Yes / Loneliness in older people is associated with poor health-related quality of life (HRQoL). We undertook a parallel-group randomised controlled trial to evaluate the effectiveness and cost-effectiveness of telephone befriending for the maintenance of HRQoL in older people. An internal pilot tested the feasibility of the trial and intervention. Methods: Participants aged >74 years, with good cognitive function, living independently in one UK city were recruited through general practices and other sources, then randomised to: (1) 6 weeks of short one-to-one telephone calls, followed by 12 weeks of group telephone calls with up to six participants, led by a trained volunteer facilitator; or (2) a control group. The main trial required the recruitment of 248 participants in a 1-year accrual window, of whom 124 were to receive telephone befriending. The pilot specified three success criteria which had to be met in order to progress the main trial to completion: recruitment of 68 participants in 95 days; retention of 80% participants at 6 months; successful delivery of telephone befriending by local franchise of national charity. The primary clinical outcome was the Short Form (36) Health Instrument (SF-36) Mental Health (MH) dimension score collected by telephone 6 months following randomisation. Results: We informed 9,579 older people about the study. Seventy consenting participants were randomised to the pilot in 95 days, with 56 (80%) providing valid primary outcome data (26 intervention, 30 control). Twenty-four participants randomly allocated to the research arm actually received telephone befriending due to poor recruitment and retention of volunteer facilitators. The trial was closed early as a result. The mean 6-month SF-36 MH scores were 78 (SD 18) and 71 (SD 21) for the intervention and control groups, respectively (mean difference, 7; 95% CI, −3 to 16). Conclusions: Recruitment and retention of participants to a definitive trial with a recruitment window of 1 year is feasible. For the voluntary sector to recruit sufficient volunteers to match demand for telephone befriending created by trial recruitment would require the study to be run in more than one major population centre, and/or involve dedicated management of volunteers. Trial registration: ISRCTN28645428.

Background: Drugs are one of the cornerstones in the management of many diseases. In general, drugs are used for diagnosis, prevention, mitigation of symptoms, and, sometimes, to cure disease. However, drug treatment in elderly people, especially those with dementia and cognitive impairments, may involve significant risk of adverse drug events.  The aim of this thesis was to identify the extent of potentially inappropriate drug treatment among people with dementia and cognitive impairment and to assess the occurrence and character of drug-related problems that lead to acute hospital admissions. Another aim was to assess the potential impact of a comprehensive medication review conducted by clinical pharmacists as part of a health care team on quality of patients’ drug therapy and drug-related hospital readmission rates. Method: Long-term use of antipsychotic/psychotropic drugs and associated factors were investigated among 344 and 278 people respectively with dementia living in specialized care units. Trends in the prescribing of potentially inappropriate drugs between 2007 and 2013, comprising 2772 and 1902 people, living in nursing homes in the county of Västerbotten, were assessed using six national quality indicators. Data on drug use, function in the activities of daily living, cognitive function and behavioral and psychological symptoms were collected using the Multi-Dimensional Dementia Assessment Scale. Further, an investigation of a separate corresponding population from 2012 was done, where potentially inappropriate drug use was measured before and after a total of 895 medication reviews. Finally, a randomized, controlled trial was carried out among people 65 years or older with dementia or cognitive impairment in internal medicine and orthopedic wards at two hospitals in northern Sweden. The proportion of hospital admissions that were drug-related were estimated, and also whether comprehensive medication reviews conducted by clinical pharmacists as part of a health care team could affect the risk of drug-related hospital readmissions. Results: Antipsychotic and other psychotropic drugs were frequently prescribed to people with dementia living in specialized care units for prolonged periods. Associations were found between behavioral and psychological symptoms and different psychotropic drugs. The extent of potentially inappropriate drug use declined between 2007 and 2013. In the separate corresponding population from 2012, the frequency of potentially inappropriate drug use was significantly reduced among people who underwent medication reviews. Hospitalizations due to drug-related problems among old people with dementia or cognitive impairment were prevalent. We found that inclusion of a clinical pharmacist in the health care team significantly reduced the risk of drug-related 30-day and 180-day readmissions. However, in a subset of patients with concomitant heart failure no effect was seen. Conclusion: Among patients with dementia or cognitive impairment long-term treatment with antipsychotic and other psychotropic drugs is common. The results indicate that these drugs are prescribed to treat behavioral and psychological symptoms among cognitively impaired individuals, despite limited evidence of their efficacy and the high risk of adverse effects. Drug-related problems, such as adverse drug reactions, constituted a major cause of hospital admissions. By reducing potentially inappropriate drug use and optimizing overall drug therapy, inclusion of clinical pharmacists in a health care team might improve the quality of patient care and reduce the risk of hospital readmissions among people with dementia.

