Neuroimaging assessment of early and late neurobiological sequelae of traumatic brain injury: implications for CTE.

Traumatic brain injury (TBI) has been increasingly accepted as a major external risk factor for neurodegenerative morbidity and mortality. Recent evidence indicates that the resultant chronic neurobiological sequelae following head trauma may, at least in part, contribute to a pathologically distinct disease known as Chronic Traumatic Encephalopathy (CTE). The clinical manifestation of CTE is variable, but the symptoms of this progressive disease include impaired memory and cognition, affective disorders (i.e., impulsivity, aggression, depression, suicidality, etc.), and diminished motor control. Notably, mounting evidence suggests that the pathology contributing to CTE may be caused by repetitive exposure to subconcussive hits to the head, even in those with no history of a clinically evident head injury. Given the millions of athletes and military personnel with potential exposure to repetitive subconcussive insults and TBI, CTE represents an important public health issue. However, the incidence rates and pathological mechanisms are still largely unknown, primarily due to the fact that there is no in vivo diagnostic tool. The primary objective of this manuscript is to address this limitation and discuss potential neuroimaging modalities that may be capable of diagnosing CTE in vivo through the detection of tau and other known pathological features. Additionally, we will discuss the challenges of TBI research, outline the known pathology of CTE (with an emphasis on Tau), review current neuroimaging modalities to assess the potential routes for in vivo diagnosis, and discuss the future directions of CTE research.

Effects of chronic mild traumatic brain injury on white matter integrity in iraq and afghanistan war veterans

Mild traumatic brain injury (TBI) is a common source of morbidity from the wars in Iraq and Afghanistan. With no overt lesions on structural MRI, diagnosis of chronic mild TBI in military veterans relies on obtaining an accurate history and assessment of behavioral symptoms that are also associated with frequent comorbid disorders, particularly posttraumatic stress disorder (PTSD) and depression. Military veterans from Iraq and Afghanistan with mild TBI (n = 30) with comorbid PTSD and depression and non-TBI participants from primary (n = 42) and confirmatory (n = 28) control groups were assessed with high angular resolution diffusion imaging (HARDI). White matter-specific registration followed by whole-brain voxelwise analysis of crossing fibers provided separate partial volume fractions reflecting the integrity of primary fibers and secondary (crossing) fibers. Loss of white matter integrity in primary fibers (P < 0.05; corrected) was associated with chronic mild TBI in a widely distributed pattern of major fiber bundles and smaller peripheral tracts including the corpus callosum (genu, body, and splenium), forceps minor, forceps major, superior and posterior corona radiata, internal capsule, superior longitudinal fasciculus, and others. Distributed loss of white matter integrity correlated with duration of loss of consciousness and most notably with "feeling dazed or confused," but not diagnosis of PTSD or depressive symptoms. This widespread spatial extent of white matter damage has typically been reported in moderate to severe TBI. The diffuse loss of white matter integrity appears consistent with systemic mechanisms of damage shared by blast- and impact-related mild TBI that involves a cascade of inflammatory and neurochemical events. © 2012 Wiley Periodicals, Inc.

Platelet Counts, Acute Kidney Injury, and Mortality after Coronary Artery Bypass Grafting Surgery.

BACKGROUND: Cardiac surgery requiring cardiopulmonary bypass is associated with platelet activation. Because platelets are increasingly recognized as important effectors of ischemia and end-organ inflammatory injury, the authors explored whether postoperative nadir platelet counts are associated with acute kidney injury (AKI) and mortality after coronary artery bypass grafting (CABG) surgery. METHODS: The authors evaluated 4,217 adult patients who underwent CABG surgery. Postoperative nadir platelet counts were defined as the lowest in-hospital values and were used as a continuous predictor of postoperative AKI and mortality. Nadir values in the lowest 10th percentile were also used as a categorical predictor. Multivariable logistic regression and Cox proportional hazard models examined the association between postoperative platelet counts, postoperative AKI, and mortality. RESULTS: The median postoperative nadir platelet count was 121 × 10/l. The incidence of postoperative AKI was 54%, including 9.5% (215 patients) and 3.4% (76 patients) who experienced stages II and III AKI, respectively. For every 30 × 10/l decrease in platelet counts, the risk for postoperative AKI increased by 14% (adjusted odds ratio, 1.14; 95% CI, 1.09 to 1.20; P < 0.0001). Patients with platelet counts in the lowest 10th percentile were three times more likely to progress to a higher severity of postoperative AKI (adjusted proportional odds ratio, 3.04; 95% CI, 2.26 to 4.07; P < 0.0001) and had associated increased risk for mortality immediately after surgery (adjusted hazard ratio, 5.46; 95% CI, 3.79 to 7.89; P < 0.0001). CONCLUSION: The authors found a significant association between postoperative nadir platelet counts and AKI and short-term mortality after CABG surgery.

