Functional screening for compounds that promote remyelination represents a major hurdle in the development of rational therapeutics for multiple sclerosis. Screening for remyelination is problematic, as myelination requires the presence of axons. Standard methods do not resolve cell-autonomous effects and are not suited for high-throughput formats. Here we describe a binary indicant for myelination using micropillar arrays (BIMA). Engineered with conical dimensions, micropillars permit resolution of the extent and length of membrane wrapping from a single two-dimensional image. Confocal imaging acquired from the base to the tip of the pillars allows for detection of concentric wrapping observed as ‘rings’ of myelin. The platform is formatted in 96-well plates, amenable to semiautomated random acquisition and automated detection and quantification. Upon screening 1,000 bioactive molecules, we identified a cluster of antimuscarinic compounds that enhance oligodendrocyte differentiation and remyelination. Our findings demonstrate a new high-throughput screening platform for potential regenerative therapeutics in multiple sclerosis.
Background While leadership training is increasingly incorporated into residency education, existing assessment tools to provide feedback on leadership skills are only applicable in limited contexts.Objective We developed an instrument, the Leadership Observation and Feedback Tool (LOFT), for assessing clinical leadership.
MethodsWe used an iterative process to develop the tool, beginning with adapting the Leadership Practices Inventory to create an open-ended survey for identification of clinical leadership behaviors. We presented these to leadership experts who defined essential behaviors through a modified Delphi approach. In May 2014 we tested the resulting 29-item tool among residents in the internal medicine and pediatrics departments at 2 academic medical centers. We analyzed instrument performance using Cronbach's alpha, interrater reliability using intraclass correlation coefficients (ICCs), and item performance using linear-by-linear test comparisons of responses by postgraduate year, site, and specialty.Results A total of 377 (of 526, 72%) team members completed the LOFT for 95 (of 519, 18%) residents. Overall ratings were high-only 14% scored at the novice level. Cronbach's alpha was 0.79, and the ICC ranged from 0.20 to 0.79. Linear-by-linear test comparisons revealed significant differences between postgraduate year groups for some items, but no significant differences by site or specialty. Acceptability and usefulness ratings by respondents were high.Conclusions Despite a rigorous approach to instrument design, we were unable to collect convincing validity evidence for our instrument. The tool may still have some usefulness for providing formative feedback to residents on their clinical leadership skills.
These findings confirm that initial laser fiber power output is significantly influenced by cleave technique, and the ceramic scissor is the optimal tool for cleaving between procedures. However, because of rapid fiber tip degradation and power loss, this study argues against routine cleaving to improve procedural efficiency in lengthy ureteroscopy cases.
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