Consumer decisions are largely influenced by prior experiences via memory. Consumer research is limited in its consideration of the separate memory system conceptualisations dominant in psychology, and rather has primarily focused on semantic memory (SM). As Autobiographical Memory (AM) may equally affect one’s brand consumption decisions, it is critical to integrate AM into brand-related memory studies for a complete understanding of the consumer learning and decision-making process. The study conceptualises affective, self-relevant brand episodes as Brand-Related Autobiographical Memory (BRAM), and storage of abstract brand knowledge as Brand-Related Semantic Memory (BRSM). The conceptual review identified hypothesised relationships between BRAM, BRSM, self-brand congruence and affective brand commitment. Within a positivist paradigm, the study employed methodological triangulation with qualitative interviews, functional magnetic resonanace imaging (fMRI) experiment and a survey to collect data. Findings suggest that brand memories are stored in AM and SM, and brand memories that are in AM are self-relevant and emotion-laden. The construct of Specificity explains the self-brand congruence relationship while BRAM (Vividness and Affect) influence brand commitment. No relationship was discovered between BRSM, self-brand congruence and brand commitment. This is of particular significance as dominant consumer research focuses on semantic memory. The research contributes to marketing theory by: 1). identifying the importance of multiple memory systems in understanding consumers’ decision-making; 2). exploring how BRAM contributes towards emotional decision-making models; 3). identifying the importance of BRAM in self-brand congruence theory and brand commitment decisions; 4). demonstrating the use of nuroimaging (fMRI) methods to study consumer memories and 5). introducing the BRAM scale as a complementary measure to recall and recognition tests.

ADHS ist eine häufig diagnostizierte Erkrankung in der Kinder- und Jugendpsychiatrie; etwa 5 % aller Kinder sind betroffen. Als Kardinalsymptome gelten Hyperaktivität, Aufmerksamkeitsprobleme und erhöhte Impulsivität. Die familiäre Häufung lässt auf eine genetische Prädisposition schließen. In dieser Arbeit werden mittels eines EEGs elektrophysiologische Aktivitäten des Gehirns der teilnehmenden Kinder aufgezeichnet. Dabei bilden die ereignisbezogenen Potentiale (EPs) den Informationsverarbeitungsprozess ab, welcher während der Bearbeitung eines Konfliktparadigmas - in unserer Untersuchung der Eriksen-Flanker Task - entsteht. Es ist bekannt, dass ADHS-Patienten höhere Fehlerraten und längere Reaktionszeiten in derartigen Aufgaben zeigen und Fehler vermehrt in Serien auftreten. Von besonderem Interesse sind Potentiale die direkt nach einem Fehler abgeleitet werden können; die error-related negativitiy (Ne) bzw. positivity (Pe). Die Datenauswertung erfolgte mittels in vorherigen Studien aufgezeichneten Datensätzen. Ziel der Arbeit ist es, den Einfluss der vorangegangenen Antwort, und damit des Primings bzw. der Sequenzeffekte bei ADHS-betroffenen Kindern und einer Kontrollgruppe auf die folgende Antwort und die dabei auftretenden Hirnpotentiale zu untersuchen. Bezüglich der Ne und Pe besteht für ADHS-Patienten eine heterogene Befundlage. Wir konnten feststellen und damit Ergebnisse vorheriger Studien replizieren, dass die Ne- Amplitude bei Kindern mit ADHS – im Gegensatz zur Kontrollgruppe- geringer ausgeprägt ist und keinen Sequenzeffekten (d.h. keinem Priming) unterliegt. Für die Pe-Amplitude konnten wir keine Abweichungen im Vergleich zu der Kontrollgruppe feststellen. Auch unterlag die Pe-Amplitude bei beiden Gruppen keinem Primingeinfluss. Dies lässt den Rückschluss zu, dass nur bei ADHS und nur für die Ne eine neuronale Dysfunktion angenommen werden kann. Dieses Ergebnis weist darauf hin, dass die veränderte Ne-Amplitude möglicherweise störungsspezifisch für ADHS sein könnte und somit die Möglichkeit für den Einsatz als diagnostisches Kriterium besteht.

