Serum detection of blood brain barrier injury in subjects with a history of stroke and transient ischemic attack.

Objective: Stroke and transient ischemic attack may have long-term negative effects on the blood-brain barrier (BBB) and promote endothelial inflammation, both of which could increase neurodegeneration and dementia risk beyond the cell death associated with the index event. Methods: Serum from 88 postmortem subjects in the Arizona Study of Aging and Neurodegenerative Disorders were analyzed by sandwich ELISA for specific biomarkers to investigate the effects of cerebrovascular accidents (CVAs) on BBB integrity and endothelial activation. Statistical analyses were performed using the Mann-Whitney U Test, Spearman rank correlation, and linear/logistic regressions adjusted for potential confounders; a P-value < .05 was considered significant for all analyses. Results: Serum PDGFRẞ, a putative biomarker of BBB injury, was significantly increased in subjects with vs without a history of CVA who had similar cardiovascular risk factors (P < .01). This difference was stable after adjusting for age, hypertension, and other potential confounders in regression analysis (odds ratio, 27.02; 95% confidence interval, 2.61-411.7; P < .01). In addition, PDGFRẞ was positively associated with VCAM-1, a biomarker of endothelial inflammation (ρ = 0.42; P < .01). Conclusions: Our data suggest that patients with stroke or transient ischemic attack have lasting changes in the BBB. Still more, this demonstrates the utility of PDGFRẞ as a serum-based biomarker of BBB physiology, a potentially powerful tool in studying the role of the BBB in various neurodegenerative diseases and COVID infection sequelae. Clinical Relevance: Our data demonstrate the utility of serum PDGFRẞ, a putative biomarker of BBB integrity in the setting of stroke and TIA (CVA). A serum biomarker of BBB integrity could be a useful tool to detect early BBB damage and allow prospective work to study how such damage affects long-term neurodegenerative risk. Since BBB disruption occurs early in ADRD development, it could be monitored to help better understand disease progression and involvement of vascular pathways in ADRD.

Broad plumes rooted at the base of the Earth's mantle beneath major hotspots.

Plumes of hot upwelling rock rooted in the deep mantle have been proposed as a possible origin of hotspot volcanoes, but this idea is the subject of vigorous debate. On the basis of geodynamic computations, plumes of purely thermal origin should comprise thin tails, only several hundred kilometres wide, and be difficult to detect using standard seismic tomography techniques. Here we describe the use of a whole-mantle seismic imaging technique--combining accurate wavefield computations with information contained in whole seismic waveforms--that reveals the presence of broad (not thin), quasi-vertical conduits beneath many prominent hotspots. These conduits extend from the core-mantle boundary to about 1,000 kilometres below Earth's surface, where some are deflected horizontally, as though entrained into more vigorous upper-mantle circulation. At the base of the mantle, these conduits are rooted in patches of greatly reduced shear velocity that, in the case of Hawaii, Iceland and Samoa, correspond to the locations of known large ultralow-velocity zones. This correspondence clearly establishes a continuous connection between such zones and mantle plumes. We also show that the imaged conduits are robustly broader than classical thermal plume tails, suggesting that they are long-lived, and may have a thermochemical origin. Their vertical orientation suggests very sluggish background circulation below depths of 1,000 kilometres. Our results should provide constraints on studies of viscosity layering of Earth's mantle and guide further research into thermochemical convection.

Waveform tomography reveals channeled flow at the base of the oceanic asthenosphere.

Understanding the relationship between different scales of convection that drive plate motions and hotspot volcanism still eludes geophysicists. Using full-waveform seismic tomography, we imaged a pattern of horizontally elongated bands of low shear velocity, most prominent between 200 and 350 kilometers depth, which extends below the well-developed low-velocity zone. These quasi-periodic fingerlike structures of wavelength ~2000 kilometers align parallel to the direction of absolute plate motion for thousands of kilometers. Below 400 kilometers depth, velocity structure is organized into fewer, undulating but vertically coherent, low-velocity plumelike features, which appear rooted in the lower mantle. This suggests the presence of a dynamic interplay between plate-driven flow in the low-velocity zone and active influx of low-rigidity material from deep mantle sources deflected horizontally beneath the moving top boundary layer.

Education on prehospital pain management: a follow-up study.

INTRODUCTION: The most common reason patients seek medical attention is pain. However, there may be significant delays in initiating prehospital pain therapy. In a 2001 quality improvement (QI) study, we demonstrated improvement in paramedic knowledge, perceptions, and management of pain. This follow-up study examines the impact of this QI program, repeated educational intervention (EI), and effectiveness of a new pain management standard operating procedure. METHODS: 176 paramedics from 10 urban and suburban fire departments and two private ambulance services participated in a 3-hour EI. A survey was performed prior to the EI and repeated one month after the EI. We reviewed emergency medical services (EMS) runs with pain complaints prior to the EI and one month after the EI. Follow-up results were compared to our prior study. We performed data analysis using descriptive statistics and chi-square tests. RESULTS: The authors reviewed 352 surveys and 438 EMS runs with pain complaints. Using the same survey questions, even before the EI, 2007 paramedics demonstrated significant improvement in the knowledge (18.2%; 95% CI 8.9%, 27.9%), perceptions (9.2%; 95% CI 6.5%, 11.9%), and management of pain (13.8%; 95% CI 11.3%, 16.2%) compared to 2001. Following EI in 2007, there were no significant improvements in the baseline knowledge (0%; 95% CI 5.3%, 5.3%) but significant improvements in the perceptions of pain principles (6.4%; 95% CI 3.9%, 9.0%) and the management of pain (14.7%; 95% CI 11.4%, 18.0%). CONCLUSION: In this follow up study, paramedics' baseline knowledge, perceptions, and management of pain have all improved from 6 years ago. Following a repeat educational intervention, paramedics further improved their field management of pain suggesting paramedics will still benefit from both initial and also ongoing continuing education on the topic of pain management.

