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203 results on '"O'Brien, William T"'

2. Pathophysiology, blood biomarkers, and functional deficits after intimate partner violence-related brain injury: Insights from emergency department patients and a new rat model

Author

Sun, Mujun, Symons, Georgia F., Spitz, Gershon, O’Brien, William T., Baker, Tamara L, Fan, Jianjia, Martins, Beatriz D., Allen, Josh, Giesler, Lauren P., Mychasiuk, Richelle, van Donkelaar, Paul, Brand, Justin, Christie, Brian, O’Brien, Terence J., O’Sullivan, Michael J., Mitra, Biswadev, Wellington, Cheryl, McDonald, Stuart J., and Shultz, Sandy R.

Published
2025
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7. Incomplete partition type II in its various manifestations: isolated, in association with EVA, syndromic, and beyond; a multicentre international study.

Author

D'Arco, Felice, Kandemirli, Sedat G., Dahmoush, Hisham M., Alves, Cesar A. P. F., Severino, Mariasavina, Dellepiane, Francesco, Robson, Caroline D., Lequin, Maarten H., Rossi-Espagnet, Camilla, O'Brien, William T., Nash, Robert, Clement, Emma, and Juliano, Amy F.

Subjects
MEMBRANE transport proteins, VESTIBULAR aqueduct, GOITER, SENSORINEURAL hearing loss, COMPUTED tomography, RETROSPECTIVE studies, MAGNETIC resonance imaging, LONGITUDINAL method, RESEARCH, MEDICAL records, ACQUISITION of data, PENDRED syndrome, GENETIC mutation, GENOTYPES, PHENOTYPES, GENETIC testing
Abstract

Purpose: Incomplete partition type II (IP-II) is characterized by specific histological features and radiological appearance. It may occur in isolation or in association with an enlarged vestibular aqueduct (EVA). Among those with IP-II and EVA, a subset has a diagnosis of Pendred syndrome. This study aimed to explore the prevalence of isolated IP-II, IP-II with EVA, and cases with a genetic or syndromic basis in our cohort. Methods: From a large, multicentre database of dysplastic cochleae (446 patients, 892 temporal bones), those with imaging features of IP-II were examined in detail, including whether there was a genetic or syndromic association. Results: A total of 78 patients with IP-II were identified. Among these, 55 patients had bilateral IP-II and EVA (only 12 with typical Mondini triad), 8 with bilateral IP-II and normal VA, 2 with bilateral IP-II and unilateral EVA, and 13 with unilateral IP-II (9 with unilateral EVA). Among the group with bilateral IP-II and bilateral EVA in whom genetic analysis was available, 14 out of 29 (48%) had SLC26A4 mutations and a diagnosis of Pendred syndrome, 1 had a FOXI1 mutation, and a few other genetic abnormalities; none had KCNJ10 pathogenic variants. Conclusion: Bilateral IP-II-bilateral EVA may be seen in the context of Pendred syndrome (SLC26A4 or FOXI1 mutations) but, in the majority of our cohort, no genetic abnormalities were found, suggesting the possibility of unknown genetic associations. IP-II in isolation (without EVA) is favored to be genetic when bilateral, although the cause is often unknown. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Cannabidiol attenuates seizure susceptibility and behavioural deficits in adult CDKL5R59X knock‐in mice.

Author

Li, Xiaofan, Yennawar, Madhumita, Wiest, Alyssa, O'Brien, William T., Babrowicz, Bergan, White, Rachel S., Talos, Delia M., and Jensen, Frances E.

Subjects
CANNABINOID receptors, TRPV cation channels, CANNABIDIOL
Abstract

Cyclin‐dependent kinase‐like 5 (CDKL5) deficiency disorder (CDD) is caused by a loss‐of‐function mutation in CDKL5 gene, encoding a serine–threonine kinase highly expressed in the brain. CDD manifests with early‐onset epilepsy, autism, motor impairment and severe intellectual disability. While there are no known treatments for CDD, the use of cannabidiol has recently been introduced into clinical practice for neurodevelopmental disorders. Given the increased clinical utilization of cannabidiol, we examined its efficacy in the CDKL5R59X knock‐in (R59X) mice, a CDD model based on a human mutation that exhibits both lifelong seizure susceptibility and behavioural deficits. We found that cannabidiol pre‐treatment rescued the increased seizure susceptibility in response to the chemoconvulsant pentylenetetrazol (PTZ), attenuated working memory and long‐term memory impairments, and rescued social deficits in adult R59X mice. To elucidate a potential mechanism, we compared the developmental hippocampal and cortical expression of common endocannabinoid (eCB) targets in R59X mice and their wild‐type littermates, including cannabinoid type 1 receptor (CB1R), transient receptor potential vanilloid type 1 (TRPV1) and 2 (TRPV2), G‐coupled protein receptor 55 (GPR55) and adenosine receptor 1 (A1R). Many of these eCB targets were developmentally regulated in both R59X and wild‐type mice. In addition, adult R59X mice demonstrated significantly decreased expression of CB1R and TRPV1 in the hippocampus, and TRPV2 in the cortex, while TRPV1 was increased in the cortex. These findings support the potential for dysregulation of eCB signalling as a plausible mechanism and therapeutic target in CDD, given the efficacy of cannabidiol to attenuate hyperexcitability and behavioural deficits in this disorder. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Utility of Acute and Subacute Blood Biomarkers to Assist Diagnosis in CT-Negative Isolated Mild Traumatic Brain Injury