This study explored the view of a small-scale group of upper secondary school seniors on school-related stress during their last school year in comparison to previous years. A qualitative research method was used and five students partook in semi-structured interviews with open-end questions. The study derived from the perspectives of two theoretical models that were selected due to their relevance; firstly, the Demand-Control Support model, and secondly, the Transactional Model of Stress and Coping. The results show that these upper secondary school seniors describe themselves as less stress than they perceived themselves to be in their second year. Regarding the stress-related effects experienced by these students, it was found that sleep deprivation and anger were the most problematic ones along with their tendencies to compare themselves to others. It was also found that the five participants perceived the school health servieces' work as insufficient in many ways. One of the most recurring suggestions, by the students, on how to improve it was to discuss stress and the availability of the school health services more openly.

Introdução: Os problemas decorrentes do uso de álcool e outras drogas, preocupantes do ponto de vista da saúde pública, geram necessidades e problemas para os indivíduos e, caso não sejam detectados, podem prejudicar o cuidado integral individualizado. Considerando a necessidade de mensuração baseada em evidências na área, a qual deve abranger as diferentes necessidades do indivíduo, este estudo busca avaliar as propriedades psicométricas dos instrumentos Global Appraisal of Individual Needs Initial e Short Screener para uso no Brasil. Objetivo: Avaliar as propriedades psicométricas dos instrumentos Avaliação Global das Necessidades Individuais Inicial e Rastreio Rápido. Métodos: Estudo delineado como metodológico, de validação dos instrumentos Avaliação Global das Necessidades Individuais versões Rastreio Rápido e Inicial. Dados com a versão Rastreio Rápido foram coletados com 128 indivíduos em fase inicial de tratamento em um Centro de Atenção Psicossocial Álcool e outras Drogas, e com a versão Inicial com 40 indivíduos em tratamento em um serviço de internação e 70 indivíduos em acolhimento no Centro de Atenção Psicossocial Álcool e outras Drogas da capital paulista. Análise da consistência interna foi realizada para ambas as versões dos instrumentos e suas subescalas. Análise do modelo de Rasch foi realizada para as subescalas da versão Rastreio Rápido e para a subescala Substance Problem Scale. Foi realizada análise da associação da subescala Substance Disorder Screener com as outras subescalas do instrumento de rastreio. Foi realizada, também, a análise da validade convergente entre as subescalas da versão Rastreio Rápido e suas versões mais amplas da versão Inicial. Resultados: Ambas as versões do instrumento apresentaram, em suas subescalas mais abrangentes, índices de consistência interna alfa de Cronbach maior do que 0,7. A Substance Problem Scale e as subescalas da versão Rastreio Rápido adequam-se ao modelo Rasch, não possuindo nenhum item que prejudique suas mensurações. A subescala Substance Problem Scale apresenta dois itens de seus dezesseis com performance diferente entre homens e mulheres e apresenta redundância para a mensuração de gravidade dos problemas em seus itens. As subescalas da versão Rastreio Rápido demonstram correlação de moderada a forte com as subescalas da versão mais ampla, sendo que as escalas de gravidade total de ambas as versões possuem validade convergente (rho = 0,801). A versão Rastreio Rápido demonstra que há associação entre a gravidade dos sintomas relacionados a uso de álcool e outras drogas e sintomas de saúde mental e problemas relacionados a crime e violência. Conclusões: Ambas as versões do instrumento possuem consistência interna e validade convergente entre si, bem como são válidas pelo modelo Rasch. Além disso, demonstram resultados compatíveis àqueles de estudos das versões americana e canadense do instrumento / Introduction: The problems arising from the use of alcohol and other drugs, major concern from a public health point of view, generate issues and special needs for the individuals and, when undetected, can harm the individualized and comprehensive care. Considering the need for measurement based on evidence