http://www.researchonline.mq.edu.au/vital/access/services/Feed ${session.getAttribute("locale")} 5 http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25526 Mouse mammary tumor virus (MMTV) sequences have been reported to be present in some human breast cancers, but it is unclear whether they have any causal role. In mice, MMTV promotes tumor formation indirectly by insertional mutagenesis of Wnt oncogenes that lead to their activation. In this study, we investigated the status of Wnt-1 in human breast cancers harboring MMTV-like sequences encoding viral envelope (env) genes. We confirmed the detection of env sequences in the nucleus of human breast cancer specimens that are similar in appearance to mouse mammary tumors expressing MMTV env sequences. MMTV env sequences in human breast cancers were also nearly indistinguishable from env sequences in mouse MMTV isolates. Further, Wnt-1 expression was higher in specimens of env-positive ductal carcinoma in situ and invasive ductal carcinoma, relative to env-negative specimens. Our findings extend the evidence that MMTV sequences found in naturally occurring mouse mammary tumors can be found in some human breast cancers, prompting further evaluation of causal roles in these settings. 2013-05-15T14:22:16.328Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25530 BACKGROUND: Men diagnosed with localised prostate cancer (LPC) face difficult choices between treatment options that can cause persistent problems with sexual, urinary and bowel function. Controlled trial evidence about the survival benefits of the full range of treatment alternatives is limited, and patients' views on the survival gains that might justify these problems have not been quantified. METHODS: A discrete choice experiment (DCE) was administered in a random subsample (n=357, stratified by treatment) of a population-based sample (n=1381) of men, recurrence-free 3 years after diagnosis of LPC, and 65 age-matched controls (without prostate cancer). Survival gains needed to justify persistent problems were estimated by substituting side effect and survival parameters from the DCE into an equation for compensating variation (adapted from welfare economics). RESULTS: Median (2.5, 97.5 centiles) survival benefits needed to justify severe erectile dysfunction and severe loss of libido were 4.0 (3.4, 4.6) and 5.0 (4.9, 5.2) months. These problems were common, particularly after androgen deprivation therapy (ADT): 40 and 41% overall (n=1381) and 88 and 78% in the ADT group (n=33). Urinary leakage (most prevalent after radical prostatectomy (n=839, mild 41%, severe 18%)) needed 4.2 (4.1, 4.3) and 27.7 (26.9, 28.5) months survival benefit, respectively. Mild bowel problems (most prevalent (30%) after external beam radiotherapy (n=106)) needed 6.2 (6.1, 6.4) months survival benefit. CONCLUSION: Emerging evidence about survival benefits can be assessed against these patient-based benchmarks. Considerable variation in trade-offs among individuals underlines the need to inform patients of long-term consequences and incorporate patient preferences into treatment decisions. 2013-05-15T14:22:11.616Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25455 Microinjection of the excitatory amino acid glutamate is commonly used to stimulate neuronal cell bodies in brainstem nuclei that are crucial for cardiovascular regulation, respiratory control, and other functions. One such nucleus, the rostral ventrolateral medulla (RVLM), integrates afferent information to coordinate cardiovascular responses to changes in the environment. In the RVLM, an increase in mean blood pressure of ³ 25 mmHg following glutamate microinjection is widely accepted as evidence of accurate localisation of this nucleus. However, the dose of glutamate, and injection volume, varies considerably between investigators, and the optimal parameters are controversial. Here we examined data from 34 publications over the past 20 years in which glutamate doses, ranging from 0.0051 to 8.5 m g, were injected to identify the rostral ventrolateral medulla (RVLM) in rat. The aim of this chapter is to describe, in a pragmatic way, the ideal parameters for this method. Our meta-analysis reveals that there is a dose–response relationship between glutamate and blood pressure at low doses, but once the dose is sufficient to elicit a ³35 mmHg rise in blood pressure, the response plateaus (~0.5 m g). Interestingly, the injection volumes used in the studies examined do not show any correlation with the observed blood pressure responses. Neither strain nor weight of rat had any influence on the blood pressure response induced by glutamate. Glutamate microinjection is a stable and reproducible method for activating cell bodies, but not fibres of passage, in most brain regions, and may also be a useful tool for normalising other drug responses. 2013-05-09T09:34:02.456Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25463 Purpose - Increased uptake of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) in atherosclerotic plaque on Positron Emission Tomography (PET), predicts vulnerability. Recent studies have shown that the PET signal is reproducible over a 2-week period and as a result drug trials are underway. However, the natural history of these lesions is unknown. The aim of this study is determine the natural history of increased vascular wall uptake of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG). Methods - Following institutional ethics committee approval, we retrospectively examined PET/CT images of patients from our Institution that had at least 4 examinations in the last 5 years. This represented 205 studies in total, from 50 patients (29 men, 21 women, mean age 49.4 ± 12.1 years, mean 5.1 ± 1.7 studies/patient). The mean follow-up was 27.2 ± 11.8 months. The carotids and the aorta were evaluated for increased 18F-FDG uptake with a maximum Standardized Uptake Value (SUVmax) >2.5, and >3.0, and calcification. Plots of SUVmax and Hounsfield units (HU) were made versus time. Results - The initial prevalence of increased focal arterial ¹⁸F-FDG uptake was 17/50 patients and of arterial calcification 19/50. 132 sites of ¹⁸F-FDG uptake in total were observed longitudinally. ¹⁸F-FDG vascular uptake did not persist with time. There was no correlation between ¹⁸F-FDG uptake and HU. No calcifications developed at sites of focal increased ¹⁸F-FDG uptake. Conclusions - Arterial lesions with increased ¹⁸F-FDG uptake represent transient phenomena. This data is important for the interpretation of findings of clinical trials using arterial ¹⁸F-FDG uptake as an imaging biomarker to monitor pharmacological intervention. 2013-05-09T09:33:22.837Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25457 The visual evoked potential (VEP) is recorded in humans in response to flash or pattern stimuli with appropriately placed electrodes over the occipital scalp. In recent years the multifocal VEP (mfVEP) has been developed as a means of obtaining focal responses rather than just a summed response from the central field. The mfVEP has been used as a form of objective perimetry to detect visual field loss in glaucoma. This chapter covers conventional VEP recording and some principles of the multifocal technique. 2013-05-07T05:25:28.238Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25452 Putative sympathetic premotor neurons in the rostral ventrolateral medulla are critically important in the regulation of sympathetic vasomotor tone and are responsible for mediating many cardiovascular reflexes. In the rat, these neurons lie within a small area of the brainstem immediately caudal to the facial nucleus and can be distinguished from neighbouring cells by their axonal projections to the thoracic spinal cord, where they are thought to form synapses with sympathetic preganglionic neurons. This protocol describes the steps required for identification of sympathetic premotor neurons in acute experiments in vivo. It provides a detailed description of the methodology we use routinely to electrophysiologically map the topography of the facial nucleus and an account of the steps needed to conduct the antidromic collision test. 2013-05-07T05:00:39.060Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:19698 3 page(s) 2013-04-26T05:59:13.718Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25325 18 pages(s) 2013-04-26T05:20:32.773Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25328 15 pages(s) 2013-04-24T09:31:16.192Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25317 18 pages(s) 2013-04-24T04:50:39.856Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25316 16 pages(s) 2013-04-24T04:50:37.902Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25319 30 pages(s) 2013-04-24T04:50:15.409Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25320 14 pages(s) 2013-04-24T04:50:07.844Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:17840 Cultured neurons tolerate low H₂O₂ concentrations (≤50 μM) through the activity of constitutive antioxidant response elements (ARE). At H₂O₂ levels (≥100 μM), neurons increase expression of the gene encoding for inducible hemoxygenase-1 while superoxide dismutase-2 and catalase remain unchanged. Despite this adaptive response, the endogenous antioxidant systems are overwhelmed, leading to decreased viability. Elevating the neuronal cell content of human neuroglobin (Ngb) prior to insult with 100 or 200 μM H₂O₂ enhanced cell viability and this resulted in a significant decrease in oxidative stress and an increase in the intracellular ATP concentration, whereas in parental cells exposed to the same H₂O₂-insult, oxidative stress and ATP increased and decreased, respectively. The mechanism for this increase in ATP involves sustained activation of the mito-KATP channel and an increase in phosphoinositide-3 kinase (PI3K)-mediated phosphorylation of Akt. Pharmacological inhibitors directed toward PI3K (wortmannin and LY294002), or the mito-KATP channel (glybenclamide) inhibited the H₂O₂-mediated increase in ATP in cells overexpressing human Ngb and consequently cell viability decreased. Neuroglobin's ability to bolster the intracellular pool of ATP in response to added H₂O₂ is central to the preservation of cytoskeletal integrity and cell viability. 