A Cross-Sectional Analysis of Barriers Associated With Non-Attendance at a Urology Telehealth Clinic in a Safety-Net Hospital.

OBJECTIVE: To analyze the factors associated with non-attendance at a urology telehealth clinic in a large urban safety-net hospital after institutional-mandated transition to telehealth due to COVID-19. METHODS: We identified all encounters scheduled for telehealth after March 17, 2020 and in the subsequent 8 weeks. Logistic regression was used to identify factors associated with attendance. RESULTS: In total there were 322 telehealth encounters, 228 (70.8%) of which were attended and 94 (29.2%) that were not attended. Racial/ethnic minorities accounted for 175 (77.0%) of attended and 73 (76.7%) of non-attended encounters. On multivariable regression, single/divorced/widowed (odds ratio [OR] 2.36, 95% confidence interval [CI] 1.26-4.43), current substance use disorder (OR 5.33, 95% CI 2.04-13.98), and being scheduled for a new patient appointment (OR 1.81, 95% CI 1.04-3.13) were associated with higher odds of not attending a telehealth encounter. Race/ethnicity, primary language, and country of birth were not associated with odds of attendance. CONCLUSION: Our findings identify several social factors (social support, substance use) associated with non-attendance at outpatient telehealth urology encounters at an urban safety-net hospital during the early stages of the COVID-19 pandemic. These barriers may have a greater impact specifically within a safety-net healthcare system and will inform equitable provision of urology telehealth programs in the future FUNDING: Goldberg-Benioff Endowed Professorship in Cancer Biology. The sponsors had no involvement with this study.

Resident-Driven Holistic Lean Daily Management System to Enhance Care Experience at a Safety Net Hospital.

OBJECTIVE: To describe the use of Lean in urology at Zuckerberg San Francisco General, a community safety-net and trauma hospital that serves as a major teaching site for the University of California San Francisco. METHODS: We examined our process improvement activities from 2016 to 2018. Our Lean Daily Management System (DMS) includes a 15-minute team huddle ("urology Lean work") of service residents, faculty, clinic and operating room nursing staff, and anesthesia liaisons. Our DMS also includes a 5-minute preoperative huddle. Besides team-building, urology Lean work surfaces logistics, safety or equipment improvement ideas, and ensures progress and completion of initiated projects. RESULTS: Over a 2-year period we developed and completed 67 projects. Projects impacted the outpatient setting (57%), followed by the operating room (22%), the Urology service (12%), and inpatient setting (9%). We completed projects in the following domains: safety (26%), quality (22%), care experience (21%), workforce care and development (13%), equity (11%), and financial stewardship (7%). Urology Lean work reduced new patient clinic access time (119-21 days) and Bacillus Calmette-Guérin in clinic treatment time (180-105 minutes). The average proportion of urology on-time surgeries was better than the overall surgery on-time surgeries (71% v 61%). CONCLUSION: Urology Lean work successfully applied DMS in a service specific yet holistic approach. Urology Lean work improved resident engagement in quality and safety endeavors and served as a DMS model throughout perioperative and clinic areas.

Androgen receptor repression of GnRH gene transcription.

Alterations in androgen levels lead to reproductive defects in both males and females, including hypogonadotropic hypogonadism, anovulation, and infertility. Androgens have been shown to down-regulate GnRH mRNA levels through an androgen receptor (AR)-dependent mechanism. Here, we investigate how androgen regulates expression from the GnRH regulatory region in the GT1-7 cell line, a model of GnRH neurons. A synthetic androgen, R1881, repressed transcription from the GnRH promoter (GnRH-P) in an AR-dependent manner, and liganded AR associated with the chromatin at the GnRH-P in live GT1-7 cells. The three known octamer-binding transcription factor-1 (Oct-1) binding sites in GnRH-P were required for AR-mediated repression, although other sequences were also involved. Although a multimer of the consensus Oct-1 binding site was not repressed, a multimer of the cluster of Oct-1, Pre-B cell leukemia transcription factor (Pbx)/Prep, and NK2 homeobox 1 (Nkx2.1) binding sites, found at -106/-91 in GnRH-P, was sufficient for repression. In fact, overexpression of any of these factors disrupted the androgen response, indicating that a balance of factors in this tripartite complex is required for AR repression. AR bound to this region in EMSA, indicating a direct interaction of AR with DNA or with other transcription factors bound to GnRH-P at this sequence. Collectively, our data demonstrate that GnRH transcription is repressed by AR via multiple sequences in GnRH-P, including three Oct-1 binding sites, and that this repression requires the complex interaction of several transcription factors.

