Amelioration of Acute Sequelae of Blast Induced Mild Traumatic Brain Injury by N-Acetyl Cysteine: A Double-Blind, Placebo Controlled Study

Background: Mild traumatic brain injury (mTBI) secondary to blast exposure is the most common battlefield injury in Southwest Asia. There has been little prospective work in the combat setting to test the efficacy of new countermeasures. The goal of this study was to compare the efficacy of N-acetyl cysteine (NAC) versus placebo on the symptoms associated with blast exposure mTBI in a combat setting. Methods: This study was a randomized double blind, placebo-controlled study that was conducted on active duty service members at a forward deployed field hospital in Iraq. All symptomatic U.S. service members who were exposed to significant ordnance blast and who met the criteria for mTBI were offered participation in the study and 81 individuals agreed to participate. Individuals underwent a baseline evaluation and then were randomly assigned to receive either N-acetyl cysteine (NAC) or placebo for seven days. Each subject was re-evaluated at 3 and 7 days. Outcome measures were the presence of the following sequelae of mTBI: dizziness, hearing loss, headache, memory loss, sleep disturbances, and neurocognitive dysfunction. The resolution of these symptoms seven days after the blast exposure was the main outcome measure in this study. Logistic regression on the outcome of 'no day 7 symptoms' indicated that NAC treatment was significantly better than placebo (OR = 3.6, p = 0.006). Secondary analysis revealed subjects receiving NAC within 24 hours of blast had an 86% chance of symptom resolution with no reported side effects versus 42% for those seen early who received placebo. Conclusion: This study, conducted in an active theatre of war, demonstrates that NAC, a safe pharmaceutical countermeasure, has beneficial effects on the severity and resolution of sequelae of blast induced mTBI. This is the first demonstration of an effective short term countermeasure for mTBI. Further work on long term outcomes and the potential use of NAC in civilian mTBI is warranted. Trial Registration: ClinicalTrials.gov NCT00822263

Improving the Accuracy of DaT Scan Interpretation: a retrospective study to identify variables that standardize the review of DaT scans for idiopathic Parkinson’s disease

Introduction: Until recently, the diagnosis of Parkinson’s disease (PD) has been based solely on clinical observation. The DaT scan is a tool that allows clinicians to visualize areas of neurodegeneration in PD and can help guide diagnosis. However, there is a discordance between clinical judgement and interpretation of DaT scans. In this study, we aim to improve the utility of DaT scans in the diagnosis of PD by identifying factors that can lead to a misdiagnosis and determine which image findings predict a clinical syndrome of parkinsonism. Methods: We will conduct a retrospective chart review to analyze DaT scans of 100 patients clinically diagnosed with PD. We will calculate the initial SN/SP/PPV/NPV for diagnoses based clinically compared to scan. We will then blindly review and reclassify all scans as definitely abnormal, definitely normal, or indeterminate. We will then recalculate a revised SN/SP/PPV/NPV to see if these values changed following reanalysis. From the discordant scans, we will attempt to identify factors that can further assist in interpreting DaT scans. Results: Patients have been identified and we are in the process of extracting data. We anticipate that after systematic, careful re-review, the specificity of DaT scans will be higher, due to improvement in identifying positive scans. Discussion: Imaging can be costly and cumbersome for patients and clinicians alike. Currently, DaT scans do not offer an improved accuracy in diagnosis over clinical judgement. If the interpretation of DaT scans can be optimized, they will be of greater utility to both patients and physicians

A Cortical Region Consisting Entirely of Face-Selective Cells

Face perception is a skill crucial to primates. In both humans and macaque monkeys, functional magnetic resonance imaging (fMRI) reveals a system of cortical regions that show increased blood flow when the subject views images of faces, compared with images of objects. However, the stimulus selectivity of single neurons within these fMRI-identified regions has not been studied. We used fMRI to identify and target the largest face-selective region in two macaques for single-unit recording. Almost all (97%) of the visually responsive neurons in this region were strongly face selective, indicating that a dedicated cortical area exists to support face processing in the macaque

Curvature dependence of the effect of ionic functionalization on the attraction among nanoparticles in dispersion

Solubilization of nanoparticles facilitates nanomaterial processing and enables new applications. An effective method to improve dispersibility in water is provided by ionic functionalization.We explore how the necessary extent of functionalization depends on the particle geometry. Using molecular dynamics/umbrella sampling simulations, we determine the effect of the solute curvature on solventaveraged interactions among ionizing graphitic nanoparticles in aqueous dispersion. We tune the hydrophilicity of molecular-brush coated fullerenes, carbon nanotubes, and graphane platelets by gradually replacing a fraction of the methyl end groups of the alkyl coating by the ionizing –COOK or –NH3Cl groups. To assess the change in nanoparticles’ dispersibility in water, we determine the potential-of-mean-force profiles at varied degrees of ionization. When the coating comprises only propyl groups, the attraction between the hydrophobic particles intensifies from spherical to cylindrical to planar geometry. This is explained by the increasing fraction of surface groups that can be brought into contact and the reduced access to water molecules, both following the above sequence. When ionic groups are added, however, the dispersibility increases in the opposite order, with the biggest effect in the planar geometry and the smallest in the spherical geometry. These results highlight the important role of geometry in nanoparticle solubilization by ionic functionalities, with about twice higher threshold surface charge necessary to stabilize a dispersion of spherical than planar particles. At 25%–50% ionization, the potential of mean force reaches a plateau because of the counterion condensation and saturated brush hydration. Moreover, the increase in the fraction of ionic groups can weaken the repulsion through counterion correlations between adjacent nanoparticles. High degrees of ionization and concomitant ionic screening gradually reduce the differences among surface interactions in distinct geometries until an essentially curvature-independent dispersion environment is created. Insights into tuning nanoparticle interactions can guide the synthesis of a broad class of nonpolar nanoparticles, where solubility is achieved by ionic functionalization

