An investigation of neuroinjury biomarkers after sport-related concussion: from the subacute phase to clinical recovery.

OBJECTIVES: To characterise a panel of neuroinjury-related blood biomarkers after sport-related concussion (SRC). We hypothesised significant differences in biomarker profiles between athletes with SRC and healthy controls at both subacute and medical clearance time points. METHODS: Thirty-eight interuniversity athletes were recruited over two athletic seasons (n = 19 SRC; n = 19 healthy matched-control). High-sensitivity immunoassay was used to evaluate 11 blood analytes at both the subacute phase after SRC and at medical clearance. RESULTS: Univariate analysis identified elevated circulating peroxiredoxin-6 (PRDX-6) in athletes with SRC compared to healthy controls at the subacute time point. Multivariate analyses yielded similar results in the subacute phase, but identified both PRDX-6 and T-tau as significant contributors to class separation between athletes with SRC and controls at medical clearance. CONCLUSIONS: Our results are consistent with the increasing recognition that physiological recovery after SRC extends beyond clinical recovery. Blood biomarkers appear to be useful in elucidating the biology of brain restitution after SRC. However, their implementation requires mindfulness of factors such as academic stress, exercise, and injury heterogeneity.

Plasma von Willebrand Factor Is Elevated Hyperacutely After Mild Traumatic Brain Injury.

Each year in the United States, ∼2.7 million persons seek medical attention for traumatic brain injury (TBI), of which ∼85% are characterized as being mild brain injuries. Many different cell types in the brain are affected in these heterogeneous injuries, including neurons, glia, and the brain vasculature. Efforts to identify biomarkers that reflect the injury of these different cell types have been a focus of ongoing investigation. We hypothesized that von Willebrand factor (vWF) is a sensitive biomarker for acute traumatic vascular injury and correlates with symptom severity post-TBI. To address this, blood was collected from professional boxing athletes (n = 17) before and within 30 min after competition. Plasma levels of vWF and neuron-specific enolase were measured using the Meso Scale Discovery, LLC. (MSD) electrochemiluminescence array-based multi-plex format (MSD, Gaithersburg, MD). Additional symptom and outcome data from boxers and patients, such as the Rivermead symptom scores (Rivermead Post Concussion Symptoms Questionnaire [RPQ-3]), were collected. We found that, subsequent to boxing bouts, there was a 1.8-fold increase in vWF levels within 30 min of injury (p < 0.0009). Moreover, fold-change in vWF correlates moderately (r = 0.51; p = 0.03) with the number of head blows. We also found a positive correlation (r = 0.69; p = 0.002) between fold-change in vWF and self-reported post-concussive symptoms, measured by the RPQ-3. The receiver operating curve analysis of vWF plasma levels and RPQ-3 scoring yielded a sensitivity of 94.12% and a specificity of 76.5% with an area under the curve of 83% for boxers after a fight compared to the pre-bout baseline. This study suggests that vWF is a potential blood biomarker measurable in the hyperacute period after blunt mild TBI. This biomarker may prove to be useful in diagnosing and monitoring traumatic vascular injury.

Quantitative serology for SARS-CoV-2 using self-collected saliva and finger-stick blood.

Convenient and widespread serology testing may alter the trajectory of the COVID-19 pandemic. This study seeks to leverage high-throughput, multiplexed serologic assays, which have been adopted as benchmarks for vaccine efficacy, to support large-scale surveys of SARS-CoV-2 immunity using finger-stick blood and/or saliva. Specifically, we optimized MSD's serology assays, which were analytically validated for serum, to test self-collected finger-stick blood and saliva samples to identify prior infection. We show that these assays can be used with FDA-registered specimen collection devices to obtain quantitative measurements for self-collected samples. First, we show that salivary antibodies are stable without refrigeration or preservatives for at least 5 days. We selected classification thresholds for antibodies against SARS-CoV-2 N, RBD and Spike in finger-stick blood and saliva that provided 98% specificity in a set of individuals without known COVID-19 exposure. Using matched samples, we show that testing of saliva and finger-stick blood equivalently identified individuals with humoral responses to CoV-2 antigens. Moreover, we piloted a simple saliva collection kit that can be used to safely send samples through the mail using written instructions only. This work establishes key parameters to robustly assay self-collected finger-stick blood and saliva using quantitative immunoassays that could support large-scale serology testing.

Use of Proteomic and Hematology Biomarkers for Prediction of Hematopoietic Acute Radiation Syndrome Severity in Baboon Radiation Models.

