2,972 research outputs found

    Acute Flavanol Supplementation Improves the Attenuated Cerebral Vasodilatory Capacity in Young African Americans

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    African Americans (AA) have increased risk for cerebral vascular disease including stroke, Alzheimer’s disease, or dementia relative to Caucasian Americans (CA). Our recent study found that AA have attenuated cerebral vasodilatory response to rebreathing-induced hypercapnia when compared with CA. Thus, we hypothesized that acute flavanol intake restores blunted cerebral responses in AA. Fourteen healthy college-aged AA and 14 age- and sex-matched CA participants were studied. A four-parameter logistic regression was used for curve fitting the responses of cerebral vascular conductance (%CVCi) relative to changes in end-tidal carbon dioxide concentration. In AA, there were significant improvements in total range of changes in %CVCi (a) and the maximum increase in %CVCi (y0) with flavanol beverage (a; pre: 46.4 ± 16 vs. post: 64.4 ± 19 %CVCi; P = 0.007, y0; pre: 151.1 ± 18 vs. post: 166.0 ± 22 %CVCi; P = 0.002); however, there were no differences in a and y0 with placebo (a; pre: 52.5 ± 19 vs. post: 51.7 ± 17 %CVCi; P = 0.35, y0; pre: 156.2 ± 20 vs. post: 151.3 ± 17 %CVCi; P = 0.26). In CA, no differences in a and y0 with flavanol (a; pre: 73.7 ± 18 vs. post: 71.7 ± 22 %CVCi; P = 0.70, y0; pre: 175.7 ± 20 %CVCi vs. post: 175.6 ± 22 %CVCi; P = 0.99) or placebo (a; pre: 75.7 ± 15 vs. post: 80.1 ± 20 %CVCi; P = 0.24, y0; pre: 177.4 ± 21 %CVCi vs. post: 180.6 ± 25 %CVCi; P = 0.45) were observed. In conclusion, acute flavanol supplementation increases the total range of changes in cerebral vascular conductance as well as maximum vascular conductance in AA, effectively abolishing the ethnic-related difference in cerebral vasodilatory capacity in response to rebreathing-induced hypercapnia

    Synthetic Aperture Radar (SAR) data processing

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    The available and optimal methods for generating SAR imagery for NASA applications were identified. The SAR image quality and data processing requirements associated with these applications were studied. Mathematical operations and algorithms required to process sensor data into SAR imagery were defined. The architecture of SAR image formation processors was discussed, and technology necessary to implement the SAR data processors used in both general purpose and dedicated imaging systems was addressed

    Novel TNF Receptor-1 Inhibitors Identified as Potential Therapeutic Candidates for Traumatic Brain Injury

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    Background: Traumatic brain injury (TBI) begins with the application of mechanical force to the head or brain, which initiates systemic and cellular processes that are hallmarks of the disease. The pathological cascade of secondary injury processes, including inflammation, can exacerbate brain injury-induced morbidities and thus represents a plausible target for pharmaceutical therapies. We have pioneered research on post-traumatic sleep, identifying that injury-induced sleep lasting for 6 h in brain-injured mice coincides with increased cortical levels of inflammatory cytokines, including tumor necrosis factor (TNF). Here, we apply post-traumatic sleep as a physiological bio-indicator of inflammation. We hypothesized the efficacy of novel TNF receptor (TNF-R) inhibitors could be screened using post-traumatic sleep and that these novel compounds would improve functional recovery following diffuse TBI in the mouse. Methods: Three inhibitors of TNF-R activation were synthesized based on the structure of previously reported TNF CIAM inhibitor F002, which lodges into a defined TNFR1 cavity at the TNF-binding interface, and screened for in vitro efficacy of TNF pathway inhibition (IκB phosphorylation). Compounds were screened for in vivo efficacy in modulating post-traumatic sleep. Compounds were then tested for efficacy in improving functional recovery and verification of cellular mechanism. Results: Brain-injured mice treated with Compound 7 (C7) or SGT11 slept significantly less than those treated with vehicle, suggesting a therapeutic potential to target neuroinflammation. SGT11 restored cognitive, sensorimotor, and neurological function. C7 and SGT11 significantly decreased cortical inflammatory cytokines 3 h post-TBI. Conclusions: Using sleep as a bio-indicator of TNF-R-dependent neuroinflammation, we identified C7 and SGT11 as potential therapeutic candidates for TBI

