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Abstract Background Public health depends largely on people’s knowledge, beliefs, or behaviors regarding their health and medical treatments. Although works based on the health belief model have shown that public beliefs about medical treatments affect willingness to take the treatments, little is known about the effects of changes in beliefs on attitudes toward treatment. How one’s past experiences relate to one’s beliefs about a given medical treatment is worth considering. Methods We implemented an online panel survey in February 2021 and March 2022 in Japan before and after COVID-19 vaccines were administered to the public within the country. We exploited delayed localized hypersensitivity reactions to COVID-19 vaccines, namely, “COVID arm”, as an exogenous shock to investigate the relationship between past negative experiences and current beliefs about medical treatments or science. “COVID arm” was an unexpected side effect and thus likely caused updated beliefs about the vaccine. Out of the nonprobability sample of 15,000 respondents in the first wave in February 2021, 9,668 respondents also responded to the second wave conducted in March 2022. Outcome variables were whether experiencing “COVID arm” affected the respondents’ 1) confidence in vaccine safety, 2) willingness to take the next dose of COVID-19 vaccines, 3) acknowledgment of the importance of vaccination, and 4) confidence in science. We measured the impact of experience with “COVID arm” on changes in the probability that survey respondents would respond affirmatively to questions posed about the issues listed above. Results Experiencing “COVID arm” significantly lowered confidence in the safety of vaccination by 4.3 percentage points, which was approximately 6% of the sample mean for the first wave, and lowered the probability of taking a second dose of the COVID-19 vaccine by 1.5 percentage points. These adverse impacts were observed after conditioning background characteristics and prior confidence in vaccination. Experiencing “COVID arm” affected neither the acknowledged importance of vaccination nor confidence in science in a statistically significant way. Conclusions An unexpected and uncomfortable shock regarding beliefs about a treatment decreases willingness to take the treatment. An appropriate public health policy should account for this effect. Trial registration The survey was preregistered with the American Economic Association’s RCT Registry (Fukai et al., 2022).

IntroductionRepetitive head impacts (RHI) have been suggested to increase the risk of developing a neurodegenerative disease, and many of these individuals develop a preceding mental health diagnosis. Given the lack of studies among amateur athletes, this study aimed to examine mental health outcomes in middle-aged amateur athletes who have been exposed to RHI through contact sport participation.MethodsThis is a single site, cohort study involving former amateur athletes aged between 30 and 60 with at least 10 years of organized contact or non-contact sport participation. All participants completed demographic and mental health questionnaires. Mental health outcomes included symptoms related to depression, anxiety, post-traumatic stress disorder (PTSD), attention deficit hyperactive disorder (ADHD), and aggression. Self-reported data on mental health diagnoses and associated prescription were elicited and used to estimate odds ratios (OR).ResultsData from 41 contact athletes and 22 age/sex-matched non-contact athletes were available for analysis. The contact group exhibited a 2.25-fold higher likelihood of being diagnosed with mental health disorders and 1.29-fold higher likelihood of using associated medications compared to the non-contact group. The contact group reported significantly higher PTSD-related symptoms [4.61 (0.03,9.2), p=0.05] compared to the non-contact control group. While not statistically significant, the contact group showed increased depressive [2.37 (0.05, 4.79), p=0.07] and ADHD symptoms [4.53 (0.51, 9.57), p=0.08] compared to controls. In a secondary analysis, a distinct trend emerged within the contact group, revealing pronounced elevations in mental health symptoms among individuals with lower socioeconomic status (

Traumatic brain injury (TBI), in any form and severity, can pose risks for developing chronic symptoms that can profoundly hinder patients’ work/academic, social, and personal lives. In the past 3 decades, a multitude of pharmacological, stimulation, and exercise-based interventions have been proposed to ameliorate symptoms, memory impairment, mental fatigue, and/or sleep disturbances. However, most research is preliminary, thus limited influence on clinical practice. This review aims to systematically appraise the evidence derived from randomized controlled trials (RCT) regarding the effectiveness of pharmacological, stimulation, and exercise-based interventions in treating chronic symptoms due to TBI. Our search results indicate that despite the largest volume of literature, pharmacological interventions, especially using neurostimulant medications to treat physical, cognitive, and mental fatigue, as well as daytime sleepiness, have yielded inconsistent results, such that some studies found improvements in fatigue (e.g., Modafinil, Armodafinil) while others failed to yield the improvements after the intervention. Conversely, brain stimulation techniques (e.g., transcranial magnetic stimulation, blue light therapy) and exercise interventions were effective in ameliorating mental health symptoms and cognition. However, given that most RCTs are equipped with small sample sizes, more high-quality, larger-scale RCTs is needed.

