Steroids in kidney transplant patients

Any evaluation of steroids in kidney transplantation is hampered by individual variability in metabolism, the lack of clinically available steroid blood levels, and overall little attention to steroid exposure. Many feel that steroids were an essential part of chronic immunosuppression in past decades but may no longer be necessary in low-risk populations when our newer and more potent drugs are used. Potential differences in long-term outcome will be unapparent in short-term antibody induction studies in low-risk patients, particularly with low on steroid doses, as may have happened in the recent, well-done Astellas trial. In many studies, the evidence for the superiority of mycophenolate (MMF) and tacrolimus (TAC) was not as strong as the evidence for the benefit of steroids in the Canadian cyclosporine study. As the practice of steroid withdrawal has increased, we have not seen the improvement in long-term graft survival that many expected with our newer agents. Steroids have immunosuppressive effects even in doses that are low by historic standards, and side effects may not justify their abandonment

Dynamics of myelination in the mammalian nervous system

Myelination was first understood to enable faster impulse propagation in axons more than 60 years ago, yet it took a long time to recognise the mechanistic complexity of this cellular process and the diverse roles that myelinating glia play in the formation and functioning of the vertebrate nervous system. Once considered a static insulator, myelinating glia are now increasingly recognised as dynamic and adaptive cell populations. The effective bidirectional signalling between axons and glia and dynamic changes in the Schwann cell population play a fundamental role in the injury response of the PNS. Furthermore, converging evidence now suggests that myelin in the CNS can be dynamically regulated by neuronal activity and continues to participate in nervous system plasticity beyond development, yet the functional role of such adaptive myelination remains unclear. While the dynamic natures and diverse functions of myelinating glia have now gained increased recognition, fundamental mechanisms and principles underlying these processes remain poorly understood. The aim of this thesis was to advance our understanding of myelin dynamics and the axon-glia communication regulating them. The first part of this thesis describes the development of myelinating co-cultures using human induced pluripotent stem cell-derived sensory neurons. Our work outlines how such a novel PNS co-cultures system can be used to provide insights into the cellular and molecular specialization of axoglial signalling, how pharmacological agents may promote or impede such signalling and the pathogenic effects of ganglioside antibodies. The second part of the thesis describes work aimed to investigate the role of neuregulin 1 (Nrg1) signalling in myelination in the PNS and CNS. While Nrg1 plays an essential role in the myelination of Schwann cells, as demonstrated in this thesis, its role in CNS myelination remains elusive. The work presented indicated that conditional global deletion of Nrg1 in mice leads to a behaviour deficit in a motor task. However, we found no conclusive evidence for a role of Nrg1 in adaptive myelination and myelinating glia dynamics in the CNS. The third part of this thesis focuses on the functional role of dynamic and adaptive myelination in the CNS, concentrating on the question if and how de novo myelination during adulthood facilitates and shapes motor behaviour and learning. The work presented replicates and extends previous findings indicating a causal relationship between adaptive myelination and behaviour change. However, not all aspects of evidence were faithfully replicated, and we conclude that further investigation is required to unravel the link between adaptive myelination and motor learning. Furthermore, our preliminary analysis of cellular and microstructural changes in CNS, acquired by combining histology and magnetic resonance imaging, remains partly inconclusive regarding the exact role that de novo myelination might play in skill acquisition. Overall, the major contributions of this thesis are the development of a novel and useful co-culture system using iPSC derived human cells and the thorough replication, critical evaluation and extension of important findings that indicated a causal link between myelin plasticity and behaviour change

Myelin plasticity and behaviour-connecting the dots.

Myelin sheaths in the vertebrate nervous system enable faster impulse propagation, while myelinating glia provide vital support to axons. Once considered a static insulator, converging evidence now suggests that myelin in the central nervous system can be dynamically regulated by neuronal activity and continues to participate in nervous system plasticity beyond development. While the link between experience and myelination gains increased recognition, it is still unclear what role such adaptive myelination plays in facilitating and shaping behaviour. Additionally, fundamental mechanisms and principles underlying myelin remodelling remain poorly understood. In this review, we will discuss new insights into the link between myelin plasticity and behaviour, as well as mechanistic aspects of myelin remodelling that may help to elucidate this intriguing process

Myelin plasticity and behaviour-connecting the dots.

Myelin sheaths in the vertebrate nervous system enable faster impulse propagation, while myelinating glia provide vital support to axons. Once considered a static insulator, converging evidence now suggests that myelin in the central nervous system can be dynamically regulated by neuronal activity and continues to participate in nervous system plasticity beyond development. While the link between experience and myelination gains increased recognition, it is still unclear what role such adaptive myelination plays in facilitating and shaping behaviour. Additionally, fundamental mechanisms and principles underlying myelin remodelling remain poorly understood. In this review, we will discuss new insights into the link between myelin plasticity and behaviour, as well as mechanistic aspects of myelin remodelling that may help to elucidate this intriguing process

Torre de Londres e Torre de Hanói: contribuições distintas para avaliação do funcionamento executivo Tower of London and Tower of Hanoi: distinct contributions to the assessment of executive functioning

OBJETIVO: Realizar um estudo teórico sobre comparações de aspectos cognitivos e metodológicos envolvidos no desempenho das Torres de Hanói e de Londres em indivíduos normais. MÉTODO: Revisão narrativa da literatura. RESULTADOS: O desempenho nesses instrumentos não compartilha a variância esperada em virtude das similaridades aparentes em sua estrutura e demanda de solução. Verificaram-se correlações significativas, porém moderadas, entre o desempenho das duas torres, refletindo em média 75% da variância não compartilhada. CONCLUSÕES: Ambas as torres recrutam diferentes processos executivos para solução da tarefa e não podem ser utilizadas como instrumentos permutáveis.<br>OBJECTIVE: To produce theoretical study about comparisons of cognitive and methodological aspects involved in the performance of Towers of Hanoi and London in normal individuals. METHOD: Narrative review of the literature. RESULTS: The performances in these instruments do not share the expected variance due to the apparent similarities in your structure and solution demand. Correlations significant, however moderate, among the two towers performance, were found reflecting the average of 75% of the nonshared variance. CONCLUSIONS: Both towers recruit different executive processes for task solution and cannot be used as exchangeable instruments