2013-04-24T00:11:15.341Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25279 Alzheimer's disease (AD) is the most common origin of dementia in the elderly. Although the cause of AD remains unknown, several factors have been identified that appear to play a critical role in the development of this debilitating disorder. In particular, amyloid precursor protein (APP), tau hyperphosphorylation, and the secretase enzymes, have become the focal point of recent research. Over the last two decades, several transgenic and non-transgenic animal models have been developed to elucidate the mechanistic aspects of AD and to validate potential therapeutic targets. Transgenic rodent models over-expressing human β-amyloid precursor protein (β-APP) and mutant forms of tau have become precious tools to study and understand the pathogenesis of AD at the molecular, cellular and behavioural levels, and to test new therapeutic agents. Nevertheless, none of the transgenic models of AD recapitulate fully all of the pathological features of the disease. Octodon degu, a South American rodent has been recently found to spontaneously develop neuropathological signs of AD in old age. This review aims to address the limitations and clinical relevance of transgenic rodent models in AD, and to highlight the potential for O. degu as a natural model for the study of AD neuropathology. 2013-04-22T20:11:16.814Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25245 We recently reported that acute intermittent hypoxia (AIH, 10x45s of 10% O₂, 5 min intervals) produces LTF of splanchnic sympathetic nerve activity (sSNA), independent of respiratory LTF (Xing & Pilowsky, 2010, J Physiol, 588:3075). We hypothesised that sympathetic LTF (sLTF) is the result of intermittent activation of RAS, by renal hypoxia caused by AIH-evoked hypotension. We recorded phrenic nerve activity (PNA) and sSNA, in anesthetised (pentobarbitone, 60mg/kg, ip), vagotomised, and ventilated Sprague-Dawley rats. Intermittent bolus injections of angiotensin II (Ang, 10x35pmol in 0.1ml, iv), at the same 5 min intervals as AIH, elicited sLTF (+42.4 ±11.5%, n=5). Intermittent phenylephrine (PE, 10x 25μg in 0.1mL, iv) also produced sLTF (+72.4±21.6%, n=5), possibly via renal vasoconstriction induced renin release. Intermittent sodium nitroprusside induced hypotension (10x50μg in 0.1mL, iv) did not elicit sLTF (+2.4±5.6%, n=5). Infusion of Ang (350pmol in 1mL) or PE (250μg in 1mL) over 10 mins, also did not cause sLTF, indicating that intermittent stimulation of RAS is essential for sLTF to develop. PNA was unchanged in all groups. This data supports the idea that sLTF and respiratory LTF are mediated by separate mechanisms and that intermittent stimulation of peripheral RAS may be sufficient to elicit sLTF. This data may be relevant to sympathetic overactivity in sleep apnea patients. Funded by NH&MRC, ARC. 2013-04-17T19:40:46.198Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25247 Episodic breathing is common in premature infants and is found in fetal rats but rarely reported in postnatal (P) in vitro preparations. We discovered that episodic breathing patterns were common (>60%) in in vitro pontomedullary-spinal cord preparations at 27°C from rat pups on the day of birth (P0), but the occurrence of this breathing pattern declined with postnatal development. Chemical inhibition and physical removal of the pons eliminated the episodic breathing pattern at P0. Interestingly, episodic breathing patterns could be restored in older preparations (P2 – P4) by decreasing temperature (23°C), with or without the pons. In preparations held at 27°C, with a continuous rhythm, an episodic rhythm could be produced by activating GABA receptors (100μM GABA). In preparations with an episodic pattern, antagonism of opioid receptors by naloxone (1–5μm) did not affect the episodic rhythm while blockade of GABAA receptors by bicuculline (BIC, 10μM) converted the episodic rhythm to a continuous rhythm. However, in preparations held at 23°C, BIC (10μM) had the opposite effect, promoting episodicity. Together, these data suggest the mechanisms required for episodic rhythm generation are intrinsic to the medulla, and are modulated by postnatal development, temperature sensitive mechanisms (such as TRP channels) and pontine factors. Funded by NSERC (Canada). 2013-04-17T19:40:37.124Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25248 Overall objective: To determine if the sustained elevation of splanchnic sympathetic nerve activity (sSNA), termed long-term facilitation (LTF), following acute intermittent hypoxia (AIH) is due to intermittent, release of sympathoexcitatory peptides, such as pituitary adenylate cyclase activating polypeptide (PACAP). Methods: In urethane-anaesthetized, artificially ventilated, male rats (n=18 Sprague–Dawley), we investigated the effect of 10, 45s, episodes of 10%O2–90%N2 every 5 min (AIH) on sSNA after intrathecal infusion of 10μl of vehicle, PACAP (300μM) or the PAC1/VPAC2 receptor antagonist, PACAP(6–38) (1mM). In a separate group of rats (n=6) without AIH, 10 doses of PACAP (10μL of 10μM) were given intrathecally every 5 min. Results: Vehicle-treated rats showed a 31.0±8.1% increase in sSNA 60min after AIH, which doubled to 67.7±14.1% in PACAP treated rats. Infusing the PACAP antagonist PACAP(6–38) prior to AIH abolished sympathetic LTF (0.1±2.7%). The responses were significantly different (P<0.0001; 2-way ANOVA). Intermittent, sub-threshold, infusion of PACAP (10x10μM) was as effective as AIH in causing LTF (sSNA increase of 38.±8.0%). Conclusion: PACAP, acting via spinal PAC1/VPAC2 receptors, is sufficient to cause sympathetic LTF in the absence of AIH and necessary for the elaboration of sympathetic LTF following AIH. 2013-04-17T19:40:32.861Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25145 Purpose: Retinal ganglion cells (RGCs) undergo degeneration in glaucoma and optic neuritis. Recent studies indicate the involvement of Caveolin (Cav-1) gene locus in the pathogenesis of POAG. Caveolin protein is principal component of Caveolae and comprises cav1, 2 and 3 isoforms. We studied the rat retinal structural and functional alterations in the lack of cav isoforms. Since insulin like growth factor receptor (IGF-1R) signalling is neuroprotective in the retina, the effect of cav loss on the IGF-1R signalling was studied. Methods: Scotopic threshold response (STR) recordings were performed in rats to assess the functional changes in the inner retina. The retinas were imaged in vivo using Optical Coherence Tomography (OCT). RGCs were isolated from rat retinas using the CD90.1 magnetic separation technique. Cav knockdown was carried out using intravitreal injections of anti- sense oligonucleotides. Co-immunoprecipitations and immunoblotting were used to investigate the expression and activation of IGF-1R. Results: The knockdown of cav isoforms in the retina resulted in a preferential loss of inner retinal function over a period of 20 weeks as measured by the STR recordings (p<0.005). A thinning of the retinal layers was observed in OCT scans (p<0.01). Cav loss resulted in increase in IGF-1R expression and its activation (p<0.05) in the rat RGCs. Conclusion: Our results indicate that cav isoforms play a critical role in maintaining the normal inner retinal function. Activation of IGF-1R in RGCs was observed with cav knockdown. Our experiments indicate that IGF-1R expression and activation in RGCs is dependent on the normal cav expression. 