in the area, which ranges the different needs of the individual, this study aimed to evaluate the psychometric properties of the instruments \"Global Appraisal of Individual Needs - Initial and Short Screener\" for use in Brazil. Objective: To evaluate the psychometric properties of the instruments \"Global Appraisal of Individual Needs Initial and Short Screener\". Methods: The study was designed as a methodological study of validation of the instruments \"Global Appraisal of Individual Needs\" in the versions Short Screener and Initial. Data with Short Screener version were collected with 128 individuals in the initial phase of treatment in a Psychosocial Care Center for Alcohol and Other Drugs, and the Initial version with 40 patients being treated in an inpatient service and 70 individuals in the embracement stage of treatment in a Psychosocial Care Center for Alcohol and Other Drugs in Sao Paulo. Internal consistency analysis was performed for both versions of the instruments and its subscales. Analysis of the Rasch model was performed for the subscales of the Short Screener version and for the subscale Substance Problem Scale. The association of the Substance Disorder Screener with the other subscales of the Short Screener was verified. We also performed the analysis of convergent validity between the subscales of the Short Screener version and its wider versions of the Initial. Results: Both versions of the instrument presented internal consistency indices greater than 0.7 Cronbachs alpha for their most comprehensive subscales. The Substance Problem Scale and subscales of the Short Screener fit the Rasch model, and none of their items distort the measurements. The subscale Substance Problem Scale has two items of its sixteen with different performance between men and women and seems to have redundancy for measuring severity. The subscales of Short Screener show moderate to strong correlation with the subscales of the Initial, and their most comprehensive scales have convergent validity (rho = 0.801). The Short Screener analysis shows that there is an association between the severity of symptoms related to alcohol and other drugs and mental health symptoms and problems related to crime and violence. Conclusions: Both instrument versions have internal consistency and convergent validity with each other and are valid according to the Rasch model. They also show to be compatible with results from American and Canadian studies with the instrument

Introdução: Os problemas decorrentes do uso de álcool e outras drogas, preocupantes do ponto de vista da saúde pública, geram necessidades e problemas para os indivíduos e, caso não sejam detectados, podem prejudicar o cuidado integral individualizado. Considerando a necessidade de mensuração baseada em evidências na área, a qual deve abranger as diferentes necessidades do indivíduo, este estudo busca avaliar as propriedades psicométricas dos instrumentos Global Appraisal of Individual Needs Initial e Short Screener para uso no Brasil. Objetivo: Avaliar as propriedades psicométricas dos instrumentos Avaliação Global das Necessidades Individuais Inicial e Rastreio Rápido. Métodos: Estudo delineado como metodológico, de validação dos instrumentos Avaliação Global das Necessidades Individuais versões Rastreio Rápido e Inicial. Dados com a versão Rastreio Rápido foram coletados com 128 indivíduos em fase inicial de tratamento em um Centro de Atenção Psicossocial Álcool e outras Drogas, e com a versão Inicial com 40 indivíduos em tratamento em um serviço de internação e 70 indivíduos em acolhimento no Centro de Atenção Psicossocial Álcool e outras Drogas da capital paulista. Análise da consistência interna foi realizada para ambas as versões dos instrumentos e suas subescalas. Análise do modelo de Rasch foi realizada para as subescalas da versão Rastreio Rápido e para a subescala Substance Problem Scale. Foi realizada análise da associação da subescala Substance Disorder Screener com as outras subescalas do instrumento de rastreio. Foi realizada, também, a análise da validade convergente entre as subescalas da versão Rastreio Rápido e suas versões mais amplas da versão Inicial. Resultados: Ambas as versões do instrumento apresentaram, em suas subescalas mais abrangentes, índices de consistência interna alfa de Cronbach maior do que 0,7. A Substance Problem