All-trans retinoic acid (RA) is a potent inducer of regeneration. Because the liver is the principal site for storage and bioactivation of vitamin A, the current study examines the effect of RA in mouse hepatocyte proliferation and liver regeneration. Mice that received a single dose of RA (25μg/g) by oral gavage developed hepatomegaly with increased number of Ki67-positive cells and induced expression of cell cycle genes in the liver. DNA binding data revealed that RA receptors retinoic acid receptor β (RARβ) and retinoid x receptor α (RXRα) bound to cell cycle genes Cdk1, Cdk2, Cyclin B, Cyclin E, and Cdc25a in mice with and without RA treatment. In addition, RA treatment induced novel binding of RARβ/RXRα to Cdk1, Cdk2, Cyclin D, and Cdk6 genes. All RARβ/RXRα binding sites contained AGGTCA-like motifs. RA treatment also promoted liver regeneration after partial hepatectomy (PH). RA signaling was implicated in normal liver regeneration as the mRNA levels of RARβ, Aldh1a2, Crabp1, and Crbp1 were all induced 1.5 days after PH during the active phase of hepatocyte proliferation. RA treatment prior to PH resulted in early up-regulation of RARβ, Aldh1a2, Crabp1, and Crbp1, which was accompanied by an early induction of cell cycle genes. Western blotting for RARβ, c-myc, Cyclin D, E, and A further supported the early induction of retinoid signal and cell proliferation by RA treatment. Taken together, our data suggest that RA may regulate cell cycle progression and accelerates liver regeneration. Such effect is associated with an early induction of RA signaling, which includes increased expression of the receptor, binding proteins, and processing enzyme for retinoids.

Background

Warfarin requires individualized dosing and monitoring in the ambulatory setting for protection against thromboembolic disease. Yet in multiple settings, patients spend upwards of 30% of time outside the therapeutic range, subjecting them to an increased risk of adverse events. At an urban, publicly funded clinic, the electronic health record (EHR) would not support integration with extant warfarin management software, which led to the creation and implementation of an electronic patient registry and a complementary team-based work flow to provide real-time health-system-level data for warfarin patients.

Methods

Creation of the registry, which began in August 2014, entailed use of an existing platform, which could interface with the outpatient EHR. The registry was designed to help ensure regular testing and monitoring of patients while enabling identification of patients and subpopulations with suboptimal management. The work flow used for the clinic's warfarin patients was also redesigned. An assessment indicated that the registry identified 341 (96%) of 357 patients actively seen in the clinic.

Results

For the cohort of the 357 patients in the registry, the no-show rate decreased from 31% (preimplementation, August 2014-December 2014) to 21% (postimplementation, January 2015-November 2015). The ratio of visits to no-shows increased from 2.3 to 4.0 visits.

Conclusion

Design and implementation of an electronic registry in conjunction with a complementary work flow established an active tracking system that improved treatment monitoring for patients on anticoagulation therapy. Registry creation also facilitated assessment of the quality of care and laid the groundwork for ongoing evaluation and quality improvement efforts.

All-trans retinoic acid (RA) is a potent inducer of regeneration. Because the liver is the principal site for storage and bioactivation of vitamin A, the current study examines the effect of RA in mouse hepatocyte proliferation and liver regeneration. Mice that received a single dose of RA (25μg/g) by oral gavage developed hepatomegaly with increased number of Ki67-positive cells and induced expression of cell cycle genes in the liver. DNA binding data revealed that RA receptors retinoic acid receptor β (RARβ) and retinoid x receptor α (RXRα) bound to cell cycle genes Cdk1, Cdk2, Cyclin B, Cyclin E, and Cdc25a in mice with and without RA treatment. In addition, RA treatment induced novel binding of RARβ/RXRα to Cdk1, Cdk2, Cyclin D, and Cdk6 genes. All RARβ/RXRα binding sites contained AGGTCA-like motifs. RA treatment also promoted liver regeneration after partial hepatectomy (PH). RA signaling was implicated in normal liver regeneration as the mRNA levels of RARβ, Aldh1a2, Crabp1, and Crbp1 were all induced 1.5 days after PH during the active phase of hepatocyte proliferation. RA treatment prior to PH resulted in early up-regulation of RARβ, Aldh1a2, Crabp1, and Crbp1, which was accompanied by an early induction of cell cycle genes. Western blotting for RARβ, c-myc, Cyclin D, E, and A further supported the early induction of retinoid signal and cell proliferation by RA treatment. Taken together, our data suggest that RA may regulate cell cycle progression and accelerates liver regeneration. Such effect is associated with an early induction of RA signaling, which includes increased expression of the receptor, binding proteins, and processing enzyme for retinoids.

Chinese Americans have low colorectal cancer (CRC) screening rates. It is unclear whether physicians should offer all CRC screening modalities (fecal occult blood test [FOBT], sigmoidoscopy, colonoscopy) to Chinese Americans to increase screening. Seven hundred and twenty-five Chinese Americans were asked in a survey if their physician had ever recommended CRC screening and to self-report receipt and type of CRC screening. Participants whose physician had recommended all CRC screening modalities were significantly more likely to report ever having screening (adjusted odds ratio 4.29, 95% CI 1.26-14.68) and being up-to-date (4.06, 95% CI 2.13-7.74) than those who reported that their physician only recommended FOBT. Participants who received a recommendation of only one type of screening did not report a significant difference in ever having or being up-to-date for screening. A potential strategy to increase CRC screening among Chinese Americans is for clinicians to recommend all available CRC screening modalities to each patient.