Convergent and Discriminant Validity of the Blast Exposure Threshold Survey in United States Military Service Members and Veterans.

The Blast Exposure Threshold Survey (BETS) is a recently developed and promising new self-report measure of lifetime blast exposure (LBE). However, there are no studies that have examined the psychometric properties of the BETS, which currently limits its clinical utility. The purpose of this study was to examine the convergent and discriminant validity of the BETS by comparing the BETS Generalized Blast Exposure Value (GBEV) to six variables hypothesized to be associated with LBE (i.e., single-item LBE, combat exposure, years in the military, number of combat deployments, and military occupation specialty [MOS]) and three variables hypothesized not to be associated with LBE (i.e., age at the time of injury, estimated pre-morbid Full-Scale Intelligence Quotient [FSIQ], and resilience). Participants were 202 United States service members and veterans prospectively enrolled from three military medical treatment facilities (68.7%) and via community recruitment initiatives (31.3%). Participants completed the BETS, Combat Exposure Scale (CES), Deployment Risk and Resiliency Inventory-2 Combat Experiences (DRRI-2 CE), Traumatic Brain Injury-Quality of Life Resilience scale, and a brief structured interview. For some analyses, participants were classified into two blast risk MOS groups: high (n = 89) and low (n = 94). The BETS GBEV was not significantly correlated with all three non-blast related variables (rs = 0.01 to rs = -0.12). In contrast, GBEV was significantly (p < 0.001) associated with all blast-related variables; single-item LBE (rs = 0.76), CES (rs = 0.58), number of combat deployments (rs = 0.53), DRRI-2 CE (rs = 0.48), and high blast risk MOS (r = 0.36, medium effect size). However, a stronger relationship was found between the blast-related variables and three modified GBEV scores when excluding some small weapons categories; single-item LBE (rs = 0.80-0.82), CES (rs = 0.64-0.67), number of combat deployments (rs = 0.56), DRRI-2 CE (rs = 0.51-0.53), and high blast risk MOS (r = 0.42-0.49, medium-large effect size). This is the first study to examine the psychometric properties of the BETS. Overall, these results offer support for the convergent and discriminant validity of the BETS. In order to ensure that the BETS can be confidently used as a valid and reliable measure of LBE, more research is needed to further examine the psychometric properties of the test, particularly with regard to the establishment of test-retest reliability.

Surveying the Landscape: A Review of Longitudinal Traumatic Brain Injury Studies in Service Member and Veteran Populations.

Traumatic brain injury (TBI) is known to be a signature wound of the post-9/11 conflicts. In response, the U.S. Department of Defense (DOD) and other federal organizations have directed significant investments toward TBI research on characterizing injury populations and understanding long-term outcomes. To address legislative requirements and research gaps, several observational, longitudinal TBI studies were initiated as an effective means of investigating TBI clinical management, outcomes, and recovery. This review synthesizes the landscape (i.e., requirements and gaps, infrastructure, geography, timelines, TBI severity definitions, military and injury populations of interest, and measures) of DOD-funded longitudinal TBI studies being conducted in service member and veteran (SMV) populations. Based on the landscape described here, we present recommended actions and solutions that would allow a consolidated and cooperative future state of longitudinal TBI research, optimized continued investments, and advances in the state of the science without redundancy.

Perspectives on Development of Measures to Estimate Career Blast Exposure History in Service Members and Veterans.

The Department of Defense (DOD) has recently prioritized the investigation of the acute and chronic adverse brain health and performance effects of low-level blast (LLB) generated by the use of weapons systems. While acute exposure can be quantified by sensor technology, career exposure has no widely accepted and validated measure for characterization. Currently, distinct research groups are developing and validating four promising measures to estimate career blast exposure history: the Salisbury Blast Interview, Blast Exposure Threshold Survey, Blast Ordnance and Occupational Exposure Measure, and the Blast Frequency and Symptom Severity. Each measure offers an assessment of blast history that is uniquely beneficial to addressing specific research questions. However, use of divergent strategies is not efficient to accelerate the field's understanding of the impact of career exposure and Service-connected health outcomes. As a DOD-wide solution, collaboration across these groups is required to develop a tool(s) that can be standardized across research studies and, ultimately, pared down to be implemented in clinical settings. Here, we overview the current four measures and provide a perspective on the way forward for optimization and/or combination in support of this solution.

The effect of omega-3 fatty acids on a biomarker of head trauma in NCAA football athletes: a multi-site, non-randomized study.

