Background: 5-HT 4 receptor (5-HT 4 R) agonists exert prokinetic actions in the GI tract, but non-selective actions and potential for stimulation of non-target 5-HT 4 Rs have limited their use. Since 5-HT 4 Rs are expressed in the colonic epithelium and their stimulation accelerates colonic propulsion in vitro, we tested whether luminally acting 5-HT 4 R agonists promote intestinal motility. Methods: Non-absorbed 5-HT 4 R agonists, based on prucalopride and naronapride, were assessed for potency at the 5-HT 4 R in vitro, and for tissue and serum distribution in vivo in mice. In vivo assessment of prokinetic potential included whole gut transit, colonic motility, fecal output, and fecal water content. Colonic motility was also studied ex vivo in mice treated in vivo. Immunofluorescence was used to evaluate receptor distribution in human intestinal mucosa. Key Results: Pharmacological screening demonstrated selectivity and potency of test agonists for 5-HT 4 R. Bioavailability studies showed negligible serum detection. Gavage of agonists caused faster whole gut transit and colonic motility, increased fecal output, and elevated fecal water content. Prokinetic actions were blocked by a 5-HT 4 R antagonist and were not detected in 5-HT 4 R knockout mice. Agonist administration promoted motility in models of constipation. Evaluation of motility patterns ex vivo revealed enhanced contractility in the middle and distal colon. Immunoreactivity for 5-HT 4 R is present in the epithelial layer of the human small and large intestines. Conclusions and Inferences: These findings demonstrated that stimulation of epithelial 5-HT 4 Rs can potentiate propulsive motility and support the concept that mucosal 5-HT 4 Rs could represent a safe and effective therapeutic target for the treatment of constipation.

Objectives-In partial mastectomy (PM) or lumpectomy, ultrasound (US) localization avoids discomfort and additional procedures associated with wire localization. The purpose of this study was to evaluate the association between ultrasound-visible clip (UVC) use at the time of biopsy and US use during resection, hypothesizing that UVCs facilitate US localization and reduce costs compared with traditional radiopaque clips or no clip placement.Methods-The study population consisted of adult female patients with breast cancer undergoing PM or lumpectomy at our institution between 2014 and 2016. The core biopsy clip type and localization method during PM were characterized as wire localization versus US localization, and associations were estimated with multivariable regression models. For the cost evaluation, breast biopsy data were obtained from the Department of Radiology.Results-Among 674 patients, 490 had data on localization and the clip type. Ultrasound-visible clip placement at biopsy increased US use during resection by 13% (95% confidence interval, 6%-21%). There was no difference in the total specimen weight with US versus wire localization. The cost savings for using UVCs for the 2209 patients who underwent breast biopsy from 2014 to 2016 was $36,000.Conclusions-This study demonstrates that US localization for PM is feasible at a single institution and cost-effective when facilitated by UVCs. Placement of a UVC at the time of biopsy is recommended, as it is cost-effective and avoids the discomfort and inconvenience of wire localization.