Coach-Like Skills for Educators: An Engaging and Applicable Workshop.

Equipping students with coach-like skills is one way to motivate and prepare them as future educators. Herein, we describe an engaging and applicable workshop designed to teach five skills to improve interactions with others. Educators who acquire coach-like skills may positively impact learners and enhance their development.

Impact on Faculty's Own Development When Assessing Student Performance.

INTRODUCTION: Assessing learner performance is a primary focus within simulation-based education in order to prepare students with the knowledge and skills they will need going forward in their careers. In order to properly conduct these assessments of learner performance, faculty must be adequately trained on the scenario, expectations, assessment measures, and debriefing. During Operation Bushmaster, a five-day "deployment" for learners, faculty assess students as they rotate through different leadership roles. The faculty development includes online and in-person training that provides them with an understanding of the scenario; what learners know; the framework used at USU to guide curriculum, development, and assessment; how to assess learners; and how to provide feedback to learners. Research has examined the value of receiving assessment and feedback from a student perspective, but the impact of being the assessor and giving feedback has not been researched from the faculty point of view. The purpose of this study, therefore, was to examine the impact of assessing students in simulation scenarios on faculty's own development as an educator and leader. MATERIALS AND METHODS: Through a phenomenological qualitative study, we explored participants' lived experiences as faculty at Operation Bushmaster. Eighteen faculty from a variety of medical specialties and military ranks volunteered to participate. Participants were interviewed in-person using a semi-structured interview. Analyses included individually reading through each transcript; then individually coding and taking notes of terms and phrases used by participants; codes were compiled and organized into categories, which became the themes of our study. RESULTS: The interviews demonstrated the following themes in which providers who serve as faculty of Operation Bushmaster believe they gain from the experience: (1) The experience helps to reground their own thinking; (2) acting as faculty during simulation-based education helps them remain up-to-date on necessary skills; and (3) working with students helps faculty continually develop as an educator and a leader. CONCLUSIONS: This work describes how even when faculty are brought in for learner assessment, they are taking away lessons and experiences that aid in their own development as an educator as well as a leader. Acting as an assessing faculty for students may allow faculty to reground their own thinking, remain up-to-date on necessary skills, and continually develop their skills as an educator and leader. These findings suggest that some faculty involved in simulation events may also gain knowledge, skills, and experiences that can help with their own development even when the focus is on learners.

Undergraduate Medical Education Leader Performance Predicts Postgraduate Military Leader Performance.

INTRODUCTION: Developing physicians as leaders has gained attention across the United States. Undergraduate medical education (UME) and graduate medical education (GME) leader development programs have increased. During postgraduate years (PGY), graduates bring their leadership education to the bedside; however, associations between leader performance in medical school and GME is largely unknown. It is important to find experiences that can assess leader performance that may be useful to predict future performance. The purpose of this study was to determine if (1) there is a correlation between leader performance during the fourth year of medical school versus leader performance in PGY1 and 3, and (2) leader performance during the fourth year of medical school is associated with military leadership performance in PGY1 and 3s while taking previous academic performance markers into account. METHODS: This study examined overall leader performance of learners (classes of 2016-2018) during the fourth year of medical school and their graduate leader performance post-medical school. Leader performance was assessed by faculty during a medical field practicum (UME leader performance) and graduate leader performance was assessed by program directors at the end of PGY1 (N = 297; 58.3%) and 3 (N = 142; 28.1%). Pearson correlation analysis examined relationships among UME leader performance and between the PGY leader performance items. In addition, stepwise multiple linear regression analyses were conducted to examine the relationship between leader performance at the end of medical school with military leadership performance in PGY1 and 3, while taking into account the academic performance markers. RESULTS: Pearson correlation analyses revealed that the UME leader performance was correlated with 3 of 10 variables at PGY1, and was correlated at PGY3 with 10 out of 10 variables. Results of the stepwise multiple linear regression analysis indicated that leader performance during the fourth year of medical school explained an additional 3.5% of the variance of PGY1 leader performance after controlling for the previous academic performance markers (MCAT total score, USMLE Step 1 score and Step 2 CK score). In contrast, leader performance during the fourth year of medical school alone accounted for an additional 10.9% of the variance of PGY3 leader performance above and beyond the set of academic performance markers. Overall, UME leader performance has more predictive power in PGY leader performance than the MCAT or USMLE Step exams. CONCLUSIONS: The findings of this study indicate that a positive relationship exists between leader performance at the end of medical school and leader performance in PGY1 and 3 years of residency. These correlations were stronger in PGY3 compared to PGY1. During PGY1, learners may be more focused on being a physician and an effective team member compared to PGY3 where they have a deeper understanding of their roles and responsibilities and can take on more leadership roles. Additionally, this study also found that MCAT and USMLE Step exams performance was not predictive of PGY1 or PGY3 leader performance. These findings provide evidence of the power of continued leader development in UME and beyond.

