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Abstract Concussion diagnosis is complicated by a lack of objective measures. Ubiquitin carboxyl-terminal esterase L1 (UCHL1) is a biomarker that has been shown to increase following traumatic brain injury but has not been investigated in concussed athletes on the sideline of athletic events. Therefore, this study was conducted to determine if UCHL1 can be used to aid in sideline concussion diagnosis. Blood was taken via standard venipuncture from a recreationally active control group, a group of rugby players prior to match play (pre-match), rugby players following match-play (match-control), and rugby players after suffering a sport-related concussion (SRC). UCHL1 was not significantly different among groups (p > 0.05) and was unable to distinguish between SRC and controls (AUROC 0.05). However, when sex-matched data were used, it was found that the female match-control group had a significantly higher serum UCHL1 concentration than the pre-match group (p = 0.041). Differences were also found in serum UCHL1 concentrations between male and female athletes in the match-control group (p = 0.007). This study does not provide evidence supporting the use of UCHL1 in sideline concussion diagnosis when blood is collected soon after concussion but does show differences in serum UCHL1 accumulation between males and females.

Concussion diagnosis is difficult and may be improved with the addition of a blood-based biomarker that indicates concussion. The purpose of this research was to investigate the capability of serum amyloid beta precursor protein (APP), neurofilament light (NfL), and visinin-like protein-1 (VILIP-1) to distinguish athletes who were diagnosed with a concussion pitch-side. An observational cross-sectional study design was used to replicate sideline concussion diagnosis. Subjects included mutually exclusive pre-match (n = 9), post-match (n = 15), and SRC (n = 7) groups. Six paired pre-and post-match subjects were analyzed for APP. APP increased significantly from pre-match (mean = 57.98 pg·mL−1, SD = 63.21 pg·mL−1) to post-match (mean = 111.37 pg·mL−1, SD = 106.89 pg·mL−1, p = 0.048) in the paired subjects. NfL was lower in the SRC group (median = 8.71 pg·mL−1, IQR = 6.09 pg·mL−1) compared to the post-match group (median = 29.60 pg·mL−1, IQR = 57.45 pg·mL−1, p < 0.001). VILIP-1 was higher in the post-match group (median = 212.18 pg·mL−1, IQR = 345.00 pg·mL−1) compared to both the pre-match (median = 32.63 pg·mL−1, IQR = 52.24 pg·mL−1), p = 0.001) and SRC (median = 30.21 pg·mL−1, IQR = 47.20 pg·mL−1), p = 0.003) groups. APP, NfL, and VILIP-1 were all able to distinguish between pre-match and post-match groups (AUROC > 0.700) but not from the SRC group (AUROC < 0.660). Our results show that APP, NfL, and VILIP-1 were not helpful in differentiating concussed from non-concussed athletes pitch-side in this study.

Human adaptation to extreme environments has been explored for over a century to understand human psychology, integrated physiology, comparative pathologies, and exploratory potential. It has been demonstrated that these environments can provide multiple external stimuli and stressors, which are sufficient to disrupt internal homeostasis and induce adaptation processes. Multiday hyperbaric and/or saturated (HBS) environments represent the most understudied of environmental extremes due to inherent experimental, analytical, technical, temporal, and safety limitations. National Aeronautic Space Agency (NASA) Extreme Environment Mission Operation (NEEMO) is a space-flight analog mission conducted within Florida International University’s Aquarius Undersea Research Laboratory (AURL), the only existing operational and habitable undersea saturated environment. To investigate human objective and subjective adaptations to multiday HBS, we evaluated aquanauts living at saturation for 9–10 days via NASA NEEMO 22 and 23, across psychologic, cardiac, respiratory, autonomic, thermic, hemodynamic, sleep, and body composition parameters. We found that aquanauts exposed to saturation over 9–10 days experienced intrapersonal physical and mental burden, sustained good mood and work satisfaction, decreased heart and respiratory rates, increased parasympathetic and reduced sympathetic modulation, lower cerebral blood flow velocity, intact cerebral autoregulation and maintenance of baroreflex functionality, as well as losses in systemic bodyweight and adipose tissue. Together, these findings illustrate novel insights into human adaptation across multiple body systems in response to multiday hyperbaric saturation.

