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Audience: This simulated automated chest compression device was designed for use in simulation cardiacarrest cases involving emergency medicine residents, but it would be applicable to other learners such asnurses, pharmacists, and medical students.Background: Automated chest compression devices (ACCD) are commonly utilized in cardiac arrest in theemergency department and by emergency medical services (EMS) as patients arrive in the ED.1 Prolongedsimulated cardiac arrest can be challenging to maintain proper chest compression depth and technique.2Resident learning may be enhanced during cardiac arrest in the simulation environment by implementing theuse of a simulated ACCD.Educational Objectives: By the end of this educational session using a resuscitation trainer or high-fidelitymanikin, learners should be able to:1. Recognize appropriate application of simulated ACCD to an ongoing resuscitation case2. Demonstrate proper positioning of simulated ACCD in manikin model3. Integrate simulated ACCD to provide compressions appropriately throughout cardiac arrest scenarioEducational Methods: We developed a cost-effective simulated ACCD for use in resuscitation simulationcases. An initial pilot session identified components of fidelity that were used to model the simulated ACCDafter those utilized in clinical situations. Three simulated devices were created and then tested for efficacyduring high-fidelity simulation with 25 emergency medicine residents.Research Methods: Visual analog scales were used to explore how the simulated ACCD affected perceivedrealism and stress level during the cardiac arrest simulation. Qualitative data were collected through open-ended learner feedback comments. The institutional review board at our institution reviewed this projectand determined that it was exempt.Results: With inclusion of the simulated ACCD device, learners rated the simulation "more realistic" with anaverage rating of 74/100 and "less stressful" with an average rating of 69/100 on the visual analog scales.Learner comments noted that the use of the ACCD in simulation resulted in better resource availability andaccurate environmental noise.Discussion: The simulated ACCD presented here was found to be effective, realistic, and practical for use bylearners in a resuscitation curriculum. Our results suggest that implementating a cost-effective simulatedACCD ($98 for supplies) in high-fidelity simulation cardiac arrest cases enhances the perceived realism of theenvironment and offers physician learners a low-stress opportunity to practice the clinical application ofACCD in cardiac arrest resuscitation. Additionally, the use of the simulated ACCD, specifically in a prolongedresuscitation, eliminated the need for physically demanding manual chest compressions. Anecdotally, insimulated environments we have observed poor-quality manual chest compressions due to an understandingthat the manikin is “not real,” leading to decreased psychological fidelity from the shared acceptance of thepoor-quality compressions. Thus, the presence of a simulated clinical device providing chest compressionscould have increased the feel of realism through improved psychological fidelity. Additionally, we note thatthe physical and psychological fidelity of this simulated device was sufficient for physicians to perceive clinicalimplementation, but may be suboptimal for assistive staff, who are focused on the specific functionality andmay benefit from training on the physical device in clinical use. Finally, our simulated ACCD resembles theclinical device our department uses; we advise modifications as appropriate to allow a simulated ACCDcreated for other learners to also resemble their clinically used ACCD.

Podocyte dysfunction and loss is an early event and a hallmark of proteinuric kidney diseases. A podocyte's normal function is maintained via its unique cellular architecture that relies on an intracellular network of filaments, including filamentous actin (Factin) and microtubules, that provides mechanical support. Damage to this filamentous network leads to changes in cellular morphology and results in podocyte injury, dysfunction, and death. Conversely, stabilization of this network protects podocytes and ameliorates proteinuria. This suggests that stabilization of podocyte architecture via its filamentous network could be a key therapeutic strategy for proteinuric kidney diseases. However, development of podocyte-directed therapeutics, especially those that target the cell's filamentous network, is still lacking, partly because of unavailability of appropriate cellular assays for use in a drug discovery environment. Here, we describe a new high-content screening-based methodology and its implementation on podocytes to identify paullone derivatives as a novel group of podocyte-protective compounds. We find that three compounds, i.e., kenpaullone, 1-azakenpaullone, and alsterpaullone, dose dependently protect podocytes from puromycin aminonucleoside (PAN)-mediated injury in vitro by reducing PAN-induced changes in both the filamentous actin and microtubules, with alsterpaullone providing maximal protection. Mechanistic studies further show that alsterpaullone suppressed PAN-induced activation of signaling downstream of GSK3γ and p38 mitogen-activated protein kinase. In vivo it reduced ADR-induced glomerular injury in a zebrafish model. Together, these results identify paullone derivatives as novel podocyte- protective agents for future therapeutic development. [ABSTRACT FROM AUTHOR]

Podocyte dysfunction and loss is an early event and a hallmark of proteinuric kidney diseases. A podocyte's normal function is maintained via its unique cellular architecture that relies on an intracellular network of filaments, including filamentous actin (F-actin) and microtubules, that provides mechanical support. Damage to this filamentous network leads to changes in cellular morphology and results in podocyte injury, dysfunction, and death. Conversely, stabilization of this network protects podocytes and ameliorates proteinuria. This suggests that stabilization of podocyte architecture via its filamentous network could be a key therapeutic strategy for proteinuric kidney diseases. However, development of podocyte-directed therapeutics, especially those that target the cell's filamentous network, is still lacking, partly because of unavailability of appropriate cellular assays for use in a drug discovery environment. Here, we describe a new high-content screening-based methodology and its implementation on podocytes to identify paullone derivatives as a novel group of podocyte-protective compounds. We find that three compounds, i.e., kenpaullone, 1-azakenpaullone, and alsterpaullone, dose dependently protect podocytes from puromycin aminonucleoside (PAN)-mediated injury in vitro by reducing PAN-induced changes in both the filamentous actin and microtubules, with alsterpaullone providing maximal protection. Mechanistic studies further show that alsterpaullone suppressed PAN-induced activation of signaling downstream of GSK3β and p38 mitogen-activated protein kinase. In vivo it reduced ADR-induced glomerular injury in a zebrafish model. Together, these results identify paullone derivatives as novel podocyte-protective agents for future therapeutic development.