A Pilot Study of Whole-Blood Transcriptomic Analysis to Identify Genes Associated with Repetitive Low-Level Blast Exposure in Career Breachers.

Repetitive low-level blast exposure is one of the major occupational health concerns among US military service members and law enforcement. This study seeks to identify gene expression using microRNA and RNA sequencing in whole-blood samples from experienced breachers and unexposed controls. We performed experimental RNA sequencing using Illumina's HiSeq 2500 Sequencing System, and microRNA analysis using NanoString Technology nCounter miRNA expression panel in whole-blood total RNA samples from 15 experienced breachers and 14 age-, sex-, and race-matched unexposed controls. We identified 10 significantly dysregulated genes between experienced breachers and unexposed controls, with FDR corrected <0.05: One upregulated gene, LINC00996 (long intergenic non-protein coding RNA 996); and nine downregulated genes, IGLV3-16 (immunoglobulin lambda variable 3-16), CD200 (CD200 molecule), LILRB5 (leukocyte immunoglobulin-like receptor B5), ZNF667-AS1 (ZNF667 antisense RNA 1), LMOD1 (leiomodin 1), CNTNAP2 (contactin-associated protein 2), EVPL (envoplakin), DPF3 (double PHD fingers 3), and IGHV4-34 (immunoglobulin heavy variable 4-34). The dysregulated gene expressions reported here have been associated with chronic inflammation and immune response, suggesting that these pathways may relate to the risk of lasting neurological symptoms following high exposures to blast over a career.

Learning to Lead: 10 Leadership Lessons From Operation Bushmaster.

Medical students at the Uniformed Services University of the Health Sciences participate in a leadership curriculum designed to develop leadership skills. Operation Bushmaster is a 5-day field practicum designed to test these skills. In this article, we describe 10 leadership lessons learned during Operation Bushmaster applicable to all leaders.

Neuronally-derived tau is increased in experienced breachers and is associated with neurobehavioral symptoms.

Military and law enforcement breachers are exposed to many low-level blasts during their training and occupational experiences in which they detonate explosives to force entry into secured structures. There is a concern that exposure to these repetitive blast events in career breachers could result in cumulative neurological effects. This study aimed to determine concentrations of neurofilament light (NF-L), tau, and amyloid-beta 42 (Aß42) in serum and in neuronal-derived extracellular vesicles (EVs) in an experienced breacher population, and to examine biomarker associations with neurobehavioral symptoms. Thirty-four participants enrolled in the study: 20 experienced breachers and 14 matched military or civilian law enforcement controls. EV tau concentrations were significantly elevated in experienced breachers (0.3301 ± 0.5225) compared to controls (-0.4279 ± 0.7557; F = 10.43, p = 0.003). No statistically significant changes were observed in EV levels of NF-L or Aß42 or in serum levels of NF-L, tau, or Aß42 (p's > 0.05). Elevated EV tau concentrations correlated with increased Neurobehavioral Symptom Inventory (NSI) score in experienced breachers (r = 0.596, p = 0.015) and predicted higher NSI score (F(1,14) = 7.702, p = 0.015, R2 = 0.355). These findings show that neuronal-derived EV concentrations of tau are significantly elevated and associated with neurobehavioral symptoms in this sample of experienced breachers who have a history of many low-level blast exposures.