Scale e as subescalas da versão Rastreio Rápido adequam-se ao modelo Rasch, não possuindo nenhum item que prejudique suas mensurações. A subescala Substance Problem Scale apresenta dois itens de seus dezesseis com performance diferente entre homens e mulheres e apresenta redundância para a mensuração de gravidade dos problemas em seus itens. As subescalas da versão Rastreio Rápido demonstram correlação de moderada a forte com as subescalas da versão mais ampla, sendo que as escalas de gravidade total de ambas as versões possuem validade convergente (rho = 0,801). A versão Rastreio Rápido demonstra que há associação entre a gravidade dos sintomas relacionados a uso de álcool e outras drogas e sintomas de saúde mental e problemas relacionados a crime e violência. Conclusões: Ambas as versões do instrumento possuem consistência interna e validade convergente entre si, bem como são válidas pelo modelo Rasch. Além disso, demonstram resultados compatíveis àqueles de estudos das versões americana e canadense do instrumento / Introduction: The problems arising from the use of alcohol and other drugs, major concern from a public health point of view, generate issues and special needs for the individuals and, when undetected, can harm the individualized and comprehensive care. Considering the need for measurement based on evidence in the area, which ranges the different needs of the individual, this study aimed to evaluate the psychometric properties of the instruments \"Global Appraisal of Individual Needs - Initial and Short Screener\" for use in Brazil. Objective: To evaluate the psychometric properties of the instruments \"Global Appraisal of Individual Needs Initial and Short Screener\". Methods: The study was designed as a methodological study of validation of the instruments \"Global Appraisal of Individual Needs\" in the versions Short Screener and Initial. Data with Short Screener version were collected with 128 individuals in the initial phase of treatment in a Psychosocial Care Center for Alcohol and Other Drugs, and the Initial version with 40 patients being treated in an inpatient service and 70 individuals in the embracement stage of treatment in a Psychosocial Care Center for Alcohol and Other Drugs in Sao Paulo. Internal consistency analysis was performed for both versions of the instruments and its subscales. Analysis of the Rasch model was performed for the subscales of the Short Screener version and for the subscale Substance Problem Scale. The association of the Substance Disorder Screener with the other subscales of the Short Screener was verified. We also performed the analysis of convergent validity between the subscales of the Short Screener version and its wider versions of the Initial. Results: Both versions of the instrument presented internal consistency indices greater than 0.7 Cronbachs alpha for their most comprehensive subscales. The Substance Problem Scale and subscales of the Short Screener fit the Rasch model, and none of their items distort the measurements. The subscale Substance Problem Scale has two items of its sixteen with different performance between men and women and seems to have redundancy for measuring severity. The subscales of Short Screener show moderate to strong correlation with the subscales of the Initial, and their most comprehensive scales have convergent validity (rho = 0.801). The Short Screener analysis shows that there is an association between the severity of symptoms related to alcohol and other drugs and mental health symptoms and problems related to crime and violence. Conclusions: Both instrument versions have internal consistency and convergent validity with each other and are valid according to the Rasch model. They also show to be compatible with results from American and Canadian studies with the instrument