IntroductionThis clinical trial aimed to determine the influence of attention-deficit/hyperactivity disorder (ADHD) on neuro-ophthalmologic function and brain-derived blood biomarkers following acute subconcussive head impacts.MethodsThe present trial consisted of age- and sex-matched samples with a ratio of 1:1 between two groups with a total sample size of 60 adults (age ± SD; 20.0 ± 1.8 years). Soccer players diagnosed with and medicated daily for ADHD were assigned into an ADHD group (n = 30). Soccer players without ADHD were assigned into a non-ADHD group (n = 30). Participants performed 10 soccer headers with a soccer ball projected at a velocity of 25mph. King-Devick test (KDT), near point of convergence (NPC), and serum levels of NF-L, tau, GFAP, and UCH-L1 were assessed at baseline (pre-heading) and at 2 h and 24 h post-heading.ResultsThere were no statistically significant group-by-time interactions in outcome measures. However, at baseline, the ADHD group exhibited lower neuro-ophthalmologic functions compared to the non-ADHD group (NPC: p = 0.019; KDT: p = 0.018), and persisted at 2 h-post (NPC: p = 0.007; KDT: p = 0.014) and 24 h-post heading (NPC: p = 0.001). NPC significantly worsened over time in both groups compared to baseline [ADHD: 2 h-post, 1.23 cm, 95%CI:(0.77, 1.69), p

Abstract Background While morphological changes to the cervical spine have been observed for over 40 years in response to contact sport participation, little is known about the secondary effects of the cervical impairment on future musculoskeletal injury and disability. Objectives and design A scoping review was performed to discuss the relationship between contact sport participation and morphological changes to the cervical spine. Moreover, the correlation between morphological changes in the musculoskeletal structures of the cervical spine and resultant deficits in cervical sensorimotor and neuromotor function are discussed. Lastly, how alterations in cervical sensorimotor function may affect overall risk of musculoskeletal injury is discussed. Methods The scientific literature was searched in PubMed, Sport Discus, and Web of Science pertaining to contact-sport athletes and/or cervical pathology and the cervicocephalic network. The Asksey and O’Malley’s framework and PRISMA for Scoping Reviews were used to conduct and report the following review. Included articles were grouped into three categories: (1) Morphological changes to the cervical spine in contact sport athletes. (2) The role of the neuromotor pathways of the cervical spine in maintenance of postural tone and coordination of the extremities. (3) The correlation between altered cervical sensorimotor function and a resultant increase in musculoskeletal injury risk. Results Our search identified 566 documents, of which 405 underwent full-text screening, resulting in 54 eligible studies for the review. Widespread cervical sensorimotor dysfunction was observed in contact sport athletes. Independently, cervical sensorimotor function was demonstrated to play a critical role in postural control and limb coordination. However, limited research exists exploring the interaction between contact sport participation and altered cervical sensorimotor function, as well as an associated increase in musculoskeletal injury risk. Conclusions Limited evidence exists linking cervical injury and/or observed deficits in cervical sensorimotor and neuromotor function to musculoskeletal injury risk. Longitudinal studies combining imaging measures (e.g., MRI, DEXA), cervical functional test, and prospective injury risk are needed to further explore the correlation between resultant cervical sensorimotor deficits following contact sport impacts and future musculoskeletal injury risk.

Abstract Introduction Being choked/strangled during partnered sex is an emerging sexual behavior, particularly prevalent among young adult women. Using a multiparameter morphometric imaging approach, we aimed to characterize neuroanatomical differences between young adult women (18–30 years old) who were exposed to frequent sexual choking and their choking naïve controls. Methods This cross‐sectional study consisted of two groups (choking [≥4 times in the past 30 days] vs. choking‐naïve group). Participants who reported being choked four or more times during sex in the past 30 days were enrolled in the choking group, whereas those without were assigned to the choking naïve group. High‐resolution anatomical magnetic resonance imaging (MRI) data were analyzed using both volumetric features (cortical thickness) and geometric features (fractal dimensionality, gyrification, sulcal depth). Results Forty‐one participants (choking n = 20; choking‐naïve n = 21) contributed to the final analysis. The choking group showed significantly increased cortical thickness across multiple regions (e.g., fusiform, lateral occipital, lingual gyri) compared to the choking‐naïve group. Widespread reductions of the gyrification were observed in the choking group as opposed to the choking‐naïve group. However, there was no group difference in sulcal depth. The fractal dimensionality showed bi‐directional results, where the choking group exhibited increased dimensionality in areas including the postcentral gyrus, insula, and fusiform, whereas decreased dimensionality was observed in the bilateral superior frontal gyrus and pericalcarine cortex. Conclusion These data in cortical morphology suggest that sexual choking events may be associated with neuroanatomical alteration. A longitudinal study with multimodal assessment is needed to better understand the temporal ordering of sexual choking and neurological outcomes.

Summary: Cannabis use has become popular among athletes, many of whom are exposed to repetitive subconcussive head impacts. We aimed to test whether chronic cannabis use would be neuroprotective or exacerbating against acute subconcussive head impacts. This trial included 43 adult soccer players (Cannabis group using cannabis at least once a week for the past 6 months, n = 24; non-cannabis control group, n = 19). Twenty soccer headings, induced by our controlled heading model, significantly impaired ocular-motor function, but the degrees of impairments were less in the cannabis group compared to controls. The control group significantly increased its serum S100B level after heading, whereas no change was observed in the cannabis group. There was no group difference in serum neurofilament light levels at any time point. Our data suggest that chronic cannabis use may be associated with an enhancement of oculomotor functional resiliency and suppression of the neuroinflammatory response following 20 soccer headings.

