Plos One
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Painful diabetic neuropathy (PDN) is a common complication of diabetes mellitus and adversely affects the patients' quality of life. Evidence has accumulated that PDN is associated with hyperexcitability of peripheral nociceptive primary sensory neurons. However, the precise cellular mechanism underlying PDN remains elusive. ⋯ Diabetes caused a prominent enhancement of I(NaT) and a decrease of potassium currents, especially slowly inactivating potassium currents (I(AS)); these effects were completely reversed by GAS in a dose-dependent manner. Furthermore, changes in activation and inactivation kinetics of I(NaT) and total potassium current as well as I(AS) currents induced by STZ were normalized by GAS. This study provides a clear cellular basis for the peripheral analgesic action of gastrodin for the treatment of chronic pain, including PDN.
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Southeast Asian deforestation rates are among the world's highest and threaten to drive many forest-dependent species to extinction. Climate change is expected to interact with deforestation to amplify this risk. Here we examine whether regional incentives for sustainable forest management will be effective in improving threatened mammal conservation, in isolation and when combined with global climate change mitigation. ⋯ We find strong quantitative support for the Sabah government's proposal to implement sustainable forest management in all its forest reserves during the current decade; failure to do so could result in a 40 to 80 per cent regional decline in orangutan abundance by 2100. The Sabah orangutan is just one (albeit iconic) example of a forest-dependent species that stands to benefit from sustainable forest management, which promotes conservation of existing forests.
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While diabetes mellitus (DM) is a known risk factor for tuberculosis, the prevalence among TB patients in India is unknown. Routine screening of TB patients for DM may be an opportunity for its early diagnosis and improved management and might improve TB treatment outcomes. We conducted a cross-sectional survey of TB patients registered from June-July 2011 in the state of Kerala, India, to determine the prevalence of DM. ⋯ Nearly half of TB patients in Kerala have DM, and approximately half of these patients were newly-diagnosed during this survey. Routine screening of TB patients for DM using HbA1c yielded a large number of DM cases and offered earlier management opportunities which may improve TB and DM outcomes. However, the most cost-effective ways of DM screening need to be established by futher operational research.
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Extracellular matrix (ECM) integrity in the central nervous system (CNS) is essential for neuronal homeostasis. Signals from the ECM are transmitted to neurons through integrins, a family of cell surface receptors that mediate cell attachment to ECM. We have previously established a causal link between the activation of the matrix metalloproteinase-9 (MMP-9), degradation of laminin in the ECM of retinal ganglion cells (RGCs), and RGC death in a mouse model of retinal ischemia-reperfusion injury (RIRI). ⋯ Finally, in vivo after RIRI, we observed an up-regulation of MMP-9, proteolytic degradation of laminin, decreased RGC expression of β1 integrin, FAK and Akt dephosphorylation, and reduced expression of the pro-survival molecule bcl-xL in the period preceding RGC apoptosis. RGC death was prevented, in the context of laminin degradation, by maintaining β1 integrin activation with agonist antibodies. Thus, disruption of homeostatic RGC-laminin interaction and signaling leads to cell death after retinal ischemia, and maintaining integrin activation may be a therapeutic approach to neuroprotection.
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Consistent resting brain activity patterns have been repeatedly demonstrated using measures derived from resting BOLD fMRI data. While those metrics are presumed to reflect underlying spontaneous brain activity (SBA), it is challenging to prove that association because resting BOLD fMRI metrics are purely model-free and scale-free variables. Cerebral blood flow (CBF) is typically closely coupled to brain metabolism and is used as a surrogate marker for quantifying regional brain function, including resting function. ⋯ Both ReHo and ALFF were found to be reliably correlated with CBF in most of brain cortex. None of the assessed SBA measures was correlated with whole brain mean CBF. These findings suggest that resting BOLD fMRI-derived measures are coupled with regional CBF and are therefore linked to regional SBA.