Head Impact Exposure in Youth and Collegiate American Football.

The relationship between head impact and subsequent brain injury for American football players is not well-defined, especially for youth. The objective of this study is to quantify and assess Head Impact Exposure (HIE) metrics among youth and collegiate football players. This multi-season study enrolled 639 unique athletes (354 collegiate; 285 youth, ages 9-14), recording 476,209 head impacts (367,337 collegiate; 108,872 youth) over 971 sessions (480 collegiate; 491 youth). Youth players experienced 43 and 65% fewer impacts per competition and practice, respectively, and lower impact magnitudes compared to collegiate players (95th percentile peak linear acceleration (PLA, g) competition: 45.6 vs 61.9; 95th percentile PLA practice: 42.6 vs 58.8; 95th percentile peak rotational acceleration (PRA, rad·s-2) competition: 2262 vs 4422; 95th percentile PRA practice: 2081 vs 4052; 95th percentile HITsp competition: 25.4 vs 32.8; 95th percentile HITsp practice: 23.9 vs 30.2). Impacts during competition were more frequent and of greater magnitude than during practice at both levels. Quantified comparisons of head impact frequency and magnitude between youth and collegiate athletes reveal HIE differences as a function of age, and expanded insight better informs the development of age-appropriate guidelines for helmet design, prevention measures, standardized testing, brain injury diagnosis, and recovery management.

Psychometric properties of the standardized assessment of concussion in youth football: Validity, reliability, and demographic factors.

The objective of this study was to determine the psychometrics (reliability, validity) of the original Standardized Assessment of Concussion (SAC) in a youth sample (ages 11 to 13). Demographic factors of race, level of vocabulary knowledge, mother's level of education were also considered. Over 150 youth football athletes completed the SAC and a brief battery of NIH Toolbox cognitive tests as part of a larger study on biomechanical factors in youth sport concussion. This was a within-subjects design (pre-season, post-season assessments), and correlational analysis of convergent and discriminant validity. Between groups analysis based on demographic differences was also employed. The pre-season SAC scores were not different by age; however, SAC scores were statistically different by race: t(155) = 3.162, p = .002, d = .519. Maternal level of education and participant vocabulary scores were related to racial group membership. Convergent and discriminant validity were established compared to NIH Toolbox tests of memory and speed. Pre-post-season tests for 108 participants established marginally acceptable test-retest reliability (ICC = .692). These data support the use of the original SAC in youth football although clinicians must be aware of racial differences in scores.

Neuropsychological Change After a Single Season of Head Impact Exposure in Youth Football.

OBJECTIVES: Head impact exposure (HIE) in youth football is a public health concern. The objective of this study was to determine if one season of HIE in youth football was related to cognitive changes. METHOD: Over 200 participants (ages 9-13) wore instrumented helmets for practices and games to measure the amount of HIE sustained over one season. Pre- and post-season neuropsychological tests were completed. Test score changes were calculated adjusting for practice effects and regression to the mean and used as the dependent variables. Regression models were calculated with HIE variables predicting neuropsychological test score changes. RESULTS: For the full sample, a small effect was found with season average rotational values predicting changes in list-learning such that HIE was related to negative score change: standardized beta (ß) = -.147, t(205) = -2.12, and p = .035. When analyzed by age clusters (9-10, 11-13) and adding participant weight to models, the R2 values increased. Splitting groups by weight (median split), found heavier members of the 9-10 cohort with significantly greater change than lighter members. Additionaly, significantly more participants had clinically meaningful negative changes: X2 = 10.343, p = .001. CONCLUSION: These findings suggest that in the 9-10 age cluster, the average seasonal level of HIE had inverse, negative relationships with cognitive change over one season that was not found in the older group. The mediation effects of age and weight have not been explored previously and appear to contribute to the effects of HIE on cognition in youth football players.

Teaching the Emergency Neurologic Life Support Course at Two Major Hospitals in Phnom Penh, Cambodia.

