Physical activity to improve cognition in older adults: can physical activity programs enriched with cognitive challenges enhance the effects? A systematic review and meta-analysis

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The Cyprinodon variegatus genome reveals gene expression changes underlying differences in skull morphology among closely related species

Genes in durophage intersection set at 15 dpf. This is a comma separated table of the genes in the 15 dpf durophage intersection set. Given are edgeR results for each pairwise comparison. Columns indicating whether a gene is included in the intersection set at a threshold of 1.5 or 2 fold are provided. (CSV 13 kb

Constitutive Expression of TNF-Related Activation-Induced Cytokine (TRANCE)/Receptor Activating NF-κB Ligand (RANK)-L by Rat Plasmacytoid Dendritic Cells

Plasmacytoid dendritic cells (pDCs) are a subset of DCs whose major function relies on their capacity to produce large amount of type I IFN upon stimulation via TLR 7 and 9. This function is evolutionary conserved and place pDC in critical position in the innate immune response to virus. Here we show that rat pDC constitutively express TNF-related activation-induced cytokine (TRANCE) also known as Receptor-activating NF-κB ligand (RANKL). TRANCE/RANKL is a member of the TNF superfamily which plays a central role in osteoclastogenesis through its interaction with its receptor RANK. TRANCE/RANK interaction are also involved in lymphoid organogenesis as well as T cell/DC cross talk. Unlike conventional DC, rat CD4high pDC were shown to constitutively express TRANCE/RANKL both at the mRNA and the surface protein level. TRANCE/RANKL was also induced on the CD4low subsets of pDC following activation by CpG. The secreted form of TRANCE/RANKL was also produced by rat pDC. Of note, levels of mRNA, surface and secreted TRANCE/RANKL expression were similar to that observed for activated T cells. TRANCE/RANKL expression was found on pDC in all lymphoid organs as well blood and BM with a maximum expression in mesenteric lymph nodes. Despite this TRANCE/RANKL expression, we were unable to demonstrate in vitro osteoclastogenesis activity for rat pDC. Taken together, these data identifies pDC as novel source of TRANCE/RANKL in the immune system

Osteoclast Activated FoxP3+ CD8+ T-Cells Suppress Bone Resorption in vitro

BACKGROUND: Osteoclasts are the body's sole bone resorbing cells. Cytokines produced by pro-inflammatory effector T-cells (T(EFF)) increase bone resorption by osteoclasts. Prolonged exposure to the T(EFF) produced cytokines leads to bone erosion diseases such as osteoporosis and rheumatoid arthritis. The crosstalk between T-cells and osteoclasts has been termed osteoimmunology. We have previously shown that under non-inflammatory conditions, murine osteoclasts can recruit naïve CD8 T-cells and activate these T-cells to induce CD25 and FoxP3 (Tc(REG)). The activation of CD8 T-cells by osteoclasts also induced the cytokines IL-2, IL-6, IL-10 and IFN-γ. Individually, these cytokines can activate or suppress osteoclast resorption. PRINCIPAL FINDINGS: To determine the net effect of Tc(REG) on osteoclast activity we used a number of in vitro assays. We found that Tc(REG) can potently and directly suppress bone resorption by osteoclasts. Tc(REG) could suppress osteoclast differentiation and resorption by mature osteoclasts, but did not affect their survival. Additionally, we showed that Tc(REG) suppress cytoskeletal reorganization in mature osteoclasts. Whereas induction of Tc(REG) by osteoclasts is antigen-dependent, suppression of osteoclasts by Tc(REG) does not require antigen or re-stimulation. We demonstrated that antibody blockade of IL-6, IL-10 or IFN-γ relieved suppression. The suppression did not require direct contact between the Tc(REG) and osteoclasts. SIGNIFICANCE: We have determined that osteoclast-induced Tc(REG) can suppress osteoclast activity, forming a negative feedback system. As the CD8 T-cells are activated in the absence of inflammatory signals, these observations suggest that this regulatory loop may play a role in regulating skeletal homeostasis. Our results provide the first documentation of suppression of osteoclast activity by CD8 regulatory T-cells and thus, extend the purview of osteoimmunology