Functional and Structural Neuroimaging Correlates of Repetitive Low-Level Blast Exposure in Career Breachers.

Combat military and civilian law enforcement personnel may be exposed to repetitive low-intensity blast events during training and operations. Persons who use explosives to gain entry (i.e., breach) into buildings are known as "breachers" or dynamic entry personnel. Breachers operate under the guidance of established safety protocols, but despite these precautions, breachers who are exposed to low-level blast throughout their careers frequently report performance deficits and symptoms to healthcare providers. Although little is known about the etiology linking blast exposure to clinical symptoms in humans, animal studies demonstrate network-level changes in brain function, alterations in brain morphology, vascular and inflammatory changes, hearing loss, and even alterations in gene expression after repeated blast exposure. To explore whether similar effects occur in humans, we collected a comprehensive data battery from 20 experienced breachers exposed to blast throughout their careers and 14 military and law enforcement controls. This battery included neuropsychological assessments, blood biomarkers, and magnetic resonance imaging measures, including cortical thickness, diffusion tensor imaging of white matter, functional connectivity, and perfusion. To better understand the relationship between repetitive low-level blast exposure and behavioral and imaging differences in humans, we analyzed the data using similarity-driven multi-view linear reconstruction (SiMLR). SiMLR is specifically designed for multiple modality statistical integration using dimensionality-reduction techniques for studies with high-dimensional, yet sparse, data (i.e., low number of subjects and many data per subject). We identify significant group effects in these data spanning brain structure, function, and blood biomarkers.

Blast exposure results in tau and neurofilament light chain changes in peripheral blood.

OBJECTIVES: To evaluate how blast exposure impacts peripheral biomarkers.in military personnel enrolled in 10-day blast training. METHODS: On day 7, 21 military personnel experienced peak overpressure <2 pounds per square inch (psi); while 29 military personnel experienced peak overpressure ≥5 psi. Blood samples were collected each day to measure changes in amyloid beta (Aß), neurofilament light chain (NFL), and tau concentrations. RESULTS: Within 24 hours following exposure ≥5 psi, the ≥5 psi group had lower Aß42 (p = .004) and NFL (p < .001) compared to the <2 psi group and lower Aß42 (9.35%) and NFL (22.01%) compared to baseline. Twenty-four hours after ≥5 psi exposure, the ≥5 psi group had lower tau (p < .001) and NFL (p < .001) compared to the <2 psi group and baseline. Seventy-two hours after exposure ≥5 psi, tau increased in the ≥5 psi group compared to the <2 psi group (p = .02) and baseline. The tau:Aß42 ratio 24 hours after blast (p = .012), and the Aß40:Aß42 ratio 48 hours after blast (p = .04) differed in the ≥5 psi group compared to the <2 psi group. CONCLUSIONS: These findings provide an initial report of acute alterations in biomarker concentrations following blast exposure.

Hearing Loss and Irritability Reporting Without Vestibular Differences in Explosive Breaching Professionals.

Background: Blast exposure is a potential hazard in modern military operations and training, especially for some military occupations. Helmets, peripheral armor, hearing protection, and eye protection worn by military personnel provide some acute protection from blast effects but may not fully protect personnel against cumulative effects of repeated blast overpressure waves experienced over a career. The current study aimed to characterize the long-term outcomes of repeated exposure to primary blast overpressure in experienced career operators with an emphasis on the assessment of hearing and vestibular outcomes. Methods: Participants included experienced "breachers" (military and law enforcement explosives professionals who gain entry into structures through controlled detonation of charges) and similarly aged and experienced "non-breachers" (non-breaching military and law enforcement personnel). Responses to a clinical interview and performance on audiological and vestibular testing were compared. Results: Hearing loss, ringing in the ears, irritability, and sensitivity to light or noise were more common among breachers than non-breachers. Breachers reported more combat exposure than non-breachers, and subsequently, memory loss and difficulty concentrating were associated with both breaching and combat exposure. Vestibular and ocular motor outcomes were not different between breachers and non-breachers. Conclusion: Hearing-related, irritability, and sensitivity outcomes are associated with a career in breaching. Future studies examining long-term effects of blast exposure should take measures to control for combat exposure.