Use of plasma proteomic and hematological biomarkers represents a promising approach to provide useful diagnostic information for assessment of the severity of hematopoietic acute radiation syndrome. Eighteen baboons were evaluated in a radiation model that underwent total-body and partial-body irradiations at doses of Co gamma rays from 2.5 to 15 Gy at dose rates of 6.25 cGy min and 32 cGy min. Hematopoietic acute radiation syndrome severity levels determined by an analysis of blood count changes measured up to 60 d after irradiation were used to gauge overall hematopoietic acute radiation syndrome severity classifications. A panel of protein biomarkers was measured on plasma samples collected at 0 to 28 d after exposure using electrochemiluminescence-detection technology. The database was split into two distinct groups (i.e., "calibration," n = 11; "validation," n = 7). The calibration database was used in an initial stepwise regression multivariate model-fitting approach followed by down selection of biomarkers for identification of subpanels of hematopoietic acute radiation syndrome-responsive biomarkers for three time windows (i.e., 0-2 d, 2-7 d, 7-28 d). Model 1 (0-2 d) includes log C-reactive protein (p < 0.0001), log interleukin-13 (p < 0.0054), and procalcitonin (p < 0.0316) biomarkers; model 2 (2-7 d) includes log CD27 (p < 0.0001), log FMS-related tyrosine kinase 3 ligand (p < 0.0001), log serum amyloid A (p < 0.0007), and log interleukin-6 (p < 0.0002); and model 3 (7-28 d) includes log CD27 (p < 0.0012), log serum amyloid A (p < 0.0002), log erythropoietin (p < 0.0001), and log CD177 (p < 0.0001). The predicted risk of radiation injury categorization values, representing the hematopoietic acute radiation syndrome severity outcome for the three models, produced least squares multiple regression fit confidences of R = 0.73, 0.82, and 0.75, respectively. The resultant algorithms support the proof of concept that plasma proteomic biomarkers can supplement clinical signs and symptoms to assess hematopoietic acute radiation syndrome risk severity.

Plasma creatine kinase B correlates with injury severity and symptoms in professional boxers.

INTRODUCTION: Each year in the United States, approximately 1.7 million people sustain a traumatic brain injury (TBI). Of these TBI events, about 75 percent are characterized as being mild brain injuries. Immediately following TBI, a secondary brain damage persists for hours, days, and even months. Previously, detection of neuronal and glial biomarkers have proven to be useful to predict neurological outcomes. Here, we hypothesized that creatine kinase, brain (CKBB) is a sensitive biomarker for acute secondary brain injury in professional boxers. METHODS: Blood (8cc) was collected from the boxing athletes (n=18) prior to and after competition (∼30min). The plasma levels of CKBB were measured using the Meso Scale Diagnostic (MSD) electrochemiluminescence (ECL) array-based multiplex format. Additional data such as number of blows to the head and symptom score (Rivermead Post Concussion Symptoms Questionnaire) were collected. RESULTS: At approximately 30min after the competition, the plasma levels of CKBB were significantly elevated in concussed professional boxers and correlated with the number of blows to the head and symptom scores. Additionally, receiver operating curve (ROC) analysis yielded a 77.8% sensitivity and a specificity of 82.4% with an area under the curve (AUC) of 90% for CKBB as an identifier of secondary brain injury within this population. CONCLUSION: This study describes the detection of CKBB as a brain biomarker to detect secondary brain injury in professional athletes that have experienced multiple high impact blows to the head. This acute biomarker may prove useful in monitoring secondary brain injury after injury.

Anodic Coupling of Diphenylbenzo[k]fluoranthene: Mechanistic and Kinetic Studies Utilizing Cyclic Voltammetry and Electrogenerated Chemiluminescence.

Upon oxidation at a platinum electrode, (7,12-diphenyl)benzo[k]fluoranthene (1) undergoes intermolecular dehydrogenative coupling to form bis-4,4'-(7,12-diphenyl)benzo[k]fluoranthene (2). Further oxidation of this product results in a much slower intramolecular coupling reaction that yields dibenzo{[f,f']-4,4',7,7'-tetraphenyl}diindeno[1,2,3-cd:1',2',3'-lm]perylene (3). 2 can be synthesized via bulk electrolysis of 1 and also by the chemical coupling of 4-bromo-7,12-diphenylbenzo[k]fluoranthene (4) with a nickel catalyst. Compounds 1-3 are capable of electrogenerated chemiluminescence (ECL), and their coupling reactions have been detected and followed using this technique. Cyclic voltammograms of 1 have been digitally simulated to provide mechanistic and kinetic insight into the initial intermolecular oxidative coupling reaction. Evidence supports an EC(2)()EE mechanism, in which the coupling of radical cations of 1 is the rate-limiting step. A second-order rate constant of k = 7500 M(-)(1) s(-)(1) has been determined for the dimerization process by fitting experimental data to theoretical working curves.