The aim of this work is to uncover the preferences and perspectives of college educators as they interpret medical documentation outlining medically requested return-to-learn (RTL) instructions. Participants were recruited from five colleges across campus at a large Midwest public university. They each engaged in a private, one-on-one, audio-recorded interview. All recordings were transcribed and inductively analyzed using a grounded theory approach and two-coder system. All codes and themes were finalized once agreement was reached by both coders. Resultant themes from axial coding had to represent the voices of at least 80% of participants. Three characteristics emerged as being desired by college educators: brevity, clarity, and direction. Educators also expressed considerably less utility with medical documentation designed for pediatric students with concussion. College educators desire medical notes that are brief, clear, and provide straightforward direction, in addition to documentation that is tailored for the college setting.

Background: Extracellular vesicles (EV) released from neurons into the blood can reflect the state of nervous tissue. Measurement of neuron derived EV (NDE) may serve as an indicator of brain injury. Methods: A sandwich immunoassay was established to measure plasma NDE using anti-neuron CD171 and anti-EV CD9 ([CD171 + CD9 + ]). Plasma samples were obtained from commercial sources, cross-country (n = 9), football (n = 22), soccer (n = 19), and rugby (n = 18) athletes over time. Plasma was also collected from patients undergoing total aortic arch replacement (TAR) with selective cerebral perfusion during cardiopulmonary bypass before and after surgery (n = 36). Results: The specificity, linearity, and reproducibility of NDE assay (measurement of [CD171 + CD9 + ]) were confirmed. By scanning electron microscopy and nanoparticle tracking, spherical vesicles ranging in size from 150 to 300 nm were confirmed. Plasma levels of NDE were widely spread over 2 to 3 logs in different individuals with a significant age-dependent decrease. However, NDE were very stable in each individual within a ± 50% change over time (cross-country, football, soccer), whereas rugby players were more variable over 4 years. In patients undergoing TAR, NDE increased rapidly in days post-surgery and were significantly ( P = .0004) higher in those developing postoperative delirium (POD) (n = 13) than non-delirium patients (n = 23). Conclusions: The blood test to determine plasma levels of NDE was established by a sandwich immunoassay using 2 antibodies against neuron (CD171) and exosomes (CD9). NDE levels varied widely in different individuals and decreased with age, indicating that NDE levels should be considered as a normalizer of NDE biomarker studies. However, NDE levels were stable over time in each individual, and increased rapidly after TAR with greater increases associated with patients developing POD. This assay may serve as a surrogate for evaluating and monitoring brain injuries.

Objective: Medicine is a scarce resource and a public good that benefits others by bettering patients’ health. COVID-19 vaccines in shortage are, 1) a scarce resource and 2) a public good with the positive externality of building herd immunity. These features are expected to drive citizens’ attitudes in opposite directions, exclusionist and inclusionist, respectively. Scarcity would drive citizens’ exclusionism, while the positive externality might mitigate exclusionism. Setting and design: We recruited 15,000 Japanese adults and asked them to rank, in the context of a COVID-19 vaccine shortage, the deservingness of hypothetical vaccine recipients who differed according to 1) citizenship status, 2) visa type and duration of stay (if foreign), 3) occupation, 4) age, 5) whether they lived with a child, and 6) whether they lived with an elderly individual. Citizenship options were Japanese, Chinese, Taiwanese, South Korean, American, or European. The occupations were healthcare, education, other employed, self-employed, or not employed. The 6 attributes were randomly combined, and respondents were shown 3 hypothetical vaccine recipients: one was Japanese, and the others were foreigners. Treatments: First, through a conjoint design, we created hypothetical vaccine recipients whose attributes were randomized except for the benchmark citizenship, Japanese national. Second, we randomly presented two scenarios for vaccination payments: 1) billed at cost or 2) fully subsidized by the government. Results: 1) Whether the vaccines were billed at cost or fully subsidized did not affect the rankings of deservingness. 2) Japanese citizenship was prioritized. 3) The penalty for being a foreigner was higher for individuals from nations with which Japan has geopolitical tensions. 4) Working in health or education reduced the penalty on foreigners, indicating that the positive externality related to occupation amplifies the positive externality associated with vaccination and mitigates exclusionist attitudes. Conclusions: The positive occupational externalities that amplify the positive externality of vaccination substantially allay the foreigner penalty.

The learning gap between urban and rural areas is a persistent problem in many sub-Saharan African countries. Previous studies have found that the urban-rural learning gap is attributed to the fact that student characteristics and school resources are different in urban and rural areas. Our study updates this finding by using the latest dataset and further examines the changes in the attributed sources over time. Using 15 educational systems in sub-Saharan Africa, we examined 4 potential sources of the gap: student, family, teacher, and school characteristics. Our results reveal that the urban-rural learning gap in recent years is attributed mostly to differences in school and family characteristics. We also found that the attribution remains the same over time from 2004 to 2011 and that the attribution to family characteristics’ differences became slightly greater than the one to school characteristics’ differences.