Background: Higher cerebral blood flow (CBF) pulsatility was found to be associated with severer brain white matter lesions in the elderly [1]. It was hypothesized that the central/elastic arterial stiffness/compliance may directly affect CBF pulsatility. However, it is still unclear which carotid stiffness parameters may better reflect this impact, and whether race and sex differences are present. Methods: To study the correlations among those parameters with comparisons between different races and sexes, we enrolled 35 young healthy subjects (19 females), aged 29 ± 5 (18∼40) years, with three races of comparable age and sex ratio, i.e. White (n = 16), Black (n = 7), and Asian (n = 12). All subjects were in resting seated position, with continuous transcranial Doppler recording of CBF velocity at middle cerebral artery (MCA), simultaneous 1-min ultrasound echo-tracking on bilateral common carotid arteries, and multiple measurements of brachial blood pressure (BP). Results: All derived parameters [2], including MCA pulsatility index (PI), showed no significant racial differences but with significantly (p < 0.05) higher carotid stiffness index (β), Peterson’s pressure modulus (Ep), BP pulsatility index (mostly driven by higher systolic BP but similar diastolic BP), and lower arterial compliance (AC, p = 0.07) in males than in females. Only AC (but not β and Ep) showed a significant correlation with PI (r = 0.49, p = 0.004) even after controlling for BP pulsatility index, which negatively correlated with AC (ρ = −0.35, p = 0.038). Conclusions: Higher carotid AC (i.e. decreased stiffness) seems to enhance CBF pulsatility in young healthy populations, which might differ from the elderly.

Abstract A high sodium (Na+) meal impairs peripheral vascular function. In rodents, chronic high dietary Na+ impairs cerebral vascular function, and in humans, habitual high dietary Na+ is associated with increased stroke risk. However, the effects of acute high dietary Na+ on the cerebral vasculature in humans are unknown. The purpose of this study was to determine if acute high dietary Na+ impairs cerebrovascular reactivity in healthy adults. Thirty‐seven participants (20F/17M; 25 ± 5 years; blood pressure [BP]: 107 ± 9/61 ± 6 mm Hg) participated in this randomized, cross‐over study. Participants were given a low Na+ meal (LSM; 138 mg Na+) and a high Na+ meal (HSM; 1,495 mg Na+) separated by ≥ one week. Serum Na+, beat‐to‐beat BP, middle cerebral artery velocity (transcranial Doppler), and end‐tidal carbon dioxide (PETCO2) were measured pre‐ (baseline) and 60 min post‐prandial. Cerebrovascular reactivity was assessed by determining the percent change in middle cerebral artery velocity to hypercapnia (via 8% CO2, 21% oxygen, balance nitrogen) and hypocapnia (via mild hyperventilation). Peripheral vascular function was measured using brachial artery flow‐mediated dilation (FMD). Changes in serum Na+ were greater following the HSM (HSM: Δ1.6 ± 1.2 mmol/L vs. LSM: Δ0.7 ± 1.2 mmol/L, p

Abstract Background Chronic kidney disease increases stroke incidence and severity but the mechanisms behind this cerebro-renal interaction are mostly unexplored. Since both vascular beds share similar features, microvascular dysfunction could be the possible missing link. Therefore, we examined the relationship between renal function and cerebral autoregulation in the early hours post ischemia and its impact on outcome. Methods We enrolled 46 ischemic strokes (middle cerebral artery). Dynamic cerebral autoregulation was assessed by transfer function (coherence, phase and gain) of spontaneous blood pressure oscillations to blood flow velocity within 6 h from symptom-onset. Estimated glomerular filtration rate (eGFR) was calculated. Hemorrhagic transformation (HT) and white matter lesions (WML) were collected from computed tomography performed at presentation and 24 h. Outcome was evaluated with modified Rankin Scale at 3 months. Results High gain (less effective autoregulation) was correlated with lower eGFR irrespective of infarct side (p

Groundtruth is a Matlab Graphical User Interface (GUI) developed for the identification of key features and artifacts within physiological signals. The ultimate aim of this GUI is to provide a simple means of assessing the performance of new sensors. Secondary, to this is providing a means of providing marked data, enabling assessment of automated artifact rejection and feature identification algorithms. With the emergence of new wearable sensor technologies, there is an unmet need for convenient assessment of device performance, and a faster means of assessing new algorithms. The proposed GUI allows interactive marking of artifact regions as well as simultaneous interactive identification of key features, e.g., respiration peaks in respiration signals, R-peaks in Electrocardiography signals, etc. In this paper, we present the base structure of the system, together with an example of its use for two simultaneously worn respiration sensors. The respiration rates are computed for both original as well as artifact removed data and validated using Bland–Altman plots. The respiration rates computed based on the proposed GUI (after artifact removal process) demonstrated consistent results for two respiration sensors after artifact removal process. Groundtruth is customizable, and alternative processing modules are easy to add/remove. Groundtruth is intended for open-source use.

