1,279 research outputs found

    Predictors of depression recovery in HIV-infected individuals managed through measurement-based care in infectious disease clinics

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    Treatment of comorbid chronic disease, such as depression, in people living with HIV/AIDS (PLWHA) increasingly falls to HIV treatment providers. Guidance in who will best respond to depression treatment and which patient-centered symptoms are best to target is limited

    PurposeNet: A Knowledge Base Organized around Purpose

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    Correction and Extension of WordNet 1.7

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    Ecto-5'-Nucleotidase (CD73) Inhibits Nociception by Hydrolyzing AMP to Adenosine in Nociceptive Circuits

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    Ecto-5’-nucleotidase (NT5E, CD73) is a membrane-anchored protein that hydrolyzes extracellular adenosine 5’-monophosphate (AMP) to adenosine in diverse tissues but has not been directly studied in nociceptive neurons. We found that NT5E was located on peptidergic and nonpeptidergic nociceptive neurons in dorsal root ganglia (DRG) and on axon terminals in lamina II (the substantia gelatinosa) of spinal cord. NT5E was also located on epidermal keratinocytes, cells of the dermis and on nociceptive axon terminals in the epidermis. Following nerve injury, NT5E protein and AMP histochemical staining were coordinately reduced in lamina II. In addition, AMP hydrolytic activity was reduced in DRG neurons and spinal cord of Nt5e−/− mice. The antinociceptive effects of AMP, when combined with the adenosine kinase inhibitor 5-iodotubericidin, were reduced by ~50% in Nt5e−/− mice and were eliminated in Adenosine A1 receptor (A1R, Adora1) knockout mice. Additionally, Nt5e−/− mice displayed enhanced sensitivity in the tail immersion assay, in the complete Freund's adjuvant (CFA) model of inflammatory pain and in the spared nerve injury (SNI) model of neuropathic pain. Collectively, our data indicate that the ectonucleotidase NT5E regulates nociception by hydrolyzing AMP to adenosine in nociceptive circuits and represents a new molecular target for the treatment of chronic pain. Moreover, our data suggest NT5E is well localized to regulate nucleotide signaling between skin cells and sensory axons

    Prostatic Acid Phosphatase Reduces Thermal Sensitivity and Chronic Pain Sensitization by Depleting Phosphatidylinositol 4,5-Bisphosphate

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    Prostatic acid phosphatase (PAP) is expressed in nociceptive dorsal root ganglia (DRG) neurons, functions as an ectonucleotidase and generates adenosine extracellularly. Here, we found that PAP inhibits noxious thermal sensitivity and sensitization that is associated with chronic pain through sustained activation of the adenosine A1 receptor (A1R) and phospholipase C-mediated depletion of phosphatidylinositol 4,5-bisphosphate (PIP2). In mice, intrathecal injection of PAP reduced PIP2 levels in DRG, inhibited thermosensation through TRPV1 and enduringly reduced thermal hyperalgesia and mechanical allodynia caused by inflammation, nerve injury and pronociceptive receptor activation. This included inhibitory effects on lysophosphatidic acid (LPA), purinergic (ATP), bradykinin and protease activated (thrombin) receptors. Conversely, PIP2 levels were significantly elevated in DRG from Pap−/− mice and this correlated with enhanced thermal hyperalgesia and mechanical allodynia in Pap−/− mice. To directly test the importance of PIP2 in nociception, we intrathecally injected PIP2 into mice. This transiently (2 hr) elevated PIP2 levels in lumbar DRG and transiently (2 hr) enhanced thermosensation. Additionally, thermal hyperalgesia and mechanical allodynia were enduringly enhanced when PIP2 levels were elevated coincident with injury/pronociceptive receptor stimulation. Nociceptive sensitization was not affected if PIP2 levels were elevated in the absence of ongoing pronociceptive receptor stimulation. Taken together, our data suggest that PIP2 levels in DRG directly influence thermosensation and the magnitude of nociceptive sensitization. Moreover, our data suggest there is an underlying “phosphoinositide tone” that can be manipulated by an adenosine-generating ectonucleotidase. This tone regulates how effectively acute nociceptive insults promote the transition to chronic pain

    A combined XAS and XRD Study of the High-Pressure Behaviour of GaAsO4 Berlinite

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    Combined X-ray absorption spectroscopy (XAS) and X-ray diffraction (XRD) experiments have been carried out on GaAsO4 (berlinite structure) at high pressure and room temperature. XAS measurements indicate four-fold to six-fold coordination changes for both cations. The two local coordination transformations occur at different rates but appear to be coupled. A reversible transition to a high pressure crystalline form occurs around 8 GPa. At a pressure of about 12 GPa, the system mainly consists of octahedral gallium atoms and a mixture of arsenic in four-fold and six-fold coordinations. A second transition to a highly disordered material with both cations in six-fold coordination occurs at higher pressures and is irreversible.Comment: 8 pages, 5 figures, LaTeX2

    Feasibility studies of the time-like proton electromagnetic form factor measurements with PANDA at FAIR

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    The possibility of measuring the proton electromagnetic form factors in the time-like region at FAIR with the \PANDA detector is discussed. Detailed simulations on signal efficiency for the annihilation of pˉ+p\bar p +p into a lepton pair as well as for the most important background channels have been performed. It is shown that precision measurements of the differential cross section of the reaction pˉ+pe++e\bar p +p \to e^++ e^- can be obtained in a wide angular and kinematical range. The individual determination of the moduli of the electric and magnetic proton form factors will be possible up to a value of momentum transfer squared of q214q^2\simeq 14 (GeV/c)2^2. The total pˉ+pe++e\bar p +p\to e^++e^- cross section will be measured up to q228q^2\simeq 28 (GeV/c)2^2. The results obtained from simulated events are compared to the existing data. Sensitivity to the two photons exchange mechanism is also investigated.Comment: 12 pages, 4 tables, 8 figures Revised, added details on simulations, 4 tables, 9 figure
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