332 research outputs found
Attitudes of Older Adults in a Group-Based Exercise Program Toward a Blended Intervention:A Focus-Group Study
Ageing is associated with a decline in daily functioning and mobility. A physically active life and physical exercise can minimize the decline of daily functioning and improve the physical-, psychological- and social functioning of older adults. Despite several advantages of group-based exercise programs, older adults participating in such interventions often do not meet the frequency, intensity or duration of exercises needed to gain health benefits. An exercise program that combines the advantages of group-based exercises led by an instructor with tailored home-based exercises can increase the effectiveness. Technology can assist in delivering a personalized program. The aim of the study was to determine the susceptibility of older adults currently participating in a nationwide group-based exercise program to such a blended exercise program. Eight focus-groups were held with adults of 55 years of age or older. Two researchers coded independently the remarks of the 30 participants that were included in the analysis according to the three key concepts of the Self Determination Theory: autonomy, competence and relatedness. The results show that maintaining self-reliance and keeping in touch with others were the main motives to participate in the weekly group-based exercises. Participants recognized benefits of doing additional home-based exercises, but had concerns regarding guidance, safety and motivation. Furthermore, some participants strongly rejected the idea to use technology to support them in doing exercises at home, but the majority was open to it. Insights are discussed how these findings can help design novel interventions that can increase the wellbeing of older adults and preserve an independent living.
Quality of life in couples living with Huntington’s disease: the role of patients’ and partners’ illness perceptions
Research suggests that chronically ill patients and their partners perceive illness differently, and that these differences have a negative impact on patients’ quality of life (QoL). This study assessed whether illness perceptions of patients with Huntington’s disease (HD) differ from those of their partners, and examined whether spousal illness perceptions are important for the QoL of the couples (n = 51 couples). Partners reported that their HD-patient spouses suffered more symptoms and experienced less control than the patients themselves reported. Illness perceptions of patients and partners correlated significantly with patient QoL. Partners’ beliefs in a long duration of the patients’ illness and less belief in cure, were associated with patient vitality scores. Suggestions for future research emphasize the importance of qualitative research approaches in combination with cognitive-behavioural approaches
WEE1 inhibition sensitizes osteosarcoma to radiotherapy
<p>Abstract</p> <p>Background</p> <p>The use of radiotherapy in osteosarcoma (OS) is controversial due to its radioresistance. OS patients currently treated with radiotherapy generally are inoperable, have painful skeletal metastases, refuse surgery or have undergone an intralesional resection of the primary tumor. After irradiation-induced DNA damage, OS cells sustain a prolonged G<sub>2 </sub>cell cycle checkpoint arrest allowing DNA repair and evasion of cell death. Inhibition of WEE1 kinase leads to abrogation of the G<sub>2 </sub>arrest and could sensitize OS cells to irradiation induced cell death.</p> <p>Methods</p> <p>WEE1 expression in OS was investigated by gene-expression data analysis and immunohistochemistry of tumor samples. WEE1 expression in OS cell lines and human osteoblasts was investigated by Western blot. The effect of WEE1 inhibition on the radiosensitivity of OS cells was assessed by cell viability and caspase activation analyses after combination treatment. The presence of DNA damage was visualized using immunofluorescence microscopy. Cell cycle effects were investigated by flow cytometry and WEE1 kinase regulation was analyzed by Western blot.</p> <p>Results</p> <p>WEE1 expression is found in the majority of tested OS tissue samples. Small molecule drug PD0166285 inhibits WEE1 kinase activity. In the presence of WEE1-inhibitor, irradiated cells fail to repair their damaged DNA, and show higher levels of caspase activation. The inhibition of WEE1 effectively abrogates the irradiation-induced G<sub>2 </sub>arrest in OS cells, forcing the cells into premature, catastrophic mitosis, thus enhancing cell death after irradiation treatment.</p> <p>Conclusion</p> <p>We show that PD0166285, a small molecule WEE1 kinase inhibitor, can abrogate the G<sub>2 </sub>checkpoint in OS cells, pushing them into mitotic catastrophe and thus sensitizing OS cells to irradiation-induced cell death. This suggests that WEE1 inhibition may be a promising strategy to enhance the radiotherapy effect in patients with OS.</p
Pichia pastoris regulates its gene-specific response to different carbon sources at the transcriptional, rather than the translational, level