Author

Reyes, Jonathan, primary, Spitz, Gershon, additional, Major, Brendan P., additional, O'Brien, William T., additional, Giesler, Lauren P., additional, Bain, Jesse W.P., additional, Xie, Becca, additional, Rosenfeld, Jeffrey V., additional, Law, Meng, additional, Ponsford, Jennie L., additional, O'Brien, Terence J., additional, Shultz, Sandy R., additional, Willmott, Catherine, additional, Mitra, Biswadev, additional, and McDonald, Stuart J., additional

Published
2023
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12. MicroRNA biomarkers for diagnosis of mild traumatic brain injury and prediction of persistent symptoms: A prospective cohort study

Author

Mitra, Biswadev, primary, Major, Brendan P., additional, Reyes, Jonathan, additional, Surendran, Nanda, additional, Bain, Jesse, additional, Giesler, Lauren P., additional, O'Brien, William T., additional, Sorich, Edmond, additional, Willmott, Catherine, additional, Shultz, Sandy R., additional, O'Brien, Terence J., additional, Rosenfeld, Jeffrey V., additional, and McDonald, Stuart J., additional

Published
2023
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17. Towards Preclinical Validation of Arbaclofen (R-baclofen) Treatment for 16p11.2 Deletion Syndrome

Author

Gundersen, Brigitta B, primary, O'Brien, William T, additional, Schaffler, Melanie D, additional, Schultz, Maria N, additional, Tsukahara, Tatsuya, additional, Lorenzo, Sandra M, additional, Nalesso, Valerie, additional, Clayton, Alice H Luo, additional, Abel, Ted, additional, Crawley, Jacqueline N, additional, Datta, Sandeep R, additional, and Herault, Yann, additional

Published
2023
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18. MicroRNA Biomarkers on Day of Injury Among Patients with Post Concussive Symptoms at 28-Days: A Prospective Cohort Study

Author

Mitra, Biswadev, Major, Brendan, Reyes, Jonathan, Surendran, Nanda, Bain, Jesse, Giesler, Lauren P., O'Brien, William T., Sorich, Edmond, Willmott, Catherine, Shultz, Sandy R., O'Brien, Terence J., Rosenfeld, Jeffrey V., and McDonald, Stuart J.

Abstract

Background: After mild traumatic brain injury (mTBI), some patients experience symptoms that persist for weeks to months. Recovery from mTBI is primarily assessed using selfreported symptom questionnaires. Blood biomarkers, including microRNA species, have shown promise to assist diagnosis of mTBI, however, little is known about how blood microRNA measures might predict symptom recovery.Objective: The aim of this study was to investigate the variances in plasma microRNAs on the day of injury between individuals with mTBI who report post-concussive symptoms at the 28- day mark and those who do not.Methods: Patients who presented to an adult, tertiary referral hospital emergency department on the day of the injury and were diagnosed with isolated mTBI (n=35) were followed up for 28 days. Venous blood samples were collected and symptom severity was assessed using the Rivermead Post-Concussion Symptom Questionnaire (RPQ) on the day of injury and at 28 days. Patients who reported ongoing symptoms of total RPQ score ≥10 or at least one symptom severity ≥2, were compared to those with lesser symptom severity or symptom resolution.Results: There were 9 (25.7%; 95%CI: 12.5-43.3) patients who reported persistent symptoms. Day of injury plasma miR-223-3p levels were significantly higher in individuals with ongoing symptoms compared to those without, however, no such differences were observed for miRs 142- 3p, 423-3p, 32-5p, 144-3p, and let-7f-5p.Conclusion: Acute plasma miR-223-3p levels appear to detect patients who later have persistent symptoms after mTBI. The results demonstrate the potential utility for such biomarkers to assist in decisions towards early referral for therapy after mTBI.

