orthopedic surgery floors.

INTERVENTION

Installation of dual-handset interpreter phones at every bedside enabling 24-h immediate access to professional interpreters.

MAIN MEASURES

Primary predictor: pre- vs. post-implementation group; secondary predictor: post-implementation patients with LEP vs. English speakers. Primary outcomes: three central informed consent elements, patient-reported understanding of the (1) reasons for and (2) risks of the procedure and (3) having had all questions answered. We considered consent adequately informed when all three elements were met.

KEY RESULTS

We enrolled 152 Chinese- and Spanish-speaking patients with LEP (84 pre- and 68 post-implementation) and 86 English speakers. Post-implementation (vs. pre-implementation) patients with LEP were more likely to meet criteria for adequately informed consent (54% vs. 29%, p = 0.001) and, after propensity score adjustment, had significantly higher odds of adequately informed consent (AOR 2.56; 95% CI, 1.15-5.72) as well as of each consent element individually. However, compared to post-implementation English speakers, post-implementation patients with LEP had significantly lower adjusted odds of adequately informed consent (AOR, 0.38; 95% CI, 0.16-0.91).

CONCLUSIONS

A bedside interpreter phone system intervention to increase rapid access to professional interpreters was associated with improvements in patient-reported informed consent and should be considered by hospitals seeking to improve care for patients with LEP; however, these improvements did not eliminate the language-based disparity. Additional clinician educational interventions and more language-concordant care may be necessary for informed consent to equal that for English speakers.

Genomic instability is a hallmark of human cancer, and results in widespread somatic copy number alterations. We used a genome-scale shRNA viability screen in human cancer cell lines to systematically identify genes that are essential in the context of particular copy-number alterations (copy-number associated gene dependencies). The most enriched class of copy-number associated gene dependencies was CYCLOPS (Copy-number alterations Yielding Cancer Liabilities Owing to Partial losS) genes, and spliceosome components were the most prevalent. One of these, the pre-mRNA splicing factor , is also frequently mutated in cancer. We validated as a CYCLOPS gene and found that human cancer cells harboring partial copy-loss lack a reservoir of SF3b complex that protects cells with normal copy number from cell death upon partial suppression. These data provide a catalog of copy-number associated gene dependencies and identify partial copy-loss of wild-type as a novel, non-driver cancer gene dependency.

OBJECTIVE

The objective was to quantify the association of pregnancy context and health-related quality of life (HRQoL).

STUDY DESIGN

English- or Spanish-speaking women, aged 16-44, with pregnancies <24 weeks' gestation were enrolled in this cross-sectional study between June 2014 and June 2015. Participants completed self-assessments of pregnancy "context," including timing, intention, wantedness, desirability, happiness, and planning (measured with the London Measure of Unplanned Pregnancy). HRQoL was measured using the Patient Reported Outcomes Measurement Information System Global Short Form. Associations between measures of pregnancy context and HRQoL scores in the lowest tertile were examined using multivariable logistic regression to adjust for potential confounding variables.

RESULTS

We enrolled 161 participants (mean age=27.2±6.6 years). Only 14% self-identified as White, non-Hispanic; 42% Hispanic; 37% Black, non-Hispanic; and 7% multiracial. Most (79%) participants were unmarried, and 75% were parenting. Mean gestational age was 9±4.6 weeks. In unadjusted models, women reporting mixed feelings about wanting to have a baby, an undesired pregnancy or feeling unhappy about learning of their pregnancy more frequently had low mental and physical HRQoL compared to women reporting wanted, desired, happy pregnancies. Women with an unplanned pregnancy or pregnancy occurring at the wrong time also had lower physical HRQoL than women reporting pregnancies that were planned or happened at the right time. However, after multivariate adjustment, including history of depression, pregnancy contexts were not associated with low mental or physical HRQoL.

CONCLUSIONS

After adjusting for multiple confounders, pregnancy context is not significantly associated with HRQoL.

IMPLICATIONS

The focus on pregnancy intention in public health programs may not sufficiently assess multidimensional aspects of pregnancy context and may not align with patient-centered outcomes such as HRQoL.