No abstract

SUMMARYCells adopt distinct signaling pathways to optimize cell locomotion in different physical microenvironments. However, the underlying mechanism that enables cells to sense and respond to physical confinement is unknown. Using microfabricated devices and substrate-printing methods along with FRET-based biosensors, we report that, as cells transition from unconfined to confined spaces, intracellular Ca2+ level is increased, leading to phosphodiesterase 1 (PDE1)-dependent suppression of PKA activity. This Ca2+ elevation requires Piezo1, a stretch-activated cation channel. Moreover, differential regulation of PKA and cell stiffness in unconfined versus confined cells is abrogated by dual, but not individual, inhibition of Piezo1 and myosin II, indicating that these proteins can independently mediate confinement sensing. Signals activated by Piezo1 and myosin II in response to confinement both feed into a signaling circuit that optimizes cell motility. This study provides a mechanism by which confinement-induced signaling enables cells to sense and adapt to different physical microenvironments.

Critically ill patients commonly experience poor sleep quality in the intensive care unit (ICU) because of various modifiable factors. To address this issue, an ICU-wide, multifaceted quality improvement (QI) project was undertaken to promote sleep in the Johns Hopkins Hospital Medical ICU (MICU). To supplement previously published results of this QI intervention, the present article describes the specific QI framework used to develop and implement this intervention, which consists of 4 steps: (a) summarizing the evidence to create a list of sleep-promoting interventions, (b) identifying and addressing local barriers to implementation, (c) selecting performance measures to assess intervention adherence and patient outcomes, and (d) ensuring that all patients receive the interventions through staff engagement and education and regular project evaluation. Measures of performance included daily completion rates of daytime and nighttime sleep improvement checklists and completion rates of individual interventions. Although long-term adherence and sustainability pose ongoing challenges, this model provides a foundation for future ICU sleep promotion initiatives.