Background:Considering the potential cumulative effects of repetitive head impact(HI)exposure,we need sensitive biomarkers to track shortand long-term effects.Circulating small extracellular vesicles(sEVs)(<200 nm)...Background:Considering the potential cumulative effects of repetitive head impact(HI)exposure,we need sensitive biomarkers to track shortand long-term effects.Circulating small extracellular vesicles(sEVs)(<200 nm)traffic biological molecules throughout the body and may have diagnostic value as biomarkers for disease.The purpose of this study was to identify the microRNA(miRNA)profile in circulating sEVs derived from human plasma following repetitive HI exposure.Methods:Healthy adult(aged 18-35 years)soccer players were randomly assigned to one of 3 groups:the HI group performed 10 standing headers,the leg impact group performed 10 soccer ball trapping maneuvers over 10 min,and the control group did not participate in any soccer drills.Plasma was collected before testing and 24 h afterward,and sEVs were isolated and characterized via nanoparticle tracking analysis.Next-generation sequencing was utilized to identify candidate miRNAs isolated from sEVs,and candidate microRNAs were analyzed via quantitative polymerase chain reaction.In silico target prediction was performed using TargetScan(Version 7.0;targetscan.org)and miRWalk(http://mirwalk.umm.uni-heidelberg.de/)programs,and target validation was performed using luciferase reporter vectors with a miR-7844-5p mimic in human embryonic kidney(HEK)293T/17 cells.Results:Plasma sEV concentration and size were not affected across time and group following repetitive HI exposure.After 24 h,the HI read count from next-generation sequencing showed a 4-fold or greater increase in miR-92b-5p,miR-423-5p,and miR-24-3p and a 3-fold or greater decrease in miR-7844-5p,miR-144-5p,miR-221-5p,and miR-22-3p.Analysis of quantitative polymerase chain reaction revealed that leg impact did not alter the candidate miRNA levels.To our knowledge,miR-7844-5p is a previously unknown miRNA.We identified 8 miR-7844-5p mRNA targets:protein phosphatase 1 regulatory inhibitor subunit 1B(PPP1R1B),LIM and senescent cell antigen-like domains 1(LIMS1),autophagy-related 12(ATG12),microtubule-associated protein 1 light chain 3 beta(MAP1LC3B),integrin subunit alpha-1(ITGA1),mitogenactivated protein kinase 1(MAPK1),glycogen synthase kinase 3b(GSK3b),and mitogen-activated protein kinase 8(MAPK8).Conclusion:Collectively,these data indicate repetitive HI exposure alters plasma sEV miRNA content,but not sEV size or number.Furthermore,for the first time we demonstrate that previously unknown miR-7844-5p targets mRNAs known to be involved in mitochondrial apoptosis,autophagy regulation,mood disorders,and neurodegenerative disease.展开更多
Objective:Since concussion is the most common injury in ice hockey,the objective of the current study was to elucidate risk factors,specific mechanisms,and clinical presentations of concussion in men’s and women’s i...Objective:Since concussion is the most common injury in ice hockey,the objective of the current study was to elucidate risk factors,specific mechanisms,and clinical presentations of concussion in men’s and women’s ice hockey.Methods:Ice hockey players from 5 institutions participating in the Concussion Assessment,Research,and Education Consortium were eligible for the current study.Participants who sustained a concussion outside of this sport were excluded.There were 332(250 males,82 females)athletes who participated in ice hockey,and 47(36 males,11 females)who sustained a concussion.Results:Previous concussion(odds ratio(OR)=2.00;95%confidence interval(95%CI):1.02‒3.91)was associated with increased incident concussion odds,while wearing a mouthguard was protective against incident concussion(OR=0.43;95%CI:0.22‒0.85).Overall,concussion mechanisms did not significantly differ between sexes.There were specific differences in how concussions presented clinically across male and female ice hockey players,however.Females(9.09%)were less likely than males(41.67%)to have a delayed symptom onset(p=0.045).Additionally,females took significantly longer to reach asymptomatic(p=0.015)and return-to-play clearance(p=0.005).Within the first 2 weeks post-concussion,86.11%of males reached asymptomatic,while only 45.50%of females reached the same phase of recovery.Most males(91.67%)were cleared for return to play within 3 weeks of their concussion,compared to less than half(45.50%)of females.Conclusion:The current study proposes possible risk factors,mechanisms,and clinical profiles to be validated in future concussions studies with larger female sample sizes.Understanding specific risk factors,concussion mechanisms,and clinical profiles of concussion in collegiate ice hockey may generate ideas for future concussion prevention or intervention studies.展开更多
Concussion,or mild traumatic brain injury,incidence rates have reached epidemic levels and impaired postural control is a cardinal symptom.The purpose of this review is to provide an overview of the linear and non-lin...Concussion,or mild traumatic brain injury,incidence rates have reached epidemic levels and impaired postural control is a cardinal symptom.The purpose of this review is to provide an overview of the linear and non-linear assessments of post-concussion postural control.The current acute evaluation for concussion utilizes the subjective balance error scoring system(BESS) to assess postural control.While the sensitivity of the overall test battery is high,the sensitivity of the BESS is unacceptably low and,with repeat administration,is unable to accurately identify recovery.Sophisticated measures of postural control,utilizing traditional linear assessments,have identified impairments