Long-term use of motion-based video games in care home settings

Recent research suggests that motion-based video games have the potential to provide both mental and physical stimulation for older adults in residential care. However, little research has explored the practical challenges and opportunities that arise from integrating these games within existing schedules of activities in these contexts. In our work, we report on a qualitative enquiry that was conducted over a three month period at two long-term care facilities. Findings suggest that older adults enjoyed playing video games, and that games can be a valuable means of re-introducing challenge in late life, but that the impact of age-related changes and impairment can influence people’s ability to engage with games in a group setting. We outline core challenges in the design for care context and discuss implications of our work regarding the suitability of games as a self-directed leisure activity

Cyclic 5-membered disulfides are not selective substrates of thioredoxin reductase, but are opened nonspecifically

The cyclic five-membered disulfide 1,2-dithiolane has been widely used in chemical biology and in redox probes. Contradictory reports have described it either as nonspecifically reduced in cells, or else as a highly specific substrate for thioredoxin reductase (TrxR). Here we show that 1,2-dithiolane probes, such as “TRFS” probes, are nonspecifically reduced by thiol reductants and redox-active proteins, and their cellular performance is barely affected by TrxR inhibition or knockout. Therefore, results of cellular imaging or inhibitor screening using 1,2-dithiolanes should not be interpreted as reflecting TrxR activity, and previous studies may need re-evaluation. To understand 1,2-dithiolanes’ complex behaviour, probe localisation, environment-dependent fluorescence, reduction-independent ring-opening polymerisation, and thiol-dependent cellular uptake must all be considered; particular caution is needed when co-applying thiophilic inhibitors. We present a general approach controlling against assay misinterpretation with reducible probes, to ensure future TrxR-targeted designs are robustly evaluated for selectivity, and to better orient future research

Destruction of Dopaminergic Neurons in the Midbrain by 6-Hydroxydopamine Decreases Hippocampal Cell Proliferation in Rats: Reversal by Fluoxetine

Background Non-motor symptoms (e.g., depression, anxiety, and cognitive deficits) in patients with Parkinson disease (PD) precede the onset of the motor symptoms. Although these symptoms do not respond to pharmacological dopamine replacement therapy, their precise pathological mechanisms are currently unclear. The present study was undertaken to examine whether the unilateral 6-hydroxydopamine (6-OHDA) lesion to the substantia nigra pars compacta (SNc), which represents a model of long-term dopaminergic neurotoxicity, could affect cell proliferation in the adult rat brain. Furthermore, we examined the effects of the selective serotonin reuptake inhibitor (SSRI) fluoxetine and the selective noradrenaline reuptake inhibitor maprotiline on the reduction in cell proliferation in the subgranular zone (SGZ) by the unilateral 6-OHDA lesion. Methodology/Principal Findings A single unilateral injection of 6-OHDA into the rat SNc resulted in an almost complete loss of tyrosine hydroxylase (TH) immunoreactivity in the striatum and SNc, as well as in reductions of TH-positive cells and fibers in the ventral tegmental area (VTA). On the other hand, an injection of vehicle alone showed no overt change in TH immunoreactivity. A unilateral 6-OHDA lesion to SNc significantly decreased cell proliferation in the SGZ ipsilateral to the 6-OHDA lesion, but not in the contralateral SGZ or the subventricular zone (SVZ), of rats. Furthermore, subchronic (14 days) administration of fluoxetine (5 mg/kg/day), but not maprotiline significantly attenuated the reduction in cell proliferation in the SGZ by unilateral 6-OHDA lesion. Conclusions/Significance The present study suggests that cell proliferation in the SGZ of the dentate gyrus might be, in part, under dopaminergic control by SNc and VTA, and that subchronic administration of fluoxetine reversed the reduction in cell proliferation in the SGZ by 6-OHDA. Therefore, SSRIs such as fluoxetine might be potential therapeutic drugs for non-motor symptoms as well as motor symptoms in patients with PD, which might be associated with the reduction in cell proliferation in the SGZ

The effects of reminiscence on psychological well-being in older adults: a meta-analysis.

