The effects of carer-delivered individual Cognitive Stimulation Therapy for people with dementia on carer wellbeing

Background Cognitive stimulation therapy has been developed to improve cognition and quality of life (QoL) for people with dementia. Little is known of the effects on carer wellbeing when individual cognitive stimulation therapy (iCST) is delivered by family carers. Aims • To investigate the effects of carer involvement in cognition-based interventions (CBIs) for people with dementia on carer wellbeing • To assess the effects of iCST for people with dementia on carer wellbeing Methods A meta-analysis review was performed. A multicentre randomised controlled trial (RCT) recruited 356 dyads of people with dementia and their carers. Dyads in the intervention group received iCST three times weekly over 25 weeks. A qualitative study recruited a subgroup of 23 dyads who completed iCST to take part in semi-structured interviews. Results The meta-analysis review indicates that carer involvement in CBIs may improve carers’ QoL with effect size Hedges’ g = 0.22; 95% CI of 0.02-0.42, p≤ 0.03 and reduce carers’ depressive symptoms with effect size Hedges’ g = 0.17; 95% CI of 0.02-0.32, p≤0.03. The findings of the RCT show that there are no effects of carer-delivered iCST on carers’ mental/physical health, mood and relationship quality with their relative. Carers randomised to receive iCST however reported an improvement in their health-related QoL with a mean difference of 0.06, 95% CI 0.01-0.10, p≤0.01 and less depressive symptoms when they completed more sessions. The qualitative results show that participating in iCST may be a useful tool that provides people with dementia and their carers with opportunities to enjoy mentally stimulating activities and stay active. Conclusion Carer involvement in CBI for people with dementia may improve carers’ QoL and reduce their depressive symptoms when they complete more sessions with their relative. The findings have important implications for developing interventions to support people with dementia and their carers

Tissue Engineering for Intervertebral Disk Degeneration

Many challenges confront intervertebral disk engineering owing to complexity and the presence of extraordinary stresses. Rebuilding a disk of native function could be useful for removal of the symptoms and correction of altered spine kinematics. Improvement in understanding of disk properties and techniques for disk engineering brings promise to the fabrication of a functional motion segment for the treatment of disk degeneration. Increasing sophistication of techniques available in biomedical sciences will bring its application into clinics. This review provides an account of current progress and challenges of intervertebral disk bioengineering and discusses means to move forward and toward bedside translation. © 2011.postprin

A novel therapeutic approach to cytokine modulation in articular inflammation using filarial nematode derived ES-62

Meeting abstract on a novel therapeutic approach to cytokine modulation in articular inflammation. Discovering safe, novel immunomodulators that are effective in RA is currently a major therapeutic objective. Long-term immune system deviation is most striking in the host-parasite relationship, in which microbes may coexist with a human host. ES-62 exhibited powerful immunomodulation of CIA, preventing initiation of inflammatory arthritis. Crucially, ES-62 suppressed even established disease. These effects were due to inhibition of cytokine release, specifically TNF-α, and reversal of collagen specific Th1 responses associated with reduced expression of IFN-γ. The physiologic relevance of these observations was confirmed, as ES-62 down-regulated the release of proinflammatory cytokines (TNF-α and IL-6) from patient-derived samples

Delivering mesenchymal stem cells in collagen microsphere carriers to rabbit degenerative disc - Reduced risk of osteophyte formation.

Mesenchymal stem cells (MSCs) have the potential to treat early intervertebral disc (IVD) degeneration. However, during intradiscal injection, the vast majority of cells leaked out even in the presence of hydrogel carrier. Recent evidence suggests that annulus puncture is associated with cell leakage and contributes to osteophyte formation, an undesirable side effect. This suggests the significance of developing appropriate carriers for intradiscal delivery of MSCs. We previously developed a collagen microencapsulation platform, which entraps MSCs in a solid microsphere consisting of collagen nanofiber meshwork. These solid yet porous microspheres support MSC attachment, survival, proliferation, migration, differentiation, and matrix remodeling. Here we hypothesize that intradiscal injection of MSCs in collagen microspheres will outperform that of MSCs in saline in terms of better functional outcomes and reduced side effects. Specifically, we induced disc degeneration in rabbits and then intradiscally injected autologous MSCs, either packaged within collagen microspheres or directly suspended in saline, into different disc levels. Functional outcomes including hydration index and disc height were monitored regularly until 6 months. Upon sacrifice, the involved discs were harvested for histological, biochemical, and biomechanical evaluations. MSCs in collagen microspheres showed advantage over MSCs in saline in better maintaining the dynamic mechanical behavior but similar performance in hydration and disc height maintenance and matrix composition. More importantly, upon examination of gross appearance, radiograph, and histology of IVD, delivering MSCs in collagen microspheres significantly reduced the risk of osteophyte formation as compared to that in saline. This work demonstrates the significance of using cell carriers during intradiscal injection of MSCs in treating disc degeneration.published_or_final_versio