Published
2024
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19. Clinical and Blood Biomarker Trajectories after Concussion: New Insights from a Longitudinal Pilot Study of Professional Flat-Track Jockeys

Author

McDonald, Stuart J., primary, Piantella, Stefan, additional, O'Brien, William T., additional, Hale, Matthew W., additional, O'Halloran, Paul, additional, Kinsella, Glynda, additional, Horan, Ben, additional, O'Brien, Terence J, additional, Maruff, Paul, additional, Shultz, Sandy R., additional, and Wright, Bradley J., additional

Published
2023
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20. Serum neurofilament light as a biomarker of vulnerability to a second mild traumatic brain injury

Author

O'Brien, William T., primary, Wright, David K., additional, van Emmerik, Ashley L.J.J., additional, Bain, Jesse, additional, Brkljaca, Robert, additional, Christensen, Jennaya, additional, Yamakawa, Glenn R., additional, Chen, Zhibin, additional, Giesler, Lauren P., additional, Sun, Mujun, additional, O'Brien, Terence J., additional, Monif, Mastura, additional, Shultz, Sandy R., additional, and McDonald, Stuart J., additional

Published
2022
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22. Serum Protein Biomarkers of Inflammation, Oxidative Stress, and Cerebrovascular and Glial Injury in Concussed Australian Football Players

Author

Sun, Mujun, primary, Symons, Georgia F., additional, O'Brien, William T., additional, Mccullough, Jesse, additional, Aniceto, Roxanne, additional, Lin, I-Hsuan, additional, Eklund, Michael, additional, Brady, Rhys D., additional, Costello, Daniel, additional, Chen, Zhibin, additional, O'Brien, Terence J., additional, McDonald, Stuart J., additional, Agoston, Denes V., additional, and Shultz, Sandy R., additional

Published
2022
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24. A phase 1b open-label study of sodium selenate as a disease-modifying treatment for possible behavioral variant frontotemporal dementia

Author

Vivash, Lucy, Malpas, Charles B, Meletis, Christian, Gollant, Meghan, Eratne, Dhamidhu, Li, Qiao-Xin, McDonald, Stuart, O'Brien, William T, Brodtmann, Amy, Darby, David, Kyndt, Christopher, Walterfang, Mark, Hovens, Christopher M, Velakoulis, Dennis, and O'Brien, Terence J

Subjects
110999 Neurosciences not elsewhere classified, FOS: Clinical medicine, 110399 Clinical Sciences not elsewhere classified
Abstract

Introduction: Sodium selenate increases tau dephosphorylation through protein phosphatase 2 activation. Here we report an open-label Phase 1b study of sodium selenate as a disease-modifying treatment for behavioral variant frontotemporal dementia (bvFTD). Methods: Twelve participants with bvFTD received sodium selenate (15 mg, three times a day) for 52 weeks. Safety assessments were carried out throughout the trial. Primary outcomes were frequency of adverse events (AEs), serious adverse events (SAEs), and discontinuations. Secondary outcomes of potential efficacy included cognitive and behavioral assessments, magnetic resonance imaging (MRI) whole brain volume, and cerebrospinal fluid (CSF) and blood total tau (t-tau), phosphorylated tau (p-tau), and neurofilament light (NfL) levels, which were measured at baseline and at week 52. Results: Sodium selenate was safe and well tolerated. All participants completed the study, and the majority (64.7%) of reported AEs were mild. One SAE occurred, which was not treatment related. Small declines in MRI and cognitive and behavioral measures were observed over the treatment period. There was no evidence for change in CSF protein levels (t-tau, p-tau, or NfL). Further analysis showed two distinct groups when measuring disease progression markers over the course of the study-one (n = 4) with substantial brain atrophy (2.5% to 6.5% reduction) and cognitive and behavioral decline over the 12-month treatment period, and the second group (n = 7) with no detectable change in cognitive and behavioral measures and less brain atrophy (0.3% to 1.7% reduction). Conclusion: Sodium selenate is safe and well tolerated in patients with bvFTD. Randomized-controlled trials are warranted to investigate potential efficacy.

