55 research outputs found
Gender-specific hip fracture risk in community-dwelling and institutionalized seniors age 65years and older
Summary: In this study of acute hip fracture patients, we show that hip fracture rates differ by gender between community-dwelling seniors and seniors residing in nursing homes. While women have a significantly higher rate of hip fracture among the community-dwelling seniors, men have a significantly higher rate among nursing home residents. Introduction: Differences in gender-specific hip fracture risk between community-dwelling and institutionalized seniors have not been well established, and seasonality of hip fracture risk has been controversial. Methods: We analyzed detailed data from 1,084 hip fracture patients age 65years and older admitted to one large hospital center in Zurich, Switzerland. In a sensitivity analysis, we extend to de-personalized data from 1,265 hip fracture patients from the other two large hospital centers in Zurich within the same time frame (total nâ=â2,349). The denominators were person-times accumulated by the Zurich population in the corresponding age/gender/type of dwelling stratum in each calendar season for the period of the study. Results: In the primary analysis of 1,084 hip fracture patients (mean age 85.1years; 78% women): Among community-dwelling seniors, the risk of hip fracture was twofold higher among women compared with men (RRâ=â2.16; 95% CI, 1.74-2.69) independent of age, season, number of comorbidities, and cognitive function; among institutionalized seniors, the risk of hip fracture was 26% lower among women compared with men (RRâ=â0.77; 95% CI: 0.63-0.95) adjusting for the same confounders. In the sensitivity analysis of 2,349 hip fracture patients (mean age 85.0years, 76% women), this pattern remained largely unchanged. There is no seasonal swing in hip fracture incidence. Conclusion: We confirm for seniors living in the community that women have a higher risk of hip fracture than men. However, among institutionalized seniors, men are at higher risk for hip fracture
Regulation of dendritic development by neurotrophic factors
AbstractEstablishment of a functional nervous system occurs through an orchestrated multistep process during embryogenesis. As dendrites are the primary sites of synaptic connections, development of dendritic arborization is essential for the formation of functional neural circuits. Maturation of dendritic arbor occurs through dynamic processes that are regulated by intrinsic genetic factors and external signals, such as environmental stimuli, neuronal activity and growth factors. Among the latter, the neurotrophic factor BDNF is a key regulator of dendritic growth. However, the mechanisms by which BDNF controls dendritic development remain elusive.In this study, we first showed that activation of the MAPK signaling pathway and phosphorylation of the transcription factor CREB are required to mediate the effects of BDNF on dendritic development of cortical neurons. However, phosphorylation of CREB alone is not sufficient to induce dendritic growth in response to BDNF. Thus, by using a mutant form of CREB unable to bind its coactivator CRTC1, we demonstrated that BDNF-induced dendritic elaboration requires the functional interaction between CREB and CRTC1. Consistent with these observations, inhibition of CRTC1 expression by shRNA-mediated knockdown was found to suppress the effects of BDNF on dendritic length and branching of cortical neurons.The nuclear translocation of CRTC1, a step necessary for the interaction between CREB and CRTC1, was shown to result from the activation of NMD A receptors by glutamate, leading to the dephosphorylation of CRTC1 by the protein phosphatase calcineurin. In line with these findings, prevention of CRTC1 nuclear translocation in the absence of glutamate, or by inhibiting NMDA receptors or calcineurin suppressed the promotion of dendritic growth by BDNF.Increasing evidence supports a role for the growth factor HGF in the regulation of dendritic morphology during brain development. Despite these observations, little is known about the cellular mechanisms underlying the effects of HGF on dendritic elaboration of cortical neurons. The second part of this study was aimed at elucidating the cellular processes that mediate the effects of HGF on dendritic differentiation. We found that HGF increases cortical dendritic growth through mechanisms that involve MAPK-dependent phosphorylation of CREB, and interaction of CREB with its coactivator CRTC1. These data indicate that the mechanisms underlying the promotion of dendritic growth by HGF are similar to those that mediate the effects of BDNF, suggesting that