Neuroimaging Weighs In: Humans Meet Macaques in “Primate” Visual Cortex

It has been only a decade since functional magnetic resonance imaging (fMRI) was introduced, but approximately four fMRI papers are now published every working day. Here we review this progress in a well studied system: primate visual cortex

A Bayesian Climate Change Detection and Attribution Assessment

A Bayesian analysis of the evidence for human-induced climate change in global surface temperature observations is described. The analysis uses the standard optimal detection approach and explicitly incorporates prior knowledge about uncertainty and the influence of humans on the climate. This knowledge is expressed through prior distributions that are noncommittal on the climate change question. Evidence for detection and attribution is assessed probabilistically using clearly defined criteria. Detection requires that there is high likelihood that a given climate-model-simulated response to historical changes in greenhouse gas concentration and sulphate aerosol loading has been identified in observations. Attribution entails a more complex process that involves both the elimination of other plausible explanations of change and an assessment of the likelihood that the climate-model-simulated response to historical forcing changes is correct. The Bayesian formalism used in this study deals with this latter aspect of attribution in a more satisfactory way than the standard attribution consistency test. Very strong evidence is found to support the detection of an anthropogenic influence on the climate of the twentieth century. However, the evidence from the Bayesian attribution assessment is not as strong, possibly due to the limited length of the available observational record or sources of external forcing on the climate system that have not been accounted for in this study. It is estimated that strong evidence from a Bayesian attribution assessment using a relatively stringent attribution criterion may be available by 2020

Fine-Scale Spatial Organization of Face and Object Selectivity in the Temporal Lobe: Do Functional Magnetic Resonance Imaging, Optical Imaging, and Electrophysiology Agree?

The spatial organization of the brain's object and face representations in the temporal lobe is critical for understanding high-level vision and cognition but is poorly understood. Recently, exciting progress has been made using advanced imaging and physiology methods in humans and nonhuman primates, and the combination of such methods may be particularly powerful. Studies applying these methods help us to understand how neuronal activity, optical imaging, and functional magnetic resonance imaging signals are related within the temporal lobe, and to uncover the fine-grained and large-scale spatial organization of object and face representations in the primate brain

The M, E, and N structural proteins of the severe acute respiratory syndrome coronavirus are required for efficient assembly, trafficking, and release of virus-like particles

Copyright @ 2008 American Society for Microbiology.The production of virus-like particles (VLPs) constitutes a relevant and safe model to study molecular determinants of virion egress. The minimal requirement for the assembly of VLPs for the coronavirus responsible for severe acute respiratory syndrome in humans (SARS-CoV) is still controversial. Recent studies have shown that SARS-CoV VLP formation depends on either M and E proteins or M and N proteins. Here we show that both E and N proteins must be coexpressed with M protein for the efficient production and release of VLPs by transfected Vero E6 cells. This suggests that the mechanism of SARS-CoV assembly differs from that of other studied coronaviruses, which only require M and E proteins for VLP formation. When coexpressed, the native envelope trimeric S glycoprotein is incorporated onto VLPs. Interestingly, when a fluorescent protein tag is added to the C-terminal end of N or S protein, but not M protein, the chimeric viral proteins can be assembled within VLPs and allow visualization of VLP production and trafficking in living cells by state-of-the-art imaging technologies. Fluorescent VLPs will be used further to investigate the role of cellular machineries during SARS-CoV egress.The University of Hong Kong and the French Ministry of Health

The application of ultrasonic NDT techniques in tribology

The use of ultrasonic reflection is emerging as a technique for studying tribological contacts. Ultrasonic waves can be transmitted non-destructively through machine components and their behaviour at an interface describes the characteristics of that contact. This paper is a review of the current state of understanding of the mechanisms of ultrasonic reflection at interfaces, and how this has been used to investigate the processes of dry rough surface contact and lubricated contact. The review extends to cover how ultrasound has been used to study the tribological function of certain engineering machine elements

Heme Oxygenase-1 Expression Affects Murine Abdominal Aortic Aneurysm Progression.

Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme degradation, is a cytoprotective enzyme upregulated in the vasculature by increased flow and inflammatory stimuli. Human genetic data suggest that a diminished HO-1 expression may predispose one to abdominal aortic aneurysm (AAA) development. In addition, heme is known to strongly induce HO-1 expression. Utilizing the porcine pancreatic elastase (PPE) model of AAA induction in HO-1 heterozygous (HO-1+/-, HO-1 Het) mice, we found that a deficiency in HO-1 leads to augmented AAA development. Peritoneal macrophages from HO-1+/- mice showed increased gene expression of pro-inflammatory cytokines, including MCP-1, TNF-alpha, IL-1-beta, and IL-6, but decreased expression of anti-inflammatory cytokines IL-10 and TGF-beta. Furthermore, treatment with heme returned AAA progression in HO-1 Het mice to a wild-type profile. Using a second murine AAA model (Ang II-ApoE-/-), we showed that low doses of the HMG-CoA reductase inhibitor rosuvastatin can induce HO-1 expression in aortic tissue and suppress AAA progression in the absence of lipid lowering. Our results support those studies that suggest that pleiotropic statin effects might be beneficial in AAA, possibly through the upregulation of HO-1. Specific targeted therapies designed to induce HO-1 could become an adjunctive therapeutic strategy for the prevention of AAA disease