我们的研究是基于发现镁金属的成骨现象。在我们组之前的工作中，我们发现大鼠股骨骨髓腔内植入镁棒后，在很短时间内（一周后）就会在股骨骨膜下部位形成新骨。这种镁导致的成骨现象是怎样发生的，以及我们能否利用镁金属的这种特性去促进骨质疏松骨折的愈合？对这两个问题的解答便构成了本篇论文的主要内容。 / 因为镁诱导的新生骨产生在骨膜下方，并且植入镁棒产生的成骨现象在骨膜剥除的部位消失，所以我们认为骨膜是镁成骨的关键点。骨膜是富含感觉神经纤维和干细胞的组织，而且动物骨的感觉神经分布主要集中在骨膜（约占总的神经数量的99%以上）。骨膜神经末端不仅仅感知痛觉触觉和温度觉，而且在外界刺激下释放感觉神经递质。神经递质包裹于处于神经末梢的囊泡当中，CGRP 是经典的也是分布最广的感觉神经递质。在动物体内，血液中CGRP 的含量随年龄的增加而减少，同时骨内的镁含量也随之流失。这也是老年龄动物骨折愈合较慢的原因之一。所以我们提出本课题的研究假设：镁金属降解产生的镁离子作用于骨膜部位的感觉神经末梢，刺激神经递质CGRP 的释放。骨膜内增多的CGRP 作用于骨膜内的干细胞进行成骨分化，最后形成新骨。我们进一步检测镁的这种成骨作用能否促进骨质疏松鼠骨折的愈合。 / 首先我们用过量的辣椒素破坏大鼠股骨的感觉神经末端之后，镁的成骨显著减少，这说明镁的成骨作用相当程度上依赖于通过骨膜的神经组织。我们通过免疫组化染色及蛋白定量测定发现，植入镁后的骨组织内CGRP（降钙素基因相关肽，一种感觉神经末端分泌的主要神经递质）含量增加了一倍多。我们用CGRP 受体拮抗剂同样发现可以部分抑制镁的成骨作用。我们推测镁降解过程中产生的镁离子在骨膜部位增加了感觉神经递质的释放，骨膜部位增多的神经递质作用于骨膜源性间充质干细胞以及骨髓源性间充质干细胞想成骨方向分化成骨。体外试验结果表明，CGRP 在高浓度下显著促进骨膜及骨髓源性干细胞的成骨分化。我们从大鼠的脊髓腰段L3-5 背根神经节分离出背根神经节神经元，在体外用荧光对神经元内的突触小泡进行染色，发现当培养液中的镁离子浓度升高时（1-2mM），这些富含神经递质CGRP 的突触小泡不但数目增加，而且从胞体中心向轴突末梢迁移。在这个过程中，我们同时记录到显著的镁离子内流。实验结果表明，镁离子可以促进神经元的复极化以及神经递质向轴突末端迁移聚集，从而在下一次刺激中释放出更多的神经递质。同时体外干细胞分化实验结果表明高浓度的镁离子（5-10mM）显著促进干细胞的成骨分化。对干细胞和神经元的胞内镁离子内流检测发现，在胞外镁离子浓度升高的情况下，胞内镁离子内流主要通过一种膜通道MagT1。至此，关于镁成骨的机制可以归纳为：镁金属在降解过程中产生的镁离子作用于骨膜感觉神经末梢，使之释放出更多的神经递质，增加释放的神经递质和镁离子共同促进分布在骨膜和骨髓的干细胞进行成骨分化，从而增加成骨。 / 镁的成骨效应使之有很大的潜力用于骨质疏松骨折的修复。由于镁金属强度不足以直接用来固定大鼠骨折，所以我们设计了一种中空的不锈钢针管作为髓内骨折固定针。针管中部与骨折线对应的部位开出一些小孔，细的镁棒可以插入针管，在体内镁降解产生的镁离子可以从中部的小孔释放出去发挥其成骨效应，进而促进骨折的愈合。我们用卵巢切除大鼠进行闭合性骨折造模，然后用我们设计的髓内针固定。X 射线结果表明，手术后第二、四周镁治疗组骨折愈合组织的面积和宽度显著大于对照组。Micro-CT 扫描结果也同样表明，镁治疗组骨折部位愈合组织的总体积和骨组织体积在术后第四周显著大于对照组。组织学染色表明，在术后第二周，镁治疗组的骨折部位的骨膜内成骨大量增加，并且有大量间充质细胞充塞与骨折部位。第术后第四周，更多的软骨组织形成于镁治疗组的骨折部位。荧光双染色结果也表明，镁治疗组的骨折部位在第四周有更多的新生骨形成。第八周和十二周的偏振光图像表明，镁治疗组的骨折愈合部位形成的胶原纤维比对照组更规则且更多更亮。这说明在骨折愈合后期软骨内成骨以及编制骨向层状骨转化的过程中，镁治疗组的骨重建更加规则。最后在第十二周的力学实验结果证明，镁治疗组的骨干所能承受的最大压力显著高于对照组（大约增强了27%）。这部分体内试验证明镁金属可以加速并优化大鼠骨质疏松骨折的愈合，而且我们设计的中空含镁髓内针可以作为将来临床新型骨折髓内固定针的原型。 / 结论：我们对镁成骨的作用和其机制进行了比较深入全面的研究，并初步证实镁金属可以用于动物骨质疏松骨折的修复。我们的研究结果为将来镁金属在临床尤其是骨科领域的实际应用提供了一些基本的理论依据。 / In the rodent femur, almost 99% of all sensory nerves are distributed densely in the periosteum. Neuropeptides encapsulated in the synaptic vesicles are located at the axon terminals and released through exocytosis after being stimulated at the sensory nerve endings. The neuropeptides released from nerve endings have an osteo-anabolic effect on osteoblasts. Among the many kinds of neuropeptides, which include α-calcitonin gene-related peptide (CGRP), substance P, and other amino molecules, CGRP is the classical and dominantly distributed peptide in sensory nerve endings. In aged animals, decreased serum CGRP and loss of bone Mg content may be the factors inhibiting fracture healing. / In this study, Mg was found to significantly promote new bone formation in the subperiosteal cortical region after it was intramedullarily implanted in the rat femur canal. Histomorphological analysis revealed that the newly formed bone grew from periosteum, a fibrous membrane constituted of blood vessels, sensory serves, and mesenchymal stem cells, and did not form any cartilage-like tissue, the latter of which is a feature of intramembranous ossification. Observation that Mg-induced new bone formation disappeared at the periosteum-stripped region revealed the existence of an interaction between the periosteum and Mg ions. / Based on previous findings, this study examined the following hypotheses: (1) Mg ions from Mg implanted in the rat femur canal act on sensory nerve endings in the periosteum and promote neuropeptide CGRP release, (2) mass CGRP release in the periosteum promotes periosteum-derived stem cells osteoblastogenesis and leads to new bone formation. Mg ions affect synaptic replasticity in dorsal root ganglia neurons, and (3) pure Mg metal affects fracture healing in ovariectomized (OVX) rats. / Neuropeptide CGRP plays a pivotal role in Mg-induced new bone formation. This hypothesis was supported by femur bone analysis showing that CGRP content significantly increased in Mg-implanted femur bone compared to control femur bone. When rat sensory nerves were destroyed by administration of high-dose capsaicin, induction of new bone formation by Mg implantation significantly decreased, proving that sensory nerves play an important role in Mg-induced osteogenesis. Because neuropeptide CGRP from sensory nerve endings may play a pivotal role in Mg’s osteogenic process, the effective CGRP antagonist BIBN4096bs was administered to Mg-implanted rats. Administration of the CGRP antagonist significantly reduced newly formed bone volume after Mg implantation. To examine whether this phenomenon is dependent on the interaction between neuropeptides and MSCs, which are richly distributed in the periosteum, periosteum-derived stem cells (PDSCs) and bone marrow-derived mesenchymal stem cells (BMSCs) were isolated from the periosteum and bone marrow, respectively. It was observed that high concentrations of CGRP significantly promoted osteogenic differentiation in both PDSCs and BMSCs