2013-04-11T11:22:52.138Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25146 Purpose: To evaluate neuroprotective effects of 7,8-dihydroxyflavone (7,8-DHF) on isolated rat retinal ganglion cells (RGCs) and RGC-5 cells to assess for the activation of TrkB and downstream survival signaling pathways. Methods: To determine the optimal concentration for TrkB signalling activation, we initially used RGC-5 cell line treated with various concentrations of the 7,8-DHF (0-500 nM). Cells were also incubated with the drug (100 nM) for 0-16 hrs to study the time-course of TrkB signaling. The effects on the TrkB receptor and its downstream signaling on isolated RGCs and RGC-5 were then monitored by western blotting. Cells were exposed to Glutamate+H2O2 for stress induction. Changes in cell density and neurite outgrowth were analyzed by Thy-1 immunostaining. TrkB receptor kinase activity was assessed by immunoprecipitations followed by ELISA. Cell viability and apoptosis were evaluated using Quick Cell proliferation assay and caspase-3 activation respectively. Results: 7,8-DHF treatment resulted in the phosphorylation of TrkB receptor and activation of TrkB kinase activity (p<0.001) as well as downstream Akt and Erk signaling in both RGC-5 and isolated rat RGCs. 7,8-DHF also induced neuritogenesis by stimulating neurite outgrowth in the RGC-5 cells. Cell counting, proliferation assay and Caspase-3 activation demonstrated that 7,8-DHF treatment protected RGCs significantly (p<0.03) against glutamate and H2O2 induced cell death in culture. Conclusions: 7,8-DHF suppresses caspase-3 activation and improves RGC viability under excitotoxic and oxidative stress thereby suggesting a possible therapeutic strategy for protection of RGCs in glaucoma. The results obtained with RGC-5 cells were confirmed in isolated rat RGCs. 2013-04-11T11:22:49.644Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25148 1 page(s) 2013-04-11T11:22:49.156Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25153 Purpose: To evaluate the efficacy of corneal collagen cross linking in the management of cases of progressive keratoconus. Methods: Thirty five patients (fifty one eyes) with progressive keratoconus who underwent cross linking with a mean follow up of 14.38 + 9.36 months (range 6–48 months) were compared with a control group of twenty five fellow eyes that did not undergo the procedure. Collagen cross linking was performed using 0.1% riboflavin (in 20% dextran T500) and ultraviolet A (UVA) irradiation (370 nm,3 mW/cm2, 30 min). Results: Analysis of the treated group demonstrated a significant flattening of maximum keratometry by 0.96+2.33 D (p =0.005) and a significant improvement in visual acuity by 0.05 + 0.13 logMAR (p =0.04). In the control group, maximum keratometry increased significantly by 0.43 +0.85 D (p=0.05) and visual acuity decreased by mean 0.05 + 0.14 (p=0.2). No tatistical differences were noted regarding cylindrical power, spherical equivalent or corneal thickness in both groups. Conclusions: Results indicate that corneal collagen cross linking using riboflavin and ultraviolet A is effective as a therapeutic option in cases of progressive keratoconus by reducing the corneal curvature and improving the visual acuity in these patients. 2013-04-11T11:22:33.963Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25156 1 page(s) 2013-04-11T11:22:27.976Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25158 1 page(s) 2013-04-11T11:22:23.801Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25157 1 page(s) 2013-04-11T11:22:22.141Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25160 Background: The beta-amyloid (Aβ) peptide comprises the amyloid plaques that characterise Alzheimer's disease (AD), and is thought to significantly contribute towards disease pathogenesis. Oxidative stress is elevated in the AD brain, and there is substantial evidence that the interaction between Aβ and redox-active copper is a major contributing factor towards oxidative stress in AD. Results: The major findings of this study are that redox-active Cu(II)-Aβ causes pronounced axonal pathology in long-term neuronal cultures, including axonal fragmentation and the formation of hyperphosphorylated tau-immunoreactive axonal swellings. Notably, MAP-2 expressing dendritic processes remain largely un-affected by Cu(II)-Aβ treatment. These dystrophic axonal manifestations resemble some of the characteristic neuritic pathology of the AD brain. We show that Cu(II)-Aβ directly causes formation of intra-axonal swellings via the generation of free radicals and subsequent efflux of K + out of neurons. Conclusion: In summary, we report that redox-active Cu(II)-Aβ can induce substantial neurodegenerative changes in mature neurons, and may have an important role to play in the slowly progressing pathogenesis of AD. 2013-04-11T11:22:16.155Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25163 Nature has gifted mankind with a plethora of flora-bearing fruits, vegetables and nuts. The diverse array of bioactive nutrients present in these natural products plays a pivotal role in prevention and cure of various neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease and other neuronal dysfunctions. Accumulated evidence suggests that naturally occurring phyto-compounds, such as polyphenolic antioxidants found in fruits, vegetables, herbs and nuts, may potentially hinder neurodegeneration, and improve memory and cognitive function. Nuts such as walnut have also demonstrated neuroprotective effect against AD. The molecular mechanisms behind the curative effects rely mainly on the action of phytonutrients on distinct signalling pathways associated with protein folding and neuroinflammation. The neuroprotective effects of various naturally occurring compounds in AD is evaluating in this review. 2013-04-11T11:22:08.605Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25167 Objective: To define the clinical syndrome of functional popliteal entrapment comparing pre and post surgical clinical outcomes with pre and post-operative provocative ultrasonic investigations. Further, to suggest a management pathway to differentiate chronic exertional compartment syndromes and concomitant venous popliteal compression. Methods: In 32 claudicant sportspersons, 55 limbs were characterised pre-surgery clinically, with provocative testing including hopping, and following a series of non-invasive tests. The clinical findings, ankle brachial indices (ABI) and duplex outcomes were compared pre-operatively, at 3 months post-operatively (n = 52) and in the long term i.e. 16 months (n = 17). Results: At 3 months, all 55 limbs had clinical follow up. 52 of the 55 limbs had follow up with ultrasound with provocative manoeuvres. The ABIs normalised in 46 (88%). There were 40 of 52 (76%) that became asymptomatic post surgery with a normal scan. There were 4 of 52 (8%) who were clinically asymptomatic but with residual obstruction on duplex and who were able to resume their usual lifestyle. There were 4 (8%) that had abnormal findings both on post-operative scan and clinically. Re-operation on 2 limbs corrected the duplex findings and the symptoms. There were 4 (8%) limbs that had normal duplexes but continued with symptoms albeit varied from the presenting symptoms. In the longer term, a further 2 became symptomatic at 2.8 years requiring a further successful intervention. (Concomitant popliteal venous obstruction was present in 5 limbs (10%) on standing.) Conclusions: In the claudicating sportsperson, where there are no well characterised specific anatomical abnormalities, the syndrome can be characterised by provocative clinical (particularly hopping) and non-invasive tests. A positive clinical outcome with surgery can be predicted by abnormal pre-surgical ultrasonic investigations and confirmed later by a similar normal post surgical study. Concomitant venous compression may occur while standing with both syndromes related to muscle hypertrophy. 2013-04-11T11:21:57.624Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25166 Mutations in the gene encoding fused in sarcoma (FUS) are linked to amyotrophic lateral sclerosis (ALS), but the mechanisms by which these mutants trigger neurodegeneration remain unknown. Endoplasmic reticulum (ER) stress is increasingly recognized as an important and early pathway to motor neuron death in ALS. FUS is normally located in the nucleus but in ALS, FUS redistributes to the cytoplasm and forms inclusions. In this study, we investigated whether FUS induces ER stress in a motor neuron like cell line (NSC-34). We demonstrate that ER stress is triggered in cells expressing mutant FUS, and this is closely associated with redistribution of mutant FUS to the cytoplasm. Mutant FUS also colocalized with protein disulfide-isomerase (PDI), an important ER chaperone, in NSC-34 cells and PDI was colocalized with FUS inclusions in human ALS lumbar spinal cords, in both sporadic ALS and mutant FUS-linked familial ALS tissues. These findings implicate ER stress in the pathophysiology of FUS, and provide evidence for common pathogenic pathways in ALS linked to the ER. 2013-04-11T11:21:57.570Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25168 Retinal ganglion cells of different species have been categorised using different paradigms and resulting in different number of suggested classes/types based on traditional morphological parameters such as cell body size or dendritic diameter. The inherent nature of the neuron's branching pattern has also been shown to play a role in signal processing and therefore additional features such as fractal dimension and lacunarity were added. Machine learning algorithms (MLA) provide a basis for classification tasks based on large numbers of features. However there are numerous ways of presenting data, different algorithms, validation methods and determination of performance. No studies have been undertaken that investigate the influence of model validation on small datasets with diverse feature parameters. This paper outlines the differences when balanced and imbalanced data is used in combination with six supervised MLAs and two different validation algorithms (LOO and 10-fold) as well as interpreting the results using two performance measures (AUC or accuracy). Our results indicate that that the largest effect on MLA outcomes is whether data is balanced or imbalanced. AUC is a more robust decision rule compared to accuracy. The best classifiers for our data were neural networks and logistic regression with an AUC of greater than 0.9. 2013-04-11T11:21:52.546Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25169 This study was designed to investigate parameters of autonomic dysfunction that may be under the influence of ACE ID genotypes. 