Developmental regulation of gonadotropin-releasing hormone gene expression by the MSX and DLX homeodomain protein families.

Gonadotropin-releasing hormone (GnRH) is the central regulator of the hypothalamic-pituitary-gonadal axis, controlling sexual maturation and fertility in diverse species from fish to humans. GnRH gene expression is limited to a discrete population of neurons that migrate through the nasal region into the hypothalamus during embryonic development. The GnRH regulatory region contains four conserved homeodomain binding sites (ATTA) that are essential for basal promoter activity and cell-specific expression of the GnRH gene. MSX and DLX are members of the Antennapedia class of non-Hox homeodomain transcription factors that regulate gene expression and influence development of the craniofacial structures and anterior forebrain. Here, we report that expression patterns of the Msx and Dlx families of homeodomain transcription factors largely coincide with the migratory route of GnRH neurons and co-express with GnRH in neurons during embryonic development. In addition, MSX and DLX family members bind directly to the ATTA consensus sequences and regulate transcriptional activity of the GnRH promoter. Finally, mice lacking MSX1 or DLX1 and 2 show altered numbers of GnRH-expressing cells in regions where these factors likely function. These findings strongly support a role for MSX and DLX in contributing to spatiotemporal regulation of GnRH transcription during development.

Sitosterolemia in ABC-transporter G5-deficient mice is aggravated on activation of the liver-X receptor.

BACKGROUND AND AIMS: Mutations in either adenosine triphosphate- binding cassette (ABC) half-transporter G5 or G8 cause sitosterolemia. It has been proposed that ABCG5/ABCG8 heterodimers mediate secretion of plant sterols and cholesterol by hepatocytes into bile and their efflux from enterocytes into the intestinal lumen. METHODS: To test whether deficiency of ABCG5 alone is sufficient to induce sitosterolemia, Abcg5-null mice were generated and characterized with respect to sterol metabolism. RESULTS: Abcg5 deficiency was associated with strongly elevated plasma levels of beta-sitosterol (37-fold) and campesterol (7.7-fold) as well as reduced plasma cholesterol concentrations (-40%). Retention of orally administered [(3)H]beta-sitosterol in the intestinal wall (+550%) and plasma (+640%) was higher in Abcg5-null mice than in wild-type controls. Surprisingly, high plasma beta-sitosterol and campesterol concentrations were even further elevated in Abcg5-null mice on treatment with the synthetic LXR agonist T0901317 (0.015% dietary supplementation, 10 days), whereas these concentrations were reduced by approximately 75% in wild-type mice. Both cholesterol and phospholipid concentrations in gallbladder bile were decreased, but, unexpectedly, cholesterol/phospholipid ratios were unchanged in the absence of Abcg5 and increased in both genotypes on LXR activation. Hepatic expression of Abcg8 was reduced by about 35% in Abcg5-deficient mice when compared with controls. No compensatory overexpression of other ABC transporters potentially involved in hepatic cholesterol trafficking was observed on messenger RNA level. CONCLUSIONS: Our data show that disruption of the Abcg5 gene alone is sufficient to cause hyperabsorption of dietary plant sterols and sitosterolemia in mice, whereas the ability to secrete cholesterol into bile is maintained.

Loss of nuclear receptor SHP impairs but does not eliminate negative feedback regulation of bile acid synthesis.

The in vivo role of the nuclear receptor SHP in feedback regulation of bile acid synthesis was examined. Loss of SHP in mice caused abnormal accumulation and increased synthesis of bile acids due to derepression of rate-limiting CYP7A1 and CYP8B1 hydroxylase enzymes in the biosynthetic pathway. Dietary bile acids induced liver damage and restored feedback regulation. A synthetic agonist of the nuclear receptor FXR was not hepatotoxic and had no regulatory effects. Reduction of the bile acid pool with cholestyramine enhanced CYP7A1 and CYP8B1 expression. We conclude that input from three negative regulatory pathways controls bile acid synthesis. One is mediated by SHP, and two are SHP independent and invoked by liver damage and changes in bile acid pool size.