the role of CREB and CRTC1 in the regulation of dendritic development may not be limited to HGF and BDNF, but may extend to other neurotrophic factors that control dendritic differentiation.Together, these results identify a previously unrecognized mechanism by which CREB and its coactivator CRTC1 mediate the effects of BDNF and HGF on dendritic growth of cortical neurons. Moreover, these data highlight the important role of the cooperation between BDNF/HGF and glutamate that converges on CREB to stimulate the expression of genes that contribute to the development of dendritic arborization.RĂ©sumĂ©L'Ă©tablissement d'un systĂšme nerveux fonctionnel s'accomplit grĂące Ă des mĂ©canismes prĂ©cis, orchestrĂ©s en plusieurs Ă©tapes au cours de l'embryogenĂšse. Les dendrites Ă©tant les principaux sites de connexions synaptiques, le dĂ©veloppement de l'arborisation dendritique est essentiel Ă la formation de circuits neuronaux fonctionnels. La maturation de l'arbre dendritique s'effectue grĂące Ă des processus dynamiques qui sont rĂ©gulĂ©s par des facteurs gĂ©nĂ©tiques intrinsĂšques ainsi que par des facteurs externes tels que les stimuli environnementaux, l'activitĂ© neuronale ou les facteurs de croissance. Parmi ces derniers, le facteur neurotrophique BDNF est - connu pour ĂȘtre un rĂ©gulateur clĂ© de la croissance dendritique. Cependant, les mĂ©canismes par lesquels BDNF contrĂŽle le dĂ©veloppement dendritique demeurent mal connus.Au cours de cette Ă©tude, nous avons montrĂ© dans un premier temps que l'activation de la voie de signalisation de la MAPK et la phosphorylation du facteur de transcription CREB sont nĂ©cessaires aux effets du BDNF sur le dĂ©veloppement dendritique des neurones corticaux. Toutefois, la phosphorylation de CREB en tant que telle n'est pas sĂ»ffisante pour permettre la pousse des dendrites en rĂ©ponse au BDNF. Ainsi, en utilisant une forme mutĂ©e de CREB incapable de se lier Ă son coactivateur CRTC1, nous avons dĂ©montrĂ© que l'Ă©laboration des dendrites induite par le BDNF nĂ©cessite Ă©galement une interaction fonctionnelle entre CREB et CRTC1. Ces rĂ©sultats ont Ă©tĂ© confirmĂ©s par d'autres expĂ©riences qui ont montrĂ© que l'inhibition de l'expression de CRTC1 par l'intermĂ©diaire de shRNA supprime les effets du BDNF sur la longueur et le branchement dendritique des neurones corticaux.Les rĂ©sultats obtenus au cours de ce travail montrent Ă©galement que la translocation nuclĂ©aire de CRTC1, qui est une Ă©tape nĂ©cessaire Ă l'interaction entre CREB et CRTC1, rĂ©sulte de l'activation des rĂ©cepteurs NMDA par le glutamate, entraĂźnant la dĂ©phosphorylation de CRTC1 par la protĂ©ine phosphatase calcineurine. De plus, le blocage de la translocation nuclĂ©aire de CRTC1 en absence de glutamate, ou suite Ă l'inhibition des rĂ©cepteurs NMDA ou de la calcineurine, supprime complĂštement la pousse des dendrites induite par le BDNF.De nombreuses d'Ă©vidences indiquent que le facteur de croissance HGF joue Ă©galement un rĂŽle important dans la rĂ©gulation de la morphologie dendritique au cours du dĂ©veloppement cĂ©rĂ©bral. MalgrĂ© ces observations, peu d'Ă©lĂ©ments sont connus quant aux mĂ©canismes cellulaires qui sous-tendent les effets du HGF sur la croissance dendritique des neurones corticaux. Le but de la seconde partie de cette Ă©tude a eu pour but d'Ă©lucider les processus cellulaires responsables des effets du HGF sur la diffĂ©renciation dendritique des neurones corticaux. Au cours de ces expĂ©riences, nous avons pu mettre en Ă©vidence que le HGF induit la pousse dendritique par des mĂ©canismes qui impliquent la phosphorylation de CREB par la MAPK, et l'interaction de CREB avec son coactivateur CRTC1. Ces donnĂ©es indiquent que les mĂ©canismes impliquĂ©s dans la stimulation de la croissance dendritique par le HGF sont similaires Ă ceux rĂ©gulant les effets du BDNF, ce qui suggĂšre que le rĂŽle de CREB et de CRTC1 dans la rĂ©gulation du dĂ©veloppement dendritique n'est vraisemblablement pas limitĂ© aux effets du HGF ou du BDNF, mais pourrait s'Ă©tendre Ă d'autres facteurs neurotrophiques qui contrĂŽlent la diffĂ©renciation dendritique.En conclusion, ces rĂ©sultats ont permis l'identification d'un nouveau mĂ©canisme par lequel CREB et son coactivateur CRTC1 transmettent les effets du BDNF et du HGF sur la croissance dendritique de neurones corticaux. Ces observations mettent Ă©galement en Ă©vidence le rĂŽle important jouĂ© par la coopĂ©ration entre BDNF/HGF et le glutamate, dans l'activation de CREB ainsi que dans l'expression de gĂšnes qui participent au dĂ©veloppement de l'arborisation dendritique des neurones corticaux
Cellular mechanisms underlying the regulation of dendritic development by hepatocyte growth factor.