Being strangled, or “choked,” by a sexual partner has emerged as a prevalent, often wanted and consensual sexual behavior among adolescent and young adult women, yet the neurological consequences of repeated exposure to this behavior are unknown. The objective of the study was to examine the association between a history of repeated, recent choking/strangling episodes during sex and fMRI activation during working memory tasks in young adult women. This case-control study involved young adult women (18–30 years old) at a large, public university, and consisted of two study groups: a choking group consisting of participants who were recently and frequently choked/strangled during sex by a partner (≥4 times in the past 30 days) and a choking-naïve (control) group who had never been choked/strangled during sex. Participants completed two variations of the N-back (0-back, 1-back, and 2-back) working memory task during functional magnetic resonance imaging (fMRI): verbal and visual N-back tasks. Data from 20 participants per group were available for analysis. Between-group differences for accuracy and reaction time were not significant for either variation of the N-back task. Significant differences in fMRI activation patterns were detected between the choking and the choking-naïve groups for the three contrasts of interest (1-back > 0-back, 2-back > 0-back, and 2-back > 1-back). The choking group exhibited increased activation in multiple clusters relative to the choking-naïve group for the contrasts between the 1-back and 2-back conditions compared to the 0-back conditions (e.g., superior frontal gyrus, corpus callosum). However, the choking-naïve group exhibited increased activation relative to the choking group in several clusters for the 2-back > 1 back contrast (e.g., splenium, middle frontal gyrus). These data indicate that recent, frequent exposure to partnered sexual strangulation is associated with different neural activation patterns during verbal and visual working memory tasks compared to controls, suggesting that being choked/strangled during sex may modify the allocation of neural resources at increasing levels of cognitive load. Further investigation into the neurologic effects of this sexual behavior is warranted, given the prevalence of sexual choking among adolescent and young adult women.

Recently, there has been increased attention in the scientific community to the phenomenon of sub-concussive impacts, those hits to the head that do not cause the signs and symptoms of a concussion. Some authors suggest that sub-concussive impacts may alter behavior and cognition, if sustained repetitively, but the mechanisms underlying these changes are not well-defined. Here, we adapt our well-established weight drop model of repetitive mild traumatic brain injury (rmTBI) to attempt to produce a model of low-level repetitive head impacts (RHI). The model was modified to eliminate differences in latency to right following impact and gross behavioral changes after a single cluster of hits. Further, we varied our model in terms of repetition of impact over a 4-h span to mimic the repeated sub-concussive impacts that may be experienced by an athlete within a single day of play. To understand the effects of a single cluster of RHIs, as well as the effect of an increased impact frequency within the cluster, we evaluated classical behavioral measures, serum biomarkers, cortical protein quantification, and immunohistochemistry both acutely and sub-acutely following the impacts. In the absence of gross behavioral changes, the impact protocol did generate pathology, in a dose-dependent fashion, in the brain. Evaluation of serum biomarkers revealed limited changes in GFAP and NF-L, which suggests that their diagnostic utility may not emerge until the exposure to low-level head impacts reaches a certain threshold. Robust decreases in both IL-1β and IL-6 were observed in the serum and the cortex, indicating downregulation of inflammatory pathways. These experiments yield initial data on pathology and biomarkers in a mouse model of low-level RHIs, with relevance to sports settings, providing a starting point for further exploration of the potential role of anti-inflammatory processes in low-level RHI outcomes, and how these markers may evolve with repeated exposure.

Summary: Research suggests contact sports affect neurological health. This study used permutation-based mediation statistics to integrate measures of metabolomics, neuroinflammatory miRNAs, and virtual reality (VR)-based motor control to investigate multi-scale relationships across a season of collegiate American football. Fourteen significant mediations (six pre-season, eight across-season) were observed where metabolites always mediated the statistical relationship between miRNAs and VR-based motor control (pSobelperm ≤ 0.05; total effect > 50%), suggesting a hypothesis that metabolites sit in the statistical pathway between transcriptome and behavior. Three results further supported a model of chronic neuroinflammation, consistent with mitochondrial dysfunction: (1) Mediating metabolites were consistently medium-to-long chain fatty acids, (2) tricarboxylic acid cycle metabolites decreased across-season, and (3) accumulated head acceleration events statistically moderated pre-season metabolite levels to directionally model post-season metabolite levels. These preliminary findings implicate potential mitochondrial dysfunction and highlight probable peripheral blood biomarkers underlying repetitive head impacts in otherwise healthy collegiate football athletes.