BACKGROUND: American-style football (ASF) athletes are at risk for cardiovascular disease (CVD) and exhibit elevated levels of serum neurofilament light (Nf-L), a biomarker of axonal injury that is associated with repetitive head impact exposure over the course of a season of competition. Supplementation with the w-3 fatty acid (FA) docosahexaenoic acid (DHA) attenuates serum Nf-L elevations and improves aspects of CVD, such as the omega-3 index (O3I). However, the effect of combining the w-3 FA eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA) with DHA on, specifically, serum Nf-L in ASF athletes is unknown. Therefore, this study assessed the effect of supplemental w-3 FA (EPA+DPA+DHA) on serum Nf-L, plasma w-3 FAs, the O3I, and surrogate markers of inflammation over the course of a season. METHODS: A multi-site, non-randomized design, utilizing two American football teams was employed. One team (n = 3 1) received supplementation with a highly bioavailablew-3 FA formulation (2000mg DHA, 560mg EPA, 320mg DPA, Mindset®, Struct Nutrition, Missoula, MT) during pre-season and throughout the regular season, while the second team served as the control (n = 35) and did not undergo supplementation. Blood was sampled at specific times throughout pre- and regular season coincident w ith changes in intensity, physical contact, and changes in the incidence and severity of head impacts. Group differences were determined via a mixed-model between-within subjects ANOVA. Effect sizes were calculated using Cohen's dfor all between-group differences. Significance was set a priori at p< .05. RESULTS: Compared to the control group, ASF athletes in the treatment group experienced large increases in plasma EPA (p < .001, d = 1.71) and DHA (p < .001, d = 2.10) which contributed to increases in the O3I (p < .001, d = 2.16) and the EPA:AA ratio (p = .001, d = 0.83) and a reduction in the w-6: w-3 ratio (p < .001, d = 1.80). w-3 FA supplementation attenuated elevations in Nf-L (p = .024). The control group experienced a significant increase in Nf-L compared to baseline at several measurement time points (T2, T3, and T4 [p range < .001 - .005, drange = 0.59-0.85]). CONCLUSIONS: These findings suggest a cardio- and neuroprotective effect of combined EPA+DPA+DHA w-3 FA supplementation in American-style football athletes. TRIAL REGISTRATION: This trial was registered with the ISRCTN registry ( ISRCTN90306741 ).

Blood Biomarkers of Sports-Related Concussion in Pediatric Athletes.

OBJECTIVE: To examine changes in blood biomarkers, serum neurofilament light (Nf-L), and plasma tau, as well as the relationship between blood biomarkers and symptom reports, in athletes with a sports-related concussion. DESIGN: Prospective cohort study. SETTING: Private community-based concussion clinic. PARTICIPANTS: Athletes aged 13 to 18 years old with a diagnosed sports-related concussion presenting to a concussion clinic within 7 days of injury and noninjured athletes with no history of concussion aged 13 to 23 years old. ASSESSMENT AND MAIN OUTCOME MEASURES: Injured athletes provided a blood sample at the initial clinical evaluation and again at least 6 months after injury. Noninjured athletes provided a single blood sample. All participants completed symptom reports during each visit. Statistical comparisons of biomarker concentrations and symptom reports were conducted. RESULTS: The mean rank for tau was significantly lower for concussed athletes compared with nonconcussed athletes. In contrast, the mean rank of Nf-L was higher for concussed athletes than for nonconcussed athletes, although the difference was nonsignificant. Plasma tau was significantly lower postinjury compared with 6 months after injury, whereas serum Nf-L was significantly higher postinjury. There was a weak but significant inverse relationship observed between tau and the number of symptoms reported, but no relationship was observed between Nf-L and the number of symptoms reported. CONCLUSIONS: These data indicate that in the days following a sports-related concussion, the blood biomarkers tau and Nf-L display contrasting patterns of change but may not be related to self-reported symptom scores.

Fluctuations in blood biomarkers of head trauma in NCAA football athletes over the course of a season.

