Articles: function.
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A myriad of studies have argued that tactile sensibility is underpinned exclusively by large myelinated mechanoreceptors. However, the functional significance of their slow-conducting counterparts, termed C-low threshold mechanoreceptors (C-LTMRs), remains largely unexplored. We recently showed the emergence of brush- and vibration-evoked allodynia in human hairy and glabrous skin during background muscle pain. The allodynia persisted following the preferential blockade of myelinated fibres but was abolished by the preferential blockade of cutaneous C fibres, thereby suggesting a pathway involving hairy skin C-LTMRs and their functional counterparts in glabrous skin in this phenomenon. In the present study, we tested the effects of preferential A- and C-fibre conduction blocks and pharmacological blockade of T-type calcium channel Cav3.2 (expressed selectively on small-fibre LTMRs) on monofilament detection thresholds in healthy participants by compression, low-dose intradermal anaesthesia (xylocaine 0.25 %) and selective T-channel antagonist, TTA-A2. ⋯ These observations suggest that C-LTMRs need not be regarded as a redundant tactile system, but appear to complement normal large-myelinated-fibre tactile function. Convergent findings in glabrous and hairy skin lend support for an underlying system of innocuous mechanoreception with Cav3.2-expressing unmyelinated fibres.
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Anesthesia and analgesia · Aug 2015
Mechanistic Modeling of the Effects of Acidosis on Thrombin Generation.
Acidosis, a frequent complication of trauma and complex surgery, results from tissue hypoperfusion and IV resuscitation with acidic fluids. While acidosis is known to inhibit the function of distinct enzymatic reactions, its cumulative effect on the blood coagulation system is not fully understood. Here, we use computational modeling to test the hypothesis that acidosis delays and reduces the amount of thrombin generation in human blood plasma. Moreover, we investigate the sensitivity of different thrombin generation parameters to acidosis, both at the individual and population level. ⋯ Acidosis affected all quantitative parameters of thrombin and TAT generation. While maximum slope of the thrombin curve showed the highest sensitivity to acidosis at the individual-subject level, it may be outperformed by CT, thrombin peak time, and prothrombin time as an indicator of acidosis at the subject-group level.
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Blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) has been used to study the effects of anesthetic agents on correlated intrinsic neural activity. Previous studies have focused primarily on intravenous agents. The authors studied the effects of sevoflurane, an inhaled anesthetic. ⋯ Sevoflurane-induced unconsciousness is associated with both globally reduced BOLD signal amplitudes and selectively reduced functional connectivity within cortical networks associated with consciousness (default mode network) and orienting to salient external stimuli (ventral attention network). Scrupulous attention to minimizing the impact of head motion artifact is critical in fMRI studies using anesthetic agents.
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Sepsis is characterized by an inappropriate systemic inflammatory response and bacteremia that promote multiorgan failure and mortality. Sphingosine 1-phosphate receptor 2 (S1PR2) modulates endotoxin-induced inflammation in endothelium. However, as a highly expressed S1P receptor in macrophages, its role in regulating macrophage response to bacterial infection remains unclear. ⋯ This study implies that S1PR2, as a critical receptor in macrophage, impairs phagocytosis and antimicrobial defense in the pathogenesis of sepsis. Interventions targeting S1PR2 signaling may serve as promising therapeutic approaches for sepsis.
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The timing of physical therapy (PT) services and its association with later function and pain are not clear, especially in older adults. ⋯ We found that among older adults presenting to their primary care providers for a new episode of back pain, early referral to PT resulted in no or minimal differences in pain, function, or health-related quality at 3, 6, or 12 months compared with a matched group that did not receive early PT. Secondary analysis show that patients initiating early PT may be somewhat more likely to experience 50% improvement in function at 12 months.