136 patients with (47) and without type II diabetes were genotyped. Biomarkers such as HbAlc and eGFR, blood pressure, blood cholesterol are in part regulated by the autonomic nervous system and heart rate variability is an indicator of autonomic balance between the sympathetic and parasympathetic division. Several statistical methods were used, including the J48 decision tree machine learning algorithm to associate parameters of autonomic dysfunction and other biomarkers with ACE genotype. Non-parametric and machine learning methods detected more variables, which were able to contribute to classification of patients into genotypes. We found that HbAlc and TC:HDL were important nodes for separation of ACE genotype classes when the J48 decision tree algorithm was used. These were also verified by the Mann-Whitney analysis. Parametric comparisons of normally distributed variables revealed that only HDL was significantly different between the genotypes. Our findings potentially demonstrate an association between parameters of autonomic dysfunction with ACE genotypes. 2013-04-11T11:21:50.911Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25172 Gliomas are the most common type of brain tumours in adults and a significant cause of cancer-related mortality. The 1p/19q chromosome deleted oligodendroglioma subtype has been shown to have a good prognosis following chemotherapy. However the subjectivity inherent with associated tissue features in classifying this tumour has led to some uncertainty in diagnosis and identifying optimal treatment options. This study investigated the use of the Higuchi dimension (DH) as a diagnostic tool to differentiate between the oligodendrogliomas with and without loss of heterozygosity (LOH & noLOH respectively). Sixty-five neurosurgical resection specimens were analysed. DH was lower in the LOH tissue (mean±sd; 1.69±0.01; CI:1.69-1.71; p<0.05) compared to the non-deletion group (1.83±0.04; CI: 1.81-1.85; p<0.05). Our results indicate that oligodendroglioma tissue showed scale invariance and that the complexity of the tissue as determined by the Higuchi dimension decreased with loss of genetic heterozygosity. Determination of the fractal dimension of gliomas provides an inexpensive and accurate alternative for classification of oligodendrogliomas. 2013-04-11T11:21:44.422Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25173 In the twentieth century, NAD⁺ research generated multiple discoveries. Identification of the important role of NAD⁺ as a cofactor in cellular respiration and energy production was followed by discoveries of numerous NAD⁺ biosynthesis pathways. In recent years, NAD⁺ has been shown to play a unique role in DNA repair and protein deacetylation. As discussed in this review, there are close interactions between oxidative stress and immune activation, energy metabolism, and cell viability in neurodegenerative disorders and ageing. Profound interactions with regard to oxidative stress and NAD⁺ have been highlighted in the present work. This review emphasizes the pivotal role of NAD⁺ in the regulation of DNA repair, stress resistance, and cell death, suggesting that NAD⁺ synthesis through the kynurenine pathway and/or salvage pathway is an attractive target for therapeutic intervention in age-associated degenerative disorders. NAD⁺ precursors have been shown to slow down ageing and extend lifespan in yeasts, and protect severed axons from degeneration in animal models neurodegenerative diseases. 2013-04-11T11:21:38.810Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25177 Nicotinamide adenine dinucleotide (NAD⁺) is an essential electron transporter in mitochondrial respiration and oxidative phosphorylation. In genomic DNA, NAD⁺ also represents the sole substrate for the nuclear repair enzyme, poly(ADP-ribose) polymerase (PARP) and the sirtuin family of NAD-dependent histone deacetylases. Age associated increases in oxidative nuclear damage have been associated with PARP-mediated NAD⁺ depletion and loss of SIRT1 activity in rodents. In this study, we further investigated whether these same associations were present in aging human tissue. Human pelvic skin samples were obtained from consenting patients aged between 15-77 and newborn babies (0-1 year old) (n = 49) previously scheduled for an unrelated surgical procedure. DNA damage correlated strongly with age in both males (p = 0.029; r = 0.490) and females (p = 0.003; r = 0.600) whereas lipid oxidation (MDA) levels increased with age in males (p = 0.004; r = 0.623) but not females (p = 0.3734; r = 0.200). PARP activity significantly increased with age in males (p<0.0001; r = 0.768) and inversely correlated with tissue NAD⁺ levels (p = 0.0003; r = -0.639). These associations were less evident in females. A strong negative correlation was observed between NAD⁺ levels and age in both males (p = 0.001; r = -0.706) and females (p = 0.01; r = -0.537). SIRT1 activity also negatively correlated with age in males (p = 0.007; r = -0.612) but not in females. Strong positive correlations were also observed between lipid peroxidation and DNA damage (p<0.0001; r = 0.4962), and PARP activity and NAD+ levels (p = 0.0213; r = 0.5241) in post pubescent males. This study provides quantitative evidence in support of the hypothesis that hyperactivation of PARP due to an accumulation of oxidative damage to DNA during aging may be responsible for increased NAD⁺ catabolism in human tissue. The resulting NAD⁺ depletion may play a major role in the aging process, by limiting energy production, DNA repair and genomic signalling. 2013-04-11T11:21:29.830Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25179 In this study, the effects of bioactive glass nanoparticles' (nBGs) size and shape incorporated into hydroxyapatite/β-tricalcium phosphate (BCP) scaffolds were investigated. We prepared a highly porous (> 85%) BCP scaffold and coated its surface with a nanocomposite layer consisted of polycaprolactone (PCL) and rod (∼153 nm in height and ∼29 nm in width) or spherical (∼33 nm and 64 nm in diameter) nBGs. Osteogenic gene expression by primary human osteoblast-like cells (HOB) was investigated using quantitative real time polymerase chain reaction (q-RT-PCR). We demonstrated for the first time that in vitro osteogenesis is dramatically affected by the shape of the nBGs, whereby rod shaped nBGs showed the most significant osteogenic induction, compared to spherical particles (regardless of their size). Importantly, the good biological effect observed for the rod shaped nBGs was coupled by a marked increase in the modulus (∼48 MPa), compressive strength (∼1 MPa) and failure strain (∼6%), compared to those for the BCP scaffolds (∼4 MPa, ∼1 MPa and ∼0.5% respectively). The findings of this study demonstrated that the shape of the nBGs is of significant importance when considering bone regeneration. 2013-04-11T11:21:20.202Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25178 Study Design: An investigation of mechanical destabilization of the lumbar ovine intervertebral disc (IVD) inducing IVD degeneration (IVDD) as determined by multiparameter outcome measures (magnetic resonance imaging [MRI], IVD composition, biomechanical testing, gene profiling, immunohistochemistry, and immunoblotting). Objective: To assess the effect of IVD mechanical destabilization on matrix protein and metalloproteinase gene expression to investigate the pathophysiological mechanisms of lumbar IVDD. Summary of Background Data: Several earlier studies have used annular transection to induce IVDD in sheep, but none have optimized or validated the most appropriate lesion size. Methods: The annulus fibrosus (AF) incision inducing maximal change in IVD biomechanics was applied to L1-L2, L3-L4, and L5-L6 discs in vivo to compare with a sham procedure at 3 months post operation. IVDs were evaluated by MRI, biomechanics, histopathology, proteoglycan and collagen content, gene expression, and aggrecan proteolysis by Western blotting. Results: Significant changes were observed in lesion (6 × 20 mm 2) compared with sham IVDs at 3 months post operation: reduced disc height on MRI; increased neutral zone in biomechanical testing; depleted proteoglycan and collagen content in the nucleus pulposus (NP) and lesion half of the AF but not in the contralateral AF; increased messenger RNA for collagen I and II, aggrecan, versican, perlecan, matrix metalloproteinase (MMP)-1 & 13, and ADAMTS-5, in the lesion-site AF and NP but not in the contralateral AF. ADAMTS-4 messenger RNA was increased in the lesion-site AF but decreased in the NP. Despite an upregulation in MMPs, there was no change in MMP- or ADAMTS-generated aggrecan neoepitopes in any region of the IVD in lesion or sham discs. Conclusion: Lumbar IVDD was reproducibly induced with a 6 × 20 mm 2 annular lesion, with focal dysregulation of MMP gene expression, cell cloning in the inner AF, loss of NP aggrecan, and disc height. Loss of aggrecan from the NP was not attributable to increased proteolysis in the interglobular domain by MMPs or ADAMTS. 2013-04-11T11:21:18.516Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25184 Mutations in the optineurin gene (OPTN) have been reported in rare familial and sporadic amyotrophic lateral sclerosis (ALS) cases. It is yet to be established whether mutations segregate with dominantly inherited familial ALS. We therefore performed mutation analysis in a cohort of 96 autosomal dominant ALS families. A novel heterozygous nonsynonymous variant (c.218C > T, S73L) was identified in one patient; however, analysis in the extended pedigree demonstrated that this variant was inherited from an unaffected parent. The variant was absent in 480 control individuals. The affected serine residue is highly conserved and its substitution is predicted to alter phosphorylation. Despite this, our evidence indicates that this variant is unlikely to play a pathogenic role in the disease. Cell and animal models will be required to functionally support the pathogenic role of OPTN mutations. 