OBJECTIVE: To determine the effect of offering a subset of the Emergency Neurological Life Support (ENLS) course modules on provider knowledge and self-reported confidence in acute management of neurocritically ill patients in a low-middle income country (LMIC). METHODS: Eight ENLS modules were provided by in-person lecture using English to Khmer translated slides and a medical translator to physicians and nurses of 2 hospitals in Phnom Penh, Cambodia in May 2019. Providers included emergency, neurology, neurologic surgery, and general intensive care. Demographics, pre- and postcourse knowledge of ENLS content areas, and pre- and postcourse confidence in managing neurocritically ill patients were assessed. Data were pooled across both hospitals for analysis. RESULTS: A total of 57 health care providers were approached for participation: 52 (25 physicians, 27 nurses) participated; 45 completed all study instruments. Pre- and postcourse knowledge scores showed no significant differences between providers. Postcourse, 37/45 (82.2%) participants reported that the content had prepared them for acute management of neurocritically ill patients. Satisfaction with module content ranged from 77.8%-80.0% per module. For the 8 modules, a majority of participants agreed that course material had provided them with knowledge and skills to provide acute care for patients' neurologic emergencies (68.4%-88.6%). CONCLUSIONS: Provision of ENLS course module content increased LMIC provider self-reported knowledge and confidence in acute management of neurocritically ill patients immediately postcourse. Tailoring ENLS course presentation to a particular LMIC setting warrants additional investigation, as does the effect of ENLS course training on neurocritically ill patient outcomes in the LMIC setting.

Development of a Concussion Risk Function for a Youth Population Using Head Linear and Rotational Acceleration.

Physical differences between youth and adults, which include incomplete myelination, limited neck muscle development, and a higher head-body ratio in the youth population, likely contribute towards the increased susceptibility of youth to concussion. Previous research efforts have considered the biomechanics of concussion for adult populations, but these known age-related differences highlight the necessity of quantifying the risk of concussion for a youth population. This study adapted the previously developed Generalized Acceleration Model for Brian Injury Threshold (GAMBIT) that combines linear and rotational head acceleration to model the risk of concussion for a youth population with the Generalized Acceleration Model for Concussion in Youth (GAM-CY). Survival analysis was used in conjunction with head impact data collected during participation in youth football to model risk between individuals who sustained medically-diagnosed concussions (n = 15). Receiver operator characteristic curves were generated for peak linear acceleration, peak rotational acceleration, and GAM-CY, all of which were observed to be better injury predictors than random guessing. GAM-CY was associated with an area under the curve of 0.89 (95% confidence interval: 0.82-0.95) when all head impacts experienced by the concussed players were considered. Concussion tolerance was observed to be lower for youth athletes, with average peak linear head acceleration of 62.4 ± 29.7 g compared to 102.5 ± 32.7 g for adults and average peak rotational head acceleration of 2609 ± 1591 rad/s2 compared to 4412 ± 2326 rad/s2. These data provide further evidence of age-related differences in concussion tolerance and may be used for the development of youth-specific protective designs.

Do American Youth Football Players Intentionally Use Their Heads for High-Magnitude Impacts?

BACKGROUND: Concern for head injuries is widespread and has been reported by the media to be the number one cause of decreased participation in football among the American youth population. Identifying player mechanisms associated with intentional, or purposeful, head impacts should provide critical data for rule modifications, educational programs, and equipment design. PURPOSE: To investigate the frequency of intentional and unintentional head impacts and to examine the player mechanisms associated with intentional high-magnitude head impacts by comparing the impact mechanism distributions among session type, player position, and ball possession. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Head impact sensors and video footage of 68 players were used to analyze and classify 1319 high-magnitude impacts recorded over 1 season of youth football. RESULTS: In total, 80% of the high-magnitude head impacts were classified as being caused by intentional use of the head. Head-to-head impact was the primary impact mechanism (n = 868; 82.7%) within the 1050 intentional high-magnitude impacts, with classifiable mechanisms, followed by head-to-body (n = 139; 13.2%), head-to-ground (n = 34; 3.2%), and head-to-equipment (n = 9; 0.9%). Head-to-head impacts also accounted for a greater proportion of impacts during practices (n = 625; 88.9%) than games, for linemen (n = 585; 90.3%) than perimeters and backs, and for ball carriers (n = 72; 79.1%) than tacklers. CONCLUSION: Overall, the majority of high-magnitude head impacts were intentional and resulted from head-to-head contact. The proportion of head-to-head contact was significantly higher for practices than games, linemen than backs and perimeter players, and ball carriers than tacklers.

