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Sensory sensitivity as a link between concussive traumatic brain injury and PTSD.
Traumatic brain injury (TBI) is one of the most common injuries to military personnel, a population often exposed to stressful stimuli and emotional trauma. Changes in sensory processing after TBI might contribute to TBI-post traumatic stress disorder (PTSD) comorbidity. Combining an animal model of TBI with an animal model of emotional trauma, we reveal an interaction between auditory sensitivity after TBI and fear conditioning where 75 dB white noise alone evokes a phonophobia-like phenotype and when paired with footshocks, fear is robustly enhanced. TBI reduced neuronal activity in the hippocampus but increased activity in the ipsilateral lateral amygdala (LA) when exposed to white noise. The white noise effect in LA was driven by increased activity in neurons projecting from ipsilateral auditory thalamus (medial geniculate nucleus). These data suggest that altered sensory processing within subcortical sensory-emotional circuitry after TBI results in neutral stimuli adopting aversive properties with a corresponding impact on facilitating trauma memories and may contribute to TBI-PTSD comorbidity
No Evidence for a Cumulative Impact Effect on Concussion Injury Threshold
Recent studies using a helmet-based accelerometer system (Head Impact Telemetry System [HITS]) have demonstrated that concussions result from a wide range of head impact magnitudes. Variability in concussion thresholds has been proposed to result from the cumulative effect of non-concussive head impacts prior to injury. We used the HITS to collect biomechanical data representing >100,000 head impacts in 95 high school football players over 4 years. The cumulative impact histories prior to 20 concussive impacts in 19 athletes were compared to the cumulative impact histories prior to the three largest magnitude non-concussive head impacts in the same athletes. No differences were present in any impact history variable between the concussive and non-concussive high magnitude impacts. These analyses included the number of head impacts, cumulative HIT severity profile value, cumulative linear acceleration, and cumulative rotational acceleration during the same practice or game session, as well as over the 30-min and 1 week preceding these impacts. Our data do not support the proposal that impact volume or intensity influence concussion threshold in high school football athletes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90490/1/neu-2E2011-2E1910.pd
Conceptual design of the MHD Engineering Test Facility
The reference conceptual design of the MHD engineering test facility, a prototype 200 MWe coal-fired electric generating plant designed to demonstrate the commerical feasibility of open cycle MHD is summarized. Main elements of the design are identified and explained, and the rationale behind them is reviewed. Major systems and plant facilities are listed and discussed. Construction cost and schedule estimates are included and the engineering issues that should be reexamined are identified
Common data elements for pediatric traumatic brain injury: Recommendations from the working group on demographics and clinical assessment
The Common Data Elements (CDEs) initiative is a National Institutes of Health (NIH) interagency effort to standardize naming, definitions, and data structure for clinical research variables. Comparisons of the results of clinical studies of neurological disorders have been hampered by variability in data coding, definitions, and procedures for sample collection. The CDE project objective is to enable comparison of future clinical trials results in major neurological disorders, including traumatic brain injury (TBI), stroke, multiple sclerosis, and epilepsy. As part of this effort, recommendations for CDEs for research on TBI were developed through a 2009 multi-agency initiative. Following the initial recommendations of the Working Group on Demographics and Clinical Assessment, a separate workgroup developed recommendations on the coding of clinical and demographic variables specific to pediatric TBI studies for subjects younger than 18 years. This article summarizes the selection of measures by the Pediatric TBI Demographics and Clinical Assessment Working Group. The variables are grouped into modules which are grouped into categories. For consistency with other CDE working groups, each variable was classified by priority (core, supplemental, and emerging). Templates were produced to summarize coding formats, guide selection of data points, and provide procedural recommendations. This proposed standardization, together with the products of the other pediatric TBI working groups in imaging, biomarkers, and outcome assessment, will facilitate multi-center studies, comparison of results across studies, and high-quality meta-analyses of individual patient data
The Association Between Persistent White-Matter Abnormalities and Repeat Injury After Sport-Related Concussion
Objective: A recent systematic review determined that the physiological effects of concussion may persist beyond clinical recovery. Preclinical models suggest that ongoing physiological effects are accompanied by increased cerebral vulnerability that is associated with risk for subsequent, more severe injury. This study examined the association between signal alterations on diffusion tensor imaging following clinical recovery of sport-related concussion in athletes with and without a subsequent second concussion. Methods: Average mean diffusivity (MD) was calculated in a region of interest (ROI) in which concussed athletes (n = 82) showed significantly elevated MD acutely after injury (<48 h), at an asymptomatic time point, 7 days post-return to play (RTP), and 6 months relative to controls (n = 69). The relationship between MD in the identified ROI and likelihood of sustaining a subsequent concussion over a 1-year period was examined with a binary logistic regression (re-injured, yes/no). Results: Eleven of 82 concussed athletes (13.4%) sustained a second concussion within 12 months of initial injury. Mean MD at 7 days post-RTP was significantly higher in those athletes who went on to sustain a repeat concussion within 1 year of initial injury than those who did not (p = 0.048; d = 0.75). In this underpowered sample, the relationship between MD at 7 days post-RTP and likelihood of sustaining a secondary injury approached significance [χ2 (1) = 4.17, p = 0.057; B = 0.03, SE = 0.017; OR = 1.03, CI = 0.99, 1.07]. Conclusions: These preliminary findings raise the hypothesis that persistent signal abnormalities in diffusion imaging metrics at RTP following concussion may be predictive of a repeat concussion. This may reflect a window of cerebral vulnerability or increased susceptibility following concussion, though understanding the clinical significance of these findings requires further study