2013-04-11T11:20:51.255Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25186 Phenotypic variation in amyotrophic lateral sclerosis (ALS) is common, and one atypical form is the flail arm variant (FAV). Some classic ALS patients carry TARDBP mutations, and so we sought to establish whether TARDBP mutations are also present in the FAV of ALS. Mutation analysis of TARDBP, the gene encoding TDP-43, was performed in cohorts of classic and FAV ALS patients. An analysis of mutation effects was performed in patient fibroblasts. Results showed that a novel heterozygous in-frame insertion/deletion (indel), c.1158-1159delAT; c.1158-1159insCACCAACC, was identified in a highly conserved region encoding the glycine-rich area of TDP-43 in a patient with FAV. This indel was confirmed in the proband's mother, an obligate carrier, and was absent from 480 ethnically-matched control individuals. Transcription of the mutant allele was confirmed. Under induced stress, indel-mutant fibroblasts showed a loss of normal nuclear TDP-43 immunoreactivity and formation of cytoplasmic inclusions of TDP-43, consistent with features seen in affected neurons. In conclusion, TARDBP missense mutations have previously been reported in classic ALS and frontotemporal lobar degeneration. The identification of a TARDBP indel mutation in a patient with FAV extends the spectrum of mutations and further supports the role of TDP-43 in a range of neurodegenerative phenotypes. 2013-04-11T11:20:45.034Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25187 Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive loss of motor neurons in the motor cortex, brain stem and spinal cord. Mutations in the valosin-containing protein gene (VCP) were recently described in ALS families. Some of these families included diagnoses of other clinical features including frontotemporal dementia, Paget's disease, inclusion body myopathy, Parkinsonism and limb weakness. We sought to determine the prevalence of VCP mutations in Australian familial (n = 131) and sporadic (n = 48) ALS cohorts diagnosed with classic ALS. No mutations were identified indicating that VCP mutations are not a common cause of classic ALS among Australian cases with predominantly European ancestry. 2013-04-11T11:20:38.616Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25188 Early detection of cardiac autonomic neuropathy (CAN) in patients with diabetes mellitus (DM) is of prime importance, as it will facilitate the prevention of its serious consequences. In the present work, the non-linear dynamics of electrocardiogram (ECG) recordings in 41 Type 2 DM patients with early CAN and 40 controls without clinical signs and symptoms of CAN were analysed with different implementations of Lempel-Ziv (LZ) complexity. LZ complexity is a non-linear analysis method that estimates the complexity of time series of finite length and reflects the arising rate of new patterns along the sequence. Results suggest that ECG traces are less complex in patients with early CAN than in those with no CAN. Differences were statistically significant (p < 0.05, Kruskal-Wallis test) when the LZ complexity was implemented with a three symbol conversion and the mean used to define the thresholds. Furthermore, the discriminative abilities of the different LZ complexity implementations in the context of CAN were evaluated with ROC curves. Accuracies over 65% were obtained when the mean was used to define the thresholds, with a sensitivity of 75.61% with a two symbol conversion. Our results suggest that LZ complexity might be a useful tool for an early detection of CAN from ECG recordings. Nevertheless, further studies are needed to address the possible usefulness of this methodology in the characterisation and early detection of CAN in type 2 DM patients. 2013-04-11T11:20:33.450Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25189 Amyotrophic lateral sclerosis (ALS) shows clinical and pathological overlap with frontotemporal dementia that includes the presence of hallmark ubiquitinated inclusions in affected neurons. Mutations in UBQLN2, which encodes ubiquilin 2, were recently identified in X-linked juvenile and adult-onset ALS and ALS/dementia. As part of an established exome sequencing program to identify disease genes in familial ALS, we identified a novel missense UBQLN2 mutation (c.1460C>T, p.T487I) in 2 apparently unrelated multigenerational ALS families with no evidence of frontotemporal dementia. This mutation segregated with the disease and was absent in 820 healthy controls and all public single nucleotide polymorphism databases. The UBQLN2 p.T487I mutation substitutes a highly conserved residue and is located immediately upstream of a PXX region where all previous mutations have been identified. Immunostaining of spinal cord from a patient with UBQLN2 p.T487I mutation showed colocalization of ubiquilin 2 with ubiquitin in all neuronal inclusions examined and frequent colocalization with TAR DNA-binding protein 43 (TDP-43) and fused in sarcoma protein (FUS). To examine ubiquilin 2 pathology in broader ALS, we showed that ubiquilin 2 pathology also extends to ALS with a FUS mutation. These data further support the importance of ubiquilin 2 in the pathogenesis of ALS. 2013-04-11T11:20:29.144Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25190 Autism spectrum disorder (ASD) is a neurodevelopmental disorder of early childhood, and an enumeration about its etiology and consequences is still limited. Oxidative stress-induced mechanisms are believed to be the major cause for ASD. In this study 19 autistic and 19 age-matched normal Omani children were recruited to analyze their degree of redox status and a prewritten consent was obtained. Blood was withdrawn from subjects in heparin-coated tube, and plasma was separated. Plasma oxidative stress indicators such as nitric oxide (NO), malondialdehyde (MDA), protein carbonyl, and lactate to pyruvate ratio were quantified using commercially available kits. A significant elevation was observed in the levels of NO, MDA, protein carbonyl, and lactate to pyruvate ratio in the plasma of Omani autistic children as compared to their age-matched controls. These oxidative stress markers are strongly associated with major cellular injury and manifest severe mitochondrial dysfunction in autistic pathology. Our results also suggest that oxidative stress might be involved in the pathogenesis of ASD, and these parameters could be considered as diagnostic markers to ensure the prevalence of ASD in Omani children. However, the oxidative stress-induced molecular mechanisms in ASD should be studied in detail. 2013-04-11T11:20:20.206Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25193 Increasing evidence suggests that an inflammatory microenvironment promotes invasion by glioblastoma (GBM) cells. Together with p38 mitogen-activated protein kinase (MAPK) activation being regarded as promoting inflammation, we hypothesized that elevated inflammatory cytokine secretion and p38 MAPK activity contribute to expansion of GBMs. Here we report that IL-1β, IL-6, and IL-8 levels and p38 MAPK activity are elevated in human glioblastoma specimens and that p38 MAPK inhibitors attenuate the secretion of pro-inflammatory cytokines by microglia and glioblastoma cells. RNAi knockdown and immunoprecipitation experiments suggest that the p38α MAPK isoform drives inflammation in GBM cells. Importantly, p38 MAPK inhibition strongly reduced invasion of U251 glioblastoma cells in an inflammatory microenvironment, providing evidence for a p38 MAPK-regulated link between inflammation and invasiveness in GBM pathophysiology. 2013-04-11T11:20:17.731Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25192 Heat and mass transfer in macellular materials signifies an important topic of research for a range of advanced applications such as in thermal, aerospace, geotechnical and scaffold tissue engineering etc. Based on the mathematical similarity of various transport problems, this paper proposes a modified bidirectional evolutionary structural optimization (BESO) method for design of biphasic microstructural composites with desirable transport properties. The cellular materials considered herein comprise periodic base cells and the homogenization technique is adopted to determine their effective (bulk) properties. The key is to optimize the topology of base cell model for minimizing the difference between the effective and target transport properties. Numerical examples agree well with the well-known benchmarking microstructures and some of them are prototyped using biphasic solid free-form fabrication (SFF) technology. To facilitate comprehension of the algorithm, a short MATLAB program is provided in the Appendix. 