Elevated tau and interleukin-6 concentrations in adults with obstructive sleep apnea

The article of record as published may be found at http://dx.doi.org/10.1016/j.sleep.2017.11.1121Obstructive sleep apnea (OSA) is characterized by apneas and hypopneas that result in hypoxia, cerebral hypoperfusion, endothelial dysfunction, inflammation, and oxidative stress. These pathophysiologic processes likely contribute to neuronal damage. Tau is a protein that stabilizes microtubules and, along with amyloid beta (Ab), is associated with neurodegenerative processes. We sought to determine if tau and other biomarkers of inflammation were related to OSA severity. Concentrations of tau, Ab40, Ab42, c-reactive protein (CRP), TNF-a, interleukin (IL)-6, and IL-10 were measured in blood and compared between participants with moderate-severe OSA (n 1⁄4 28), those with mild OSA (n 1⁄4 22), and healthy controls (n 1⁄4 24). The cohort included relatively young, primarily male active duty military personnel without a history of traumatic brain injury or neurodegenerative disease. Total biomarker concentrations were determined from plasma samples using an ultra-sensitive detection method, SimoaTM, and CRP was assayed by ELISA. Total tau and IL-6 concentrations were elevated in participants with moderate-severe OSA, with a mean apnea-hypopnea index (AHI) of 26.1/h, compared to those with mild OSA (mean AHI 8.6/h) and healthy controls (mean AHI 2.1/h). Tau concentrations were also significantly correlated with the AHI (r 1⁄4 0.342, p 1⁄4 0.004). Our findings show that tau is elevated in the blood of young patients with moderate-severe OSA, suggesting that this degree of sleep-disordered breathing is a contributing factor in the development of neurodegenerative disorders. The finding of increased IL-6 further suggests that inflammatory biomarkers are present early in the course of this chronic disease

Proteomic Profiling of Plasma Biomarkers Associated With Return to Sport Following Concussion: Findings From the NCAA and Department of Defense CARE Consortium

ObjectiveTo investigate the plasma proteomic profiling in identifying biomarkers related to return to sport (RTS) following a sport-related concussion (SRC).MethodsThis multicenter, prospective, case-control study was part of a larger cohort study conducted by the NCAA-DoD Concussion Assessment, Research, and Education (CARE) Consortium, athletes (n = 140) with blood collected within 48 h of injury and reported day to asymptomatic were included in this study, divided into two groups: (1) recovery <14-days (n = 99) and (2) recovery ≥14-days (n = 41). We applied a highly multiplexed proteomic technique that uses DNA aptamers assay to target 1,305 proteins in plasma samples from concussed athletes with <14-days and ≥14-days.ResultsWe identified 87 plasma proteins significantly dysregulated (32 upregulated and 55 downregulated) in concussed athletes with recovery ≥14-days relative to recovery <14-days groups. The significantly dysregulated proteins were uploaded to Ingenuity Pathway Analysis (IPA) software for analysis. Pathway analysis showed that significantly dysregulated proteins were associated with STAT3 pathway, regulation of the epithelial mesenchymal transition by growth factors pathway, and acute phase response signaling.ConclusionOur data showed the feasibility of large-scale plasma proteomic profiling in concussed athletes with a <14-days and ≥ 14-days recovery. These findings provide a possible understanding of the pathophysiological mechanism in neurobiological recovery. Further study is required to determine whether these proteins can aid clinicians in RTS decisions

Proteomic Profiling of Plasma Biomarkers Associated With Return to Sport Following Concussion: Findings From the NCAA and Department of Defense CARE Consortium

ObjectiveTo investigate the plasma proteomic profiling in identifying biomarkers related to return to sport (RTS) following a sport-related concussion (SRC).MethodsThis multicenter, prospective, case-control study was part of a larger cohort study conducted by the NCAA-DoD Concussion Assessment, Research, and Education (CARE) Consortium, athletes (n = 140) with blood collected within 48 h of injury and reported day to asymptomatic were included in this study, divided into two groups: (1) recovery &lt;14-days (n = 99) and (2) recovery ≥14-days (n = 41). We applied a highly multiplexed proteomic technique that uses DNA aptamers assay to target 1,305 proteins in plasma samples from concussed athletes with &lt;14-days and ≥14-days.ResultsWe identified 87 plasma proteins significantly dysregulated (32 upregulated and 55 downregulated) in concussed athletes with recovery ≥14-days relative to recovery &lt;14-days groups. The significantly dysregulated proteins were uploaded to Ingenuity Pathway Analysis (IPA) software for analysis. Pathway analysis showed that significantly dysregulated proteins were associated with STAT3 pathway, regulation of the epithelial mesenchymal transition by growth factors pathway, and acute phase response signaling.ConclusionOur data showed the feasibility of large-scale plasma proteomic profiling in concussed athletes with a &lt;14-days and ≥ 14-days recovery. These findings provide a possible understanding of the pathophysiological mechanism in neurobiological recovery. Further study is required to determine whether these proteins can aid clinicians in RTS decisions