Published
2022
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25. Decrease in Plasma miR-27a and miR-221 After Concussion in Australian Football Players

Author

Shultz, Sandy R, primary, Taylor, Caroline J, additional, Aggio-Bruce, Riemke, additional, O’Brien, William T, additional, Sun, Mujun, additional, Cioanca, Adrian V, additional, Neocleous, George, additional, Symons, Georgia F, additional, Brady, Rhys D, additional, Hardikar, Anandwardhan A, additional, Joglekar, Mugdha V, additional, Costello, Daniel M, additional, O’Brien, Terence J, additional, Natoli, Riccardo, additional, and McDonald, Stuart J, additional

Published
2022
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26. A phase 1b open‐label study of sodium selenate as a disease‐modifying treatment for possible behavioral variant frontotemporal dementia

Author

Vivash, Lucy, primary, Malpas, Charles B., additional, Meletis, Christian, additional, Gollant, Meghan, additional, Eratne, Dhamidhu, additional, Li, Qiao‐Xin, additional, McDonald, Stuart, additional, O'Brien, William T., additional, Brodtmann, Amy, additional, Darby, David, additional, Kyndt, Christopher, additional, Walterfang, Mark, additional, Hovens, Christopher M., additional, Velakoulis, Dennis, additional, and O'Brien, Terence J., additional

Published
2022
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30. White and Gray Matter Abnormalities in Australian Footballers With a History of Sports-Related Concussion: An MRI Study

Author

Major, Brendan, primary, Symons, Georgia F, additional, Sinclair, Ben, additional, O’Brien, William T, additional, Costello, Daniel, additional, Wright, David K, additional, Clough, Meaghan, additional, Mutimer, Steven, additional, Sun, Mujun, additional, Yamakawa, Glenn R, additional, Brady, Rhys D, additional, O’Sullivan, Michael J, additional, Mychasiuk, Richelle, additional, McDonald, Stuart J, additional, O’Brien, Terence J, additional, Law, Meng, additional, Kolbe, Scott, additional, and Shultz, Sandy R, additional

Published
2021
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31. Additional file 1 of Prolonged elevation of serum neurofilament light after concussion in male Australian football players

Author

McDonald, Stuart J., O’Brien, William T., Symons, Georgia F., Zhibin Chen, Bain, Jesse, Major, Brendan P., Costello, Daniel, Yamakawa, Glenn, Mujun Sun, Brady, Rhys D., Biswadev Mitra, Mychasiuk, Richelle, O’Brien, Terence J., and Shultz, Sandy R.

Abstract

Additional file 1: Supplementary Table 1. SCAT and serum biomarker analyses of concussed male and female Australian football players. Supplementary Table 2. Baseline comparisons between non-SRC control footballers and SRC footballers. Supplementary Table 3. Serum biomarker comparisons of non-concussed and concussed Australian footballers. Supplementary Figure 1. Temporal profile of serum biomarkers pre- and post-concussion.

Published
2021
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32. Elevated Serum Interleukin-1β Levels in Male, but not Female, Collision Sport Athletes with a Concussion History

Author

O'Brien, William T., primary, Symons, Georgia F., additional, Bain, Jesse, additional, Major, Brendan P., additional, Costello, Daniel M., additional, Sun, Mujun, additional, Kimpton, Joshua S., additional, Chen, Zhibin, additional, Brady, Rhys D., additional, Mychasiuk, Richelle, additional, O'Brien, Terence J., additional, Monif, Mastura, additional, Shultz, Sandy R., additional, and McDonald, Stuart J., additional

Published
2021
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33. Diffusion Imaging Reveals Sex Differences in the White Matter Following Sports-Related Concussion

Author

Wright, David K, primary, Symons, Georgia F, additional, O’Brien, William T, additional, McDonald, Stuart J, additional, Zamani, Akram, additional, Major, Brendan, additional, Chen, Zhibin, additional, Costello, Daniel, additional, Brady, Rhys D, additional, Sun, Mujun, additional, Law, Meng, additional, O’Brien, Terence J, additional, Mychasiuk, Richelle, additional, and Shultz, Sandy R, additional

Published
2021
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35. Behavioral, axonal, and proteomic alterations following repeated mild traumatic brain injury: Novel insights using a clinically relevant rat model

Author

Pham, Louise, primary, Wright, David K., additional, O'Brien, William T., additional, Bain, Jesse, additional, Huang, Cheng, additional, Sun, Mujun, additional, Casillas-Espinosa, Pablo M., additional, Shah, Anup D., additional, Schittenhelm, Ralf B., additional, Sobey, Christopher G., additional, Brady, Rhys D., additional, O'Brien, Terence J., additional, Mychasiuk, Richelle, additional, Shultz, Sandy R., additional, and McDonald, Stuart J., additional

Published
2021
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36. Cognitive ocular motor deficits and white matter damage chronically after sports-related concussion

Author

Symons, Georgia F, primary, Clough, Meaghan, additional, Mutimer, Steven, additional, Major, Brendan P, additional, O’Brien, William T, additional, Costello, Daniel, additional, McDonald, Stuart J, additional, Chen, Zhibin, additional, White, Owen, additional, Mychasiuk, Richelle, additional, Law, Meng, additional, Wright, David K, additional, O’Brien, Terence J, additional, Fielding, Joanne, additional, Kolbe, Scott C, additional, and Shultz, Sandy R, additional

Published
2021
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39. Biomarkers of Neurobiologic Recovery in Adults With Sport-Related Concussion.