Acute and Chronic Molecular Signatures and Associated Symptoms of Blast Exposure in Military Breachers.

Injuries from exposure to explosions rose dramatically during the Iraq and Afghanistan wars, which motivated investigations of blast-related neurotrauma and operational breaching. In this study, military "breachers" were exposed to controlled, low-level blast during a 10-day explosive breaching course. Using an omics approach, we assessed epigenetic, transcriptional, and inflammatory profile changes in blood from operational breaching trainees, with varying levels of lifetime blast exposure, along with daily self-reported symptoms (with tinnitus, headaches, and sleep disturbances as the most frequently reported). Although acute exposure to blast did not confer epigenetic changes, specifically in DNA methylation, differentially methylated regions (DMRs) with coordinated gene expression changes associated with lifetime cumulative blast exposures were identified. The accumulative effect of blast showed increased methylation of PAX8 antisense transcript with coordinated repression of gene expression, which has been associated with sleep disturbance. DNA methylation analyses conducted in conjunction with reported symptoms of tinnitus in the low versus high blast incidents groups identified DMRS in KCNE1 and CYP2E1 genes. KCNE1 and CYP2E1 showed the expected inverse correlation between DNA methylation and gene expression, which have been previously implicated in noise-related hearing loss. Although no significant transcriptional changes were observed in samples obtained at the onset of the training course relative to chronic cumulative blast, we identified a large number of transcriptional perturbations acutely pre- versus post-blast exposure. Acutely, 67 robustly differentially expressed genes (fold change ≥1.5), including UFC1 and YOD1 ubiquitin-related proteins, were identified. Inflammatory analyses of cytokines and chemokines revealed dysregulation of MCP-1, GCSF, HGF, MCSF, and RANTES acutely after blast exposure. These data show the importance of an omics approach, revealing that transcriptional and inflammatory biomarkers capture acute low-level blast overpressure exposure, whereas DNA methylation marks encapsulate chronic long-term symptoms.

Sleep extension reduces pain sensitivity.

INTRODUCTION: Insufficient sleep increases pain sensitivity in healthy individuals. Additionally, extending sleep (eg, increasing nocturnal sleep time or adding a mid-day nap) has been shown to restore pain sensitivity to baseline levels in sleep deprived/restricted individuals. Whether sleep extension can reduce pain sensitivity beyond baseline levels in non-sleep restricted/deprived individuals remains unknown. METHODS: In a sample of 27 healthy, pain-free, normally-sleeping individuals (17 males, mean age ∼24 yrs), we examined the impact of five nights of sleep extension on pain sensitivity. Pain threshold (elapsed time until the participant reported pain) and pain tolerance (total time the participant kept the hand submerged in the cold water) were measured using the Cold Pressor Task. Furthermore, we assessed the extent to which self-reported sleep amount in relation to the minimal subjective sleep requirement for adequate performance (sleep credit) was associated with pain sensitivity changes. RESULTS: On average individuals slept almost 2 extra hours per night. Our results indicate that sleep extension increases pain tolerance beyond baseline levels. However, sleep extension did not impact pain threshold. We also found that individuals with a smaller sleep credit (ie, those who habitually obtain less sleep than they feel they need) experienced greater increases in pain tolerance after extending sleep. CONCLUSIONS: The present findings suggest that sleep extension may increase pain tolerance but not pain threshold in healthy individuals who normally sleep the recommended amount. Our findings also support the idea that sleep credit may be a strong indicator of sleep debt in the context of pain sensitivity.