The effect of osteoprotegerin administration on the intra-tibial growth of the osteoblastic LuCaP 23.1 prostate cancer xenograft

Osteoprotegerin (OPG) plays a central role in controlling bone resorption. Exogenous administration of OPG has been shown to be effective in preventing osteolysis and limiting the growth of osteolytic metastasis. The objective of this study was to investigate the effects of OPG on osteoblastic prostate cancer (CaP) metastases in an animal model. LuCaP 23.1 cells were injected intra-tibially and Fc-OPG (6.0 mg/kg) was administered subcutaneously three times a week starting either 24 hours prior to cell injection (prevention regimen) or at 4 weeks post-injection (treatment regimen). Changes in bone mineral density at the tumor site were determined by dual x-ray absorptiometry. Tumor growth was monitored by evaluating serum prostate specific antigen (PSA). Fc-OPG did not inhibit establishment of osteoblastic bone lesions of LuCaP 23.1, but it decreased growth of the tumor cells, as determined by decreases in serum PSA levels of 73.0 ± 44.3% ( P < 0.001) and 78.3 ± 25.3% ( P < 0.001) under the treatment and prevention regimens, respectively, compared to the untreated tumor-bearing animals. Administration of Fc-OPG decreased the proliferative index by 35.0% ( P = 0.1838) in the treatment group, and 75.2% ( P = 0.0358) in the prevention group. The results of this study suggest a potential role for OPG in the treatment of established osteoblastic CaP bone metastases.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42587/1/10585_2004_Article_2869.pd

Doctoral dissertation management at the University of Granada

La Universidad de Granada (UGR) cuenta desde 2005 con el Proyecto DIGIBUG, un modelo que mejora la visibilidad y accesibilidad de su producción científica, con el objetivo de acercarla a los investigadores, doctorandos, estudiantes y a la sociedad en general, ofreciendo una nueva perspectiva de difusión, utilización, citación y seguimiento de las diferentes líneas de investigación existentes en la UGR.Since 2005 the University of Granada (UGR) has implemented the DIGIBUG Project, which aims to improve visibility of and access to its scientific output so as to bring it closer to researchers, doctorate and undergraduate students and society in general, providing a new way of disseminating, using, citing and following up the different lines of enquiry at the UGR

Does multicomponent physical exercise with simultaneous cognitive training boost cognitive performance in older adults? A 6-month rando&shy;mized controlled trial with a 1-year follow-up

Patrick Eggenberger,1 Vera Schumacher,2,3 Marius Angst,1 Nathan Theill,4,5 Eling D de Bruin1,6,7 1Institute of Human Movement Sciences and Sport, Department of Health Sciences and Technology, ETH Zurich, 2Department of Gerontopsychology and Gerontology, 3University Research Priority Program &ldquo;Dynamics of Healthy Aging&rdquo;, University of Zurich, Zurich, 4Division of Psychiatry Research, University of Zurich, Schlieren, 5Center for Gerontology, University of Zurich, Zurich, Switzerland; 6CAPHRI School for Public Health and Primary Care, Department of Epidemiology, 7Centre for Evidence Based Physiotherapy, Maastricht University, Maastricht, the Netherlands Background: Cognitive impairment is a health problem that concerns almost every second elderly person. Physical and cognitive training have differential positive effects on cognition, but have been rarely applied in combination. This study evaluates synergistic effects of multicomponent physical exercise complemented with novel simultaneous cognitive training on cognition in older adults. We hypothesized that simultaneous cognitive&ndash;physical components would add training specific cognitive benefits compared to exclusively physical training.Methods: Seniors, older than 70&nbsp;years, without cognitive impairment, were randomly assigned to either: 1) virtual reality video game dancing (DANCE), 2) treadmill walking with simultaneous verbal memory training (MEMORY), or 3) treadmill walking (PHYS). Each program was complemented with strength and balance exercises. Two 1-hour training sessions per week over 6&nbsp;months were applied. Cognitive performance was assessed at baseline, after 3 and 6&nbsp;months, and at 1-year follow-up. Multiple regression analyses with planned comparisons were calculated.Results: Eighty-nine participants were randomized to the three groups initially, 71 completed the training, while 47 were available at 1-year follow-up. Advantages of the simultaneous cognitive&ndash;physical programs were found in two dimensions of executive function. &ldquo;Shifting attention&rdquo; showed a time&times;intervention interaction in favor of DANCE/MEMORY versus PHYS (F[2, 68] =1.95, trend P=0.075, r=0.17); and &ldquo;working memory&rdquo; showed a time&times;intervention interaction in favor of DANCE versus MEMORY (F[1, 136] =2.71, trend P=0.051, R2=0.006). Performance improvements in executive functions, long-term visual memory (episodic memory), and processing speed were maintained at follow-up in all groups.Conclusion: Particular executive functions benefit from simultaneous cognitive&ndash;physical training compared to exclusively physical multicomponent training. Cognitive&ndash;physical training programs may counteract widespread cognitive impairments in the elderly. Keywords: elderly, executive function, transfer, cognitive impairment, dance, video gam