Reconstitution of bone-like matrix in osteogenically differentiated mesenchymal stem cells-collagen constructs: a three-dimensional in vitro model to study hematopoietic stem cell niche

published_or_final_versio

Battery management system and control strategy for hybrid and electric vehicle

Author name used in this publication: K. W. E. ChengAuthor name used in this publication: K. DingAuthor name used in this publication: W. TingVersion of RecordPublishe

Simvastatin inhibits TLR8 signaling in primary human monocytes and spontaneous TNF production from rheumatoid synovial membrane cultures

Simvastatin has been shown to have anti-inflammatory effects that are independent of its serum cholesterol lowering action, but the mechanisms by which these anti-inflammatory effects are mediated have not been elucidated. To explore the mechanism involved, the effect of simvastatin on Toll-like receptor (TLR) signalling in primary human monocytes was investigated. A short pre-treatment with simvastatin dose-dependently inhibited the production of tumor necrosis factor-α (TNF) in response to TLR8 (but not TLRs 2, 4, or 5) activation. Statins are known inhibitors of the cholesterol biosynthetic pathway, but intriguingly TLR8 inhibition could not be reversed by addition of mevalonate or geranylgeranyl pyrophosphate; downstream products of cholesterol biosynthesis. TLR8 signalling was examined in HEK 293 cells stably expressing TLR8, where simvastatin inhibited IKKα/β phosphorylation and subsequent NF-κB activation without affecting the pathway to AP-1. Since simvastatin has been reported to have anti-inflammatory effects in RA patients and TLR8 signalling contributes to TNF production in human RA synovial tissue in culture, simvastatin was tested in these cultures. Simvastatin significantly inhibited the spontaneous release of TNF in this model which was not reversed by mevalonate. Together, these results demonstrate a hitherto unrecognized mechanism of simvastatin inhibition of TLR8 signalling that may in part explain its beneficial anti-inflammatory effects

Identifying Cis-Regulatory Sequences by Word Profile Similarity

Recognizing regulatory sequences in genomes is a continuing challenge, despite a wealth of available genomic data and a growing number of experimentally validated examples.We discuss here a simple approach to search for regulatory sequences based on the compositional similarity of genomic regions and known cis-regulatory sequences. This method, which is not limited to searching for predefined motifs, recovers sequences known to be under similar regulatory control. The words shared by the recovered sequences often correspond to known binding sites. Furthermore, we show that although local word profile clustering is predictive for the regulatory sequences involved in blastoderm segmentation, local dissimilarity is a more universal feature of known regulatory sequences in Drosophila.Our method leverages sequence motifs within a known regulatory sequence to identify co-regulated sequences without explicitly defining binding sites. We also show that regulatory sequences can be distinguished from surrounding sequences by local sequence dissimilarity, a novel feature in identifying regulatory sequences across a genome. Source code for WPH-finder is available for download at http://rana.lbl.gov/downloads/wph.tar.gz

Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin

Pathological processes involved in the initiation of rheumatoid synovitis remain unclear. We undertook the present study to identify immune and stromal processes that are present soon after the clinical onset of rheumatoid arthritis ( RA) by assessing a panel of T cell, macrophage, and stromal cell related cytokines and chemokines in the synovial fluid of patients with early synovitis. Synovial fluid was aspirated from inflamed joints of patients with inflammatory arthritis of duration 3 months or less, whose outcomes were subsequently determined by follow up. For comparison, synovial fluid was aspirated from patients with acute crystal arthritis, established RA and osteoarthritis. Rheumatoid factor activity was blocked in the synovial fluid samples, and a panel of 23 cytokines and chemokines measured using a multiplex based system. Patients with early inflammatory arthritis who subsequently developed RA had a distinct but transient synovial fluid cytokine profile. The levels of a range of T cell, macrophage and stromal cell related cytokines ( e. g. IL-2, IL-4, IL-13, IL-17, IL-15, basic fibroblast growth factor and epidermal growth factor) were significantly elevated in these patients within 3 months after symptom onset, as compared with early arthritis patients who did not develop RA. In addition, this profile was no longer present in established RA. In contrast, patients with non-rheumatoid persistent synovitis exhibited elevated levels of interferon-gamma at initiation. Early synovitis destined to develop into RA is thus characterized by a distinct and transient synovial fluid cytokine profile. The cytokines present in the early rheumatoid lesion suggest that this response is likely to influence the microenvironment required for persistent RA