Besieged in the Bronx: Lessons from an in-hospital mass casualty.

BACKGROUND: An active shooter in a hospital is an emergency extraordinaire. We report a single institution's response to the largest active shooter mass casualty event in American History. METHODS: Review of notification, flow of prioritized patients, and key elements of the day's dynamic after a hospital attack by a lone gunman were commenced. The review includes outcomes on seven victims and assailants. RESULTS: "Code Silver" announced: open display of a weapon. Concise, known, and published chain of command implemented. All house staff to the Emergency Department (ED) via text blast. Operating room (OR) notified. Injured to ED, then triaged to OR. Armed NYPD stationed throughout OR. Senior surgeons controlled key triage during attack with flow controlled from the ED and OR control desk. One fatality plus shooter. CONCLUSION: Success favors the prepared. The response to attack, readiness of medical personnel, mitigation, and recovery have brought the following recommendations: (1) single entrance access; (2) armed, professional guards at all entrances; (3) camouflage metal detectors; (4) mandatory, recurrent hospital-wide active shooter training, mock, and table top; (5) published physician chain of command; (6) intercom code system known to all hospital personnel indicating a weapon is openly displayed; (7) a "no fly" list of former employees who are prohibited on premises; (8) stop the bleed training with kits on every floor; (9) one voice, one face to disseminate information. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level I.

Riluzole increases the amount of latent HSF1 for an amplified heat shock response and cytoprotection.

BACKGROUND: Induction of the heat shock response (HSR) and increased expression of the heat shock proteins (HSPs) provide mechanisms to ensure proper protein folding, trafficking, and disposition. The importance of HSPs is underscored by the understanding that protein mis-folding and aggregation contribute centrally to the pathogenesis of neurodegenerative diseases. METHODOLOGY/PRINCIPAL FINDINGS: We used a cell-based hsp70-luciferease reporter gene assay system to identify agents that modulate the HSR and show here that clinically relevant concentrations of the FDA-approved ALS drug riluzole significantly increased the heat shock induction of hsp70-luciferse reporter gene. Immuno-Western and -cytochemical analysis of HSF1 show that riluzole increased the amount of cytosolic HSF1 to afford a greater activation of HSF1 upon heat shock. The increased HSF1 contributed centrally to the cytoprotective activity of riluzole as hsf1 gene knockout negated the synergistic activity of riluzole and conditioning heat shock to confer cell survival under oxidative stress. Evidence of a post-transcriptional mechanism for the increase in HSF1 include: quantitation of mRNA(hsf1) by RT-PCR showed no effect of either heat shock or riluzole treatment; riluzole also increased the expression of HSF1 from a CMV-promoter; analysis of the turnover of HSF1 by pulse chase and immunoprecipitation show that riluzole slowed the decay of [(35)S]labeled-HSF1. The effect of riluzole on HSF1 was qualitatively different from that of MG132 and chloroquine, inhibitors of the proteasome and lysosome, respectively, and appeared to involve the chaperone-mediated autophagy pathway as RNAi-mediated knockdown of CMA negated its effect. CONCLUSION/SIGNIFICANCE: We show that riluzole increased the amount of HSF1 to amplify the HSR for cytoprotection. Our study provides novel insight into the mechanism that regulates HSF1 turnover, and identifies the degradation of HSF1 as a target for therapeutics intervention.

Neural differentiation and the attenuated heat shock response.

Differentiation of neural progenitor cells of neuroblastoma, pheochromocytoma, and surrogate stem cell lineages from a state resembling stem cells to a state resembling neurons is accompanied by a marked attenuation in induction of the heat shock protein 70 promoter driven-luciferase reporter gene, and induction of the reporter gene in primary embryonic neurons from hippocampus, cortex, and spinal cord is lower still when compared to the differentiated cells. Neural specificity of this phenotype is demonstrated by a negative correlation of hsp70-reporter gene expression and neurite extension under various experimental conditions. Analysis of biochemical events involved in induction of the heat shock response (HSR) reveal a blunted activation of HSF1 DNA-binding activity, and decreased induction of the mRNA(hsp70) and the 72 kDa HSP70 protein. Immunocytochemical staining for HSP70 demonstrates a cytoplasmic staining pattern; heat shock greatly increased the HSP70 staining intensity in the undifferentiated cells and less so in the differentiated cells. Vulnerability of the differentiated cells towards the oxidizer, arsenite, and the excitotoxic glutamate/glycine is demonstrated by the dose-dependent cytotoxic effects of these agents on cell viability and activation of caspase 3/7. Importantly, conditioning heat shock as well as increased expression of HSP70 by gene transfer conferred protection against such cytotoxicity. Together, our results show that neural differentiation is associated with a decreased induction of the heat shock response and an increased vulnerability to stress induced pathologies and death.

Cognitive rehabilitation in the elderly: effects on memory.

This study reports the effects of a 12-week multimodular cognitive rehabilitation training program on memory performance in two groups of older adults. In the Memory Training module, participants were instructed on the nature of memory and how to improve memory performance; internal and external strategies were described and practiced over the training sessions. Memory performance was assessed by four tests: Alpha Span, Brown-Peterson, Hopkins Verbal Learning Test - Revised (HVLT-R), and Logical Stories. One group received training on entry into the study (Early Training Group, ETG), the other after a 3-month delay (Late Training Group, LTG). The results showed no training-related improvement in working memory (Alpha Span), primary memory (Brown-Peterson, HVLT-R), or recognition memory (HVLT-R). While the most direct analyses of a training effect (analyses of covariance) rarely demonstrated significant effects, exploratory analyses provided some evidence for a training benefit in several measures of secondary memory (Logical Stories; HVLT-R) and strategic processing (Brown-Peterson; Logical Stories; HVLT-R). Positive results were largely restricted to the ETG, possibly because the LTG lost motivation as a consequence of their delayed training. The results need to be treated with caution, but are promising for the rehabilitation of memory functioning in older adults.

Cognitive rehabilitation in the elderly: effects on strategic behavior in relation to goal management.

Executive functions are highly sensitive to the effects of aging and other conditions affecting frontal lobe function. Yet there are few validated interventions specifically designed to address executive functions, and, to our knowledge, none validated in a healthy aging sample. As part of a large-scale cognitive rehabilitation randomized trial in 49 healthy older adults, a modified Goal Management Training program was included to address the real-life deficits caused by executive dysfunction. This program emphasized periodic suspension of ongoing activity to establish goal hierarchies and monitor behavioral output. Tabletop simulated real-life tasks (SRLTs) were developed to measure the processes targeted by this intervention. Participants were randomized to two groups, one of which received the intervention immediately and the other of which was wait-listed prior to rehabilitation. Results indicated improvements in SRLT performance and self-rated executive deficits coinciding with the training in both groups. These gains were maintained at long-term follow-up. Future research will assess the specificity of these effects in patient groups.

Cognitive rehabilitation in the elderly: an evaluation of psychosocial factors.

In this study, we report changes in psychosocial function in two groups of older adults that participated in the experimental trial of our cognitive rehabilitation program. The results, based on tests that measured a range of psychosocial attributes, showed that, following training, participants improved in terms of overall well-being, as well as in specific areas that included perceived happiness, coping strategies, and quality of life. An important finding was that improvements were also observed in long-term follow-up testing. Both groups benefited from training, but the effect was greater in the group that received training before undergoing a control procedure. The results, which show that the benefits of our rehabilitation program extend into the psychosocial domain, underscore the potentially important relationship between psychosocial factors and cognitive performance in older adults.