Evaluating Target: Stroke guideline implementation on assessment and treatment times for patients with suspected stroke.

OBJECTIVES: Immediate ischemic stroke treatment improves outcomes and early alteplase administration is recommended for patients within window. We implemented stroke guidelines through a neuro-resuscitation initiative (NRI) and hypothesized that the intervention would decrease times to assessment and treatment. METHODS: We analyzed quality assurance data for EMS and triage patients arriving to our academic emergency department with suspected ischemic stroke to compare outcomes 12 months before to 6 months after initiative implementation at an academic certified primary stroke center in the U.S. Southwest. We examined four time-based outcomes: neurology at bedside, CT head without contrast, CT head angiogram, and alteplase administration. We summarized times with median and IQR values and compared pre and post times to event (in minutes) with Wilcoxon rank sum tests and Kaplan-Meier survival curves. RESULTS: We identified 203 EMS (83 pre, 120 post) and 66 (11 pre, 55 post) triage Stroke Alert patients. We observed decreased times for all outcomes in both the EMS and triage samples; however, only those in the EMS sample were significant. In the EMS sample, neurology at bedside median times decreased from 20 min to 2 min (p < 0.001); median minutes to CT head without contrast decreased from 16 min to 9 min (p < 0.001); median minutes to CT head angiogram decreased from 71 min to 21 min (p = 0.007); and, median minutes to alteplase decreased from 72 min to 49.5 min (p = 0.04). CONCLUSIONS: An academic ED led stroke care initiative streamlined evaluation and care with significantly shortened times to all four events.

Observational Study of Grand Canyon Rim-to-Rim Day Hikers: Determining Behavior Patterns to Aid in Preventive Search and Rescue Efforts.

INTRODUCTION: Grand Canyon National Park has seen an increase in visitors traversing the canyon from rim to rim (R2R) in a single day. R2R hikers travel over 33.8 km (21 mi) over 3300 m (11,000 ft) of elevation change and endure large temperature changes. Grand Canyon emergency medical service providers provide emergency medical services to over 1100 visitors annually. Direct guidance by Preventive Search and Rescue rangers has improved safety. The objective of this study was to examine visitors attempting an R2R traverse and to enhance PSAR rangers' anticipatory guidance. METHODS: We conducted an observational study of R2R hikers in the spring and fall of 2015. Hikers consented to study inclusion and were interviewed at the starting trailhead, canyon bottom, and exit trailhead. We performed a survey and collected biometric data. RESULTS: We enrolled 617 visitors with a median age of 43 y (interquartile range [IQR] 33-53); 65% were male and 46% had hiked the R2R a median number of 3 times previously (IQR 2-7). Hydration strategies included water bottle only (20%), hydration bladder only (31%), and both water bottle and hydration bladder (48%). R2R crossers had an average start time of 0530 (SD 1.3 h) and median crossing time of 11.9 h (IQR 10.7-13.3). Crossing time and self-reported fatigue were negatively correlated with prior R2R experience (P=0.02). CONCLUSIONS: Crossing R2R in a day is hazardous and associated with risk of injury and illness. The results of this study can be used by Preventive Search and Rescue to reduce these risks by educating hikers.

Inhibition of GSK3ß improves hippocampus-dependent learning and rescues neurogenesis in a mouse model of fragile X syndrome.

Fragile X syndrome (FXS), a common inherited form of intellectual disability with learning deficits, results from a loss of fragile X mental retardation protein (FMRP). Despite extensive research, treatment options for FXS remain limited. Since FMRP is known to play an important role in adult hippocampal neurogenesis and hippocampus-dependent learning and FMRP regulates the adult neural stem cell fate through the translational regulation of glycogen synthase kinase 3ß (GSK3ß), we investigated the effects of a GSK3ß inhibitor, SB216763, on Fmr1 knockout mice (Fmr1 KO). We found that the inhibition of GSK3ß could reverse the hippocampus-dependent learning deficits and rescue adult hippocampal neurogenesis at multiple stages in Fmr1 KO mice. Our results point to GSK3ß inhibition as a potential treatment for the learning deficits seen in FXS.

Real-time breath analysis towards a healthy human breath profile.

The direct analysis of molecules contained within human breath has had significant implications for clinical and diagnostic applications in recent decades. However, attempts to compare one study to another or to reproduce previous work are hampered by: variability between sampling methodologies, human phenotypic variability, complex interactions between compounds within breath, and confounding signals from comorbidities. Towards this end, we have endeavored to create an averaged healthy human 'profile' against which follow-on studies might be compared. Through the use of direct secondary electrospray ionization combined with a high-resolution mass spectrometry and in-house bioinformatics pipeline, we seek to curate an average healthy human profile for breath and use this model to distinguish differences inter- and intra-day for human volunteers. Breath samples were significantly different in PERMANOVA analysis and ANOSIM analysis based on Time of Day, Participant ID, Date of Sample, Sex of Participant, and Age of Participant (p< 0.001). Optimal binning analysis identify strong associations between specific features and variables. These include 227 breath features identified as unique identifiers for 28 of the 31 participants. Four signals were identified to be strongly associated with female participants and one with male participants. A total of 37 signals were identified to be strongly associated with the time-of-day samples were taken. Threshold indicator taxa analysis indicated a shift in significant breath features across the age gradient of participants with peak disruption of breath metabolites occurring at around age 32. Forty-eight features were identified after filtering from which a healthy human breath profile for all participants was created.

Ablation of Fmrp in adult neural stem cells disrupts hippocampus-dependent learning.

Deficiency in fragile X mental retardation protein (FMRP) results in fragile X syndrome (FXS), an inherited form of intellectual disability. Despite extensive research, it is unclear how FMRP deficiency contributes to the cognitive deficits in FXS. Fmrp-null mice show reduced adult hippocampal neurogenesis. As Fmrp is also enriched in mature neurons, we investigated the function of Fmrp expression in neural stem and progenitor cells (aNSCs) and its role in adult neurogenesis. Here we show that ablation of Fmrp in aNSCs by inducible gene recombination leads to reduced hippocampal neurogenesis in vitro and in vivo, as well as markedly impairing hippocampus-dependent learning in mice. Conversely, restoration of Fmrp expression specifically in aNSCs rescues these learning deficits in Fmrp-deficient mice. These data suggest that defective adult neurogenesis may contribute to the learning impairment seen in FXS, and these learning deficits can be rectified by delayed restoration of Fmrp specifically in aNSCs.