Plasma phosphorylated tau181 as a biomarker of mild traumatic brain injury: findings from THINC and NCAA-DoD CARE Consortium prospective cohorts

Objective The aim of this study was to investigate phosphorylated tau (p-tau181) protein in plasma in a cohort of mild traumatic brain injury (mTBI) patients and a cohort of concussed athletes. Methods This pilot study comprised two independent cohorts. The first cohort—part of a Traumatic Head Injury Neuroimaging Classification (THINC) study—with a mean age of 46 years was composed of uninjured controls (UIC, n = 30) and mTBI patients (n = 288) recruited from the emergency department with clinical computed tomography (CT) and research magnetic resonance imaging (MRI) findings. The second cohort—with a mean age of 19 years—comprised 133 collegiate athletes with (n = 112) and without (n = 21) concussions. The participants enrolled in the second cohort were a part of a multicenter, prospective, case-control study conducted by the NCAA-DoD Concussion Assessment, Research and Education (CARE) Consortium at six CARE Advanced Research Core (ARC) sites between 2015 and 2019. Blood was collected within 48 h of injury for both cohorts. Plasma concentration (pg/ml) of p-tau181 was measured using the Single Molecule Array ultrasensitive assay. Results Concentrations of plasma p-tau181 in both cohorts were significantly elevated compared to controls within 48 h of injury, with the highest concentrations of p-tau181 within 18 h of injury, with an area under the curve (AUC) of 0.690–0.748, respectively, in distinguishing mTBI patients and concussed athletes from controls. Among the mTBI patients, the levels of plasma p-tau181 were significantly higher in patients with positive neuroimaging (either CT+/MRI+, n = 74 or CT−/MRI+, n = 89) compared to mTBI patients with negative neuroimaging (CT−/MRI−, n = 111) findings and UIC (P-values < 0.05). Conclusion These findings indicate that plasma p-tau181 concentrations likely relate to brain injury, with the highest levels in patients with neuroimaging evidence of injury. Future research is needed to replicate and validate this protein assay's performance as a possible early diagnostic biomarker for mTBI/concussions

Plasma phosphorylated tau181 as a biomarker of mild traumatic brain injury: findings from THINC and NCAA-DoD CARE Consortium prospective cohorts

ObjectiveThe aim of this study was to investigate phosphorylated tau (p-tau181) protein in plasma in a cohort of mild traumatic brain injury (mTBI) patients and a cohort of concussed athletes.MethodsThis pilot study comprised two independent cohorts. The first cohort—part of a Traumatic Head Injury Neuroimaging Classification (THINC) study—with a mean age of 46 years was composed of uninjured controls (UIC, n = 30) and mTBI patients (n = 288) recruited from the emergency department with clinical computed tomography (CT) and research magnetic resonance imaging (MRI) findings. The second cohort—with a mean age of 19 years—comprised 133 collegiate athletes with (n = 112) and without (n = 21) concussions. The participants enrolled in the second cohort were a part of a multicenter, prospective, case-control study conducted by the NCAA-DoD Concussion Assessment, Research and Education (CARE) Consortium at six CARE Advanced Research Core (ARC) sites between 2015 and 2019. Blood was collected within 48 h of injury for both cohorts. Plasma concentration (pg/ml) of p-tau181 was measured using the Single Molecule Array ultrasensitive assay.ResultsConcentrations of plasma p-tau181 in both cohorts were significantly elevated compared to controls within 48 h of injury, with the highest concentrations of p-tau181 within 18 h of injury, with an area under the curve (AUC) of 0.690–0.748, respectively, in distinguishing mTBI patients and concussed athletes from controls. Among the mTBI patients, the levels of plasma p-tau181 were significantly higher in patients with positive neuroimaging (either CT+/MRI+, n = 74 or CT−/MRI+, n = 89) compared to mTBI patients with negative neuroimaging (CT−/MRI−, n = 111) findings and UIC (P-values &lt; 0.05).ConclusionThese findings indicate that plasma p-tau181 concentrations likely relate to brain injury, with the highest levels in patients with neuroimaging evidence of injury. Future research is needed to replicate and validate this protein assay's performance as a possible early diagnostic biomarker for mTBI/concussions