while high concentrations of CGRP had an obvious chemotaxis effect on BMSCs. / Mg increases CGRP release by affecting DRG neurons. The results of immunochemical staining and ELISA CGRP quantification analysis of femur samples showed that femur CGRP content in Mg-implanted samples was almost twice that of controls. Previous studies reported that Mg ions could promote neural synaptic replasticity in hippocampus neurons in vitro. This study examined the hypothesis that Mg ions could promote synaptic replasticity in DRG neurons. The neural synaptic vesicles, which contain neuropeptides of DRG neurons, including CGRP, derived from the L3-5 dorsal root ganglion were stained in vitro. The synaptic vesicles were found to significantly increase in number when their medium was changed from Mg-free medium to Mg-rich medium of 1 mM and 2 mM and to migrate from the neuron body to its axon terminals. These results proved that Mg could facilitate neuron replasticity and prompt synaptic vesicle aggregation at axon terminals, indicating that much neuropeptide release occurs after stimulation. Real-time recording of the intracellular Mg signal revealed that DRG neuron Mg influx significantly increased after Mg medium had been added and that Mg influx into neurons was mainly through the membrane Mg ion channel MagT1. Implantation of Mg ions (MgCl₂) of high concentration was found to promote stem cell (PDSCs and BMSCs) osteogenic differentiation. Although the mechanism of Mg’s osteogenic effect on stem cells was not thoroughly studied, cellular Mg influx was found to increase in high-Mg medium through the membrane ion channel MagT1. / Mg accelerated bone fracture in ovariectomized rats. Mg metal is too soft to repair bone fracture in animal models. To overcome this challenge, we designed a novel intramedullary nail containing Mg to accelerate osteoporotic bone fracture healing in ovariectomized (OVX) rats. The novel nail is a hollow stainless steel needle with several interlacing arranged holes drilled midway through the needle. The Mg pin is inserted into the needle canal and Mg ions released through the holes on the needle reach the fracture line during degradation in vivo. Our findings indicate that use of this Mg-containing intramedullary nail could accelerate bone fracture healing in OVX rats. Review of post-surgery X-ray results showed that the fracture callus of the Mg-treated group was significantly larger than that of the control group at weeks 2 and 4. Review of micro-computed tomography (micro-CT) scanning images indicated that both the total volume and area of callus bone in the Mg-treated group exceeded those of the control group at week 4. However, no significant difference was found between the two groups regarding callus area and volume at week 12. / Histomorphological analysis showed a wider intramembranous ossification area and woven bone area in the Mg-treated group at weeks 2 and 4 and more cartilage tissue at the callus site in the Mg-treated group at week 4. Double fluorescence labeling staining revealed more densely stained newly formed bone in the Mg-treated group than the control group at week 4, indicating accelerated callus bone formation in the Mg-treated group. The callus was observed to be undergoing endochondral ossification and woven bone remodeling at weeks 8 and 12. Review of polarized light images showed brighter and more regularly arranged collagen fibers in the Mg-treated group compared to the control group. Biomechanical testing at week 12 revealed that the ultimate load of shaft bone in the Mg-treated group had increased 30% more than that of the control group. These results indicate that the novel Mg-containing intramedullary nail designed in this study could significantly accelerate and optimize osteoporotic fracture healing in OVX rat model. / Significance: The results of this study contribute to a thorough understanding of the osteogenic effect of Mg by explicating its bioeffect on neurons and stem cells. The novel Mg-containing intramedullary nail designed in this study appears promising in osteoporotic fracture healing and to have many potential clinical applications. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Zhang, Yifeng. / Thesis (Ph.D.) Chinese University of Hong Kong, 2015. / Includes bibliographical references (leaves 170-180). / Abstracts also in Chinese.