2013-04-11T11:20:12.214Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25094 30 page(s) 2013-04-08T13:25:10.340Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25102 Background: Nephronophthisis (NPHP) as a cause of cystic kidney disease is the most common genetic cause of progressive renal failure in children and young adults. NPHP is characterized by abnormal and/or loss of function of proteins associated with primary cilia. Previously, we characterized an autosomal recessive phenotype of cystic kidney disease in the Lewis Polycystic Kidney (LPK) rat. Results: In this study, quantitative trait locus analysis was used to define a similar to 1.6Mbp region on rat chromosome 10q25 harbouring the lpk mutation. Targeted genome capture and next-generation sequencing of this region identified a non-synonymous mutation R650C in the NIMA (never in mitosis gene a)- related kinase 8 (Nek8) gene. This is a novel Nek8 mutation that occurs within the regulator of chromosome condensation 1 (RCC1)-like region of the protein. Specifically, the R650C substitution is located within a G[QRC]LG repeat motif of the predicted seven bladed beta-propeller structure of the RCC1 domain. The rat Nek8 gene is located in a region syntenic to portions of human chromosome 17 and mouse 11. Scanning electron microscopy confirmed abnormally long cilia on LPK kidney epithelial cells, and fluorescence immunohistochemistry for Nek8 protein revealed altered cilia localisation. Conclusions: When assessed relative to other Nek8 NPHP mutations, our results indicate the whole propeller structure of the RCC1 domain is important, as the different mutations cause comparable phenotypes. This study establishes the LPK rat as a novel model system for NPHP and further consolidates the link between cystic kidney disease and cilia proteins. 2013-04-08T13:24:51.352Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25097 Brain tumors are among the most common and most chemoresistant tumors. Despite treatment with aggressive treatment strategies, the prognosis for patients harboring malignant gliomas remains dismal. The kynurenine pathway (KP) is the principal route of L-tryptophan catabolism leading to the formation of the essential pyridine nucleotide, nicotinamide adenine dinucleotide (NAD +), and important neuroactive metabolites, including the neurotoxin, quinolinic acid (QUIN), the neuroprotective agent, picolinic acid (PIC), the TH17/Treg balance modulator, 3-hydroxyanthranilic acid (3-HAA), and the immunosuppressive agent, L-Kynurenine (KYN). This review provides a new perspective on KP dysregulation in defeating antitumor immune responses, specifically bringing light to the lower segment of the KP, particularly QUIN-induced neurotoxicity and downregulation of the enzyme α-amino- β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) as a potential mechanism of tumor progression. Given its immunosuppressive effects, 3-HAA produced from the KP may also play a role in suppressing antitumor immunity in human tumors. The enzyme indoleamine 2, 3-dioxygenase (IDO-1) initiates and regulates the first step of the KP in most cells. Mounting evidence directly implicates that the induction and overexpression of IDO-1 in various tumors is a crucial mechanism facilitating tumor immune evasion and persistence. Tryptophan 2, 3-dioxygenase (TDO-2), which initiates the same first step of the KP as IDO-1, has likewise recently been shown to be a mechanism of tumoral immune resistance. Further, it was also recently shown that TDO-2-dependent production of KYN by brain tumors might be a novel mechanism for suppressing antitumor immunity and supporting tumor growth through the activation of the Aryl hydrocarbon receptor (AhR). This newly identified TDO-2-KYN-AhR signaling pathway opens up exciting future research opportunities and may represent a novel therapeutic target in cancer therapy. Our discussion points to a number of KP components, namely TDO-2, IDO-1, and ACMSD, as important therapeutic targets for the treatment of brain cancer. Targeting the KP in brain tumors may represent a viable strategy likely to prevent QUIN-induced neurotoxicity and KYN and 3-HAA-mediated immune suppression. 2013-04-08T13:24:50.111Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25099 There are currently few clinical strategies in place, which provide effective neuroprotection and repair, despite an intense international effort over the past decades. One possible explanation for this is that a deeper understanding is required of how endogenous mechanisms act to confer neuroprotection. This mini-review reports the proceedings of a recent workshop "Neuroprotection and Neurorepair: New Strategies" (Iguazu Falls, Misiones, Argentina, April 11-13, 2011, Satellite Symposium of the V Neurotoxicity Society Meeting, 2011) in which four areas of active research were identified to have the potential to generate new insights into this field. Topics discussed were (i) metallothionein and other multipotent neuroprotective molecules; (ii) oxidative stress and their signal mediated pathways in neuroregeneration; (iii) neurotoxins in glial cells, and (iv) drugs of abuse with neuroprotective effects. 2013-04-08T13:24:43.704Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25104 1 page(s) 2013-04-08T13:24:27.651Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25115 The toxicity of the cyanobacterial modified amino acid, BMAA, has been described in rat, mouse and leech neurons. Particular emphasis has been placed on the potential ability of BMAA to induce neuronal damage via excitotoxic mechanisms. Here we present data indicating that the effects observed on lower organisms are also evident in a human model. Our data indicates that BMAA induces increased intracellular Ca 2+ influx, DNA damage, mitochondrial activity, lactate dehydrogenase (LDH) release and generation of reactive oxygen species (ROS). The amelioration of LDH release in the presence of the N-methyl-d-aspartate (NMDA) receptor antagonist MK801 indicates that the neurotoxic effects of BMAA are mediated via NMDA receptor activation. Additionally, we have shown that BMAA induces the expression of neuronal nitric oxide synthase (nNOS) and caspase-3 indicating that it can stimulate apoptosis in human neurons, presumably via activation of NMDA receptors. 2013-04-08T13:22:33.490Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25120 Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting motor neurons. Mutations in related RNA-binding proteins TDP-43, FUS/TLS and TAF15 have been connected to ALS. These three proteins share several features, including the presence of a bioinformatics-predicted prion domain, aggregation-prone nature in vitro and in vivo and toxic effects when expressed in multiple model systems. Given these commonalities, we hypothesized that a related protein, EWSR1 (Ewing sarcoma breakpoint region 1), might also exhibit similar properties and therefore could contribute to disease. Here, we report an analysis of EWSR1 in multiple functional assays, including mutational screening in ALS patients and controls. We identified three missense variants in EWSR1 in ALS patients, which were absent in a large number of healthy control individuals. We show that disease-specific variants affect EWSR1 localization in motor neurons. We also provide multiple independent lines of in vitro and in vivo evidence that EWSR1 has similar properties as TDP-43, FUS and TAF15, including aggregation-prone behavior in vitro and ability to confer neurodegeneration in Drosophila. Postmortem analysis of sporadic ALS cases also revealed cytoplasmic mislocalization of EWSR1. Together, our studies highlight a potential role for EWSR1 in ALS, provide a collection of functional assays to be used to assess roles of additional RNA-binding proteins in disease and support an emerging concept that a class of aggregation-prone RNA-binding proteins might contribute broadly to ALS and related neurodegenerative diseases. 2013-04-08T13:21:51.495Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25105 Closing an encounter is a co-constructed activity through which participants conclude verbal and non-verbal action in a way that allows each to raise any matters they wish prior to the termination of the encounter (West, 2006). Although medical encounters are often time restricted, the scheduled length of the appointment "does not determine just when or how such a visit will be brought to a close" (West, 2006: 379). There are, however, points within the consultation where closing becomes a relevant activity. In this article, I examine these points in surgeon-patient consultations. There are seven types of surgeon-initiated pre-closings found in the data presented here. These are: final-concern sequences; arranging surgery; referring back; referring on; arranging diagnostic testing; organising a follow-up; and instructions regarding front desk paperwork. There is also one instance of patient-initiated possible pre-closing, which is also described. After an analysis of these seven types, there is also an analysis of the types of non-minimal responses that can be produced by patients. 