A systematic review and meta-analysis of sleep architecture and chronic traumatic brain injury.

Sleep quality appears to be altered by traumatic brain injury (TBI). However, whether persistent post-injury changes in sleep architecture are present is unknown and relatively unexplored. We conducted a systematic review and meta-analysis to assess the extent to which chronic TBI (>6 months since injury) is characterized by changes to sleep architecture. We also explored the relationship between sleep architecture and TBI severity. In the fourteen included studies, sleep was assessed with at least one night of polysomnography in both chronic TBI participants and controls. Statistical analyses, performed using Comprehensive Meta-Analysis software, revealed that chronic TBI is characterized by relatively increased slow wave sleep (SWS). A meta-regression showed moderate-severe TBI is associated with elevated SWS, reduced stage 2, and reduced sleep efficiency. In contrast, mild TBI was not associated with any significant alteration of sleep architecture. The present findings are consistent with the hypothesis that increased SWS after moderate-severe TBI reflects post-injury cortical reorganization and restructuring. Suggestions for future research are discussed, including adoption of common data elements in future studies to facilitate cross-study comparability, reliability, and replicability, thereby increasing the likelihood that meaningful sleep (and other) biomarkers of TBI will be identified.

Limited Efficacy of Caffeine and Recovery Costs During and Following 5 Days of Chronic Sleep Restriction.

Objectives: To investigate the effects of caffeine on psychomotor vigilance and sleepiness during sleep restriction and following subsequent recovery sleep. Methods: Participants were N = 48 healthy good sleepers. All participants underwent five nights of sleep satiation (time-in-bed [TIB]: 10 hours), followed by five nights of sleep restriction (TIB: 5 hours), and three nights of recovery sleep (TIB: 8 hours) in a sleep laboratory. Caffeine (200 mg) or placebo was administered in the form of chewing gum at 08:00 am and 12:00 pm each day during the sleep restriction phase. Participants completed hourly 10-minute psychomotor vigilance tests and a modified Maintenance of Wakefulness Test approximately every 4 hours during the sleep restriction and recovery phases. Results: Caffeine maintained objective alertness compared to placebo across the first 3 days of sleep restriction, but this effect was no longer evident by the fourth day. A similar pattern of results was found for Maintenance of Wakefulness Test sleep latencies, such that those in the caffeine group (compared to placebo) did not show maintenance of wakefulness relative to baseline after the second night of restriction. Compared to placebo, participants in the caffeine condition displayed slower return to baseline in alertness and wakefulness across the recovery sleep period. Finally, the caffeine group showed greater N3 sleep duration during recovery. Conclusions: Caffeine appears to have limited efficacy for maintaining alertness and wakefulness across 5 days of sleep restriction. Perhaps more importantly, there may be recovery costs associated with caffeine use following conditions of prolonged sleep loss.

Sleep deprivation impairs recognition of specific emotions.

Emotional processing is particularly sensitive to sleep deprivation, but research on the topic has been limited and prior studies have generally evaluated only a circumscribed subset of emotion categories. Here, we evaluated the effects of one night of sleep deprivation and a night of subsequent recovery sleep on the ability to identify the six most widely agreed upon basic emotion categories (happiness, surprise, fear, sadness, disgust, anger). Healthy adults (29 males; 25 females) classified a series of 120 standard facial expressions that were computer morphed with their most highly confusable expression counterparts to create continua of expressions that differed in discriminability between emotion categories (e.g., combining 70% happiness+30% surprise; 90% surprise+10% fear). Accuracy at identifying the dominant emotion for each morph was assessed after a normal night of sleep, again following a night of total sleep deprivation, and finally after a night of recovery sleep. Sleep deprivation was associated with significantly reduced accuracy for identifying the expressions of happiness and sadness in the morphed faces. Gender differences in accuracy were not observed and none of the other emotions showed significant changes as a function of sleep loss. Accuracy returned to baseline after recovery sleep. Findings suggest that sleep deprivation adversely affects the recognition of subtle facial cues of happiness and sadness, the two emotions that are most relevant to highly evolved prosocial interpersonal interactions involving affiliation and empathy, while the recognition of other more primitive survival-oriented emotional face cues may be relatively robust against sleep loss.