in postural control well beyond BESS recovery.Both assessments of quiet stance and gait have identified lingering impairments for at least 1 month post-concussion.Recently,the application of non-linear metrics to concussion recovery have begun to receive limited attention with the most commonly utilized metric being approximate entropy(Ap En).Ap En,most commonly in the medial-lateral plane,has successfully identified impaired postural control in the acute post-concussion timeframe even when linear assessments of instrumented measures are equivalent to healthy pre-injury values;unfortunately these studies have not gone beyond the acute phase of recovery.One study has identified lingering deficits in postural control,utilizing Shannon and Renyi entropy metrics,which persist at least through clinical recovery and return to participation.Finally,limited evidence from two studies suggest that individuals with a previous history of a single concussion,even months or years prior,may display altered Ap En metrics.Overall,non-linear metrics provide a fertile area for future study to further the understanding of postural control impairments acutely post-concussion and address the current challenge of sensitive identification of recovery.展开更多
Background:To determine the effect of contact/collision sport participation on measures of single-task(ST)and dual-task(DT)gait among early-to middle-aged adults.Methods:The study recruited 113 adults(34.88±11.80...Background:To determine the effect of contact/collision sport participation on measures of single-task(ST)and dual-task(DT)gait among early-to middle-aged adults.Methods:The study recruited 113 adults(34.88±11.80 years,(mean±SD);53.0%female)representing 4 groups.Groups included(a)former non-contact/collision athletes and non-athletes who are not physically active(n=28);(b)former non-contact/collision athletes who are physically active(n=29);(c)former contact/collision sport athletes who participated in high-risk sports and are physically active(n=29);and(d)former rugby players with prolonged repetitive head impact exposure history who are physically active(n=27).Gait parameters were collected using inertial measurement units during ST and DT gait.DT cost was calculated for all gait parameters(double support,gait speed,and stride length).Groups were compared first using one-way analysis of covariance.Then a multiple regression was performed for participants in the highrisk sport athletes and repetitive head impact exposure athletes groups only to predict gait outcomes from contact/collision sport career duration.Results:There were no significant differences between groups on any ST,DT,or DT cost outcomes(p>0.05).Contact/collision sport duration did not predict any ST,DT,or DT cost gait outcomes.Conclusion:Years and history of contact/collision sport participation does not appear to negatively affect or predict neurobehavioral function in early-to mid-adulthood among physically active individuals.展开更多
基金National Institutes of Health(NIH)-National Institute of Neurological Disorders and Stroke(NINDS)R01(NS102157-01)National Institutes of Health(NIH)-National Institute of General Medical Sciences(NIGMS)P20(GM113125-01).
文摘Background:Considering the potential cumulative effects of repetitive head impact(HI)exposure,we need sensitive biomarkers to track shortand long-term effects.Circulating small extracellular vesicles(sEVs)(<200 nm)traffic biological molecules throughout the body and may have diagnostic value as biomarkers for disease.The purpose of this study was to identify the microRNA(miRNA)profile in circulating sEVs derived from human plasma following repetitive HI exposure.Methods:Healthy adult(aged 18-35 years)soccer players were randomly assigned to one of 3 groups:the HI group performed 10 standing headers,the leg impact group performed 10 soccer ball trapping maneuvers over 10 min,and the control group did not participate in any soccer drills.Plasma was collected before testing and 24 h afterward,and sEVs were isolated and characterized via nanoparticle tracking analysis.Next-generation sequencing was utilized to identify candidate miRNAs isolated from sEVs,and candidate microRNAs were analyzed via quantitative polymerase chain reaction.In silico target prediction was performed using TargetScan(Version 7.0;targetscan.org)and miRWalk(http://mirwalk.umm.uni-heidelberg.de/)programs,and target validation was performed using luciferase reporter vectors with a miR-7844-5p mimic in human embryonic kidney(HEK)293T/17 cells.Results:Plasma sEV concentration and size were not affected across time and group following repetitive HI exposure.After 24 h,the HI read count from next-generation sequencing showed a 4-fold or greater increase in miR-92b-5p,miR-423-5p,and miR-24-3p and a 3-fold or greater decrease in miR-7844-5p,miR-144-5p,miR-221-5p,and miR-22-3p.Analysis of quantitative polymerase chain reaction revealed that leg impact did not alter the candidate miRNA levels.To our knowledge,miR-7844-5p is a previously unknown miRNA.We identified 8 miR-7844-5p mRNA targets:protein phosphatase 1 regulatory inhibitor subunit 1B(PPP1R1B),LIM and senescent cell antigen-like domains 1(LIMS1),autophagy-related 12(ATG12),microtubule-associated protein 1 light chain 3 beta(MAP1LC3B),integrin subunit alpha-1(ITGA1),mitogenactivated protein kinase 1(MAPK1),glycogen synthase kinase 3b(GSK3b),and mitogen-activated protein kinase 8(MAPK8).Conclusion:Collectively,these data indicate repetitive HI exposure alters plasma sEV miRNA content,but not sEV size or number.Furthermore,for the first time we demonstrate that previously unknown miR-7844-5p targets mRNAs known to be involved in mitochondrial apoptosis,autophagy regulation,mood disorders,and neurodegenerative disease.