2013-04-05T01:20:50.426Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25050 Traumatic brain injury (TBI) is one of the leading causes of major disability and death worldwide. Neural stem cells (NSCs) have recently been shown to contribute to the cellular remodelling that occurs following TBI and attention has been drawn to the area of neural stem cell as possible therapy for TBI. The NSCs may play an important role in the treatment of TBI by replacing the damaged cells and eventual remyelination. This paper summarized a critical assessment of recent data and developed a view comprising of six points to possible quality translation of NSCs in TBI. 2013-04-02T23:22:02.686Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:12370 Bulbospinal neurons in the rostral ventrolateral medulla (RVLM) are critical for the maintenance of sympathetic vasomotor tone and normal cardiovascular reflex function. So far, selectively eliminating/inhibiting distinct subpopulations of RVLM neurons has not significantly altered arterial pressure. Here we show that RVLM presympathetic neurons that express somatostatin 2A receptors are essential for maintaining and potentially generating sympathetic vasomotor tone. Combined immunocytochemistry and in situ hybridization were used to map the expression of somatostatin receptors 1, 2A, 2B, 3, and 4 (sst1 through 4, respectively) in the rat RVLM. sst1 and sst2B were absent; sst3 and sst4 were sparse. However, sst2A was found postsynaptically and detected in 35±5% of bulbospinal RVLM neurons a population that included 54±4% of catecholaminergic and 30±3% of enkephalinergic neurons. Bilateral microinjection into the RVLM of either somatostatin or the receptor-selective agonist lanreotide evoked dramatic, dose-dependent sympathoinhibition, hypotension, and bradycardia that were blocked by the sst2 receptor antagonist BIM-23627 in anesthetized rats. Bilateral RVLM microinjection of somatostatin also attenuated chemoreceptor and somatosympathetic reflex function. Somatostatin only eliminated the first sympathoexcitatory peak evoked by somatosympathetic reflex activation, whereas muscimol abolished both excitatory peaks providing functional evidence that the activity of only a subpopulation of RVLM presympathetic neurons is inhibited by somatostatin. We suggest that the subpopulation of bulbospinal RVLM neurons that expresses the sst2A receptor sets sympathetic vasomotor output. These neurons are essential for maintaining resting blood pressure under anesthesia and contribute to adaptive reflexes mediated through the RVLM. 2013-03-28T02:38:41.054Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:24916 This protocol describes a procedure for combining non-radioactive in situ hybridization (ISH) histochemistry with multi-label fluorescence immunohistochemistry (IHC) on rat brain tissue sections. This allows visualization of multiple mRNA and protein targets located within the same or different subcellular compartments. A comprehensive description of RNA probe preparation, validation and storage conditions is described. This is followed by the tissue preparation and tissue processing procedure for combined ISH/IHC on free-floating brain sections. Both the tissue and the RNA probes must be prepared and handle under strict RNase-free conditions up until the point of RNA hybridization. 2013-03-28T02:24:44.826Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:24921 Purpose: To investigate anterograde degenerative changes along the visual pathway in a rat model of optic nerve axotomy. Methods: Optic nerve transection was performed in adult Sprague-Dawley rats. Animals were sacrificed at regular time intervals and tissues harvested. Immunoblotting followed by densitometric analysis was used to determine the phosphorylation profile of Akt in the dorsal lateral geniculate nucleus (dLGN) and the primary visual cortex (V1). The neuronal cell size and cell density were measured in the dLGN and the V1 using Nissl staining. The prevalence of apoptosis was characterized by terminal deoxynucleotidyl-transferase-mediated biotin-dUTP nick end labelling (TUNEL) histochemistry. Caspase-3 antibodies were also used to identify apoptotic cells. Neurons and astrocytes were detected using NeuN and glial fibrillary acidic protein (GFAP), respectively. Results: An early and sustained loss of Akt phosphorylation was observed after optic nerve transection in both dLGN and V1. At week one, a decrease in the neuronal cell size (50.5±4.9 vs 60.3±5.0 μm2, P = 0.042) and an increase of TUNEL positive cells (7.9±0.6 vs 1.4±0.5 ×102 cells/mm2, P<0.001) were evident in the dLGN but not in V1. A significant decline in neuronal cell number (14.5±0.1 vs 17.4±1.3 ×102 cells/mm2, P = 0.048), cell size (42.5±4.3 vs 62.1±4.7 μm2, P = 0.001) and an increase in apoptotic cells (5.6±0.5 vs 2.0±0.4 ×102 cells/mm2, P<0.001) appeared in V1 initially at one month post-transection. The changes in the visual pathway continued through two months. Both neuronal cells and GFAP-positive glial cells were affected in this anterograde degeneration along the visual pathway. Conclusions: Anterograde degeneration along the visual pathway takes place in target relay (LGN) and visual cortex following the optic nerve injury. Apoptosis was observed in both neural and adjacent glial cells. Reduction of Akt phosphorylation preceded cellular and apoptotic changes. 2013-03-28T02:24:32.867Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:24973 Ih, which influences neuronal excitability, has recently been measured in vivo in sensory neuron subtypes in dorsal root ganglia (DRGs). However, expression levels of HCN (hyperpolarization-activated cyclic nucleotide-gated) channel proteins that underlie Ih were unknown. We therefore examined immunostaining of the most abundant isoforms in DRGs, HCN1 and HCN2 in these neuron subtypes. This immunostaining was cytoplasmic and membrane-associated (ring). Ring-staining for both isoforms was in neurofilament-rich A-fiber neurons, but not in small neurofilament-poor C-fiber neurons, although some C-neurons showed cytoplasmic HCN2 staining. We recorded intracellularly from DRG neurons in vivo, determined their sensory properties (nociceptive or low-threshold-mechanoreceptive, LTM) and conduction velocities (CVs). We then injected fluorescent dye enabling subsequent immunostaining. For each dye-injected neuron, ring- and cytoplasmic-immunointensities were determined relative to maximum ring-immunointensity. Both HCN1- and HCN2-ring-immunointensities were positively correlated with CV in both nociceptors and LTMs; they were high in Aβ-nociceptors and Aα/β-LTMs. High HCN1 and HCN2 levels in Aα/β-neurons may, via Ih, influence normal non-painful (e.g. touch and proprioceptive) sensations as well as nociception and pain. HCN2-, not HCN1-, ring-intensities were higher in muscle spindle afferents (MSAs) than in all other neurons. The previously reported very high Ih in MSAs may relate to their very high HCN2. In normal C-nociceptors, low HCN1 and HCN2 were consistent with their low/undetectable Ih. In some C-LTMs HCN2-intensities were higher than in C-nociceptors. Together, HCN1 and HCN2 expressions reflect previously reported Ih magnitudes and properties in neuronal subgroups, suggesting these isoforms underlie Ih in DRG neurons. Expression of both isoforms was NT3-dependent in cultured DRG neurons. HCN2-immunostaining in small neurons increased 1 day after cutaneous inflammation (CFA-induced) and recovered by 4 days. This could contribute to acute inflammatory pain. HCN2-immunostaining in large neurons decreased 4 days after CFA, when NT3 was decreased in the DRG. Thus HCN2-expression control differs between large and small neurons. 2013-03-28T02:22:48.356Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:25034 17 page(s) 2013-03-28T02:20:42.341Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:24520 The hyperpolarization-activated current (Ih) has been implicated in nociception/pain, but its expression levels in nociceptors remained unknown. We recorded Ih magnitude and properties by voltage clamp from dorsal root ganglion (DRG) neurons in vivo, after classifying them as nociceptive or low-threshold-mechanoreceptors (LTMs) and as having C-, Aδ- or Aα/β-conduction velocities (CVs). For both nociceptors and LTMs, Ih amplitude and Ih density (at -100 mV) were significantly positively correlated with CV. Median Ih magnitudes and Ih density in neuronal subgroups were respectively: muscle spindle afferents (MSAs): -4.6 nA, -33 pA pF⁻¹; cutaneous Aα/β LTMs: -2.2 nA, -20 pA pF⁻¹; Aβ-nociceptors: -2.6 nA, -21 pA pF⁻¹; both Aδ-LTMs and nociceptors: -1.3 nA, ∼-14 pA pF⁻¹; C-LTMs: -0.4 nA, -7.6 pA pF⁻¹; and C-nociceptors: -0.26 nA, -5 pA pF⁻¹. Ih activation slow time constants (slow τ values) were strongly correlated with fast τ values; both were shortest in MSAs. Most neurons had τ values consistent with HCN1-related Ih; others had τ values closer to HCN1+HCN2 channels, or HCN2 in the presence of cAMP. In contrast, median half-activation voltages (V0.5) of -80 to -86 mV for neuronal subgroups suggest contributions of HCN2 to Ih. τ values were unrelated to CV but were inversely correlated with Ih and Ih density for all non-MSA LTMs, and for Aδ-nociceptors. From activation curves ∼2-7% of Ih would be activated at normal membrane potentials. The high Ih may be important for excitability of A-nociceptors (responsible for sharp/pricking-type pain) and Aα/β-LTMs (tactile sensations and proprioception). Underlying HCN expression in these subgroups therefore needs to be determined. Altered Ih expression and/or properties (e.g. in chronic/pathological pain states) may influence both nociceptor and LTM excitability. 