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Wilkinson D.,Royal Adelaide Hospital | Chapman I.M.,University of Adelaide | Heilbronn L.K.,University of Adelaide | Heilbronn L.K.,Robinson Institute
Diabetic Medicine | Year: 2012

Aim Hyperbaric oxygen therapy is known to reduce fasting blood glucose in individuals with Type2 diabetes. However, the mechanisms of this effect are not clear. The aim of this study was to determine whether peripheral insulin sensitivity by hyperinsulinaemic euglycaemic clamp is increased in patients presenting for hyperbaric oxygen therapy. Methods Participants were non-obese individuals without Type2 diabetes (n=5) or obese patients with Type2 diabetes (n=5). Patients were given 100% oxygen at 2.0 absolute atmospheres for 2h, six sessions per week for 5weeks. Results Peripheral insulin sensitivity was increased in the whole cohort (P=0.04). Subsequent analysis revealed that this was significant at both treatment3 (+37.3±12.7%, P=0.02) and treatment30 (+40.6±12.6%, P=0.009). HbA 1c was significantly reduced in subjects without diabetes only (P<0.05). Conclusion Insulin sensitivity increased within 3days of hyperbaric oxygen treatment and this was maintained for 30 sessions. This increase in insulin sensitivity is equivalent to that observed following moderate weight loss. The mechanisms underlying the insulin-sensitizing effect of hyperbaric oxygen require further elucidation. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.


Smith A.E.,Robinson Institute | Sale M.V.,Robinson Institute | Higgins R.D.,Robinson Institute | Wittert G.A.,University of Adelaide | Pitcher J.B.,Robinson Institute
Journal of Applied Physiology | Year: 2011

Evidence suggests that there are aging-related changes in corticospinal stimulus-response curve characteristics in later life. However, there is also limited evidence that these changes may only be evident in postmenopausal women and not in men. This study compared corticospinal stimulus-response curves from a group of young men [19.8 ± 1.6 yr (range 17-23 yr)] and a group of old men [n = 18, aged 64.1 ± 5.0 yr (range 55-73 yr)]. Transcranial magnetic stimulation (TMS) over the contralateral motor cortex was used to evoke motor potentials at a range of stimulus intensities in the first dorsal interosseous muscle of each hand separately. There was no effect of age group or hemisphere (i.e., left vs. right motor cortex) on motor evoked potential (MEP) amplitude or any other stimulus-response characteristic. MEP variability was strongly modulated by resting motor threshold but not by age. M-wave (but not F-wave) amplitude was reduced in old men, but expressing MEP amplitude as a ratio of M-wave amplitude did not reveal any age-related differences in cortically evoked stimulusresponse characteristics. We conclude that male corticospinal stimulus-response characteristics are not altered by advancing age and that previously reported age-related changes in motor cortical excitability assessed with TMS are likely due to changes inherent in the female participants only. Future studies are warranted to fully elucidate the relationship between, and functional significance of, changes in circulating neuroactive sex hormones and motor function in later life. Copyright © 2011 the American Physiological Society.


Sui Z.,University of Adelaide | Sui Z.,Robinson Institute | Turnbull D.A.,University of Adelaide | Dodd J.M.,University of Adelaide
Maternal and Child Health Journal | Year: 2013

Overweight and obesity during pregnancy is associated with risk of a range of adverse health outcomes. While intervention studies aim to promote behavioral change, little is known about the underlying psychological mechanisms facilitating and hindering change. The aim of this study was to evaluate overweight and obese women's perceptions of making behavior change during pregnancy. We explored beliefs through self-administrated questionnaires (n = 464) and semi-structured face-to-face interviews (n = 26). Questions were designed according to the Health Belief Model. A triangulation protocol was followed to combine quantitative and qualitative data. A total of 269 women (58 %) indicated that high gestational weight gain is a concern, with 348 (75 %) indicating excessive weight gain is associated with complications during pregnancy or child birth. Women were aware of maternal complications associated with high gestational weight gain, but had more limited awareness of neonatal complications. While most women indicated in questionnaires that healthy eating and physical activity were associated with improved health during pregnancy, they were unable to identify specific benefits at interview. Barriers to making healthy behavior changes were highly individualized, the main barrier being lack of time. While the majority (91 %) of women indicated that they would make behavior changes if the change made them feel better, only half felt confident in their ability to do so. Interventions for overweight and obese pregnant women should incorporate education about neonatal health consequences and benefits of healthy behavior change in addition to incorporating strategies to enhance self-efficacy. © Springer Science+Business Media New York 2012.


