A complex multimodal activity intervention to reduce the risk of dementia in mild cognitive impairment - ThinkingFit: : pilot and feasibility study for a randomized controlled trial

© 2014 Dannhauser et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The version of record, Thomas M. Dannhauser, Martin Cleverly, Tim J. Whitfield, Ben (C) Fletcher, and Tim Stevens, 'A complex multimodal activity intervention to reduce the risk of dementia in mild cognitive impairment - ThinkingFit: pilot and feasibility study for a randomized controlled trial', BMC Psychiatry, 2014, 14: 129, is available online via doi: 10.1186/1471-244X-14-129Dementia affects 35 million people worldwide and is currently incurable. Many cases may be preventable because regular participation in physical, mental and social leisure activities during middle age is associated with up to 47% dementia risk reduction. However, the majority of middle-aged adults are not active enough. MCI is therefore a clear target for activity interventions aimed at reducing dementia risk. An active lifestyle during middle age reduces dementia risk but it remains to be determined if increased activity reduces dementia risk when MCI is already evident. Before this can be investigated conclusively, complex multimodal activity programmes are required that (1) combine multiple health promoting activities, (2) engage people with MCI, and (3) result in sufficient adherence ratesPeer reviewedFinal Published versio

Exploiting notochord cells for stem cell-based regeneration of the intervertebral disc

The nucleus pulposus is an avascular and aneural tissue that has significant influence on the homeostasis and overall function of the intervertebral disc. The nucleus pulposus is comprised of a heterogeneous population of cells including large notochord cells and smaller chondrocyte-like cells. Loss of notochord cells has been correlated with the pathogenesis of disc degeneration and consequently, it has been hypothesized that regeneration of the disc could be mediated by notochord cells. Attempts to grow and expand notochord cells in vitro have thus far been limited by cell availability and ineffective culturing methodologies. As a result, co-culturing techniques have been developed in order to exploit notochord-derived signals for the differentiation of proliferative mesenchymal stem cells. A recent study by Korecki et al. has demonstrated that notochord cell conditioned medium has the ability to differentiate mesenchymal stem cells toward a nucleus pulposus-like fate, producing high levels of glycosaminoglycans and type III collagen. These findings suggest that growth factors and other soluble proteins may be able to stimulate endogenous IVD tissue maintenance in vivo. While this study advances our understanding of intervertebral disc cell-cell interactions, limitations remain in our ability to determine the phenotype of terminally differentiated cells within the nucleus pulposus (ie mature notochord cells) and therefore assess the relevance of differentiated mesenchymal stem cells for disc regeneration. In order for the field to progress, elucidation of the notochord phenotype remains of utmost importance

Interactions between Blood-Borne Streptococcus pneumoniae and the Blood-Brain Barrier Preceding Meningitis

<p>Streptococcus pneumoniae (the pneumococcus) is a Gram-positive bacterium and the predominant cause of bacterial meningitis. Meningitis is thought to occur as the result of pneumococci crossing the blood-brain barrier to invade the Central Nervous System (CNS); yet little is known about the steps preceding immediate disease development. To study the interactions between pneumococci and the vascular endothelium of the blood-brain barrier prior to meningitis we used an established bacteremia-derived meningitis model in combination with immunofluorescent imaging. Brain tissue of mice infected with S. pneumoniae strain TIGR4, a clinical meningitis isolate, was investigated for the location of the bacteria in relation to the brain vasculature in various compartments. We observed that S. pneumoniae adhered preferentially to the subarachnoid vessels, and subsequently, over time, reached the more internal cerebral areas including the cerebral cortex, septum, and choroid plexus. Interestingly, pneumococci were not detected in the choroid plexus till 8 hours-post infection. In contrast to the lungs, little to no leukocyte recruitment to the brain was observed over time, though Iba-1 and GFAP staining showed that microglia and astrocytes were activated as soon as 1 hour post-infection. Our results imply that i) the local immune system of the brain is activated immediately upon entry of bacteria into the bloodstream and that ii) adhesion to the blood brain barrier is spatiotemporally controlled at different sites throughout the brain. These results provide new information on these two important steps towards the development of pneumococcal meningitis.</p>