    Diffuse Traumatic Brain Injury Induces Prolonged Immune Sysregulation and Potentiates Hyperalgesia Following a Peripheral Immune Challenge

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    Background: Nociceptive and neuropathic pain occurs as part of the disease process after traumatic brain injury (TBI) in humans. Central and peripheral inflammation, a major secondary injury process initiated by the traumatic brain injury event, has been implicated in the potentiation of peripheral nociceptive pain. We hypothesized that the inflammatory response to diffuse traumatic brain injury potentiates persistent pain through prolonged immune dysregulation. Results: To test this, adult, male C57BL/6 mice were subjected to midline fluid percussion brain injury or to sham procedure. One cohort of mice was analyzed for inflammation-related cytokine levels in cortical biopsies and serum along an acute time course. In a second cohort, peripheral inflammation was induced seven days after surgery/injury with an intraplantar injection of carrageenan. This was followed by measurement of mechanical hyperalgesia, glial fibrillary acidic protein and Iba1 immunohistochemical analysis of neuroinflammation in the brain, and flow cytometric analysis of T-cell differentiation in mucosal lymph. Traumatic brain injury increased interleukin-6 and chemokine ligand 1 levels in the cortex and serum that peaked within 1–9 h and then resolved. Intraplantar carrageenan produced mechanical hyperalgesia that was potentiated by traumatic brain injury. Further, mucosal T cells from brain-injured mice showed a distinct deficiency in the ability to differentiate into inflammation-suppressing regulatory T cells (Tregs). Conclusions: We conclude that traumatic brain injury increased the inflammatory pain associated with cutaneous inflammation by contributing to systemic immune dysregulation. Regulatory T cells are immune suppressors and failure of T cells to differentiate into regulatory T cells leads to unregulated cytokine production which may contribute to the potentiation of peripheral pain through the excitation of peripheral sensory neurons. In addition, regulatory T cells are identified as a potential target for therapeutic rebalancing of peripheral immune homeostasis to improve functional outcome and decrease the incidence of peripheral inflammatory pain following traumatic brain injury

    Copper Complexes as Influenza Antivirals: Reduced Zebrafish Toxicity

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    Copper complexes have previously been developed to target His37 in influenza M2 and are effective blockers of both the wild type (WT) and the amantadine-resistant M2S31N. Here, we report that the complexes were much less toxic to zebrafish than CuCl2. In addition, we characterized albumin binding, mutagenicity, and virus resistance formation of these metal complexes, and employed steered molecular dynamics simulations to explore whether the complexes would fit in M2. We also examined their anti-viral efficacy in a multi-generation cell culture assay to extend the previous work with an initial-infection assay, discovering that this is complicated by cell culture medium components. The number of copper ions binding to bovine serum albumin (BSA) correlates well with the number of surface histidines and BSA binding affinity is low compared to M2. No mutagenicity of the complexes was observed when compared to sodium azide. After 10 passages of virus in MDCK culture, the EC50 was unchanged for each of the complexes, i.e. resistance did not develop. The simulations revealed that the compounds fit well in the M2 channel, much like amantadine

    Evaluation of Biosecurity Measures on a Commercial Swine Operation Using Glo Germ Powder as a Visible Learning Aid

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    Glo germ, a fluorescent powder, was used to determine the efficacy of common biosecurity practices to prevent the powder from spreading to other areas within a commercial swine farm. The areas tested included an entry bench, the shower where all incoming personnel are required to shower upon farm entry and exit, the clean area following the shower, and inside the barn, which acted as the control with no biosecurity procedures in place given it is fully contained within the broader biosecurity measures of the facility. Pictures, from a standard iPhone, were taken before and after student and personnel movement to observe any differences in Glo Germ coverage. The percentage of Glo Germ coverage in the before and after pictures was evaluated once by 47 untrained panelists and averaged for each location and time point. The control area with no biosecurity measures in the barn had significantly more Glo Germ coverage than the other three locations (P \u3c 0.0001). There was no evidence of a difference in Glo Germ coverage between the entry bench, shower floor, or clean side of shower (P \u3e 0.05). In conclusion, the use of Glo Germ was successfully able to emulate disease entry into the farm and can be used as a learning aid to demonstrate the efficacy of entry benches, clean/dirty lines, and showers
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