Objective: To determine whether the acute cerebral hemodynamic responses to oxygen inhalation are impacted by race or acclimation to high altitude.Methods: Three groups of young healthy males, who were Tibetans (highlanders, n = 15) with lifelong exposure to high altitude, and Han Chinese (lowlanders) with five-year (Han-5 yr, n = 15) and three-day (Han-3 d, n = 16) exposures, participated in the study at an altitude of 3658 m. Cerebral blood flow velocity (CBFV) was recorded for three minutes prior to and during pure oxygen inhalation (2 L/min), respectively, using a transcranial color-coded duplex (TCCD) sonography at the middle cerebral artery (MCA). The blood draw and simultaneous monitoring of blood pressure (BP), heart rate (HR), and finger arterial oxygen saturation (SaO2) were also performed.Results: Values are Mean ± SEM. The three groups had similar demographic characteristics and HR responses, with the group differences (P < 0.05) found in hemoglobin concentration (16.9 ± 0.9, 18.4 ± 1.3, and 15.5 ± 1.0 gm/dL), baseline BPs and HR as expected. Both the Tibetans and Han-5yr groups presented blunted BP responses to O2-inhalation when compared to the Han-3d group; more interestingly, the Tibetans showed significantly reduced responses compared with Han-5yr and Han-3d in CBFV, cerebral oxygen delivery (COD), and pulsatility index (PI) as assessed by Δ%CBFV/ΔSaO2 (-1.50 ± 0.25 vs. -2.24 ± 0.25 and -2.23 ± 0.27, P = 0.049 and 0.048), Δ%COD/ΔSaO2 (-0.52 ± 0.27 vs. -1.33 ± 0.26 and -1.38 ± 0.28, P = 0.044 and 0.031), and Δ%PI (7 ± 2 vs. 16 ± 3 and 16 ± 3 %, P = 0.036 and 0.023), respectively.Conclusion: These findings provide evidence on the Tibetans trait of a distinct cerebral hemodynamic regulatory pattern to keep more stable cerebral blood flow (CBF), oxygen delivery, and pulsatility in response to oxygen inhalation as compared with Han Chinese, which is likely due to a genetic adaptation to altitude.

BackgroundExertional dyspnea and exercise intolerance are frequently endorsed in Veterans of post 9/11 conflicts in Southwest Asia (SWA). Studying the dynamic behavior of ventilation during exercise may provide mechanistic insight into these symptoms. Using maximal cardiopulmonary exercise testing (CPET) to experimentally induce exertional symptoms, we aimed to identify potential physiological differences between deployed Veterans and non-deployed controls.Materials and methodsDeployed (n = 31) and non-deployed (n = 17) participants performed a maximal effort CPET via the Bruce treadmill protocol. Indirect calorimetry and perceptual rating scales were used to measure rate of oxygen consumption ([Formula: see text]), rate of carbon dioxide production ([Formula: see text]), respiratory frequency (f R), tidal volume (VT), minute ventilation ([Formula: see text]), heart rate (HR), perceived exertion (RPE; 6-20 scale), and dyspnea (Borg Breathlessness Scale; 0-10 scale). A repeated measures analysis of variance (RM-ANOVA) model (2 groups: deployed vs non-deployed X 6 timepoints: 0%, 20%, 40%, 60%, 80%, and 100% [Formula: see text]) was conducted for participants meeting valid effort criteria (deployed = 25; non-deployed = 11).ResultsSignificant group (η2partial = 0.26) and interaction (η2partial = 0.10) effects were observed such that deployed Veterans exhibited reduced f R and a greater change over time relative to non-deployed controls. There was also a significant group effect for dyspnea ratings (η2partial = 0.18) showing higher values in deployed participants. Exploratory correlational analyses revealed significant associations between dyspnea ratings and fR at 80% (R2 = 0.34) and 100% (R2 = 0.17) of [Formula: see text], but only in deployed Veterans.ConclusionRelative to non-deployed controls, Veterans deployed to SWA exhibited reduced fR and greater dyspnea during maximal exercise. Further, associations between these parameters occurred only in deployed Veterans. These findings support an association between SWA deployment and affected respiratory health, and also highlight the utility of CPET in the clinical evaluation of deployment-related dyspnea in Veterans.