Contact sports affect measures at multiple scales such as transcriptomics, metabolomics, brain function, and behavior, but studies have not yet studied the statistical structure of how they are integrated. This preliminary study, examining collegiate American football players, integrated across-season changes (Δ) from transcriptomic and metabolomic variables (neuroinflammatory miRNAs and metabolites), neuroimaging (resting-state fMRI network fingerprint similarity), and virtual reality (VR)-based motor control. These findings were then assessed against head acceleration events (HAE). Using permutation-based moderation analysis (all pFperm,pβ3perm ≤0.05), we observed that (1) Δtridecenedioate, a mono-unsaturated fatty acid, interacted with ΔmiR-505 to predict default mode network (DMN) fingerprint similarity, meaning the interaction between two molecular biology measures predicted a neuroimaging measure. Further, (2) Δtridecenedioate and DMN fingerprint similarity interacted to predict motor control, indicating the interaction of a molecular and a neuroimaging measure predicted behavior. ΔmiR-505 was positively related to HAE and DMN fingerprint similarity was negatively related to HAE and reduced relative to non-athlete subjects. These multi-scale, moderating relationships between a potential ROS scavenger, neuroinflammatory miRNA, reduced brain connectivity, and diminished motor control argue that seemingly healthy athletes with frequent HAE may experience chronic neuroinflammation. This imaging-omics framework using permutation-based mediation/moderation analysis has general applicability for human-animal translational studies.

Objective: Vaccination is a critical measure for containing the COVID-19 pandemic. We survey the determinants that affect the preference for COVID-19 vaccines in Japan, a vaccine hesitant nation. Setting and design: We conducted a randomized conjoint analysis survey of the preference for vaccines on the Internet by recruiting a nonprobability sample of 15,000 Japanese adults. The survey assigned 5 choice tasks to the respondents. In each task, the respondents evaluated 2 hypothetical COVID-19 vaccines and were asked which they would choose. The vaccine attributes included efficacy, major and minor adverse side effects, country of vaccine development and clinical trial, and vaccine type. Treatment: The choice task asked the participants to select a vaccine from 2 hypothetical vaccines as an optional vaccine or select a vaccine as mandated one with a probability of 0.5 for each. Results: Compared to China-developed vaccines, domestically developed or US-developed vaccines raised the choice probability by 37.3 and 27.4 percentage points, respectively. A domestic clinical trial increased the choice probability by 14.8, an increase in efficacy from 50% to 90% increased that by 18.0, and a decrease in the risk of severe adverse side effects from 1 per 10 thousand to 1 per 1 million increased that by 16.9 percentage points, respectively. The vaccine type was irrelevant. Making vaccination compulsory increased the choice probability of China- and Russia-developed vaccines by 0.6 and 0.4, high-risk vaccines by 0.5, and a modestly effective (70%) vaccine by 0.4 percentage points, respectively. General vaccination hesitancy, political positions, demographic characteristics, education, and income were irrelevant. Conclusions: A domestically developed vaccine with a domestic clinical trial could substantially increase the preference for the vaccine. Making vaccination compulsory could modestly reduce the penalty for a vaccine with adverse side effects, geopolitical, and efficacy concerns, possibly through mitigating free-riding concerns to achieve herd immunity.

Objectives To gather the perspectives of collegiate instructors regarding how concussion is managed within the college classroom. To introduce the themes surrounding collegiate return-to-learn (RTL) and the classroom management of students with concussion.Design Qualitative grounded theory.Setting Large, public university in the Midwest.Participants Twenty-three college instructors participated in a private, semistructured, audio-recorded, one-on-one interview. Participants included 12 males and 11 females. Interview recordings were transcribed verbatim, followed by an iterative process of open-coding and axial-coding, performed by two researchers.Results Three themes emerged from the coded data: (1) awareness—external knowledge of concussion and previous experiences, (2) legitimacy—medical note provided and no note provided and (3) accommodating the student—instructor’s role and feasibility of the accommodation. Psychosocial factors such as small class sizes, graduate-level students and an instructor’s empathy appeared to influence an instructor’s decision making when accommodating a student recovering from concussion.Conclusion These novel data provide foundational evidence regarding how college instructors perceive and subsequently manage concussion within the classroom, while also offering accuracy to aims of subsequent collegiate RTL investigationsArticle summary RTL is an emerging field within concussion management, yet is grossly underexplored within the college setting. By utilising a grounded theory approach, this article introduces the themes that dictate the landscape of RTL for a college student.

While neuroimaging and blood biomarker have been two of the most active areas of research in the neurotrauma community, these fields rarely intersect to delineate subconcussive brain injury. The aim of the study was to examine the association between diffusion MRI techniques [diffusion tensor imaging (DTI) and neurite orientation/dispersion density imaging (NODDI)] and brain-injury blood biomarker levels [tau, neurofilament-light (NfL), glial-fibrillary-acidic-protein (GFAP)] in high-school football players at their baseline, aiming to detect cumulative neuronal damage from prior seasons. Twenty-five football players were enrolled in the study. MRI measures and blood samples were obtained during preseason data collection. The whole-brain, tract-based spatial statistics was conducted for six diffusion metrics: fractional anisotropy (FA), mean diffusivity (MD), axial/radial diffusivity (AD, RD), neurite density index (NDI), and orientation dispersion index (ODI). Five players were ineligible for MRIs, and three serum samples were excluded due to hemolysis, resulting in 17 completed set of diffusion metrics and blood biomarker levels for association analysis. Our permutation-based regression model revealed that serum tau levels were significantly associated with MD and NDI in various axonal tracts; specifically, elevated serum tau levels correlated to elevated MD (p = 0.0044) and reduced NDI (p = 0.016) in the corpus callosum and surrounding white matter tracts (e.g., longitudinal fasciculus). Additionally, there was a negative association between NfL and ODI in the focal area of the longitudinal fasciculus. Our data suggest that high school football players may develop axonal microstructural abnormality in the corpus callosum and surrounding white matter tracts, such as longitudinal fasciculus. A future study is warranted to determine the longitudinal multimodal relationship in response to repetitive exposure to sports-related head impacts.

