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Craig A.,Kolling Institute for Medical Research | Tran Y.,Kolling Institute for Medical Research | Guest R.,Kolling Institute for Medical Research | Gopinath B.,Kolling Institute for Medical Research | And 7 more authors.
BMJ Open | Year: 2016

Objective: The aim of this meta-analysis was to determine the psychological impact associated with motor vehicle crash (MVC)-related physical injuries. Design: Systematic review and meta-analysis. Data sources: Multiple search engines included MEDLINE (via OVID), PsycINFO and Embase, and studies were sourced from scientific journals, conference papers and doctoral theses. Study selection: A high-yield search strategy was employed. Terms like 'psychological distress', 'depression', 'PTSD' and 'motor vehicle accident' were employed. These key words were run primarily and secondary searches were then conducted in association with the major injury types. Studies needed to compare psychological distress in people injured in an MVC with uninjured controls who had not recently experienced an MVC. Data extraction: Searches resulted in the identification of 2537 articles, and after eliminating duplicates and studies not meeting inclusion criteria, 24 studies were selected involving 4502 injured participants. These studies were entered into separate meta-analyses for mild to moderate traumatic brain injury (mTBI), whiplash-associated disorder (WAD) and spinal cord injury (SCI). Results: Elevated psychological distress was associated with MVC-related injuries with a large summary effect size in WAD (0.90), medium to large effect size in SCI (0.69) and small to medium effect size in mTBI (0.23). No studies meeting inclusion criteria were found for burns, fractures and low back injury. Increased psychological distress remains elevated in SCI, mTBI and WAD for at least 3 years post-MVC. Conclusions: Rehabilitation strategies are needed to minimise distress subsequent to MVC-related physical injuries and the scientific robustness of studies requires improvement.


Tseng H.-Y.,University of Newcastle | Tseng H.-Y.,Hunter Medical Research Institute | Chen L.H.,University of Newcastle | Chen L.H.,Hunter Medical Research Institute | And 11 more authors.
Carcinogenesis | Year: 2012

Emerging evidence has pointed to biological roles of melanoma-associated antigens (MAGEs) in cancer development, progression and resistance to treatment. However, the mechanisms involved remain to be fully elucidated. In this report, we show that one of the MAGE proteins, MAGE-D2, suppresses the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor 2 (TRAIL-R2) and plays an important role in protecting melanoma cells from apoptosis induced by TRAIL. MAGE-D2 was commonly expressed at increased levels in melanoma cells compared with melanocytes. Although its inhibition by small interfering RNA (siRNA) did not cause cell death, it rendered melanoma cells more sensitive to TRAIL-induced apoptosis. This was associated with enhanced formation of TRAIL death-inducing signaling complex and up-regulation of TRAIL-R2, and was blocked by a recombinant TRAIL-R2/Fc chimeric protein or siRNA knockdown of TRAIL-R2. Regulation of TRAIL-R2 by MAGE-D2 appeared to be mediated by p53, in that knockdown MAGE-D2 did not up-regulate TRAIL-R2 in p53-null or mutant p53 melanoma cells. In addition, inhibition of MAGE-D2 did not result in up-regulation of TRAIL-R2 in wild-type p53 cell lines with p53 inhibited by short hairpin RNA. Indeed, knockdown of MAGE-D2 led to up-regulation of p53 due to a transcriptional increase. The regulatory effect of MAGE-D2 on TRAIL-R2 expression and TRAIL-induced apoptosis was recapitulated in studies on fresh melanoma isolates. Taken together, these results identify the expression of MAGE-D2 as an important mechanism that inhibit TRAIL-induced apoptosis and suggest that targeting MAGE-D2 may be a useful strategy in improving the therapeutic efficacy of TRAIL in melanoma. © The Author 2012. Published by Oxford University Press. All rights reserved.