Le sujet de ma thèse était de décrire sur le plan moléculaire le processus d'embryogenèse somatique chez la vigne. Pour cela, les étapes-clés d'entrée et de sortie du cycle d'embryogenèse secondaire ont été caractérisées par l'analyse de l'expression de quelques gènes impliqués dans le développement ou la défense, en particulier les gènes PR10.Grâce à l'exploitation de la séquence complète du génome de Vitis vinifèra disponible sur le site du Genoscope, j'ai pu caractériser exhaustivement la famille multigènique des PR10. Celle-ci est composée de 17 séquences disposées en tandem et formant un cluster compact sur le chromosome 5, dont 3 pseudogènes et au moins 13 séquences transcrites. L'expression de 10 de ces gènes a d'abord été analysée par RT-PCR semi-quantitative dans différents organes de la plante et dans des tissus traités au 2,4-D. Elle suggère une diversification fonctionnelle marquée. De plus, le niveau d'expression de plusieurs gènes PR10 est élevé dans les cals embryogènes, suggérant qu'ils pourraient jouer un rôle lors de l'embryogenèse somatique. L'étude de l'expression des gènes PR10 par RT-PCR quantitative en temps réel dans différents tissus ayant montré une capacité embryogénique variable lorsqu'ils sont soumis à un traitement par le 2,4-D met en évidence que le niveau d'expression varie entre les gènes et selon les tissus. L'expression de certains gènes est fortement induite par le 2,4-D dans les tissus à capacité embryogénique et seulement faiblement dans les tissus ne donnant jamais d'embryons somatiques, ce qui suggère fortement que ceux-ci pourraient être des marqueurs de la capacité embryogénique chez la vigne. / The objective of my work was to analyse the somatic embryogenesis process of Vitis vinifera at a molecular scale. Thus, the expression of genes implied in development or defence, especially PR10 genes, was monitored during the key-steps of entrance and exit of secondary somatic embryogenesis. The complete sequence of the Vitis vinifera genome available on the Genoscope website allowed the exhaustive characterization of the PR10 multigene family, which is constituted by 17 sequences localised on a tandem array on the chromosome 5. Among these 17 sequences, 3 are pseudogenesand at !east 13 are transcribed sequences. The expression of 10 PR10 genes was first monitored in various grapevine tissues and in tissues after 2,4-D treatment using semi-quantitative RT-PCR. The results suggest a strong functional diversification. Moreover, the expression of several PR10 genes is high in embryogenic calli, suggesting that these genes could intervene in somatic embryogenesis. The expression of PR10 genes was also monitored in tissues showing different somatic embryogenic capabilities under 2,4-D treatment using quantitative RT-PCR. The results show that regulation of PR10 genes is dependent of the gene and tissue considered. Moreover, the expression of some genes is highly induced by 2,4-D treatment in tissues having embryogenic capability, white it is only weakly induced in tissues having no embryogenic capability, suggesting that these gene could be markers of embryogenic capability in grapevine.

Contemporary research has been examining potential links existing among sensory, motor and attentional systems. Previous studies using TMS have shown that the abrupt onset of sounds can both capture attention and modulate motor cortex excitability, which may reflect the potential need for a behavioral response to the attended event. TMS, however, only quantifies motor cortex excitability immediately following the deliverance of a TMS pulse. Therefore, the temporal development of how the motor cortex is modulated by sounds can’t be quantified using TMS. Thus, the purpose of the present study is to use time frequency analysis of EEG to identify the time course of cortical mechanisms underlying increased motor cortex excitability after sound onset. Subjects sat in a sound attenuated booth with their hands outstretched at 45-degree angles while frequency modulated sounds were intermittently presented from a speaker either in the left and right hemispace. Our results indicated a transient reduction in EEG power from 18-24 Hz (300-600 ms latency) and then a long lasting increase in EEG power that began at ~800 ms and continued until at least 1.7 sec. The latency of EEG power changes was shorter for sounds presented from the right speaker at both time periods. When sounds were presented from the right speaker the contralateral hemisphere over motor regions also showed greater power increases after 800 ms relative to the ipsilateral hemisphere. In addition, power increases were greater in the left-handed subjects (8-12 Hz). Results showed that sounds increased EEG power at the time of a previously observed increase in motor cortex excitability. Findings also suggest an increased attentional salience to the right hemispace in neurologically normal subjects and asymmetrical hemispheric activations in right and left-handers. / acase@tulane.edu