King-Devick Test Score is Linked to Cerebral Vasoreactivity During Acute Recovery Phase Post-Concussion

The King-Devick (KD) test is a quick screening tool used to detect oculomotor and attention related brain function impairments following a concussion. Adequate cerebral blood flow (CBF) is an indicator of structural and functional integrity and impairments in CBF have been linked to cognitive deficits following concussion. Cerebral vasoreactivity (CVR), a key measure of hemodynamic reserve, is an important factor in CBFregulation. PURPOSE: To examine the association between CVR and oculomotor and attention function, using KD test scores, in collegiate athletes following a concussion. METHOD: Eighteen male and female athletes diagnosed with a sports-related concussion were enrolled in the prospective cohort study. Twenty-two non-injured athletes were enrolled as controls. Data was collected longitudinally on day-3, day-21, and day-90 following a concussion. Middle cerebral artery blood velocity (MCAV) was obtained using transcranial Doppler ultrasonography (TCD). CO2 was used as a stimulus to assess CVR. End-tidal CO2 (EtCO2) was monitored with an infrared CO2 analyzer attached to a nasal cannula. Continuous MCAV was obtained for 2-minutes each in response to three CO2 stimuli; normal room-air (normocapnia), inspiring 8% CO2 and 21% O2 gas mixture (hypercapnia), and during hyperventilation (hypocapnia). MCAV and EtCO2 data were plotted and CVR was estimated as the slope of the MCAV and EtCO2 relationship. For the KD test, subjects read aloud single-digit-numbers left to right from three test cards with progressive level of difficulty. Subjects were instructed to read as fast as possible without making errors. KD test score was determined as the sum of the total time required to complete the three test cards. Nonparametric Wilcoxon test was used to assess CVR and KD test scores between control and the concussed group at each of the three time points. Spearman rank order correlation was used to assess the association between CVR and KD scores at each time point. RESULTS: Compared to the control, CVR (1.33±0.31vs.1.14±0.43U; p=0.03) was blunted and KD score (44.4±7.7vs.48.1±6.9sec; p=0.04) was slower on day-3. CVR was comparable to the controls on days 21 and 90. However, a learning effect was observed in KD test score over time (42.1±8.9, p=0.02 [day-21]; 42.03±8.5, p=0.03 [day90]). In addition, a negative correlation between CVR and KD test was observed on day-3 (p= 0.04). CONCLUSION: The preliminary results indicate that deficits in oculomotor function and attention, as identified by KD test, may result from inadequate CBF regulation during the acute recovery phase post-concussion. Further studies should be done to evaluate the potential role of CVR in oculomotor function following concussion in collegiate athletes

Baroreflex Sensitivity is Impaired in Athletes Following a Sports-Related Concussion

Sport-related concussions are a major public health concern, with approximately 3.8 million incidences occurring annually in the United States alone. Autonomic nervous system (ANS) dysfunction is implicated in early and later stages of sports-related concussion recovery. Arterial baroreflex, a crucial mechanism by which the ANS controls short-term fluctuations in blood pressure, remains understudied in this population. PURPOSE: Examine baroreflex sensitivity (BRS) at rest during acute and sub-acute recovery phases following a sport-related concussion in collegiate athletes in comparison to non-injured athletes as controls. METHODS: Athletes (20±1 years) with sports-related concussions were tested on days 3 (N=13), 21 (N=13), and 90 (N=11) following the injury. Control athletes (N=12) were assessed at one time-point. Continuous arterial blood pressure (finger photoplethysmography) and R-R intervals (3-lead electrocardiogram) were obtained at rest for 6 minutes and while subjects were seated in an upright position. BRS was estimated with transfer function analysis to assess the fluctuations in systolic blood pressure and R-R intervals during the time period. Transfer gain in the low-frequency range (0.05– 0.15 Hz) quantified the magnitude of the relationship between changes in systolic blood pressure and R-R interval. Therefore, higher gain indicates higher BRS. A linear mixed model was used to examine symptoms and transfer function variables between the controls and the concussed athletes at the three time points. RESULTS: As anticipated, symptoms were worse on day-3 and resolved during the day-21 sub-acute phase. BRS was lower on day-3 (0.656±0.2U; p=0.003), day-21 (0.711±0.29U; p=0.013), and day-90 (0.77±0.27; p=0.04) following the injury compared to the controls (1.05±0.3U). CONCLUSION: The findings confirm impairments in baroreflex sensitivity during the acute and subacute recovery phases following a concussion despite symptom resolution. Blunted baroreflex sensitivity following injury may position athletes in a vulnerable situation while performing tasks that elicit sudden changes in blood pressure on and off the field