OBJECTIVERepetitive subconcussive head trauma is a consequence of participation in contact sports and may be linked to neurodegenerative diseases. The degree of neurological injury caused by subconcussive head trauma is not easily detectible, and this injury does not induce readily identifiable clinical signs or symptoms. Recent advancements in immunoassays make possible the detection and quantification of blood biomarkers linked to head trauma. Identification of a blood biomarker that can identify the extent of neurological injury associated with subconcussive head trauma may provide an objective measure for informed decisions concerning cumulative exposure to subconcussive head trauma. The purpose of the current study was to examine changes in the blood biomarkers of subconcussive head trauma over the course of an American football season.METHODSThirty-five National Collegiate Athletic Association (NCAA) American football athletes underwent blood sampling throughout the course of a football season. Serial samples were obtained throughout the 2016 season, during which the number and magnitude of head impacts changed. Blood samples were analyzed for plasma concentrations of tau and serum concentrations of neurofilament light polypeptide (NF-L). Athletes were grouped based on their starter status, because athletes identified as starters are known to sustain a greater number of impacts. Between-group differences and time-course differences were assessed.RESULTSIn nonstarters, plasma concentrations of tau decreased over the course of the season, with lower values observed in starters; this resulted in a lower area under the curve (AUC) (starters: 416.78 ± 129.17 pg/ml/day; nonstarters: 520.84 ± 163.19 pg/ml/day; p = 0.050). Plasma concentrations of tau could not be used to discern between starters and nonstarters. In contrast, serum concentrations of NF-L increased throughout the season as head impacts accumulated, specifically in those athletes categorized as starters. The higher serum concentrations of NF-L observed in starters resulted in a larger AUC (starters: 1605.03 ± 655.09 pg/ml/day; nonstarters: 1067.29 ± 272.33 pg/ml/day; p = 0.007). The AUC of the receiver operating characteristic curve analyses displayed fair to modest accuracy to identify athletes who were starters with the use of serum NF-L following periods of repetitive impacts.CONCLUSIONSThe different patterns observed in serum NF-L and plasma tau concentrations provide preliminary evidence for the use of blood biomarkers to detect the neurological injury associated with repetitive subconcussive head trauma. Although further investigation is necessary, such findings might lay the foundation for the further development of an objective measure for the detection of neurological injury caused by subconcussive head trauma.

Protection Before Impact: the Potential Neuroprotective Role of Nutritional Supplementation in Sports-Related Head Trauma.

Even in the presence of underreporting, sports-related concussions/mild traumatic brain injuries (mTBI) are on the rise. In the absence of proper diagnosis, an athlete may return to play prior to full recovery, increasing the risk of second-impact syndrome or protracted symptoms. Recent evidence has demonstrated that sub-concussive impacts, those sustained routinely in practice and competition, result in a quantifiable pathophysiological response and the accumulation of both concussive and sub-concussive impacts sustained over a lifetime of sports participation may lead to long-term neurological impairments and an increased risk of developing neurodegenerative diseases. The pathophysiological, neurometabolic, and neurochemical cascade that initiates subsequent to the injury is complex and involves multiple mechanisms. While pharmaceutical treatments may target one mechanism, specific nutrients and nutraceuticals have been discovered to impact several pathways, presenting a broader approach. Several studies have demonstrated the neuroprotective effect of nutritional supplementation in the treatment of mTBI. However, given that many concussions go unreported and sub-concussive impacts result in a pathophysiological response that, too, may contribute to long-term brain health, protection prior to impact is warranted. This review discusses the current literature regarding the role of nutritional supplements that, when provided before mTBI and traumatic brain injury, may provide neurological protection.

Probiotic Streptococcus thermophilus FP4 and Bifidobacterium breve BR03 Supplementation Attenuates Performance and Range-of-Motion Decrements Following Muscle Damaging Exercise.

Probiotics have immunomodulatory effects. However, little is known about the potential benefit of probiotics on the inflammation subsequent to strenuous exercise. In a double-blind, randomized, placebo controlled, crossover design separated by a 21-day washout, 15 healthy resistance-trained men ingested an encapsulated probiotic Streptococcus (S.) thermophilus FP4 and Bifidobacterium (B.) breve BR03 at 5 bn live cells (AFU) concentration each, or a placebo, daily for 3 weeks prior to muscle-damaging exercise (ClinicalTrials.gov NCT02520583). Isometric strength, muscle soreness, range of motion and girth, and blood interleukin-6 (IL-6) and creatine kinase (CK) concentrations were measured from pre- to 72 h post-exercise. Statistical analysis was via mixed models and magnitude-based inference to the standardized difference. Probiotic supplementation resulted in an overall decrease in circulating IL-6, which was sustained to 48 h post-exercise. In addition, probiotic supplementation likely enhanced isometric average peak torque production at 24 to 72 h into the recovery period following exercise (probiotic-placebo point effect ±90% CI: 24 h, 11% ± 7%; 48 h, 12% ± 18%; 72 h, 8% ± 8%). Probiotics also likely moderately increased resting arm angle at 24 h (2.4% ± 2.0%) and 48 h (1.9% ± 1.9%) following exercise, but effects on soreness and flexed arm angle and CK were unclear. These data suggest that dietary supplementation with probiotic strains S. thermophilus FP4 and B. breve BR03 attenuates performance decrements and muscle tension in the days following muscle-damaging exercise.