Head Impact Exposure in Practices Correlates With Exposure in Games for Youth Football Players.

This study aimed to compare head impact exposures between practices and games in football players ages 9 to 14 years, who account for approximately 70% of all football players in the United States. Over a period of 2 seasons, 136 players were enrolled from 3 youth programs, and 49,847 head impacts were recorded from 345 practices and 137 games. During the study, individual players sustained a median of 211 impacts per season, with a maximum of 1226 impacts. Players sustained 50th (95th) percentile peak linear acceleration of 18.3 (46.9) g, peak rotational acceleration of 1305.4 (3316.6) rad·s-2, and Head Impact Technology Severity Profile of 13.7 (24.3), respectively. Overall, players with a higher frequency of head impacts at practices recorded a higher frequency of head impacts at games (P < .001, r2 = .52), and players who sustained a greater average magnitude of head impacts during practice also recorded a greater average magnitude of head impacts during games (P < .001). The youth football head impact data quantified in this study provide valuable insight into the player exposure profile, which should serve as a key baseline in efforts to reduce injury.

Estimated Brain Tissue Response Following Impacts Associated With and Without Diagnosed Concussion.

Kinematic measurements of head impacts are sensitive to sports concussion, but not highly specific. One potential reason is these measures reflect input conditions only and may have varying degrees of correlation to regional brain tissue deformation. In this study, previously reported head impact data recorded in the field from high school and collegiate football players were analyzed using two finite element head models (FEHM). Forty-five impacts associated with immediately diagnosed concussion were simulated along with 532 control impacts without identified concussion obtained from the same players. For each simulation, intracranial response measures (max principal strain, strain rate, von Mises stress, and pressure) were obtained for the whole brain and within four regions of interest (ROI; cerebrum, cerebellum, brain stem, corpus callosum). All response measures were sensitive to diagnosed concussion; however, large inter-athlete variability was observed and sensitivity strength depended on measure, ROI, and FEHM. Interestingly, peak linear acceleration was more sensitive to diagnosed concussion than all intracranial response measures except pressure. These findings suggest FEHM may provide unique and potentially important information on brain injury mechanisms, but estimations of concussion risk based on individual intracranial response measures evaluated in this study did not improve upon those derived from input kinematics alone.

The Disulfide Bond Formation Pathway Is Essential for Anaerobic Growth of Escherichia coli.

Disulfide bonds are critical to the stability and function of many bacterial proteins. In the periplasm of Escherichia coli, intramolecular disulfide bond formation is catalyzed by the two-component disulfide bond forming (DSB) system. Inactivation of the DSB pathway has been shown to lead to a number of pleotropic effects, although cells remain viable under standard laboratory conditions. However, we show here that dsb strains of E. coli reversibly filament under aerobic conditions and fail to grow anaerobically unless a strong oxidant is provided in the growth medium. These findings demonstrate that the background disulfide bond formation necessary to maintain the viability of dsb strains is oxygen dependent. LptD, a key component of the lipopolysaccharide transport system, fails to fold properly in dsb strains exposed to anaerobic conditions, suggesting that these mutants may have defects in outer membrane assembly. We also show that anaerobic growth of dsb mutants can be restored by suppressor mutations in the disulfide bond isomerization system. Overall, our results underscore the importance of proper disulfide bond formation to pathways critical to E. coli viability under conditions where oxygen is limited.IMPORTANCE While the disulfide bond formation (DSB) system of E. coli has been studied for decades and has been shown to play an important role in the proper folding of many proteins, including some associated with virulence, it was considered dispensable for growth under most laboratory conditions. This work represents the first attempt to study the effects of the DSB system under strictly anaerobic conditions, simulating the environment encountered by pathogenic E. coli strains in the human intestinal tract. By demonstrating that the DSB system is essential for growth under such conditions, this work suggests that compounds inhibiting Dsb enzymes might act not only as antivirulents but also as true antibiotics.

Test-retest, retest, and retest: Growth curve models of repeat testing with Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT).

