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Girgis C.M.,Westmead Millennium Institute | Girgis C.M.,University of Sydney | Girgis C.M.,Garvan Institute of Medical Research | Cha K.M.,Westmead Millennium Institute | And 11 more authors.
Calcified Tissue International | Year: 2015

Vitamin D deficiency is associated with muscle weakness, pain, and atrophy. Serum vitamin D predicts muscle strength and age-related muscle changes. However, precise mechanisms by which vitamin D affects skeletal muscle are unclear. To address this question, this study characterizes the muscle phenotype and gene expression of mice with deletion of vitamin D receptor (VDRKO) or diet-induced vitamin D deficiency. VDRKO and vitamin D-deficient mice had significantly weaker grip strength than their controls. Weakness progressed with age and duration of vitamin D deficiency, respectively. Histological assessment showed that VDRKO mice had muscle fibers that were significantly smaller in size and displayed hyper-nuclearity. Real-time PCR also indicated muscle developmental changes in VDRKO mice with dysregulation of myogenic regulatory factors (MRFs) and increased myostatin in quadriceps muscle (>2-fold). Vitamin D-deficient mice also showed increases in myostatin and the atrophy marker E3-ubiqutin ligase MuRF1. As a potential explanation for grip strength weakness, both groups of mice had down-regulation of genes encoding calcium-handling and sarco-endoplasmic reticulum calcium transport ATPase (Serca) channels. This is the first report of reduced strength, morphological, and gene expression changes in VDRKO and vitamin D-deficient mice where confounding by calcium, magnesium, and phosphate have been excluded by direct testing. Although suggested in earlier in vitro work, this study is the first to report an in vivo association between vitamin D, myostatin, and the regulation of muscle mass. These findings support a direct role for vitamin D in muscle function and corroborate earlier work on the presence of VDR in this tissue. © 2015, Springer Science+Business Media New York.

Herbert R.D.,The George Institute for Global Health | Herbert R.D.,University of Sydney | Clarke J.,University of Sydney | Kwah L.K.,The George Institute for Global Health | And 9 more authors.
Journal of Physiology | Year: 2011

Ultrasound imaging was used to measure the length of muscle fascicles in human gastrocnemius muscles while the muscle was passively lengthened and shortened by moving the ankle. In some subjects the muscle belly 'buckled' at short lengths. When the gastrocnemius muscle-tendon unit was passively lengthened from its shortest in vivo length by dorsiflexing the ankle, increases in muscle-tendon length were not initially accompanied by increases in muscle fascicle lengths (fascicle length remained constant), indicating muscle fascicles were slack at short muscle-tendon lengths. The muscle-tendon length at which slack is taken up differs among fascicles: some fascicles begin to lengthen at very short muscle-tendon lengths whereas other fascicles remain slack over a large range of muscle-tendon lengths. This suggests muscle fascicles are progressively 'recruited' and contribute sequentially to muscle-tendon stiffness during passive lengthening of the muscle-tendon unit. Even above their slack lengths muscle fascicles contribute only a small part (<∼30%) of the total change in muscle-tendon length. The contribution of muscle fascicles to muscle-tendon length increases with muscle length. The novelty of this work is that it reveals a previously unrecognised phenomenon (buckling at short lengths), posits a new mechanism of passive mechanical properties of muscle (recruitment of muscle fascicles), and confirms with high-resolution measurements that the passive compliance of human gastrocnemius muscle-tendon units is due largely to the tendon. It would be interesting to investigate if adaptations of passive properties of muscles are associated with changes in the distribution of muscle lengths at which fascicles fall slack. © 2011 The Authors. Journal compilation © 2011 The Physiological Society.

Girgis C.M.,University of New South Wales | Girgis C.M.,University of Sydney | Clifton-Bligh R.J.,University of Sydney | Clifton-Bligh R.J.,The Kolling Institute of Medical Research | And 4 more authors.
Endocrine Reviews | Year: 2013

Beyond its established role in bone and mineral homeostasis, there is emerging evidence that vitamin D exerts a range of effects in skeletal muscle. Reports of profound muscle weakness and changes in the muscle morphology of adults with vitamin D deficiency have long been described. These reports have been supplemented by numerous trials assessing the impact of vitamin D on muscle strength and mass and falls in predominantly elderly and deficient populations. At a basic level, animal models have confirmed that vitamin D deficiency and congenital aberrations in the vitamin D endocrine system may result in muscle weakness. To explain these effects, some molecular mechanisms by which vitamin D impacts on muscle cell differentiation, intracellular calcium handling, and genomic activity have been elucidated. There are also suggestions that vitamin D alters muscle metabolism, specifically its sensitivity to insulin, which is a pertinent feature in the pathophysiology of insulin resistance and type 2 diabetes. We will review the range of human clinical, animal, and cell studies that address the impact of vitamin D in skeletal muscle, and discuss the controversial issues. This is a vibrant field of researchandonethat continues to extend the frontiers ofknowledgeof vitamin D's broad functional repertoire. © 2013 by The Endocrine Society.

Clarke E.C.,University of Sydney | Clarke E.C.,The Kolling Institute of Medical Research | Martin J.H.,University of Sydney | Martin J.H.,The Kolling Institute of Medical Research | And 6 more authors.
Medical Engineering and Physics | Year: 2015

Muscle moment arms are used widely in biomechanical analyses. Often they are measured in 2D or at a series of static joint positions. In the present study we demonstrate a simple MRI method for measuring muscle moment arms dynamically in 3D from a single range-of-motion cycle. We demonstrate this method in the Achilles tendon for comparison with other methods, and validate the method using a custom apparatus. The method involves registration of high-resolution joint geometry from MRI scans of the stationary joint with low-resolution geometries from ultrafast MRI scans of the slowly moving joint. Tibio-talar helical axes and 3D Achilles tendon moment arms were calculated throughout passive rotation for 10 adult subjects, and compared with recently published data. A simple validation was conducted by comparing MRI measurements with direct physical measurements made on a phantom. The moment arms measured using our method and those of others were similar and there was good agreement between physical measurements (mean 41.0. mm) and MRI measurements (mean 39.5. mm) made on the phantom. This new method can accurately measure muscle moment arms from a single range-of-motion cycle without the need to control rotation rate or gate the scanning. Supplementary data includes custom software to assist implementation. © 2014 IPEM.

Tate R.L.,The Kolling Institute of Medical Research | Tate R.L.,University of Sydney | Perdices M.,Royal North Shore Hospital | Perdices M.,University of Sydney | And 26 more authors.
Aphasiology | Year: 2016

We developed a reporting guideline to provide authors with guidance about what should be reported when writing a paper for publication in a scientific journal using a particular type of research design: the single-case experimental design. This report describes the methods used to develop the Single-Case Reporting guideline In BEhavioural interventions (SCRIBE) 2016. As a result of 2 online surveys and a 2-day meeting of experts, the SCRIBE 2016 checklist was developed, which is a set of 26 items that authors need to address when writing about single-case research. This article complements the more detailed SCRIBE 2016 Explanation and Elaboration article (Tate et al., 2016) that provides a rationale for each of the items and examples of adequate reporting from the literature. Both these resources will assist authors to prepare reports of single-case research with clarity, completeness, accuracy, and transparency. They will also provide journal reviewers and editors with a practical checklist against which such reports may be critically evaluated. We recommend that the SCRIBE 2016 is used by authors preparing manuscripts describing single-case research for publication, as well as journal reviewers and editors who are evaluating such manuscripts. © 2016 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This article was originally published by the American Psychological Association, and is available at http://dx.doi.org/10.1037/arc0000026.

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