Road Traffic Injury Prevention Initiatives: A Systematic Review and Metasummary of Effectiveness in Low and Middle Income Countries.

BACKGROUND: Road traffic injuries (RTIs) are a growing but neglected global health crisis, requiring effective prevention to promote sustainable safety. Low- and middle-income countries (LMICs) share a disproportionately high burden with 90% of the world's road traffic deaths, and where RTIs are escalating due to rapid urbanization and motorization. Although several studies have assessed the effectiveness of a specific intervention, no systematic reviews have been conducted summarizing the effectiveness of RTI prevention initiatives specifically performed in LMIC settings; this study will help fill this gap. METHODS: In accordance with PRISMA guidelines we searched the electronic databases MEDLINE, EMBASE, Scopus, Web of Science, TRID, Lilacs, Scielo and Global Health. Articles were eligible if they considered RTI prevention in LMICs by evaluating a prevention-related intervention with outcome measures of crash, RTI, or death. In addition, a reference and citation analysis was conducted as well as a data quality assessment. A qualitative metasummary approach was used for data analysis and effect sizes were calculated to quantify the magnitude of emerging themes. RESULTS: Of the 8560 articles from the literature search, 18 articles from 11 LMICs fit the eligibility and inclusion criteria. Of these studies, four were from Sub-Saharan Africa, ten from Latin America and the Caribbean, one from the Middle East, and three from Asia. Half of the studies focused specifically on legislation, while the others focused on speed control measures, educational interventions, enforcement, road improvement, community programs, or a multifaceted intervention. CONCLUSION: Legislation was the most common intervention evaluated with the best outcomes when combined with strong enforcement initiatives or as part of a multifaceted approach. Because speed control is crucial to crash and injury prevention, road improvement interventions in LMIC settings should carefully consider how the impact of improvements will affect speed and traffic flow. Further road traffic injury prevention interventions should be performed in LMICs with patient-centered outcomes in order to guide injury prevention in these complex settings.

Investigation of Blast Wave Propagation: Correlating External Pressures to Brain Injury Predictors

Blast-induced Traumatic Brain Injury (bTBI) is the signature injury of the Iraq and Afghanistan wars; however, current understanding of bTBI is insufficient. In this study, novel analysis methods were developed to investigate correlations between external pressures and brain injury predictors. Experiments and simulations were performed to analyze placement of helmet-mounted pressure sensors. A 2D Finite Element model of a helmeted head cross-section was loaded with a blast wave. Pressure time-histories for nodes on the inner and outer surfaces of the helmet were cross-correlated to those inside the brain. Parallel physical experiments were carried out with a helmeted headform, pressure sensors, and pressure chamber. These analysis methods can potentially lead to better helmet designs and earlier detection and treatment of bTBI.

Genome-wide hydroxymethylcytosine pattern changes in response to oxidative stress

The TET enzymes convert methylcytosine to the newly discovered base hydroxymethylcytosine. While recent reports suggest that TETs may play a role in response to oxidative stress, this role remains uncertain, and results lack in vivo models. Here we show a global decrease of hydroxymethylcytosine in cells treated with buthionine sulfoximine, and in mice depleted for the major antioxidant enzymes GPx1 and 2. Furthermore, genome-wide profiling revealed differentially hydroxymethylated regions in coding genes, and intriguingly in microRNA genes, both involved in response to oxidative stress. These results thus suggest a profound effect of in vivo oxidative stress on the global hydroxymethylome.

More than a nuisance: personal injury under Rylands

Discusses, by reference to case law, whether damages for personal injury are recoverable under Rylands v Fletcher liability. Considers the issue by reference to a hypothetical scenario in which a claimant suffers personal injury as a result of a chemical leak from a factory for which the factory owner is not at fault. Considers claims based on diminution in amenity and for consequential loss.