Computerized neuropsychological testing has become an important tool in the identification and management of sports-related concussions; however, the psychometric effect of repeat testing has not been studied extensively beyond test-retest statistics. The current study analyzed data from Division I collegiate athletes who completed Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) baseline assessments at four sequential time points that varied over the course of their athletic careers. Administrations were part of a larger National Institutes of Health (NIH) study. Growth curve modeling showed that the two memory composite scores increased significantly with successive administrations: Change in Verbal Memory was best represented with a quadratic model, while a linear model best fit Visual Memory. Visual Motor Speed and Reaction Time composites showed no significant linear or quadratic growth. The results demonstrate the effect of repeated test administrations for memory composite scores, while speed composites were not significantly impacted by repeat testing. Acceptable test-retest reliability was demonstrated for all four composites as well.

Altered Escherichia coli membrane protein assembly machinery allows proper membrane assembly of eukaryotic protein vitamin K epoxide reductase.

Functional overexpression of polytopic membrane proteins, particularly when in a foreign host, is often a challenging task. Factors that negatively affect such processes are poorly understood. Using the mammalian membrane protein vitamin K epoxide reductase (VKORc1) as a reporter, we describe a genetic selection approach allowing the isolation of Escherichia coli mutants capable of functionally expressing this blood-coagulation enzyme. The isolated mutants map to components of membrane protein assembly and quality control proteins YidC and HslV. We show that changes in the VKORc1 sequence and in the YidC hydrophilic groove along with the inactivation of HslV promote VKORc1 activity and dramatically increase its expression level. We hypothesize that such changes correct for mismatches in the membrane topogenic signals between E. coli and eukaryotic cells guiding proper membrane integration. Furthermore, the obtained mutants allow the study of VKORc1 reaction mechanisms, inhibition by warfarin, and the high-throughput screening for potential anticoagulants.

Structure and multistate function of the transmembrane electron transporter CcdA.

The mechanism by which transmembrane reductases use a single pair of cysteine residues to relay electrons between protein substrates across biological membranes is a long-standing mystery in thiol-redox biochemistry. Here we show the NMR structure of a reduced-state mimic of archaeal CcdA, a protein that transfers electrons across the inner membrane, by using a redox-active NMR sample. The two cysteine positions in CcdA are separated by 20 Å. Whereas one is accessible to the cytoplasm, the other resides in the protein core, thus implying that conformational exchange is required for periplasmic accessibility. In vivo mixed disulfide-trapping experiments validated the functional positioning of the cysteines, and in vitro accessibility results confirmed conformational exchange. Our NMR and functional data together show the existence of multiple conformational states and suggest a four-state model for relaying electrons from cytosolic to periplasmic redox substrates.

Biomechanics of head impacts associated with diagnosed concussion in female collegiate ice hockey players.

Epidemiological evidence suggests that female athletes may be at a greater risk of concussion than their male counterparts. The purpose of this study was to examine the biomechanics of head impacts associated with diagnosed concussions in a cohort of female collegiate ice hockey players. Instrumented helmets were worn by 58 female ice hockey players from 2 NCAA programs over a three year period. Kinematic measures of single impacts associated with diagnosed concussion and head impact exposure on days with and without diagnosed concussion were evaluated. Nine concussions were diagnosed. Head impact exposure was greater in frequency and magnitude on days of diagnosed concussions than on days without diagnosed concussion for individual athletes. Peak linear accelerations of head impacts associated with diagnosed concussion in this study are substantially lower than those previously reported in male athletes, while peak rotational accelerations are comparable. Further research is warranted to determine the extent to which female athletes' biomechanical tolerance to concussion injuries differs from males.

Group-wise evaluation and comparison of white matter fiber strain and maximum principal strain in sports-related concussion.