PubMed | Kolling Institute for Medical Research and China National Population and Family Planning Key Laboratory of Contraceptive Drugs and Devices
Type: Journal Article | Journal: Asian journal of andrology | Year: 2015

Azoospermia, cryptozoospermia and necrospermia can markedly decrease the ability of males to achieve pregnancy in fertile females. However, patients with these severe conditions still have the option to be treated by intracytoplasmic sperm injection (ICSI) to become biological fathers. This study analyzed the fertilization ability and the developmental viabilities of the derived embryos after ICSI treatment of the sperm from these patients compared with in vitro fertilization (IVF) treatment of the proven-fertile donor sperm on sibling oocytes as a control. On the day of oocyte retrieval, the number of sperm suitable for ICSI collected from two ejaculates or testicular sperm extraction was lower than the oocytes, and therefore, excess sibling oocytes were treated by IVF with donor sperm. From 72 couples (73 cycles), 1117 metaphase II oocytes were divided into 512 for ICSI and 605 for IVF. Compared with the control, husbands sperm produced a lower fertilization rate in nonobstructive azoospermia (65.4% vs 83.2%; P< 0.001), crytozoospermia (68.8% vs 75.5%; P< 0.05) and necrospermia (65.0% vs 85.2%; P< 0.05). The zygotes derived in nonobstructive azoospermia had a lower cleavage rate (96.4% vs 99.4%; P< 0.05), but the rate of resultant good-quality embryos was not different. Analysis of the rates of cleaved and good-quality embryos in crytozoospermia and necrospermia did not exhibit a significant difference from the control. In conclusion, although the sperm from severe male infertility reduced the fertilization ability, the derived embryos had potential developmental viabilities that might be predictive for the expected clinical outcomes.


Ahmad K.E.,Royal North Shore Hospital | Fraser C.L.,University of Sydney | Sue C.M.,Kolling Institute for Medical Research | Barton J.J.S.,University of British Columbia
Survey of Ophthalmology | Year: 2016

A 45-year-old woman presented with acute sequential optic neuropathy resulting in bilateral complete blindness. No significant visual recovery occurred. Past medical history was relevant for severe preeclampsia with resultant renal failure, diabetes mellitus, and sudden bilateral hearing loss when she was 38 years old. There was a family history of diabetes mellitus in her mother. Testing for common causes of bilateral optic neuropathy did not reveal a diagnosis for her illness. The maternal and personal history of diabetes and deafness prompted testing for mitochondrial disease. The 3 primary mitochondrial DNA mutations responsible for Leber hereditary optic neuropathy were absent, but the patient was subsequently found to have a disease causing mitochondrial DNA mutation, m.13513G>A. The case illustrates the importance of early testing for mitochondrial disease and demonstrates that Leber hereditary optic neuropathy-like presentations may be missed if testing is limited to the 3 primary mutations. © 2016.


PubMed | Kolling Institute for Medical Research
Type: Journal Article | Journal: Journal of sports science & medicine | Year: 2013

The low oxidative demand and muscular adaptations accompanying eccentric exercise hold benefits for both healthy and clinical populations. Compression garments have been suggested to reduce muscle damage and maintain muscle function. This study investigated whether compression garments could benefit metabolic recovery from eccentric exercise. Following 30-min of downhill walking participants wore compression garments on one leg (COMP), the other leg was used as an internal, untreated control (CONT). The muscle metabolites phosphomonoester (PME), phosphodiester (PDE), phosphocreatine (PCr), inorganic phosphate (Pi) and adenosine triphosphate (ATP) were evaluated at baseline, 1-h and 48-h after eccentric exercise using (31)P-magnetic resonance spectroscopy. Subjective reports of muscle soreness were recorded at all time points. The pressure of the garment against the thigh was assessed at 1-h and 48-h following exercise. There was a significant increase in perceived muscle soreness from baseline in both the control (CONT) and compression (COMP) leg at 1-h and 48-h following eccentric exercise (p < 0.05). Relative to baseline, both CONT and COMP showed reduced pH at 1-h (p < 0.05). There was no difference between CONT and COMP pH at 1-h. COMP legs exhibited significantly (p < 0.05) elevated skeletal muscle PDE 1-h following exercise. There was no significant change in PCr/Pi, Mg(2+) or PME at any time point or between CONT and COMP legs. Eccentric exercise causes disruption of pH control in skeletal muscle but does not cause disruption to cellular control of free energy. Compression garments may alter potential indices of the repair processes accompanying structural damage to the skeletal muscle following eccentric exercise allowing a faster cellular repair. Key PointsEccentric exercise results in reduced cellular pH 1 hour after exercise.Graduated compression garments may influence indices of muscle membrane repair and turnover at one-hour recovery from eccentric exercise.Graduated compression garments do not change perceived muscle soreness.

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