The Revised Neurobehavioral Severity Scale (NSS-R) for Rodents.

Motor and sensory deficits are common following traumatic brain injury (TBI). Although rodent models provide valuable insight into the biological and functional outcomes of TBI, the success of translational research is critically dependent upon proper selection of sensitive, reliable, and reproducible assessments. Published literature includes various observational scales designed to evaluate post-injury functionality; however, the heterogeneity in TBI location, severity, and symptomology can complicate behavioral assessments. The importance of choosing behavioral outcomes that can be reliably and objectively quantified in an efficient manner is becoming increasingly important. The Revised Neurobehavioral Severity Scale (NSS-R) is a continuous series of specific, sensitive, and standardized observational tests that evaluate balance, motor coordination, and sensorimotor reflexes in rodents. The tasks follow a specific order designed to minimize interference: balance, landing, tail raise, dragging, righting reflex, ear reflex, eye reflex, sound reflex, tail pinch, and hindpaw pinch. The NSS-R has proven to be a reliable method differentiating brain-injured rodents from non-brain-injured rodents across many brain injury models.

Sleep As A Strategy For Optimizing Performance.

Recovery is an essential component of maintaining, sustaining, and optimizing cognitive and physical performance during and after demanding training and strenuous missions. Getting sufficient amounts of rest and sleep is key to recovery. This article focuses on sleep and discusses (1) why getting sufficient sleep is important, (2) how to optimize sleep, and (3) tools available to help maximize sleep-related performance. Insufficient sleep negatively impacts safety and readiness through reduced cognitive function, more accidents, and increased military friendly-fire incidents. Sufficient sleep is linked to better cognitive performance outcomes, increased vigor, and better physical and athletic performance as well as improved emotional and social functioning. Because Special Operations missions do not always allow for optimal rest or sleep, the impact of reduced rest and sleep on readiness and mission success should be minimized through appropriate preparation and planning. Preparation includes periods of "banking" or extending sleep opportunities before periods of loss, monitoring sleep by using tools like actigraphy to measure sleep and activity, assessing mental effectiveness, exploiting strategic sleep opportunities, and consuming caffeine at recommended doses to reduce fatigue during periods of loss. Together, these efforts may decrease the impact of sleep loss on mission and performance.

Caffeine and Performance.

The role of caffeine in enhancing performance has been studied for years, and there is no doubt that caffeine can be performance enhancing. Also, a wealth of information allows for an interesting distinction between physical and cognitive performance. Most adults in America consume moderate doses of caffeine in various forms on a daily basis as caffeine is typically found in coffee, tea, soft drinks, dietary supplements, energy drinks, energy shots, and chocolate, as well as over-the-counter pills and gums. Although caffeine is readily available and widely consumed, when using it to enhance performance, a few factors should be considered. The authors discuss caffeine use among Servicemembers, its properties and effects on physical and cognitive performance, how to use it to optimize performance, and, finally, some of safety and regulatory considerations. The bottom line is that all individuals do not respond the same way to caffeine and their response depends on how the body uses and breaks down caffeine. Thus, as a user, you should monitor your own responses and performance changes when using caffeine based on the general recommendations provided.

Autoimmune Profiling Reveals Peroxiredoxin 6 as a Candidate Traumatic Brain Injury Biomarker.