文摘Objective:Since concussion is the most common injury in ice hockey,the objective of the current study was to elucidate risk factors,specific mechanisms,and clinical presentations of concussion in men’s and women’s ice hockey.Methods:Ice hockey players from 5 institutions participating in the Concussion Assessment,Research,and Education Consortium were eligible for the current study.Participants who sustained a concussion outside of this sport were excluded.There were 332(250 males,82 females)athletes who participated in ice hockey,and 47(36 males,11 females)who sustained a concussion.Results:Previous concussion(odds ratio(OR)=2.00;95%confidence interval(95%CI):1.02‒3.91)was associated with increased incident concussion odds,while wearing a mouthguard was protective against incident concussion(OR=0.43;95%CI:0.22‒0.85).Overall,concussion mechanisms did not significantly differ between sexes.There were specific differences in how concussions presented clinically across male and female ice hockey players,however.Females(9.09%)were less likely than males(41.67%)to have a delayed symptom onset(p=0.045).Additionally,females took significantly longer to reach asymptomatic(p=0.015)and return-to-play clearance(p=0.005).Within the first 2 weeks post-concussion,86.11%of males reached asymptomatic,while only 45.50%of females reached the same phase of recovery.Most males(91.67%)were cleared for return to play within 3 weeks of their concussion,compared to less than half(45.50%)of females.Conclusion:The current study proposes possible risk factors,mechanisms,and clinical profiles to be validated in future concussions studies with larger female sample sizes.Understanding specific risk factors,concussion mechanisms,and clinical profiles of concussion in collegiate ice hockey may generate ideas for future concussion prevention or intervention studies.
文摘Concussion,or mild traumatic brain injury,incidence rates have reached epidemic levels and impaired postural control is a cardinal symptom.The purpose of this review is to provide an overview of the linear and non-linear assessments of post-concussion postural control.The current acute evaluation for concussion utilizes the subjective balance error scoring system(BESS) to assess postural control.While the sensitivity of the overall test battery is high,the sensitivity of the BESS is unacceptably low and,with repeat administration,is unable to accurately identify recovery.Sophisticated measures of postural control,utilizing traditional linear assessments,have identified impairments in postural control well beyond BESS recovery.Both assessments of quiet stance and gait have identified lingering impairments for at least 1 month post-concussion.Recently,the application of non-linear metrics to concussion recovery have begun to receive limited attention with the most commonly utilized metric being approximate entropy(Ap En).Ap En,most commonly in the medial-lateral plane,has successfully identified impaired postural control in the acute post-concussion timeframe even when linear assessments of instrumented measures are equivalent to healthy pre-injury values;unfortunately these studies have not gone beyond the acute phase of recovery.One study has identified lingering deficits in postural control,utilizing Shannon and Renyi entropy metrics,which persist at least through clinical recovery and return to participation.Finally,limited evidence from two studies suggest that individuals with a previous history of a single concussion,even months or years prior,may display altered Ap En metrics.Overall,non-linear metrics provide a fertile area for future study to further the understanding of postural control impairments acutely post-concussion and address the current challenge of sensitive identification of recovery.
基金funded in part by the University of Delaware Unidel Distinguished Graduate Scholars FellowshipDepartment of Kinesiology and Applied Physiology Doctoral Research Fund+2 种基金funding support in part by the Department of Defense grant W81XWH-21-1-0590the Penn Injury Science CenterNational Institutes of Health/National Institute of Neurological Disorders and Stroke brain injury training grant T32 NS043126。
文摘Background:To determine the effect of contact/collision sport participation on measures of single-task(ST)and dual-task(DT)gait among early-to middle-aged adults.Methods:The study recruited 113 adults(34.88±11.80 years,(mean±SD);53.0%female)representing 4 groups.Groups included(a)former non-contact/collision athletes and non-athletes who are not physically active(n=28);(b)former non-contact/collision athletes who are physically active(n=29);(c)former contact/collision sport athletes who participated in high-risk sports and are physically active(n=29);and(d)former rugby players with prolonged repetitive head impact exposure history who are physically active(n=27).Gait parameters were collected using inertial measurement units during ST and DT gait.DT cost was calculated for all gait parameters(double support,gait speed,and stride length).Groups were compared first using one-way analysis of covariance.Then a multiple regression was performed for participants in the highrisk sport athletes and repetitive head impact exposure athletes groups only to predict gait outcomes from contact/collision sport career duration.Results:There were no significant differences between groups on any ST,DT,or DT cost outcomes(p>0.05).Contact/collision sport duration did not predict any ST,DT,or DT cost gait outcomes.Conclusion:Years and history of contact/collision sport participation does not appear to negatively affect or predict neurobehavioral function in early-to mid-adulthood among physically active individuals.