Traumatic brain injury (TBI) results in short and long-term disability neurodegeneration. Mild traumatic brain injury (mTBI) represents up to 85% of head injuries; diagnosis and early management is based on computed tomography (CT) or in-hospital observation, which are time- and cost- intensive. CT involves exposure to potentially harmful ionizing radiation and >90% of the scans are negative. Blood-brain barrier (BBB) damage is suspected pathological event post-TBI contributing to long-term sequelae and a reliable and rapid point-of-care test to screen those who can safely forego acute head CT would be of great help in evaluating patients with an acute mTBI. In this pilot study, 15 adult patients with suspected TBI (mean age = 47 years, range 18–79) and 15 control subjects (mean age = 33 years, range 23–53) were enrolled. We found that the average salivary S100B level was 3.9 fold higher than blood S100B, regardless of the presence of pathology. [S100B]saliva positively correlated with [S100B]serum (Pearson' coefficient = 0.79; p < 0.01). Salivary S100B levels were as effective in differentiating TBI patients from control subjects as serum levels (Control vs. TBI: p < 0.01; Serum ROCAUC = 0.94 and Saliva ROCAUC = 0.75). I These initial results suggest that measuring salivary S100B could represent an alternative to serum S100B in the diagnosis of TBI. Larger and confirmatory trials are needed to define salivary biomarker kinetics in relation to TBI severity and the possible roles of gender, ethnicity and age in influencing salivary S100B levels.

While awareness and understanding of concussion have improved drastically, post-concussion management in academic settings is still at its infancy. The aim of the study was to examine to what extent concussion influences academic performance and to whether there would be a difference in concussion effects on academic performance between high school and college students. This cross-sectional survey study included students, who were between 14 and 24 years old and sustained a sport-related concussion within the previous year. The study used a modified chain-referral sampling method, by distributing a questionnaire link to 3,000 randomly stratified athletic trainers, who worked in high school or college settings. These athletic trainers were then asked to forward the questionnaire link to students in their team, who have sustained a concussion within the previous year. The questionnaire recorded responses regarding demographics (age, sex, race/ethnicity, number of previous concussions); 22 concussion-related symptoms in a binary scale (presence/absence); perception of difficulties in math, reading, writing, computer use, and attention in a 5-point Likert scale; and asymptomatic duration of academic engagement in a 7-point Likert scale. There were 130 respondents with a history of concussion in the past year (n = 59 high school, n = 71 college). While recovering from concussion, significantly more college students (84.5%) reported “difficulty concentrating” than high school students (68.6%: p = 0.049). High -school students experienced more difficulty with math than college students (p = 0.002), whereas college students experienced more difficulty with reading (p = 0.013) and computer use (p = 0.026) than high school students. Asymptomatic duration of cognitive activity was influenced by age (p = 0.0004), where younger students were less tolerant in performing academic tasks after a concussion than older students. Our data indicate that concussions can induce negative symptoms in the academic setting regardless of age. The post-concussion difficulties in academic performance may be a grade-dependent manner, where concussions triggered difficulty in math among high school students and in reading and computer use among college students. It is clear that there is a need for guidelines and accommodations to support students with concussion in academic settings, and the guideline should reflect the age-dependent response to concussions.

USA Football established five levels-of-contact to guide the intensity of high school football practices. The objective of this study was to examine head impact frequency and magnitude by levels-of-contact to determine which drills had the greatest head impact exposure. Our primary hypothesis was that there would be an incremental increase in season-long head impact exposure between levels-of-contact: air100g) head impacts were more frequently observed during live and thud drills. Level-of-contact influences cumulative head impact frequency and magnitude in high-school football, with players incurring frequent, high magnitude head impacts during live, thud, and control. It is important to consider level-of-contact to refine clinical exposure guidelines to minimize head impact burden in high-school football.