Background: The methylotrophic, Crabtree-negative yeast Pichia pastoris is widely used as a heterologous protein production host. Strong inducible promoters derived from methanol utilization genes or constitutive glycolytic promoters are typically used to drive gene expression. Notably, genes involved in methanol utilization are not only repressed by the presence of glucose, but also by glycerol. This unusual regulatory behavior prompted us to study the regulation of carbon substrate utilization in different bioprocess conditions on a genome wide scale. Results: We performed microarray analysis on the total mRNA population as well as mRNA that had been fractionated according to ribosome occupancy. Translationally quiescent mRNAs were defined as being associated with single ribosomes (monosomes) and highly-translated mRNAs with multiple ribosomes (polysomes). We found that despite their lower growth rates, global translation was most active in methanol-grown P. pastoris cells, followed by excess glycerol- or glucose-grown cells. Transcript-specific translational responses were found to be minimal, while extensive transcriptional regulation was observed for cells grown on different carbon sources. Due to their respiratory metabolism, cells grown in excess glucose or glycerol had very similar expression profiles. Genes subject to glucose repression were mainly involved in the metabolism of alternative carbon sources including the control of glycerol uptake and metabolism. Peroxisomal and methanol utilization genes were confirmed to be subject to carbon substrate repression in excess glucose or glycerol, but were found to be strongly de-repressed in limiting glucose-conditions (as are often applied in fed batch cultivations) in addition to induction by methanol. Conclusions: P. pastoris cells grown in excess glycerol or glucose have similar transcript profiles in contrast to S. cerevisiae cells, in which the transcriptional response to these carbon sources is very different. The main response to different growth conditions in P. pastoris is transcriptional; translational regulation was not transcript-specific. The high proportion of mRNAs associated with polysomes in methanol-grown cells is a major finding of this study; it reveals that high productivity during methanol induction is directly linked to the growth condition and not only to promoter strength
Human platelet lysate as a fetal bovine serum substitute improves human adipose-derived stromal cell culture for future cardiac repair applications
Adipose-derived stromal cells (ASC) are promising candidates for cell therapy, for example to treat myocardial infarction. Commonly, fetal bovine serum (FBS) is used in ASC culturing. However, FBS has several disadvantages. Its effects differ between batches and, when applied clinically, transmission of pathogens and antibody development against FBS are possible. In this study, we investigated whether FBS can be substituted by human platelet lysate (PL) in ASC culture, without affecting functional capacities particularly important for cardiac repair application of ASC. We found that PL-cultured ASC had a significant 3-fold increased proliferation rate and a significantly higher attachment to tissue culture plastic as well as to endothelial cells compared with FBS-cultured ASC. PL-cultured ASC remained a significant 25% smaller than FBS-cultured ASC. Both showed a comparable surface marker profile, with the exception of significantly higher levels of CD73, CD90, and CD166 on PL-cultured ASC. PL-cultured ASC showed a significantly higher migration rate compared with FBS-cultured ASC in a transwell assay. Finally, FBS- and PL-cultured ASC had a similar high capacity to differentiate towards cardiomyocytes. In conclusion, this study showed that culturing ASC is more favorable in PL-supplemented medium compared with FBS-supplemented medium
Multidisciplinaire Richtlijn Probleemgedrag bij volwassenen met een verstandelijke beperking
Probleemgedrag komt regelmatig voor bij mensen met een verstandelijke beperking (VB). Het kan een grote impact hebben op de persoon zelf, diens familie en op anderen in de omgeving. Zo kan probleemgedrag leiden tot een verminderde kwaliteit van leven en (mogelijk vermijdbaar) hoog zorggebruik. De richtlijn ‘Probleemgedrag bij volwassenen met een verstandelijke beperking’ is ontwikkeld om de kwaliteit van leven bij volwassenen met een VB en probleemgedrag te verbeteren en last en lijden bij deze groep én naastbetrokkenen te verminderen. Belangrijke bijkomende doelen zijn het beter signaleren, vaststellen en behandelen van psychiatrische stoornissen, het verbeteren van de inzet van niet-medicamenteuze behandelingen en de effectieve inzet van psychofarmaca
Electron acceleration by wave turbulence in a magnetized plasma
Astrophysical shocks are commonly revealed by the non-thermal emission of energetic electrons accelerated in situ 1-3 . Strong shocks are expected to accelerate particles to very high energies 4-6 ; however, they require a source of particles with velocities fast enough to permit multiple shock crossings. While the resulting diffusive shock acceleration 4 process can account for observations, the kinetic physics regulating the continuous injection of non-thermal particles is not well understood. Indeed, this injection problem is particularly acute for electrons, which rely on high-frequency plasma fluctuations to raise them above the thermal pool 7,8 . Here we show, using laboratory laser-produced shock experiments, that, in the presence of a strong magnetic field, significant electron pre-heating is achieved. We demonstrate that the key mechanism in producing these energetic electrons is through the generation of lower-hybrid turbulence via shock-reflected ions. Our experimental results are analogous to many astrophysical systems, including the interaction of a comet with the solar wind 9 , a setting where electron acceleration via lower-hybrid waves is possible
Simulated-Physiological Loading Conditions Preserve Biological and Mechanical Properties of Caprine Lumbar Intervertebral Discs in Ex Vivo Culture
Low-back pain (LBP) is a common medical complaint and associated with high societal costs. Degeneration of the intervertebral disc (IVD) is assumed to be an important causal factor of LBP. IVDs are continuously mechanically loaded and both positive and negative effects have been attributed to different loading conditions
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