O'Callaghan M.E.,Robinson Institute | MacLennan A.H.,Robinson Institute | Gibson C.S.,Robinson Institute | McMichael G.L.,Robinson Institute | And 6 more authors.
Pediatrics | Year: 2012

OBJECTIVE: Previous studies have suggested associations between certain genetic variants and susceptibility to cerebral palsy (CP). This study was designed to assess established and novel maternal and child genetic and epidemiologic risk factors for CP along with their interactions. METHODS: DNA from 587 case and 1154 control mother-child pairs was analyzed. A panel of 35 candidate single nucleotide polymorphisms (SNPs) were examined and included SNPs in genes associated with (1) thrombophilia, (2) inflammation, and (3) risk factors for CP (eg, preterm birth). Comparisons were specified a priori and made by using a χ 2 test. RESULTS: There were 40 fetal and 28 maternal associations with CP when analyzed by CP subtype, gestational age, genotypes of apolipoprotein E, and haplotypes of mannose-binding-lectin. After Bonferroni correction for multiple testing, no fetal or maternal candidate SNP was associated with CP or its subtypes. Only fetal carriage of prothrombin gene mutation remained marginally associated with hemiplegia in term infants born to mothers with a reported infection during pregnancy. Odds ratio directions of fetal SNP associations were compared with previously reported studies and confirmed no trend toward association. CONCLUSIONS: Except for the prothrombin gene mutation, individual maternal and fetal SNPs in our candidate panel were not found to be associated with CP outcome. Past reported SNP associations with CP were not confirmed, possibly reflecting type I error from small numbers and multiple testing in the original reports. Copyright © 2012 by the American Academy of Pediatrics.


Davies M.J.,Robinson Institute | Davies M.J.,University of Adelaide | Moore V.M.,Robinson Institute | Moore V.M.,University of Adelaide | And 7 more authors.
New England Journal of Medicine | Year: 2012

BACKGROUND: The extent to which birth defects after infertility treatment may be explained by underlying parental factors is uncertain. METHODS:We linked a census of treatment with assisted reproductive technology in South Australia to a registry of births and terminations with a gestation period of at least 20 weeks or a birth weight of at least 400 g and registries of birth defects (including cerebral palsy and terminations for defects at any gestational period). We compared risks of birth defects (diagnosed before a child's fifth birthday) among pregnancies in women who received treatment with assisted reproductive technology, spontaneous pregnancies (i.e., without assisted conception) in women who had a previous birth with assisted conception, pregnancies in women with a record of infertility but no treatment with assisted reproductive technology, and pregnancies in women with no record of infertility. RESULTS:Of the 308,974 births, 6163 resulted from assisted conception. The unadjusted odds ratio for any birth defect in pregnancies involving assisted conception (513 defects, 8.3%) as compared with pregnancies not involving assisted conception (17,546 defects, 5.8%) was 1.47 (95% confidence interval [CI], 1.33 to 1.62); the multivariate-adjusted odds ratio was 1.28 (95% CI, 1.16 to 1.41). The corresponding odds ratios with in vitro fertilization (IVF) (165 birth defects, 7.2%) were 1.26 (95% CI, 1.07 to 1.48) and 1.07 (95% CI, 0.90 to 1.26), and the odds ratios with intracytoplasmic sperm injection (ICSI) (139 defects, 9.9%) were 1.77 (95% CI, 1.47 to 2.12) and 1.57 (95% CI, 1.30 to 1.90). A history of infertility, either with or without assisted conception, was also significantly associated with birth defects. CONCLUSIONS: The increased risk of birth defects associated with IVF was no longer significant after adjustment for parental factors. The risk of birth defects associated with ICSI remained increased after multivariate adjustment, although the possibility of residual confounding cannot be excluded. (Funded by the National Health and Medical Research Council and the Australian Research Council.) Copyright © 2012 Massachusetts Medical Society.


Rasi Ghaemi S.,University of South Australia | Harding F.J.,University of South Australia | Delalat B.,University of South Australia | Gronthos S.,University of Adelaide | And 2 more authors.
Biomaterials | Year: 2013

In the field of stem cell technology, future advancements rely on the effective isolation, scale-up and maintenance of specific stem cell populations and robust procedures for their directed differentiation. The stem cell microenvironment - or niche - encompasses signal inputs from stem cells, supporting cells and from the extracellular matrix. In this context, the contribution of physicochemical surface variables is being increasingly recognised. This paradigm can be exploited to exert control over cellular behaviour. However, the number of parameters at play, and their complex interactions, presents a formidable challenge in delineating how the decisions of cell fate are orchestrated within the niche. Additionally, in the case of mesenchymal stem cells (MSC), more than one type of stem cell niche has been identified. By employing high throughput screening (HTS) strategies, common and specific attributes of each MSC niche can be probed. Here, we explore biological, chemical and physical parameters that are known to influence MSC self-renewal and differentiation. We then review techniques and strategies that allow the HTS of surface properties for conditions that direct stem cell fate, using MSC as a case study. Finally, challenges in recapturing the niche, particularly its three dimensional nature, in surface-based HTS formats are discussed. © 2013 Elsevier Ltd.