The purpose of this study was to test the effect of subconcussive head impacts on acute changes in plasma S100B. In this randomized controlled trial, 79 healthy adult soccer players were randomly assigned to either the heading (n = 41) or kicking-control groups (n = 38). The heading group executed 10 headers with soccer balls projected at a speed of 25 mph, whereas the kicking-control group performed 10 kicks. Plasma samples were obtained at pre-, 0h post-, 2h post- and 24h post-intervention and measured for S100B. The primary hypothesis was that there would be a significant group difference (group-by-time interaction) in plasma S100B at 2h post-intervention. Secondary hypotheses included (1) no significant group differences in plasma S100B concentrations at 0h post- and 24h post-intervention; (2) a significant within-group increase in S100B concentrations in the heading group at 2h post-intervention compared to pre-intervention; and (3) no significant within-group changes in plasma S100B in the kicking-control group. Data from 68 subjects were available for analysis (heading n = 37, kicking n = 31). There were no differences in S100B concentrations between heading and kicking groups over time, as evidenced by nonsignificant group-by-time interaction at 2h post-intervention (B = 2.20, 95%CI [-22.22, 26.63], p = 0.86) and at all the other time points (0h post: B = -11.05, 95%CI [-35.37, 13.28], p = 0.38; 24h post: B = 16.11, 95%CI [-8.29, 40.51], p = 0.20). Part of the secondary outcome, the heading group showed elevation in plasma S100B concentrations at 24h post-intervention compared to pre-heading baseline (B = 19.57, 95%CI [3.13, 36.02], p = 0.02), whereas all other within-group comparisons in both remained nonsignificant. The data suggest that 10 bouts of acute controlled soccer headings do not elevate S100B concentrations up to 24-hour post-heading. Further dose-response studies with longer follow-up time points may help determine thresholds of acute soccer heading exposure that are related to astrocyte activation. The protocol was registered under ClinicalTrials.gov (NCT03488381; retrospectively registered.).

Aim: Students re-entering the academic setting after a concussion is commonly referred to as return-to-learn and, to date, very few studies have examined the return-to-learn aspect of concussion recovery. Methodology: Nine college-aged, full-time students who were diagnosed with concussions were monitored throughout their concussion recovery. The severity for five chief symptoms (headache, dizziness, difficulty concentrating, fatigue, anxiety) were recorded six-times per day through text messages, and daily phone calls recorded participant's behavioral traits. Results: We identified five behavioral variables which significantly influenced symptom resolution (music, sleep, physical activity, water and time) (p = 0.0004 to p = 0.036). Additionally, subjects reported math and computer-oriented courses as the most difficult (33 and 44%, respectively). Conclusion: We introduce a novel approach to monitor concussed students throughout their recovery, as well as factors that may influence concussion recovery process.

Astrocyte-enriched marker, S100B, shows promise for gauging the severity of acute brain trauma, and understanding subconcussive effects will advance its utility in tracking real-time acute brain damage. The aim of the study was to investigate whether serum S100B elevations were associated with frequency and magnitude of subconcussive head impacts in adolescents. This prospective cohort study of 17 high-school football players consisted of the following 12 time points: pre-season baseline, 5 in-season pre-post games, and post-season. A sensor-installed mouthguard recorded the number of head impacts, peak linear (PLA) and peak rotational (PRA) head accelerations from every practice and game. During the 5 games, players wore chest-strap heart-rate monitors to estimate players' excess post-exercise oxygen consumption (EPOC), accounting for physical exertion effects. At each time point, blood samples were obtained and assessed for S100B and creatine kinase levels to account for astrocyte damage/activation and muscle damage, respectively. Using k-means clustering on the impact data, players were categorized into high- or low-impact group. Two players withdrew during the first month of the study. A total of 156 blood samples from 15 players were assessed for S100B and creatine kinase levels and included in the analysis. A median value of 596 head impacts from 15 players were recorded during all practices and games in a season. S100B levels were significantly elevated in all post-game measures compared with the respective pre-game values (median-increase, 0.022 μg/L; interquartile-range, 0.011–0.043 μg/L, p < 0.05 for all games). Greater acute S100B increases were significantly associated with greater impact frequency, sum of PLA and PRA, with negligible contributions from physical exertion and muscle damage effects. The high-impact group exhibited greater increases in serum S100B levels at post-games than the low-impact group (high vs. low, 0.043 ± 0.035 μg/L vs. 0.019 ± 0.017 μg/L, p = 0.002). The degree of acute S100B increases was correlated with subconcussive head impact exposure, suggesting that acute astrocyte damage may be induced in an impact-dependent manner. Acute changes in serum S100B levels may become a useful tool in monitoring real-time brain damage in sports.

ABSTRACT IMPACT: This work reveals the influence of a season of American football-related head impact exposure on two functional outcome measures in a cohort of adolescent boys, shedding light on the chronic effects of 'subconcussive head impacts.' OBJECTIVES/GOALS: To examine the influence of a season of exposure to head impacts in American football on changes in neurocognitive and oculomotor function in adolescent male athletes. METHODS/STUDY POPULATION: Participants were recruited from a local high school: the football group (FB; n = 26) was instrumented with sensor-installed mouthguards to track impact exposure during games and practices, and members of the men’s cross-country team were recruited to the control group (CON; n = 9). All participants were administered Immediate Post-concussion Assessment and Cognitive Testing (ImPACT) and were assessed for near point of convergence (NPC) at pre- and post-season. Linear models will be fit for changes in the five ImPACT composite scores and NPC values, with group and one of the head impact variables as predictors for each model. In a secondary within-group analysis, correlation coefficients will be calculated for the relationships between the head impact variables and the functional change scores for the FB group. RESULTS/ANTICIPATED RESULTS: The two groups did not differ significantly on age or number of previous concussions; the CON group had significantly lower BMI. Group assignment was significantly associated with change in NPC (p < 0.05 for all three models); no significant associations were observed for any of the head impact variables with change in NPC. Group and each of the head impact variables (total impacts, sum of peak linear acceleration [PLA], and sum of peak rotational acceleration [PRA]) were not significantly associated with change in any of the five ImPACT composite scores. Change in visual memory composite score was negatively correlated with total impacts (r = -0.37, p = 0.034) and sum of PRA (r = -0.36, p = 0.040). DISCUSSION/SIGNIFICANCE OF FINDINGS: Significant, albeit relatively weak, correlations between change in visual memory composite score and two head impact kinematic variables, coupled with significant increases in NPC in the FB group compared to the CON group, suggest that a season of exposure to football-related head impacts has the potential to elicit minor functional impairments.