Multicomponent physical exercise with simultaneous cognitive training to enhance dual-task walking of older adults: a secondary analysis of a 6-month randomized controlled trial with 1-year follow-up

Patrick Eggenberger,1 Nathan Theill,2,3 Stefan Holenstein,1 Vera Schumacher,4,5 Eling D de Bruin1,6,7 1Department of Health Sciences and Technology, Institute of Human Movement Sciences and Sport, ETH Zurich, 2Division of Psychiatry Research, 3Center for Gerontology, 4Department of Gerontopsychology and Gerontology, 5University Research Priority Program &ldquo;Dynamics of Healthy Aging&rdquo;, University of Zurich, Zurich, Switzerland; 6Department of Epidemiology, CAPHRI School for Public Health and Primary Care, 7Centre for Evidence Based Physiotherapy, Maastricht University, Maastricht, the Netherlands Background: About one-third of people older than 65&nbsp;years fall at least once a year. Physical exercise has been previously demonstrated to improve gait, enhance physical fitness, and prevent falls. Nonetheless, the addition of cognitive training components may potentially increase these effects, since cognitive impairment is related to gait irregularities and fall risk. We hypothesized that simultaneous cognitive&ndash;physical training would lead to greater improvements in dual-task (DT) gait compared to exclusive physical training.Methods: Elderly persons older than 70&nbsp;years and without cognitive impairment were randomly assigned to the following groups: 1) virtual reality video game dancing (DANCE), 2) treadmill walking with simultaneous verbal memory training (MEMORY), or 3) treadmill walking (PHYS). Each program was complemented with strength and balance exercises. Two 1-hour training sessions per week over 6&nbsp;months were applied. Gait variables, functional fitness (Short Physical Performance Battery, 6-minute walk), and fall frequencies were assessed at baseline, after 3&nbsp;months and 6&nbsp;months, and at 1-year follow-up. Multiple regression analyses with planned comparisons were carried out.Results: Eighty-nine participants were randomized to three groups initially; 71 completed the training and 47 were available at 1-year follow-up. DANCE/MEMORY showed a significant advantage compared to PHYS in DT costs of step time variability at fast walking (P=0.044). Training-specific gait adaptations were found on comparing DANCE and MEMORY: DANCE reduced step time at fast walking (P=0.007) and MEMORY reduced gait variability in DT and DT costs at preferred walking speed (both trend P=0.062). Global linear time effects showed improved gait (P&lt;0.05), functional fitness (P&lt;0.05), and reduced fall frequency (-77%, P&lt;0.001). Only single-task fast walking, gait variability at preferred walking speed, and Short Physical Performance Battery were reduced at follow-up (all P&lt;0.05 or trend).Conclusion: Long-term multicomponent cognitive&ndash;physical and exclusive physical training programs demonstrated similar potential to counteract age-related decline in physical functioning. Keywords: elderly, dance video game, gait, falls, functional fitness, detraining, se