RESUMEN
This co-design study examined salutogenic potential of mobile virtual reality (VR) experiences as an alternative to participation in a community-based symphonic engagement program (B Sharp), previously found to benefit people with dementia (PWD) and their informal caregivers. Six focus groups were conducted with sixteen adults aged 76-90; three participants had dementia, and two were informal spousal caregivers. No participants had prior VR experience. The study assessed the feasibility of replicating the community-based-arts program in VR, with the goal of enhancing its salutogenic qualities (e.g., positive distraction, engagement, and social connection). Video-recordings of participants while using a mobile head-mounted display (HMD) were analyzed using qualitative thematic analysis to compare perceptions of different virtual experiences, including replication or enhancement of B Sharp and a campus tour. Findings suggest participants had positive perceptions of enhanced VR experiences with no adverse effects, although PWD were less enthusiastic and HMD usability was complicated by eyewear use and comfort with technology. Participants reacted most favorably to the enhanced symphonic experience, where they were "virtually" onstage during the performance, suggesting unique experiences beyond what is possible in the real world have the greatest potential for deep immersion for older adults. Results suggest VR has strong potential to replicate and enhance salutogenic qualities of community-based programming by enabling greater access to experiences for older adults and by increasing enjoyment and engagement through experiences not otherwise feasible. Furthermore, this study illuminates advantages of a user-centered, co-design approach when developing VR experiences with community partners and older adults.
RESUMEN
Epothilones have demonstrated promising potential for oncology applications but suffer from a narrow therapeutic window. Epothilone D stabilizes microtubules leading to apoptosis, is active against multidrug-resistant cells, and is efficacious in animal tumor models despite lack of stability in rodent plasma. Clinical development was terminated in phase II due to dose limiting toxicities near the efficacious dose. Taken together, this made epothilone D attractive for encapsulation in a stabilized polymer micelle for improved safety and efficacy. We have designed a library of triblock copolymers to develop IT-147, a lead formulation of epothilone D that extends plasma circulation for accumulation in the tumor environment, and potentially decrease systemic exposure to reduce dose limiting toxicities. The drug loading efficiency for IT-147 exceeds 90%, is 75 nm in diameter, and demonstrates pH-dependent release of epothilone D without chemical conjugation or enzymatic activation. Administration of IT-147 at 20 mg/kg increases exposure of epothilone D to the plasma compartment over 6-fold compared to free drug. At the same dose, 20 mg/kg epothilone D from IT-147 is considered the no observed adverse effect level (NOAEL) but is the maximum tolerated dose for free drug. Consequently, IT-147 is positioned to be a safer, more effective means to deliver epothilone D.