Acquisition of a mature dendritic morphology is critical for neural information processing. In particular, hepatocyte growth factor (HGF) controls dendritic arborization during brain development. However, the cellular mechanisms underlying the effects of HGF on dendritic growth remain elusive. Here, we show that HGF increases dendritic length and branching of rat cortical neurons through activation of the mitogen-activated protein kinase (MAPK) signaling pathway. Activation of MAPK by HGF leads to the rapid and transient phosphorylation of cAMP response element-binding protein (CREB), a key step necessary for the control of dendritic development by HGF. In addition to CREB phosphorylation, regulation of dendritic growth by HGF requires the interaction between CREB and CREB-regulated transcription coactivator 1 (CRTC1), as expression of a mutated form of CREB unable to bind CRTC1 completely abolished the effects of HGF on dendritic morphology. Treatment of cortical neurons with HGF in combination with brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family that regulates dendritic development via similar mechanisms, showed additive effects on MAPK activation, CREB phosphorylation and dendritic growth. Collectively, these results support the conclusion that regulation of cortical dendritic morphology by HGF is mediated by activation of the MAPK pathway, phosphorylation of CREB and interaction of CREB with CRTC1
PMD43 Comparison of Actual Costs Versus DRG Revenue of Cervical Arthroplasty in Patients With Degenerative Disc Disease in Germany
Lifelong Learning as a goal - Do autonomy and self-regulation in school result in well prepared pupils?
Fostering lifelong learning (LLL) is a topic of high relevance for current educational policy. School lays the cornerstone for the key components of LLL, specifically persistent motivation to learn and self-regulated learning behavior. The present study investigated the impact of classroom instruction variables on concrete determinants for these LLL components. Participants in the present study were 2266 fifth, sixth and seventh graders from 125 classrooms. Multi-level analyses showed that perception of autonomy in the classroom is associated with pupilsâ motivational beliefs, and that perception that a classroom promotes self-determined performance and self-reflection of learning is a predictor of pupils' monitoring and assessment of learning. Additionally, the extent of perceived autonomy is an important factor in the reduction of gender differences in motivation. The results indicate the importance of providing pupils with appropriate learning contexts to better prepare them for successful LLL
Erwartungen in himmelblau und rosarot: ErklĂ€rung fĂŒr Geschlechterdifferenzen im lebenslangen Lernen
In-service teachersâ perceptions of project-based learning
The study analyses teachersâ perceptions of methods, teacher roles, success and evaluation in PBL and traditional classroom instruction. The analysis is based on empirical data collected in primary schools and vocational secondary schools. An analysis of 109 questionnaires revealed numerous differences based on degree of experience and type of school. In general, project-based methods were preferred among teachers, who mostly perceived themselves as facilitators and considered motivation and transmission of values central to their work. Teachers appeared not to capitalize on the use of ICT tools or emotions. Students actively participated in the evaluation process via oral evaluation
Role of salt-inducible kinase 1 in the activation of MEF2-dependent transcription by BDNF.
Substantial evidence supports a role for myocyte enhancer factor 2 (MEF2)-mediated transcription in neuronal survival, differentiation and synaptic function. In developing neurons, it has been shown that MEF2-dependent transcription is regulated by neurotrophins. Despite these observations, little is known about the cellular mechanisms by which neurotrophins activate MEF2 transcriptional activity. In this study, we examined the role of salt-inducible kinase 1 (SIK1), a member of the AMP-activated protein kinase (AMPK) family, in the regulation of MEF2-mediated transcription by the neurotrophin brain-derived neurotrophic factor (BDNF). We show that BDNF increases the expression of SIK1 in primary cultures of rat cortical neurons through the extracellular signal-regulated kinase 1/2 (ERK1/2)-signaling pathway. In addition to inducing SIK1 expression, BDNF triggers the phosphorylation of SIK1 at Thr182 and its translocation from the cytoplasm to the nucleus of cortical neurons. The effects of BDNF on the expression, phosphorylation and, translocation of SIK1 are followed by the phosphorylation and nuclear export of histone deacetylase 5 (HDAC5). Blockade of SIK activity with a low concentration of staurosporine abolished BDNF-induced phosphorylation and nuclear export of HDAC5 in cortical neurons. Importantly, stimulation of HDAC5 phosphorylation and nuclear export by BDNF is accompanied by the activation of MEF2-mediated transcription, an effect that is suppressed by staurosporine. Consistent with these data, BDNF induces the expression of the MEF2 target genes Arc and Nur77, in a staurosporine-sensitive manner. In further support of the role of SIK1 in the regulation of MEF2-dependent transcription by BDNF, we found that expression of wild-type SIK1 or S577A SIK1, a mutated form of SIK1 which is retained in the nucleus of transfected cells, is sufficient to enhance MEF2 transcriptional activity in cortical neurons. Together, these data identify a previously unrecognized mechanism by which SIK1 mediates the activation of MEF2-dependent transcription by BDNF
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