Whole Blood Transcriptome Sequencing in Individuals with Insomnia

The purpose of this dissertation was to identify a transcriptomic profile of individuals with insomnia and explore the role of the glymphatic system and sleep disturbances in neurodegenerative disease and traumatic brain injury. The first paper reports whole blood transcriptomic analysis in individuals with insomnia using RNA sequencing technology. The study incorporated innovative high throughput sequencing platform with extended pathway analysis using QIAGEN’s Ingenuity® Pathway Analysis software to identify differentially expressed genes and pathways in individuals with insomnia. The second paper provides a critical review of the sleep-wake process and the glymphatic system and how these processes contribute to neurodegenerative disorders and traumatic brain injury. The research addresses an important gap in knowledge about underlying mechanism of insomnia and how sleep disturbance, the glymphatic pathway and neurologic conditions may be interrelated

Effectiveness of Oral Hygiene Instructions Given in Computer-Assisted Format versus a Self-Care Instructor

Background: This randomized, single-blinded, controlled study compares the effectiveness of two modes of delivering the same set of oral hygiene instructions: those loaded on a computer-assisted teaching format versus those given personally by a self-care instructor. Methods: 60 participants with mild to moderate periodontitis were randomized to either the computer-teaching format or the self-care instructor. Plaque score and bleeding indices were assessed at baseline and at 4 week re-evaluation to compare the instructional modalities. Results: At baseline, there was no difference in the parameters between the two groups. At re-evaluation, all parameters were significantly improved compared to baseline; however, there was no difference between any parameters in the computer group versus the instructor. Plaque score was significantly different between younger and older participants, such that participants under 50 years old had lower plaque scores when they received instructions using the computer format (72.5 ± 12.6 vs. 87.2 ± 10.4; p &lt; 0.001). Additionally, in those under-50 year olds, plaque scores were significantly better in the group using the computer format (87.2 ± 10.4 vs. 78.3 ± 15.6; p = 0.03). Conclusion: Computer teaching formats and self-care instructors are both effective means of communicating oral hygiene instructions. Computer-assisted instruction format effectiveness may amplify as the population ages. Applications of computer formats teaching oral hygiene instructions and cost effectiveness comparison studies warrant significant future investigation

Age-Stratified Investigation of Sleep Disorders and PTSD Prevalence Among Vietnam Veterans

Military Veterans often experience a range of sleep disorders that significantly impact their physical and psychological wellbeing. Current study describes prevalence and age differences (≥ 65 to ≤ 74yrs; n =193)) vs. (≥ 75 to ≤ 90yrs; n =157) across insomnia, obstructive sleep apnea (OSA), nightmare disorder (ND), and posttraumatic stress disorder (PTSD). Vietnam Veterans (N = 350; AgeMean= 74.4 [SD= 3.6]) completed a survey (online or paper) of their sleep experiences and PTSD as part of a cross-sectional study. Veterans were mostly White (95%), male (97.7%), from the Army (55%), with some or two-year college (43%), and currently married (76%). Insomnia was screened positive in 27.7% of the Veterans, OSA in 58.6%, ND in 5.7%, and PTSD in 18.6%. There were significant mean differences in insomnia and PTSD across age groups (t(348) = 2.43, p = .016) and (t(348) = 2.06, p =.04), respectively, with younger age group showing higher insomnia, and PTSD. There were no significant mean differences in OSA and ND. Pearson correlation analyses yielded important associations. Insomnia was significantly positively correlated with PTSD (r= .60), OSA (r= .33), and ND (r= .51). PTSD was significantly positively correlated with OSA (r= .30) and ND (r= .67). ND was significantly positively correlated with OSA (r= .22). There were no significant differences in the associations across the two age groups. Recognizing and addressing various sleep disorders and comorbid PTSD are crucial to improving the quality of life of Veterans. Results emphasize need for comprehensive assessment of sleep disorders and PTSD among Veterans