Nerve growth factor signaling through p75 induces apoptosis in Schwann cells via a Bcl-2-independent pathway

Apoptosis is involved in the regulation of Schwann cell numbers during normal development and after axonal damage, but the molecular regulation of Schwann cell death remains unknown. We have used stably transfected rat Schwann cell lines to study the potential roles of nerve growth factor (NGF), the antiapoptotic protein Bcl-2 and the cytokine response modifier A (CrmA) in modulating Schwann cell death in vitro. Bcl-2 inhibited Schwann cell apoptosis induced by survival factor withdrawal, whereas CrmA did not. In contrast, Bcl-2-transfected Schwann cells were susceptible to apoptosis in response to exogenous NGF, whereas CrmA-expressing cell lines were resistant. Demonstration of high levels of the low-affinity neurotrophin receptor p75 but not the high-affinity TrkA receptor on the Bcl-2-transfected cell lines suggested that the NGF-induced killing was mediated by p75. This was confirmed by resistance of Schwann cells isolated from p75 knockout mice to the NGF-induced cell death. Nerve growth factor also promoted the death of wild-type mouse and rat Schwann cells in the absence of survival factor withdrawal. Endogenous Bcl-2 mRNA was expressed by wild-type Schwann cells in all conditions that promoted survival but was downregulated to undetectable levels after survival factor withdrawal. In conclusion, our results demonstrate the existence of two separate pathways that expedite apoptosis in Schwann cells: a Bcl-2-blockable pathway initiated on loss of trophic support, and a Bcl-2-independent, CrmA-blockable pathway mediated via the p75 receptor

Faster clinical response to the onset of adverse events: A wearable metacognitive attention aid for nurse triage of clinical alarms

<div><p>Objective</p><p>This study evaluates the potential for improving patient safety by introducing a metacognitive attention aid that enables clinicians to more easily access and use existing alarm/alert information. It is hypothesized that this introduction will enable clinicians to easily triage alarm/alert events and quickly recognize emergent opportunities to adapt care delivery. The resulting faster response to clinically important alarms/alerts has the potential to prevent adverse events and reduce healthcare costs.</p><p>Materials and methods</p><p>A randomized within-subjects single-factor clinical experiment was conducted in a high-fidelity 20-bed simulated acute care hospital unit. Sixteen registered nurses, four at a time, cared for five simulated patients each. A two-part highly realistic clinical scenario was used that included representative: tasking; information; and alarms/alerts. The treatment condition introduced an integrated wearable attention aid that leveraged metacognition methods from proven military systems. The primary metric was time for nurses to respond to important alarms/alerts.</p><p>Results</p><p>Use of the wearable attention aid resulted in a median relative within-subject improvement for individual nurses of 118% (W = 183, p = 0.006). The top quarter of relative improvement was 3,303% faster (mean; 17.76 minutes reduced to 1.33). For all unit sessions, there was an overall 148% median faster response time to important alarms (8.12 minutes reduced to 3.27; U = 2.401, p = 0.016), with 153% median improvement in consistency across nurses (F = 11.670, p = 0.001).</p><p>Discussion and conclusion</p><p>Existing device-centric alarm/alert notification solutions can require too much time and effort for nurses to access and understand. As a result, nurses may ignore alarms/alerts as they focus on other important work. There has been extensive research on reducing alarm frequency in healthcare. However, alarm safety remains a top problem. Empirical observations reported here highlight the potential of improving patient safety by supporting the meta-work of checking alarms.</p></div

Trial condition metrics for analysis of potential secondary effects.

<p>Trial condition metrics for analysis of potential secondary effects.</p

Nurses’ subjective opinions comparing their performance with and without HAIL-CAT.

<p>Nurses’ subjective opinions comparing their performance with and without HAIL-CAT.</p

Tests of normality on data for time to respond to important alarms.

<p>Tests of normality on data for time to respond to important alarms.</p

A sample of nurse quotes from a semi-structured exit interview about their impressions of using the HAIL-CAT aid wearable.

<p>A sample of nurse quotes from a semi-structured exit interview about their impressions of using the HAIL-CAT aid wearable.</p

The HAIL-CAT (Human Alerting and Interruption Logistics—Clinical Alarm Triage) wearable attention aid prototype.

<p>The smartwatch application has four screens: (A) list of all alarms/alerts (blue marks silenced; orange marks not-silenced); (B) home screen list of five patients (including number of current alarms/alerts); (C) list of alarms/alerts for selected patient; (D & F) alarm/alert announcement with message and vitals context. "E" shows a nurse participant (standing and wearing the prototype on her right wrist). She is checking a "patient" (a patient simulation mannequin in the bed) while speaking with a "family member" (experimental confederate) who sits nearby. In addition to triaging alarms/alerts, the smartwatch enabled nurses to check the vital signs for any patient at any time by selecting the patient from the home screen. The vital signs screen is the same as "D" or "F," but without the alarm/alert message and "silence" buttons.</p

Conclusions of analyses results for potential secondary effects by trial condition.

<p>Conclusions of analyses results for potential secondary effects by trial condition.</p

Relative within-subjects response to important alarms/alerts.

<p>Relative within-subjects response to important alarms/alerts.</p