Lithospheric thinning beneath rifted regions of Southern California.

The stretching and break-up of tectonic plates by rifting control the evolution of continents and oceans, but the processes by which lithosphere deforms and accommodates strain during rifting remain enigmatic. Using scattering of teleseismic shear waves beneath rifted zones and adjacent areas in Southern California, we resolve the lithosphere-asthenosphere boundary and lithospheric thickness variations to directly constrain this deformation. Substantial and laterally abrupt lithospheric thinning beneath rifted regions suggests efficient strain localization. In the Salton Trough, either the mantle lithosphere has experienced more thinning than the crust, or large volumes of new lithosphere have been created. Lack of a systematic offset between surface and deep lithospheric deformation rules out simple shear along throughgoing unidirectional shallow-dipping shear zones, but is consistent with symmetric extension of the lithosphere.

The value of bedside cardiac multibiomarker assay in rapid and accurate diagnosis of acute coronary syndromes.

For emergency department physicians, timely triage and risk stratification of chest pain patients remains a challenge. Faced with an aging population and the growing prevalence of heart disease, clinicians are seeking more effective ways to diagnose acute coronary syndromes rapidly and accurately. Emergency department physicians must make critical and time-sensitive decisions based on patient history, physical examination, and 12-lead electrocardiogram as justification for diagnosis of acute coronary syndromes. But because most of these tools are not reliable independently, these incomplete strategies can result in costly and inappropriate treatment decisions.

Effects of an educational intervention on prehospital pain management.

INTRODUCTION: Pain is a common symptom evaluated by emergency medical services (EMS) providers. Hospital pain management programs began in the early 1990s based on a multidisciplinary approach and principles of total quality improvement. To date, these programs have had limited exposure in the prehospital setting. OBJECTIVES: To evaluate the effects of a pain management educational intervention (EI) for paramedic caregivers. METHODS: All ambulance providers from ten urban and suburban fire departments and two private ambulance companies participated in a three-hour EI during a quality improvement project. A survey was performed prior to the EI and repeated one month after the EI. A two-month collection of EMS runs for pain complaints was performed prior to the EI and repeated one month after the EI. Data analysis was performed using descriptive statistics and chi-square tests. RESULTS: The authors reviewed 397 surveys and 439 EMS runs for pain. Overall, after the EI, paramedics' knowledge of basic pain management principles increased from 57.3% to 74.9% (17.5%; 95% confidence interval (CI): 14.9%-20.2%; p < 0.001). Paramedics' utilization of nonpharmacologic pain therapies improved by 32.2% (95% CI: 25.3%-39.2%; p < 0.001), but there was no significant change in the use of pain medication (20.2% to 24.5%). There were 51.0% (95% CI: 44.1%-57.9%; p < 0.001) improvement in documentation of pain severity, 24% (95% CI: 21.2%-26.8%; p < 0.001) improvement in documentation of pain characteristics, and 13% (95% CI: 7.4%-18.7%; p < 0.001) improvement in pain reassessment following intervention. CONCLUSION: As a result of a three-hour educational intervention, paramedics had an increased understanding of pain principles, were more likely to provide prehospital nonpharmacologic pain therapy, and were more likely to document the results of their interventions.

Cocaethylene's effects on coronary artery blood flow and cardiac function in a canine model.

OBJECTIVES: Cocaethylene is a toxic metabolite of cocaine formed in the presence of ethanol. Though cocaine causes coronary vasoconstriction, cocaethylene's effects on coronaryflow are unknown. The aim of our study was to describe cocaethylene 's effects on coronary flow and cardiac function. METHODS: Sixteen alpha-chloralose anesthetized dogs were monitored with Swan-Ganz, arterial and venous catheters, and an electrocardiogram. Dopplerflow probes were placed on the circumflex and left anterior descending coronary arteries. Dogs were allotted 15 mg/kg (n = 10) or 30mg/kg (n = 6) of cocaethylene given as a continuous intravenous infusion. Measurements were made at fixed time intervals during the 60-minute cocaethylene infusion and 2-hour observation period. RESULTS: The cocaethylene concentrations were maximal at the end of the infusion and cocaethylene was rapidly metabolized to benzoylecognine. One low-dose animal died of ventricular fibrillation. Five high-dose dogs experienced ventricular arrhythmias or pulseless electrical activity (PEA), and three died. In the low-dose group, cocaethylene caused a 38% increase in mean arterial pressure relative to baseline, and increased systemic vascular resistance. In the high-dose group, at maximal cocaethylene concentrations, stroke volume decreased by 42% (p < 0.0002), and circumflex blood flow decreased by 30% (p = 0.03) relative to baseline, when arrhythmias occurred. The PR, QRS, and QTc intervals increased by 48, 209, and 29%, respectively (p < 0.001). As cocaethylene levels declined, circumflex blood flow increased by 77% (p = 0.05) and mean arterial pressure increased 49% (p < 0.01), also relative to baseline. CONCLUSIONS: Cocaethylene caused hypertension and increased systemic vascular resistance. At high concentrations, it decreased myocardial function, slowed cardiac conduction, and was arrhythmogenic. The cocaethylene's toxicity does not appear to be mediated by effects on coronary blood flow.