Hatzirodos N.,Robinson Institute | Bayne R.A.,University of Edinburgh | Irving-Rodgers H.F.,Robinson Institute | Irving-Rodgers H.F.,Queensland University of Technology | And 11 more authors.
FASEB Journal | Year: 2011

Although not often discussed, the ovaries of women with polycystic ovary syndrome (PCOS) show all the hallmarks of increased TGF-β activity, with increased amounts of fibrous tissue and collagen in the ovarian capsule or tunica albuginea and ovarian stroma. Recent studies suggest that PCOS could have fetal origins. Genetic studies of PCOS have also found linkage with a microsatellite located in intron 55 of the extracellular matrix protein fibrillin 3. Fibrillins regulate TGF-β bioactivity in tissues by binding latent TGF-β binding proteins. We therefore examined expression of fibrillins 1-3, latent TGF-β binding proteins 1-4, and TGF-β 1-3 in bovine and human fetal ovaries at different stages of gestation and in adult ovaries. We also immunolocalized fibrillins 1 and 3. The results indicate that TGF-β pathways operate during ovarian fetal development, but most important, we show fibrillin 3 is present in the stromal compartments of fetal ovaries and is highly expressed at a critical stage early in developing human and bovine fetal ovaries when stroma is expanding and follicles are forming. These changes in expression of fibrillin 3 in the fetal ovary could lead to a predisposition to develop PCOS in later life. © FASEB.


PubMed | Robinson Institute, University of Adelaide and SA Pathology
Type: Journal Article | Journal: International journal of molecular sciences | Year: 2016

Vulvar cancer is the fourth most common gynecological cancer worldwide. However, limited studies have been completed on the molecular characterization of vulvar squamous cell carcinoma resulting in a poor understanding of the disease initiation and progression. Analysis and early detection of the precursor lesion of HPV-independent vulvar squamous cell carcinoma (VSCC), differentiated vulvar intraepithelial neoplasia (dVIN), is of great importance given dVIN lesions have a high level of malignant potential. Here we present an examination of adjacent normal vulvar epithelium, dVIN, and VSCC from six patients by peptide Matrix-assisted laser desorption/ionization Mass Spectrometry Imaging (MALDI-MSI). The results reveal the differential expression of multiple peptides from the protein cytokeratin 5 (CK5) across the three vulvar tissue types. The difference observed in the relative abundance of CK5 by MALDI-MSI between the healthy epithelium, dVIN, and VSCC was further analyzed by immunohistochemistry (IHC) in tissue from eight VSCC patients. A decrease in CK5 immunostaining was observed in the VSCC compared to the healthy epithelium and dVIN. These results provide an insight into the molecular fingerprint of the vulvar intraepithelial neoplasia that appears to be more closely related to the healthy epithelium than the VSCC.


Gatford K.L.,Robinson Institute | Simmons R.A.,University of Pennsylvania | De Blasio M.J.,Robinson Institute | Robinson J.S.,Robinson Institute | Owens J.A.,Robinson Institute
Placenta | Year: 2010

Being born small due to poor growth before birth increases the risk of developing metabolic disease, including type 2 diabetes, in later life. Inadequate insulin secretion and decreasing insulin sensitivity contribute to this increased diabetes risk. Impaired placental growth, development and function are major causes of impaired fetal growth and development and therefore of IUGR. Restricted placental growth (PR) and function in non-human animals induces similar changes in insulin secretion and sensitivity as in human IUGR, making these valuable tools to investigate the underlying mechanisms and to test interventions to prevent or ameliorate the risk of disease after IUGR. Epigenetic changes induced by an adverse fetal environment are strongly implicated as causes of later impaired insulin action. These have been well-characterised in the PR rat, where impaired insulin secretion is linked to epigenetic changes at the Pdx-1 promotor and reduced expression of this transcription factor. Present research is particularly focussed on developing intervention strategies to prevent or reverse epigenetic changes, and normalise gene expression and insulin action after PR, in order to translate this to treatments to improve outcomes in human IUGR. © 2010 Elsevier Ltd. All rights reserved.


Haridas V.,Indian Institute of Technology Delhi | Sadanandan S.,Indian Institute of Technology Delhi | Collart-Dutilleul P.-Y.,Montpellier University | Gronthos S.,Robinson Institute | Voelcker N.H.,University of South Australia
Biomacromolecules | Year: 2014

We report on the self-assembly based fabrication of fibrous polymers for tissue engineering applications. Directed self-assembly followed by polymerization of lysineappended diacetylenes generated a variety of polymers (P1. P5) with distinct chemical properties. The self-assembly along with the conjugated double and triple bonds and rigid geometry of diacetylene backbone imposed a nanofibrous morphology on the resulting polymers. Chemical properties including wettability of the polymers were tuned by using lysine (Lys) with orthogonal protecting groups (Boc and Fmoc). These Lys-appended polydiacetylene scaffolds were compared in terms of their efficiency toward human mesenchymal stem cells adhesion and spreading. Interestingly, polymer P4 containing Lys Nα-NH2and Lys Nε-Boc with balanced wettability supported cell adhesion better than the more hydrophobic polymer P2 with Nε-Boc and Nα-Fmoc or more hydrophilic polymer P5 containing free Nεand Nαamino groups. The molecular level control in the fabrication of nanofibrous polymers compared with other existing methods for the generation of fibrous polymers is the hallmark of this work. © 2014 American Chemical Society.

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