Autoimmune profiling in rats revealed the antioxidant enzyme, peroxiredoxin 6 (PRDX6), as a target for autoantibodies evoked in response to traumatic brain injury (TBI). Consistent with this proposal, immunohistochemical analysis of rat cerebral cortex demonstrated that PRDX6 is highly expressed in the perivascular space, presumably contained within astrocytic foot processes. Accordingly, an immunosorbent electrochemiluminescence assay was developed for investigating PRDX6 in human samples. PRDX6 was found to be measurable in human blood and highly expressed in human cerebral cortex and platelets. Circulating levels of PRDX6 were elevated fourfold over control values 4 to 24 h following mild-to-moderate TBI. These findings suggest that PRDX6 may serve as a biomarker for TBI and that autoimmune profiling is a viable strategy for the discovery of novel TBI biomarkers.

Ubiquitin carboxy-terminal hydrolase-l1 as a serum neurotrauma biomarker for exposure to occupational low-level blast.

Repeated exposure to low-level blast is a characteristic of a few select occupations and there is concern that such occupational exposures present risk for traumatic brain injury. These occupations include specialized military and law enforcement units that employ controlled detonation of explosive charges for the purpose of tactical entry into secured structures. The concern for negative effects from blast exposure is based on rates of operator self-reported headache, sleep disturbance, working memory impairment, and other concussion-like symptoms. A challenge in research on this topic has been the need for improved assessment tools to empirically evaluate the risk associated with repeated exposure to blast overpressure levels commonly considered to be too low in magnitude to cause acute injury. Evaluation of serum-based neurotrauma biomarkers provides an objective measure that is logistically feasible for use in field training environments. Among candidate biomarkers, ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) has some empirical support and was evaluated in this study. We used daily blood draws to examine acute change in UCH-L1 among 108 healthy military personnel who were exposed to repeated low-level blast across a 2-week period. These research volunteers also wore pressure sensors to record blast exposures, wrist actigraphs to monitor sleep patterns, and completed daily behavioral assessments of symptomology, postural stability, and neurocognitive function. UCH-L1 levels were elevated as a function of participating in the 2-week training with explosives, but the correlation of UCH-L1 elevation and blast magnitude was weak and inconsistent. Also, UCH-L1 elevations did not correlate with deficits in behavioral measures. These results provide some support for including UCH-L1 as a measure of central nervous system effects from exposure to low-level blast. However, the weak relation observed suggests that additional indicators of blast effect are needed.

Multivariate analysis of traumatic brain injury: development of an assessment score.

Important challenges for the diagnosis and monitoring of mild traumatic brain injury (mTBI) include the development of plasma biomarkers for assessing neurologic injury, monitoring pathogenesis, and predicting vulnerability for the development of untoward neurologic outcomes. While several biomarker proteins have shown promise in this regard, used individually, these candidates lack adequate sensitivity and/or specificity for making a definitive diagnosis or identifying those at risk of subsequent pathology. The objective for this study was to evaluate a panel of six recognized and novel biomarker candidates for the assessment of TBI in adult patients. The biomarkers studied were selected on the basis of their relative brain-specificities and potentials to reflect distinct features of TBI mechanisms including (1) neuronal damage assessed by neuron-specific enolase (NSE) and brain derived neurotrophic factor (BDNF); (2) oxidative stress assessed by peroxiredoxin 6 (PRDX6); (3) glial damage and gliosis assessed by glial fibrillary acidic protein and S100 calcium binding protein beta (S100b); (4) immune activation assessed by monocyte chemoattractant protein 1/chemokine (C-C motif) ligand 2 (MCP1/CCL2); and (5) disruption of the intercellular adhesion apparatus assessed by intercellular adhesion protein-5 (ICAM-5). The combined fold-changes in plasma levels of PRDX6, S100b, MCP1, NSE, and BDNF resulted in the formulation of a TBI assessment score that identified mTBI with a receiver operating characteristic (ROC) area under the curve of 0.97, when compared to healthy controls. This research demonstrates that a profile of biomarker responses can be used to formulate a diagnostic score that is sensitive for the detection of mTBI. Ideally, this multivariate assessment strategy will be refined with additional biomarkers that can effectively assess the spectrum of TBI and identify those at particular risk for developing neuropathologies as consequence of a mTBI event.