Cerebrovascular reactivity and cerebral autoregulation are two major mechanisms that regulate cerebral blood flow. Both mechanisms are typically assessed in either supine or seated postures, but the effects of body position and sex differences remain unclear. This study examined the effects of body posture (supine vs. seated vs. standing) on cerebrovascular reactivity during hyper and hypocapnia and on cerebral autoregulation during spontaneous and slow-paced breathing in healthy men and women using transcranial Doppler ultrasonography of the middle cerebral artery. Results indicated significantly improved cerebrovascular reactivity in the supine compared with seated and standing postures (supine = 3.45±0.67, seated = 2.72±0.53, standing = 2.91±0.62%/mmHg, P

IntroductionA significant population of our wounded veterans suffer long-term functional consequences of visual deficit, disorientation, dizziness, and an impaired ability to read. These symptoms may be related to damage within the otolith pathways that contribute to ocular alignment. The purpose of this study was to compare perception of vertical and torsional ocular alignment between veterans and healthy controls in an upright and supine test position.Materials and methodsVeterans (n = 26) with reports of dizziness were recruited from the East Orange Veterans Administration Hospital. Healthy controls (n = 26) were recruited from both Johns Hopkins University and the East Orange VA. Each subject performed 20 trials each of a novel vertical and torsional binocular alignment perception test. Veterans underwent semicircular canal and otolith pathway function testing.Results88% of the Veterans had an absent otolith response. Only the veterans had an abnormally large variability in perception of both vertical and torsional ocular alignment, and in both upright and supine position. Neither post-traumatic stress disorder, nor depression contributed to the misperception in binocular alignment.ConclusionsOur novel method of measuring vertical and torsional misalignment distinguishes veterans with dizziness from healthy controls. The high prevalence of absent otolith function seems to explain this result. Further studies are needed to better understand the fundamental mechanism responsible for the increased variability of perception of binocular alignment.

Neurological dysfunction has been reported in Gulf War Illness (GWI), including abnormal cerebral blood flow (CBF) responses to physostigmine challenge. However, it is unclear whether the CBF response to normal physiological challenges and regulation is similarly dysfunctional. The goal of the present study was to evaluate the CBF velocity response to orthostatic stress (i.e., sit-to-stand maneuver) and increased fractional concentration of carbon dioxide. 23 cases of GWI (GWI+) and 9 controls (GWI) volunteered for this study. Primary variables of interest included an index of dynamic autoregulation and cerebrovascular reactivity. Dynamic autoregulation was significantly lower in GWI+ than GWI- both for autoregulatory index (2.99±1.5 vs 4.50±1.5, p = 0.017). In addition, we observed greater decreases in CBF velocity both at the nadir after standing (-18.5±6.0 vs -9.8±4.9%, p = 0.001) and during steady state standing (-5.7±7.1 vs -1.8±3.2%, p = 0.042). In contrast, cerebrovascular reactivity was not different between groups. In our sample of Veterans with GWI, dynamic autoregulation was impaired and consistent with greater cerebral hypoperfusion when standing. This reduced CBF may contribute to cognitive difficulties in these Veterans when upright.

Posttraumatic stress disorder (PTSD) is a chronic and disabling, anxiety disorder resulting from exposure to life threatening events such as a serious accident, abuse or combat (DSM IV definition). Among veterans with PTSD, a common complaint is dizziness, disorientation and/or postural imbalance in environments such as grocery stores and shopping malls. The etiology of these symptoms in PTSD is poorly understood and some attribute them to anxiety or traumatic brain injury. There is a possibility that an impaired vestibular system may contribute to these symptoms since, symptoms of an impaired vestibular system include dizziness, disorientation and postural imbalance. To our knowledge, this is the first report to describe the nature of vestibular related symptoms in veterans with and without PTSD. We measured PTSD symptoms using the Posttraumatic Stress Disorder Checklist (PCL-C) and compared it to responses on vestibular function scales including the Dizziness Handicap Inventory (DHI), the Vertigo Symptom Scale Short Form (VSS-SF), the Chambless Mobility Inventory (CMI), and the Neurobehavioral Scale Inventory (NSI) in order to identify vestibular-related symptoms. Our findings indicate that veterans with worse PTSD symptoms report increased vestibular related symptoms. Additionally veterans with PTSD reported 3 times more dizziness related handicap than veterans without PTSD. Veterans with increased avoidance reported more vertigo and dizziness related handicap than those with PTSD and reduced avoidance. We describe possible contributing factors to increased reports of vestibular symptoms in PTSD, namely, anxiety, a vestibular component as well as an interactive effect of anxiety and vestibular impairment. We also present some preliminary analyses regarding the contribution of TBI. This data suggests possible evidence for vestibular symptom reporting in veterans with PTSD, which may be explained by possible underlying vestibular impairment, worthy of further exploration.