Impairments in Cerebral Autoregulation is Associated with Postural Control in Sports Related Concussion

Global and regional deficits in cerebral blood flow are reported with concussions, a major public health concern, with approximately 3.8 million incidences occurring annually in the United States alone. Recent studies have identified an increased risk of musculoskeletal injuries in athletes upon return-to-play. Complexity index is a sensitive marker of postural control, with low complexity index indicating a poor physiological adaptation to stress. PURPOSE: Twofold; 1. Examine complexity index and dynamic cerebral autoregulation (dCA) at rest and during physical stress (rhythmic squatting) in collegiate athletes following a concussion in comparison to non-injured controls. 2. Examine the association between complexity index and dCA. METHODS: Athletes (20±1 years) with sports-related concussions were tested on days 3 (N=33), 21 (N=29), and 90 (N=21) following the injury. Controls (N=27) were assessed at one time-point. Continuous mean arterial pressure (MAP) (finger photoplethysmography) and middle cerebral artery blood flow velocity (MCAV) (2 MHz transcranial Doppler ultrasonography) were obtained at rest for 6 minutes and during physical stress (squatting at 0.1Hz frequency) for 5 minutes. Transfer function analysis of beat-to-beat MAP and MCAV oscillations in the low frequency (LF, 0.07-0.20 Hz) range was utilized to assess dCA. Effective dCA dampens the fluctuations in MCAV in response to MAP oscillations, resulting in a low LF gain. Multiscale entropy analysis was used to determine complexity index from the center of pressure data obtained during quiet standing with eyes closed on a force platform. Two-sample Mann Whitney U test was used to compare data between control and concussed athletes at the three time points. Spearman correlation was used to examine the association between the variables. RESULTS: LF gain at rest was higher on day-3 (1.27±0.4U; p=0.007), and day-21 (1.27±0.5U; p=0.03) compared to the controls (1.03±0.2U). Similar findings were observed in LF gain with physical stress (day-3 p= 0.003; day-21 p=0.001). Postural complexity index was lower on day-3 (4.3±1.3U; p=0.004) and day-21 (4.5±1.1U; p=0.02) compared to the controls (5.4±1.4U). Moreover, a negative association was observed between complexity index and LF gain at rest (β= -0.66, p= 0.04) and during squatting (β= -1.53, p= 0.02). CONCLUSION: The findings confirm impairments in cerebral autoregulation and postural control during the acute and subacute recovery phases following a concussion despite symptom resolution. In addition, poor functional outcome, such as postural control, may be associated with alterations in cerebral blood flow regulation in this population. Tracking cerebral autoregulation during recovery phase may help in preventing musculoskeletal injuries in athletes after return-to-play following a concussion

Elucidating mechanistic principles underpinning eukaryotic translation initiation using quantitative fluorescence methods

Eukaryotic translation initiation is an intricate process involving at least 11 formally classified eIFs (eukaryotic initiation factors) which together with the ribosome comprise one of the largest molecular machines in the cell Studying such huge macromolecular complexes presents many challenges which cannot readily be overcome by traditional molecular and structural methods Increasingly novel quantitative techniques are being used to further dissect such complex assembly pathways One area of methodology involves the labelling of ribosomal subunits and/or eIFs with fluorophores and the use of techniques such as FRET (Forster resonance energy transfer) and FA (fluorescence anisotropy) The applicability of such techniques in such a complex system has been greatly enhanced by recent methodological developments In the present mini review we introduce these quantitative fluorescence methods and discuss the impact they are beginning to have on the fiel