Author

O'Brien, William T., Spitz, Gershon, Xie, Becca, Major, Brendan P., Mutimer, Steven, Giesler, Lauren P., Bain, Jesse, Evans, Lauren J., Duarte Martins, Beatriz, Piantella, Stefan, Alhassan, Afizu, Brady, Shelby, Cappellari, David, Somma, Vincenzo, McColl, Thomas, Symons, Georgia F., Gore, Tenae, Sun, Matthew, Kuek, Timothy, and Horan, Seamus

Published
2024
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42. Serum Protein Biomarker Findings Reflective of Oxidative Stress and Vascular Abnormalities in Male, but Not Female, Collision Sport Athletes

Author

Major, Brendan P., primary, McDonald, Stuart J., additional, O'Brien, William T., additional, Symons, Georgia F., additional, Clough, Meaghan, additional, Costello, Daniel, additional, Sun, Mujun, additional, Brady, Rhys D., additional, Mccullough, Jesse, additional, Aniceto, Roxanne, additional, Lin, I-Hsuan, additional, Law, Meng, additional, Mychasiuk, Richelle, additional, O'Brien, Terence J., additional, Agoston, Denes V., additional, and Shultz, Sandy R., additional

Published
2020
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46. Shortened telomeres and serum protein biomarker abnormalities in collision sport athletes regardless of concussion history and sex

Author

Symons, Georgia F, primary, Clough, Meaghan, additional, O’Brien, William T, additional, Ernest, Joel, additional, Salberg, Sabrina, additional, Costello, Daniel, additional, Sun, Mujun, additional, Brady, Rhys D, additional, McDonald, Stuart J, additional, Wright, David K, additional, White, Owen, additional, Abel, Larry, additional, O’Brien, Terence J, additional, Mccullough, Jesse, additional, Aniceto, Roxanne, additional, Lin, I-Hsuan, additional, Agoston, Denes V, additional, Fielding, Joanne, additional, Mychasiuk, Richelle, additional, and Shultz, Sandy R, additional

Published
2020
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47. The role of mTORC1 activation in seizure-induced exacerbation of Alzheimer's disease.

Author

Gourmaud, Sarah, Stewart, David A, Irwin, David J, Roberts, Nicholas, Barbour, Aaron J, Eberwine, Grace, O'Brien, William T, Vassar, Robert, Talos, Delia M, and Jensen, Frances E

Abstract

The risk of seizures is 10-fold higher in patients with Alzheimer's disease than the general population, yet the mechanisms underlying this susceptibility and the effects of these seizures are poorly understood. To elucidate the proposed bidirectional relationship between Alzheimer's disease and seizures, we studied human brain samples (n = 34) from patients with Alzheimer's disease and found that those with a history of seizures (n = 14) had increased amyloid-β and tau pathology, with upregulation of the mechanistic target of rapamycin (mTOR) pathway, compared with patients without a known history of seizures (n = 20). To establish whether seizures accelerate the progression of Alzheimer's disease, we induced chronic hyperexcitability in the five times familial Alzheimer's disease mouse model by kindling with the chemoconvulsant pentylenetetrazol and observed that the mouse model exhibited more severe seizures than the wild-type. Furthermore, kindled seizures exacerbated later cognitive impairment, Alzheimer's disease neuropathology and mTOR complex 1 activation. Finally, we demonstrated that the administration of the mTOR inhibitor rapamycin following kindled seizures rescued enhanced remote and long-term memory deficits associated with earlier kindling and prevented seizure-induced increases in Alzheimer's disease neuropathology. These data demonstrated an important link between chronic hyperexcitability and progressive Alzheimer's disease pathology and suggest a mechanism whereby rapamycin may serve as an adjunct therapy to attenuate progression of the disease. [ABSTRACT FROM AUTHOR]

Published
2022
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49. "My airway is closing"

Author

O'Brien, William T., Sr, Lattin, Grant E., Jr, and Usatine, Richard P.

Published
2005

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