IntroductionIn Lao People's Democratic Republic (PDR), community-based health insurance (CBHI) is the only voluntary insurance scheme; it typically targets self-employed people, most of whom reside in rural areas and are dependent on agricultural activities for subsistence. However, until very recently, the enrollment rate has fallen short and failed to reach a large percentage of the target group. To promote the CBHI scheme and increase demand, some supporting components should be considered for inclusion together with the health infrastructure component.ObjectivesThis paper provides empirical evidence that the benefit package components of hypothetical CBHI schemes have causal effects on enrollment probabilities. Furthermore, we examine the distribution of willingness to pay (WTP) in response to policy changes based on a sample of 5,800 observations.MethodsA randomized conjoint experiment is conducted in rural villages in Savannakhet Province, Lao PDR, to elicit stated preference data. Each respondent ranks three options-two hypothetical alternatives and the CBHI status quo scheme. The levels of seven attributes-insurance coverage for medical consultations, hospitalizations, traffic accidents, pharmaceuticals and transportation; premiums; and prepaid discounts-are randomly and simultaneously assigned to the two alternatives.ResultsThe findings suggest that the average WTP is at least as large as 10.9% of the per capita income of those who live in rural areas, which is higher than the WTP for health insurance averaged across low- and middle-income countries (LMICs) in the literature. The component of round-trip transportation insurance coverage has a significant effect on WTP distribution, particularly increasing the share of the highest bin.ConclusionTherefore, the low CBHI scheme enrollment rate in Lao PDR does not necessarily imply low demand among the targeted population, as the finding from the WTP analysis illustrates potential demand for the CBHI scheme. Specifically, if transportation is addressed, enrollment is likely to significantly increase.

The purpose of the study was to test the utility of unique panel of blood biomarkers as a means to reflect one’s recovery process after sport-related neurotrauma. We established a panel of biomarkers that reacted positive with CD81 (extracellular vesicle marker) and various neuron- and glia-specific antigens [e.g., neurofilament light polypeptide (NF-L), tau, synaptosome-associated protein 25 (SNAP25), glial fibrillary acidic protein, and myelin basic protein]. We first evaluated test–retest reliabilities of brain-derived exosome markers, followed by an application of these markers in eight professional ice hockey players to detect cumulative neuronal burden from a single ice hockey season. During the season, two players were diagnosed with concussions by team physician based on an exhibition of symptoms as well as abnormality in balance and ocular motor testing. One player reached symptom-free status 7 days after the concussion, while the other player required 36 days for symptoms to completely resolve. Blood samples and clinical assessments including balance error scoring system and near point of convergence throughout recovery process were obtained. Biomarkers indicative of axonal damage, neuronal inflammation, and glial activation showed excellent test–retest reliabilities (intraclass correlation coefficient: 0.713–0.998, p’s

Enhancing structural and functional integrity of mitochondria is an emerging therapeutic option against endothelial dysfunction. In this study, we sought to investigate the effect of fluid shear stress on mitochondrial biogenesis and mitochondrial respiratory function in endothelial cells (ECs) using in vitro and in vivo complementary studies.Human aortic- or umbilical vein-derived ECs were exposed to laminar shear stress (20 dyne/cm2) for various durations using a cone-and-plate shear apparatus. We observed significant increases in the expression of key genes related to mitochondrial biogenesis and mitochondrial quality control as well as mtDNA content and mitochondrial mass under the shear stress conditions. Mitochondrial respiratory function was enhanced when cells were intermittently exposed to laminar shear stress for 72 hrs. Also, shear-exposed cells showed diminished glycolysis and decreased mitochondrial membrane potential (ΔΨm). Likewise, in in vivo experiments, mice that were subjected to a voluntary wheel running exercise for 5 weeks showed significantly higher mitochondrial content determined by en face staining in the conduit (greater and lesser curvature of the aortic arch and thoracic aorta) and muscle feed (femoral artery) arteries compared to the sedentary control mice. Interestingly, however, the mitochondrial biogenesis was not observed in the mesenteric artery. This region-specific adaptation is likely due to the differential blood flow redistribution during exercise in the different vessel beds.Taken together, our findings suggest that exercise enhances mitochondrial biogenesis in vascular endothelium through a shear stress-dependent mechanism. Our findings may suggest a novel mitochondrial pathway by which a chronic exercise may be beneficial for vascular function.