This paper presents the results of a meta-analysis to assess the effectiveness of reminiscence on psychological well-being across different target groups and treatment modalities. Fifteen controlled outcome studies were included. An overall effect size of 0.54 was found, indicating a moderate influence of reminiscence on life-satisfaction and emotional well-being in older adults. Life-review was found to have significantly greater effect on psychological well-being than simple reminiscence. In addition, reminiscence had significantly greater effect on community-dwelling adults than adults living in nursing homes or residential care. Other characteristics of participants or interventions were not found to moderate effects. It is concluded that reminiscence in general, but especially life review, are potentially effective methods for the enhancement of psychological well-being in older adults. However, a replication of effectiveness studies of the well-defined protocols is now warranted. © 2007 Taylor & Francis

Structural and functional characterization of Plasmodium falciparum nicotinic acid mononucleotide adenylyltransferase

Nicotinic acid mononucleotide adenylyltransferase (NaMNAT) is an indispensable enzyme for the synthesis of NAD and NAD phosphate. It catalyzes the adenylylation of nicotinic acid mononucleotide (NaMN) to yield nicotinic acid adenine dinucleotide (NaAD). Since NAD(H) and NAD phosphate(H) are essentially involved in metabolic and redox regulatory reactions, NaMNAT is an attractive drug target in the fight against bacterial and parasitic infections. Notably, NaMNAT of the malaria parasite Plasmodium falciparum possesses only 20% sequence identity with the homologous human enzyme. Here, we present for the first time the two X-ray structures of P. falciparum NaMNAT (PfNaMNAT)—in the product-bound state with NaAD and complexed with an α,β-non-hydrolizable ATP analog—the structures were determined to a resolution of 2.2 Å and 2.5 Å, respectively. The overall architecture of PfNaMNAT was found to be more similar to its bacterial homologs than its human counterparts although the PPHK motif conserved in bacteria is missing. Furthermore, PfNaMNAT possesses two cysteine residues within the active site that have not been described for any other NaMNATase so far and are likely to be involved in redox regulation of PfNaMNAT activity. Enzymatic studies and surface plasmon resonance data reveal that PfNaMNAT is capable of utilizing NaMN and nicotinamide mononucleotide with a slight preference for NaMN. Surprisingly, a comparison with the active site of Escherichia coli NaMNAT showed very similar architectures, despite different substrate preferences

Targeting b-catenin dependent Wnt signaling via peptidomimetic inhibitors in murine chondrocytes and OA cartilage

Objective: The canonical Wnt signaling pathway has been shown to be involved in regulating chondrocyte hypertrophic differentiation during Osteoarthritis (OA). The aim of this study was to test the therapeutic potential of two stapled peptide canonical Wnt inhibitors – SAH-Bcl9 and StAx-35R – in preventing Wnt induced cartilage changes in OA. Methods: Primary neonatal murine chondrocytes and cartilage explants from OA patients undergoing total joint replacement for knee OA, were used for microscopy to determine matrix and cell penetrating capacity of fluorescein isothiocyanate FITC-tagged SAH-Bcl9 and StAx-35R peptides. T cell factor/lymphoid enhancer-binding factor (TCF/LEF) reporter assays were used to monitor the inhibition of Wnt3a induced β-catenin signaling by each peptide. Changes in chondrocyte phenotypic marker gene expression were analyzed by qRT PCR. Results: Both peptides localized intercellular in primary murine chondrocytes and cartilage explants. They inhibited Wnt3a induced TCF/LEF promoter activity in primary murine chondrocytes. Both inhibitors did not rescue Wnt3a altered expression of chondrocyte phenotypic genes (Sox9, Col2a1, Acan) and hypertrophy marker gene (Col10a1) at high doses (100 ng/ml). Upon application of 10 ng/ml Wnt3a, StAx-35R partially reversed the Wnt effect on Sox9 and Col2a1 gene expression. Both peptides, however, reversed the downregulation of SOX9 and aggrecan (ACAN), and decrease of COL10A1 gene expression in preserved human OA cartilage explants. Conclusion: These data indicate that blockade of canonical Wnt signaling might be a therapeutic strategy to treat early OA cases and protect further cartilage degradation by preventing chondrocyte hypertrophic differentiation