The Small Molecule BC-2059 Inhibits Wingless/Integrated (Wnt)-Dependent Gene Transcription in Cancer through Disruption of the Transducin ß-Like 1-ß-Catenin Protein Complex.

The central role of ß-catenin in the Wnt pathway makes it an attractive therapeutic target for cancers driven by aberrant Wnt signaling. We recently developed a small-molecule inhibitor, BC-2059, that promotes apoptosis by disrupting the ß-catenin/transducin ß-like 1 (TBL1) complex through an unknown mechanism of action. In this study, we show that BC-2059 directly interacts with high affinity for TBL1 when in complex with ß-catenin. We identified two amino acids in a hydrophobic pocket of TBL1 that are required for binding with ß-catenin, and computational modeling predicted that BC-2059 interacts at the same hydrophobic pocket. Although this pocket in TBL1 is involved in binding with NCoR/SMRT complex members G Protein Pathway Suppressor 2 (GSP2) and SMRT and p65 NFκB subunit, BC-2059 failed to disrupt the interaction of TBL1 with either NCoR/SMRT or NFκB. Together, our results show that BC-2059 selectively targets TBL1/ß-catenin protein complex, suggesting BC-2059 as a therapeutic for tumors with deregulated Wnt signaling pathway. SIGNIFICANCE STATEMENT: This study reports the mechanism of action of a novel Wnt pathway inhibitor, characterizing the selective disruption of the transducin ß-like 1/ß-catenin protein complex. As Wnt signaling is dysregulated across cancer types, this study suggests BC-2059 has the potential to benefit patients with tumors reliant on this pathway.

Technology Use and Preferences for Minority Diabetes Self-Management Application.

We describe technology use and preferences of minority patients with diabetes who participated in focus groups in order to help design a mobile/online health application (or, app) to assist with diabetes self-management. Self-management apps should include health-related data and suggestions about food. The authors close by recommending additional considerations for future self-management mobile/online apps.

Anatomical and histological analyses reveal that tail repair is coupled with regrowth in wild-caught, juvenile American alligators (Alligator mississippiensis).

Reptiles are the only amniotes that maintain the capacity to regenerate appendages. This study presents the first anatomical and histological evidence of tail repair with regrowth in an archosaur, the American alligator. The regrown alligator tails constituted approximately 6-18% of the total body length and were morphologically distinct from original tail segments. Gross dissection, radiographs, and magnetic resonance imaging revealed that caudal vertebrae were replaced by a ventrally-positioned, unsegmented endoskeleton. This contrasts with lepidosaurs, where the regenerated tail is radially organized around a central endoskeleton. Furthermore, the regrown alligator tail lacked skeletal muscle and instead consisted of fibrous connective tissue composed of type I and type III collagen fibers. The overproduction of connective tissue shares features with mammalian wound healing or fibrosis. The lack of skeletal muscle contrasts with lizards, but shares similarities with regenerated tails in the tuatara and regenerated limbs in Xenopus adult frogs, which have a cartilaginous endoskeleton surrounded by connective tissue, but lack skeletal muscle. Overall, this study of wild-caught, juvenile American alligator tails identifies a distinct pattern of wound repair in mammals while exhibiting features in common with regeneration in lepidosaurs and amphibia.

Accuracy of Intraocular Lens Power Calculation Using Anterior Chamber Depth from Two Devices with Barrett Universal II Formula.

PURPOSE: To compare the preoperative measurements of the anterior chamber depth (ACD) by the IOLMaster and Catalys; additionally, to compare the accuracy of the IOL power calculated by the Barrett Universal II formula using the two different measurements. SETTING: University of California, Irvine, Gavin Herbert Eye Institute in Irvine, California. DESIGN: Retrospective comparative study. METHODS: This study included 144 eyes of 90 patients with a mean age of 72.0 years (range 40.8 to 92.1 years) that underwent femtosecond laser-assisted cataract surgery using Catalys. Preoperative measurements of ACD were taken by the IOLMaster and Catalys. Manifest refraction and refractive spherical equivalent were measured 1 month postoperatively. Expected refractive results were compared with actual postoperative refractive results. RESULTS: The correlation between the ACD values from the two devices was good (r = 0.80). The Catalys ACD measurements yielded a larger ACD compared to the IOLMaster, with a mean difference of 0.22 mm (P < 0.0001). The correlation between the postoperative and predicted RSE of the implanted IOL power was excellent (r = 0.96). There was no statistically significant difference between the mean absolute error derived from the IOLMaster, 0.37 diopter (D) ± 0.34 (SD), and the Catalys, 0.37 ± 0.35 D (P=0.50). CONCLUSIONS: The Catalys biometry yielded a significantly larger ACD value than the IOLMaster. This difference in ACD value, however, did not reflect in a statistically significant difference in IOL power calculation and refractive prediction error using the Barrett Universal II Formula.

Medical Student Interpretation of Visual Art: Who's Got Empathy?

This article was migrated. The article was marked as recommended. Introduction: Physician empathy is a highly desired characteristic in clinical practice with benefits for both patients and doctors. Increasingly, medical educators have acknowledged the importance of empathy and sought effective ways of inculcating and strengthening this quality in medical students. However, empathy remains difficult to measure because of differing definitions and theoretical dimensions. Our goal was to develop a de novo visual Art scale, devised to evaluate empathetic response in medical students as well as a de novo Biosocial scale to measure medical student socioeconomic and experiential stress during childhood and adolescence; and to compare these exploratory measures to the reliable and well-validated Jefferson Scale of Empathy JSE). Methods: We constructed a survey incorporating a visual Art empathy measure, a Biosocial scale, and the JSE, which we sent to approximately 200 allopathic preclinical medical students at our home institution. We received 71 complete responses. Results: Cronbach's alpha testing found that the items in both new scales had adequate reliability. Multivariate regression analysis found a significant, positive association between both the visual art and biosocial scores and the JSE. Discussion: These results support the idea that response to visual stimuli, as well as life stressors, may be factors in medical students' capacity to formulate an empathetic response to patients.