Suchergebnisse

Primary objective: Excessive accumulation of amyloid beta (Aβ) and tau have been observed in older individuals with chronic neurological symptoms related to a traumatic brain injury (TBI), yet little is known about the possible role of Aβ in younger active duty service members following a TBI. The purpose of the study was to determine if Aβ 40 or 42 related to sustaining a TBI or to chronic neurological symptoms in a young cohort of military personnel.

Blunt and blast traumatic brain injuries (TBI) are devastating medical conditions that are prevalent in civilian and military populations, respectively. While these injuries can be mild, moderate, or severe, long-term physical, cognitive, and psychiatric sequelae are suffered across all levels of severity and significantly impact quality of life. Extensive research has been conducted on biomarkers in peripheral blood after TBI, in an effort to identify and ultimately manage medical care by prophylactically treating patients at-risk for developing chronic deficits following TBI. We recently investigated another potential peripheral biomarker for TBI and found that chronic symptoms of TBI were linked to elevated concentrations of tau, one of the two hallmark proteins in Alzheimer's disease (AD). This similar pathology between TBI and AD led us to question the role of amyloid beta (Aβ), the other hallmark protein in AD, in the development of chronic symptoms following TBI. This study assessed 71 U.S. military personnel, all of whom had been recently deployed. Blood samples were collected and analyzed for concentrations of Aβ40 and Aβ42 using Simoa, an ultrasensitive, single-molecule immunoassay. Symptomatology of depression, post-traumatic stress disorder (PTSD), and post-concussive disorder (PCD) were assessed by the Quick Inventory of Depressive Symptomatology, the PTSD Checklist Military Version, and the Neurobehavioral Symptom Inventory, respectively. Subjects with a history of TBI (TBI+) were compared to those without a history of TBI (TBI-). TBI+ subjects (n=53) were identified by either self-reporting a TBI on the Warrior Administered Retrospective Casualty Assessment Tool or by having a documented TBI in their medical record, while TBI- subjects (n=18) were classified as controls.

Abstract
Postoperative delirium (POD) can cause poor patient outcomes in older adults who undergo surgery. In this study, we tested plasma extracellular vesicle (EV) miRNAs obtained before the delirium event to find predictive POD biomarkers after spine surgery. We recruited patients who are more than 70 years old and have undergone spine surgery. Finally, POD patients (n = 31) were included, with no-POD patients matched in age, sex, medical history, and type of surgery (n = 31). Peripheral blood was collected from patients in the operating room after the operation was completed. EVs were isolated from plasma, and the 798 miRNA expression level from EVs was measured using a NanoString platform. Sixty-two patients were included in the study; all were Korean, 67.7% were females, and the median age was 75 years. Preoperative medical history was not statistically different between no-POD and POD patients except for hypertension and the American Society of Anesthesiologists physical status. From the miRNA profiling, we identified 142 significantly differentially expressed miRNAs in POD patients compared with no-POD patients, which are associated with psychological/neurological disorders. The top 10 differentially expressed miRNAs including miR-548ar-5p and miR-627-5p were all upregulated in POD patients and the results were validated using qRT-PCR from the independent sets of samples (n = 96). We demonstrated the potential of plasma EV-miRNAs as predictive biomarkers to identify the risk group of POD after spine surgery. It also provides opportunities for future studies investigating the role of EV-miRNAs in delirium pathology.

Repetitive low-level blast exposure is one of the major occupational health concerns among US military service members and law enforcement. This study seeks to identify gene expression using microRNA and RNA sequencing in whole-blood samples from experienced breachers and unexposed controls. We performed experimental RNA sequencing using Illumina's HiSeq 2500 Sequencing System, and microRNA analysis using NanoString Technology nCounter miRNA expression panel in whole-blood total RNA samples from 15 experienced breachers and 14 age-, sex-, and race-matched unexposed controls. We identified 10 significantly dysregulated genes between experienced breachers and unexposed controls, with FDR corrected <0.05: One upregulated gene, LINC00996 (long intergenic non-protein coding RNA 996); and nine downregulated genes, IGLV3-16 (immunoglobulin lambda variable 3-16), CD200 (CD200 molecule), LILRB5 (leukocyte immunoglobulin-like receptor B5), ZNF667-AS1 (ZNF667 antisense RNA 1), LMOD1 (leiomodin 1), CNTNAP2 (contactin-associated protein 2), EVPL (envoplakin), DPF3 (double PHD fingers 3), and IGHV4-34 (immunoglobulin heavy variable 4-34). The dysregulated gene expressions reported here have been associated with chronic inflammation and immune response, suggesting that these pathways may relate to the risk of lasting neurological symptoms following high exposures to blast over a career.