Plos One
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The phenotype of large diameter sensory afferent neurons changes in several models of neuropathic pain. We asked if similar changes also occur in "functional" pain syndromes. ⋯ Low pH leads to changes in several electrical properties of MSA, including initiation of ectopic action potentials which could propagate centrally but could also invade the peripheral endings causing glutamate release and activation of nearby nociceptors within the spindle capsule. This peripheral drive could contribute both to the transition to, and maintenance of, persistent muscle pain as seen in some "functional" pain syndromes.
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Cigarette smokers have an increased risk of infectious diseases involving the respiratory tract. Some effects of smoking on specific respiratory tract bacteria have been described, but the consequences for global airway microbial community composition have not been determined. Here, we used culture-independent high-density sequencing to analyze the microbiota from the right and left nasopharynx and oropharynx of 29 smoking and 33 nonsmoking healthy asymptomatic adults to assess microbial composition and effects of cigarette smoking. ⋯ Within airway habitats, microbiota from smokers were significantly more diverse than nonsmokers and clustered separately. The distributions of several genera were systematically altered by smoking in both the oro- and nasopharynx, and there was an enrichment of anaerobic lineages associated with periodontal disease in the oropharynx. These results indicate that distinct regions of the human upper respiratory tract contain characteristic microbial communities that exhibit disordered patterns in cigarette smokers, both in individual components and global structure, which may contribute to the prevalence of respiratory tract complications in this population.
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General anesthesia is routinely used as a surgical procedure and its safety has been endorsed by clinical outcomes; however, its effects at the molecular level have not been elucidated. General anesthetics influence glucose metabolism in the brain. However, the effects of anesthetics on brain metabolites other than those related to glucose have not been well characterized. We used a pattern recognition analysis of proton nuclear magnetic resonance spectra to visualize the changes in holistic brain metabolic phenotypes in response to the widely used intravenous anesthetic propofol and the volatile anesthetic isoflurane. ⋯ The results of the present study showed that propofol and isoflurane exerted differential effects on holistic brain metabolism under anesthesia.
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Reduced TOR signaling has been shown to significantly increase lifespan in a variety of organisms [1], [2], [3], [4]. It was recently demonstrated that long-term treatment with rapamycin, an inhibitor of the mTOR pathway[5], or ablation of the mTOR target p70S6K[6] extends lifespan in mice, possibly by delaying aging. Whether inhibition of the mTOR pathway would delay or prevent age-associated disease such as AD remained to be determined. ⋯ Our data suggest that inhibition of mTOR by rapamycin, an intervention that extends lifespan in mice, can slow or block AD progression in a transgenic mouse model of the disease. Rapamycin, already used in clinical settings, may be a potentially effective therapeutic agent for the treatment of AD.
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Editorial peer review is universally used but little studied. We examined the relationship between external reviewers' recommendations and the editorial outcome of manuscripts undergoing external peer-review at the Journal of General Internal Medicine (JGIM). ⋯ Reviewers at JGIM agreed on recommendations to reject vs. accept/revise at levels barely beyond chance, yet editors placed considerable weight on reviewers' recommendations. Efforts are needed to improve the reliability of the peer-review process while helping editors understand the limitations of reviewers' recommendations.