Plos One
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Alzheimer's disease (AD) is the most frequent form of dementia among elderly. Despite the vast amount of literature on non-specific immune mechanisms in AD there is still little information about the potential antigen-specific immune response in this pathology. It is known that early stages of AD include β-amyloid (Aβ)- reactive antibodies production and inflammatory response. ⋯ On the other hand, the exposure of in vitro pre-stimulated lymphocytes to soluble Aβ peptides significantly enhanced the proliferative response of these cells which had also lead to increased levels of TNF, IL-10 and IL-6. We also proved that Aβ peptide-enhanced proliferative response of CD4(+)CD28(+) cells is autonomous and independent from disease status while being associated with the initial, ex vivo activation status of the CD4(+) cells. In conclusion, we suggest that the effect of Aβ peptides on the immune system of AD patients does not depend on the specific reactivity to Aβ epitope(s), but is rather a consequence of an unspecific modulation of the cell cycle dynamics and cytokine production by T cells, occurring simultaneously in a huge proportion of Aβ peptide-exposed T lymphocytes and affecting the immune system performance.
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Voltage-gated sodium channels (VGSCs) play a key role in the initiation and propagation of action potentials in neurons. Na(V)1.8 is a tetrodotoxin (TTX) resistant VGSC expressed in nociceptors, peripheral small-diameter neurons able to detect noxious stimuli. Na(V)1.8 underlies the vast majority of sodium currents during action potentials. ⋯ Moreover, treatments with methyl-β-cyclodextrin (MβCD) and 7-ketocholesterol (7KC) led to the dissociation between rafts and Na(V)1.8. By calcium imaging we demonstrated that the lack of association between rafts and Na(V)1.8 correlated with impaired neuronal excitability, highlighted by a reduction in the number of neurons able to conduct mechanically- and chemically-evoked depolarisations. These findings reveal the sub-cellular localisation of Na(V)1.8 in nociceptors and highlight the importance of the association between Na(V)1.8 and lipid rafts in the control of nociceptor excitability.
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Postoperative cognitive decline is a clinical syndrome. Volatile anesthetics are commonly used during surgery. It is conceivable that volatile anesthetics may contribute to postoperative cognitive decline. ⋯ However, isoflurane did not affect the cognitive functions of IL-1β deficient mice. Our results suggest that isoflurane impairs the learning but may not affect the recall of the aged rats. IL-1β may play an important role in this isoflurane effect.
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Musculoskeletal disorders increase the risk for absenteeism and work disability. However, the threshold when musculoskeletal pain intensity significantly increases the risk of sickness absence among different occupations is unknown. This study estimates the risk for long-term sickness absence (LTSA) from different pain intensities in the low back, neck/shoulder and knees among female healthcare workers in eldercare. ⋯ The threshold of pain intensity significantly increasing the risk for LTSA among female healthcare workers varies across body regions, with knee pain having the lowest threshold. This knowledge may be used in the prevention of LTSA among health care workers.
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A network measure called knotty-centrality is defined that quantifies the extent to which a given subset of a graph's nodes constitutes a densely intra-connected topologically central connective core. Using this measure, the knotty centre of a network is defined as a sub-graph with maximal knotty-centrality. A heuristic algorithm for finding subsets of a network with high knotty-centrality is presented, and this is applied to previously published brain structural connectivity data for the cat and the human, as well as to a number of other networks. The cognitive implications of possessing a connective core with high knotty-centrality are briefly discussed.