Serial transurethral cystometry: A novel method for longitudinal evaluation of reflex lower urinary tract function in adult female rats.

AIMS: The aim of the study is to develop a minimally invasive method for longitudinal evaluation of lower urinary tract function that allows for simultaneous measurements of bladder pressure and external urethral sphincter (EUS) electromyographic (EMG) activity. METHODS: To evaluate the reliability of serial transurethral cystometry (STUC), rats (n = 12) underwent three sessions of STUC, one session a week for 3 weeks. During each session, rats were anesthetized with ketamine-xylazine (90 mg/kg and 10 mg/kg), and micturition reflex data were acquired using transurethral cystometry and percutaneous recording of EUS (EMG) activity during continuous infusion of saline into the bladder. The reliability and consistency of the STUC method were assessed using intra-class correlation (ICC) analysis and repeated measures ANOVA. RESULTS: ICC values calculated from five successive events during the first micturition session indicate good to excellent reliability for measurements of peak bladder pressure, threshold bladder pressure, minimum bladder pressure, volume threshold, duration of EUS bursting, and number of EUS burst events. Across the three recording sessions no significant difference was observed in peak bladder pressure, threshold bladder pressure, minimum bladder pressure, volume threshold, number of EUS burst events, and duration of EUS bursting using repeated measures ANOVA. CONCLUSION: Serial transurethral cystometry under ketamine-xylazine anesthesia with simultaneous percutaneous EUS EMG recording is a novel, reliable, accurate, and minimally invasive method for quantitative assessment of lower urinary tract (LUT) function in adult female rats over extended periods of time.

Learning the Language of Medical Device Innovation: A Longitudinal Interdisciplinary Elective for Medical Students.

PROBLEM: Physicians are playing a growing role as clinician-innovators. Academic physicians are well positioned to contribute to the medical device innovation process, yet few medical school curricula provide students opportunities to learn the conceptual framework for clinical needs finding, needs screening, concept generation and iterative prototyping, and intellectual property management. This framework supports innovation and encourages the development of valuable interdisciplinary communication skills and collaborative learning strategies. APPROACH: Our university offers a novel 3-year-long medical student Longitudinal Interdisciplinary Elective in Biodesign (MSLIEB) that teaches medical device innovation in 4 stages: (1) seminars and small-group work, (2) shared clinical experiences for needs finding, (3) concept generation and product development by serving as consultants for biomedical engineering capstone projects, and (4) reflection and mentorship. The MSLIEB objectives are to: create a longitudinal interdisciplinary peer mentorship relationship between undergraduate biomedical engineering students and medical students, and encourage codevelopment of professional identities in relation to medical device innovation. OUTCOMES: The MSLIEB enrolled 5 entering cohorts from 2017 to 2021 with a total of 37 medical student participants. The first full entering cohort of 12 medical students produced 8 mentored biomedical engineering capstone projects, 7 of which were based on clinical needs statements derived from earlier in the elective. Medical student participants have coauthored poster and oral presentations; contributed to projects that won WolfieTank, a university-wide competition modeled after the television show Shark Tank; and participated in the filing of provisional patents. Students reflecting on the course reported a change in their attitude towards existing medical problems, felt better-equipped to collaboratively design solutions for clinical needs, and considered a potential career path in device design. NEXT STEPS: The MSLIEB will be scaled up by recruiting additional faculty, broadening clinical opportunities to include the outpatient setting, and increasing medical student access to rapid prototyping equipment.

The ocular pharmacokinetics and biodistribution of phospho-sulindac (OXT-328) formulated in nanoparticles: Enhanced and targeted tissue drug delivery.

We studied the pharmacokinetics, biodistribution and metabolism of phospho-sulindac (PS), a novel agent efficacious in the treatment of dry eye, formulated in nanoparticles (PS-NPs) following its topical administration to the eye of New Zealand White rabbits. The nanoparticles were spherical with effective diameter = 108.9 ±â€¯41.7 nm, zeta potential = -21.70 ±â€¯3.78 mV, drug loading = 7%, and entrapment efficiency = 46.4%. Of the total PS delivered topically to the eye, >95% was retained in the anterior segment, predominantly in the cornea (Cmax = 101.3 µM; Tmax = 1 h; T1/2 = 2.6 h; area AUC0-16h = 164.4 µM·h) and conjunctiva (Cmax = 89.4 µM; Tmax = 0.25 h; T1/2 = 3.1 h; AUC0-16h = 63.5 µM·h), the tissues most affected by dry eye disease. No PS or its metabolites were detected in the systemic circulation. PS was metabolized to PS sulfide and PS sulfone; all three molecules were hydrolyzed to sulindac, which was converted to sulindac sulfide and sulindac sulfone. A solution formulation of PS provided lower PS levels in ocular tissues but higher levels of PS metabolites, compared to PS-NPs. Therefore, NPs represent an effective formulation for the topical ocular administration of PS for anterior segment diseases, such as dry eye disease.