Athletes’ age, sex and years of education moderate the acute neuropsychological impact of sports-related concussion: A meta-analysis
The objective of this study is to determine which pre-existing athlete characteristics, if any, are associated with greater deficits in functioning following sports-related concussion, after controlling for factors previously shown to moderate this effect (e.g., time since injury). Ninety-one independent samples of concussion were included in a fixed+systematic effects meta-analysis (n = 3,801 concussed athletes; 5,631 controls). Moderating variables were assessed using analogue-to-ANOVA and meta-regression analyses. Post-injury assessments first conducted 1-10 days following sports-related concussion revealed significant neuropsychological dysfunction, postural instability and post-concussion symptom reporting (d = -0.54, -1.10, and -1.14, respectively). During this interval, females (d = -0.87), adolescent athletes competing in high school competitions (d = -0.60), and those with 10 years of education (d = -1.32) demonstrated larger post-concussion neuropsychological deficits than males (d = -0.42), adults (d = -0.25), athletes competing at other levels of competition (d = -0.43 to -0.41), or those with 16 years of education (d = -0.15), respectively. However, these sub-groups' differential impairment/recovery beyond 10 days could not be reliably quantified from available literature. Pre-existing athlete characteristics, particularly age, sex and education, were demonstrated to be significant modifiers of neuropsychological outcomes within 10 days of a sports-related concussion. Implications for return-to-play decision-making and future research directions are discussed
Diurnal Variation of Human Sweet Taste Recognition Thresholds Is Correlated With Plasma Leptin Levels
OBJECTIVE—It has recently been proposed that the peripheral taste organ is one of the targets for leptin. In lean mice, leptin selectively suppresses gustatory neural and behavioral responses to sweet compounds without affecting responses to other taste stimuli, whereas obese diabetic db/db mice with defects in leptin receptor lack this leptin suppression on sweet taste. Here, we further examined potential links between leptin and sweet taste in humans
First metatarsophalangeal hemiarthroplasty for hallux rigidus
There is a paucity of objective information in the literature about first metatarsophalangeal (MTP) hemiarthroplasty. The authors postulate that it is a reasonable treatment option for severe hallux rigidus in selected patients. Twenty-two elective first MTP hemiarthroplasties were performed on 20 patients that met the inclusion criteria. Pre- and postoperative evaluations were done using the American Orthopaedic Foot and Ankle Society (AOFAS) forefoot score, visual analogue scale (VAS) pain score, range of motion (ROM) measurements, and radiographs. Average ROM and dorsiflexion improved by 15° and 8°, respectively. VAS pain scores improved from 5 to 2.5 after six weeks. Painless ambulation occurred after six weeks, with maximum improvement by six months. After 24 months, two patients had pain at the surgical site interfering with function, leading to an unsatisfactory result that required conversion to arthrodesis. First MTP hemiarthroplasty for severe hallux rigidus can be considered an alternative to fusion in properly selected patients who wish to maintain a functional range of motion
Slitrk5 Mediates BDNF-Dependent TrkB Receptor Trafficking and Signaling
SummaryRecent studies in humans and in genetic mouse models have identified Slit- and NTRK-like family (Slitrks) as candidate genes for neuropsychiatric disorders. All Slitrk isotypes are highly expressed in the CNS, where they mediate neurite outgrowth, synaptogenesis, and neuronal survival. However, the molecular mechanisms underlying these functions are not known. Here, we report that Slitrk5 modulates brain-derived neurotrophic factor (BDNF)-dependent biological responses through direct interaction with TrkB receptors. Under basal conditions, Slitrk5 interacts primarily with a transsynaptic binding partner, protein tyrosine phosphatase δ (PTPδ); however, upon BDNF stimulation, Slitrk5 shifts to cis-interactions with TrkB. In the absence of Slitrk5, TrkB has a reduced rate of ligand-dependent recycling and altered responsiveness to BDNF treatment. Structured illumination microscopy revealed that Slitrk5 mediates optimal targeting of TrkB receptors to Rab11-positive recycling endosomes through recruitment of a Rab11 effector protein, Rab11-FIP3. Thus, Slitrk5 acts as a TrkB co-receptor that mediates its BDNF-dependent trafficking and signaling
Effects of Fluoride on Submandibular Glands of Mice: Changes in Oxidative Biochemistry, Proteomic Profile, and Genotoxicity
Although fluoride (F) is well-known to prevent dental caries, changes in cell processes in different tissues have been associated with its excessive exposure. Thus, this study aimed to evaluate the effects of F exposure on biochemical, proteomic, and genotoxic parameters of submandibular glands. Twenty one old rats (n = 30) were allocated into three groups: 60 days administration of drinking water containing 10 mgF/L, 50 mgF/L, or only deionized water (control). The submandibular glands were collected for oxidative biochemistry, protein expression profile, and genotoxic potential analyses. The results showed that both F concentrations increased the levels of thiobarbituric acid–reactive substances (TBARS) and reduced glutathione (GSH) and changed the proteomic profile, mainly regarding the cytoskeleton and cellular activity. Only the exposure to 50 mgF/L induced significant changes in DNA integrity. These findings reinforce the importance of continuous monitoring of F concentration in drinking water and the need for strategies to minimize F intake from other sources to obtain maximum preventive/therapeutic effects and avoid potential adverse effects
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