Sports-related concussion is a major public health problem in the United States and yet its biomechanical mechanisms remain unclear. In vitro studies demonstrate axonal elongation as a potential injury mechanism; however, current response-based injury predictors (e.g., maximum principal strain, ε(ep)) typically do not incorporate axonal orientations. We investigated the significance of white matter (WM) fiber orientation in strain estimation and compared fiber strain (ε(n)) with ε(ep) for 11 athletes with a clinical diagnosis of concussion. Geometrically accurate subject-specific head models with high mesh quality were created based on the Dartmouth Head Injury Model (DHIM), which was successfully validated (performance categorized as "good" to "excellent"). For WM regions estimated to be exposed to high strains using a range of injury thresholds (0.09-0.28), substantial differences existed between ε(n) and ε(ep) in both distribution (Dice coefficient of 0.13-0.33) and extent (∼ 5-10-fold differences), especially at higher threshold levels and higher rotational acceleration magnitudes. For example, an average of 3.2% vs. 29.8% of WM was predicted above an optimal threshold of 0.18 established from an in vivo animal study using ε(n) and ε(ep), respectively, with an average Dice coefficient of 0.14. The distribution of WM regions with high ε(n) was consistent with typical heterogeneous patterns of WM disruptions in diffuse axonal injury, and the group-wise extent at the optimal threshold matched well with the percentage of WM voxels experiencing significant longitudinal changes of fractional anisotropy and mean diffusivity (3.2% and 3.44%, respectively) found from a separate independent study. These results suggest the significance of incorporating WM microstructural anisotropy in future brain injury studies.

Head-impact mechanisms in men's and women's collegiate ice hockey.

CONTEXT: Concussion injury rates in men's and women's ice hockey are reported to be among the highest of all collegiate sports. Quantification of the frequency of head impacts and the magnitude of head acceleration as a function of the different impact mechanisms (eg, head contact with the ice) that occur in ice hockey could provide a better understanding of this high injury rate. OBJECTIVE: To quantify and compare the per-game frequency and magnitude of head impacts associated with various impact mechanisms in men's and women's collegiate ice hockey players. DESIGN: Cohort study. SETTING: Collegiate ice hockey rink. PATIENTS OR OTHER PARTICIPANTS: Twenty-three men and 31 women from 2 National Collegiate Athletic Association Division I ice hockey teams. MAIN OUTCOME MEASURE(S): We analyzed magnitude and frequency (per game) of head impacts per player among impact mechanisms and between sexes using generalized mixed linear models and generalized estimating equations to account for repeated measures within players. INTERVENTION(S): Participants wore helmets instrumented with accelerometers to allow us to collect biomechanical measures of head impacts sustained during play. Video footage from 53 games was synchronized with the biomechanical data. Head impacts were classified into 8 categories: contact with another player; the ice, boards or glass, stick, puck, or goal; indirect contact; and contact from celebrating. RESULTS: For men and women, contact with another player was the most frequent impact mechanism, and contact with the ice generated the greatest-magnitude head accelerations. The men had higher per-game frequencies of head impacts from contact with another player and contact with the boards than did the women (P < .001), and these impacts were greater in peak rotational acceleration (P = .027). CONCLUSIONS: Identifying the impact mechanisms in collegiate ice hockey that result in frequent and high-magnitude head impacts will provide us with data that may improve our understanding of the high rate of concussion in the sport and inform injury-prevention strategies.

Can helmet design reduce the risk of concussion in football?

Of all sports, football accounts for the highest incidence of concussion in the US due to the large number of athletes participating and the nature of the sport. While there is general agreement that concussion incidence can be reduced through rule changes and teaching proper tackling technique, there remains debate as to whether helmet design may also reduce the incidence of concussion. A retrospective analysis was performed of head impact data collected from 1833 collegiate football players who were instrumented with helmet-mounted accelerometer arrays for games and practices. Data were collected between 2005 and 2010 from 8 collegiate football teams: Virginia Tech, University of North Carolina, University of Oklahoma, Dartmouth College, Brown University, University of Minnesota, Indiana University, and University of Illinois. Concussion rates were compared between players wearing Riddell VSR4 and Riddell Revolution helmets while controlling for the head impact exposure of each player. A total of 1,281,444 head impacts were recorded, from which 64 concussions were diagnosed. The relative risk of sustaining a concussion in a Revolution helmet compared with a VSR4 helmet was 46.1% (95% CI 28.1%-75.8%). When controlling for each player's exposure to head impact, a significant difference was found between concussion rates for players in VSR4 and Revolution helmets (χ(2) = 4.68, p = 0.0305). This study illustrates that differences in the ability to reduce concussion risk exist between helmet models in football. Although helmet design may never prevent all concussions from occurring in football, evidence illustrates that it can reduce the incidence of this injury.