2013-03-06T08:03:26.513Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:24301 Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) represents inflammatory changes throughout the nose and sinuses from a group of disorders which all lead to swelling and overgrowth of the nasal mucosa. Topical corticosteroids have been the most widely used treatment, with each clinician using different regimes, at different doses, in different settings and with or without sinus surgery. CRSwNP requires ongoing medical management to prevent recurrence. Objectives: To assess the effects of topical corticosteroids on CRSwNP and to analyse various subgroups, including patients who had sinus surgery immediately prior to the delivery of the corticosteroids, surgery any time prior to the topical corticosteroids or patients who had never had previous surgery. Also to assess the most effective dose and delivery methods for topical corticosteroids. Search methods: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the search was 10 April 2012. Selection criteria: Randomised controlled trials studying topical corticosteroids for patients with CRSwNP. Data collection and analysis: At least two authors reviewed the search results and selected trials meeting the eligibility criteria, obtaining full texts and contacting authors. We documented our justification for the exclusion of studies. At least two authors extracted data using a pre-determined, standardised data form. Main results: Forty studies (3624 patients) met the inclusion criteria. The trials were at low (21 trials), medium (13 trials) and high (six trials) risk of bias. The primary outcomes were sino-nasal symptoms, polyp size and polyp recurrence after surgery. When compared to placebo, topical corticosteroids improved overall symptom scores (standardised mean difference (SMD) -0.46; 95% confidence interval (CI) - 0.65 to -0.27, P < 0.00001; seven trials, n = 445) and had a higher proportion of patients whose symptoms improved (responders) (risk ratio (RR) 1.71; 95% CI 1.29 to 2.26, P = 0.0002; four trials, n = 234). Topical corticosteroids also decreased the polyp score (SMD - 0.73; 95% CI -1.00 to -0.46, P < 0.00001; three trials, n = 237) and had a greater proportion of patients with a reduction in polyp size (responders) (RR 2.09; 95% CI 1.65 to 2.64, P < 0.00001; eight trials, n = 785) when compared to placebo. Topical corticosteroids also prevented polyp recurrence after surgery (RR 0.59; 95% CI 0.45 to 0.79, P = 0.0004; six trials, n = 437). Subgroup analyses by sinus surgery status revealed a greater benefit in reduction of polyp score when topical steroid was administered any time after sinus surgery (SMD -1.19; 95% CI -1.54 to -0.83) compared to patients who had never had surgery (SMD -0.13; 95% CI -0.53 to 0.28, P < 0.00001). There was no difference between groups in terms of adverse events. Authors' conclusions: Topical corticosteroids are a beneficial treatment for CRSwNP and the adverse effects are minor, with benefits outweighing the risks. They improve symptoms, reduce polyp size and prevent polyp recurrence after surgery. Patients having sinus surgery may have a greater response to topical corticosteroids but further research is required. 2013-02-27T05:28:02.680Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:24343 Introduction: The lateral transpsoas approach for lumbar interbody fusion (XLIF) is gaining popularity. Studies examining a surgeon's early experience are rare. We aim to report treatment, complication, clinical, and radiographic outcomes in an early series of patients. Methods: Prospective data from the first thirty patients treated with XLIF by a single surgeon was reviewed. Outcome measures included pain, disability, and quality of life assessment. Radiographic assessment of fusion was performed by computed tomography. Results: Average follow-up was 11.5 months, operative time was 60 minutes per level and blood loss was 50 mL. Complications were observed: clinical subsidence, cage breakage upon insertion, new postoperative motor deficit and bowel injury. Approach side-effects were radiographic subsidence and anterior thigh sensory changes. Two patients required reoperation; microforaminotomy and pedicle screw fixation respectively. VAS back and leg pain decreased 63 and 56, respectively. ODI improved 41.2% with 51.3% and 8.1% improvements in PCS and MCS. Complete fusion (last follow-up) was observed in 85%. Conclusion: The XLIF approach provides superior treatment, clinical outcomes and fusion rates compared to conventional surgical approaches with lowered complication rates. Mentor supervision for early cases and strict adherence to the surgical technique including neuromonitoring is essential. 2013-02-27T05:25:56.325Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:24284 At birth, the newborn fat-tailed dunnart relies on cutaneous gas exchange to meet metabolic demands, with continuous lung ventilation emerging several days later. We hypothesised that the delayed expression of lung ventilation (V-E) in these animals is in part due to a low responsiveness of the respiratory control system to blood gas perturbations. To address this hypothesis, we assessed the ventilatory and metabolic response to hypoxia (10% O₂) and hypercapnia (5% CO₂) using closed-system respirometry from birth to 23 days postpartum (P). Neonatal fat-tailed dunnarts displayed no significant hypoxic or hypercapnic ventilatory responses at any age. Regardless, significant hyperventilation through a suppression of metabolic rate (VO₂) was observed at birth in response to hypercapnia and in response to hypoxia at all ages, except P12. Therefore, reliance on cutaneous gas exchange during early life may be partially attributed to reduced chemosensitivity or a lack of central integration of chemosensitive afferent information. This may be in part due to the relative immaturity of this species at birth, compared with other mammals. 2013-02-19T18:12:37.147Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:24237 6 page(s) 2013-02-18T06:31:40.308Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:24241 Aim: The author's group report, for the first time, on the development of a quantum dot (QD)-based fluorescent somatostatin (somatotropin release-inhibiting factor [SRIF]) probe that enables specific targeting of somatostatin receptors. Receptor-mediated endocytosis of SRIF was imaged using this probe. Materials & methods: Biotinylated SRIF-analog (SRIF-B) and streptavidin (Sav)-coated QDs were used for the probe synthesis. A dye-labeled streptavidin complex was used to evaluate the effect of Sav binding on the activity of SRIF-B. Results: A preconjugated probe of the form SRIF-B:Sav-QD, was inactive and unable to undergo receptor-mediated endocytosis. An alternative in situ bioconjugation strategy, where SRIF-B and Sav-QD were added in two consecutive steps, enabled visualization of the receptor-mediated endocytosis. The process of Sav binding appeared to be responsible for the inactivity in the first case. Conclusion: The in situ two-step bioconjugation strategy allowed QDs to be targeted to somatostatin receptors. This strategy should enable flexible fluorescent tagging of SRIF for the investigation of molecular trafficking in cells and targeted delivery in live animals. 2013-02-18T06:31:27.042Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:24267 3 page(s) 2013-02-18T06:30:37.519Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:24268 4 page(s) 2013-02-18T06:30:36.462Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:24275 4 page(s) 2013-02-18T06:30:20.943Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:24167 Worldwide experience with the DIEP flap has established its pre-eminent role in breast reconstruction after mastectomy. CT angiographic vascular imaging has enhanced the planning of reconstruction, allowing mapping of perforator patterns to increase the predictability of surgery. This study extends the role of perforator mapping, using measurement of perforator lumen diameters and flap weights to calculate an index that reliably predicts the amount of tissue which will survive. We call this the Flap Viability Index. 2013-02-12T04:40:20.505Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:24169 Brain metastasis is common in patients with melanoma and represents a significant cause of morbidity and mortality. There have been no specific randomized trials for patients with melanoma brain metastasis, so treatment is based on management of brain metastasis in general and requires multidisciplinary expertise including radiation oncology, neurosurgery, medical oncology, and palliative care. In this paper, we summarize the prognosis, general management, and the role of radiation therapy in the management of metastatic melanoma in the brain. 2013-02-12T04:40:17.305Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:24124 The visualisation of hypermetabolic brown adipose tissue (BAT) on 18F fluorodeoxyglucose (FDG) positron emission tomography (PET) lowers the efficacy of PET and is linked with the environmental temperature of the patient prior to presentation. The objective of this paper is to investigate the effectiveness of thermal control on BAT and 18F-FDG PET. 2013-02-11T03:21:20.717Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:24126 Background: Complementary and alternative medicine (CAM) may offer benefits as well as risks to people with cardiovascular disease. Understanding the prevalence and the nature of CAM use will encourage beneficial CAM therapies, prevent potential herb-drug interactions and foster communication between patients and physicians. Methods: A systematic search of eight bibliographic databases was conducted for studies that investigated CAM use in patients with cardiovascular diseases. Two independent reviewers selected relevant abstracts and evaluated the quality of included studies. Results: Twenty-seven studies were included. Prevalence of CAM use in cardiac patients ranged from 4% - 61%. Biologically-based therapies usage ranged from 22% to 68%. Herbal medicines were used by between 2% and 46%. A large proportion of patients did not inform medical practitioners about their CAM use and up to 90% of treating physicians did not discuss CAM use with their patients. Conclusions: CAM use in patients with cardiovascular disease appears common. The findings suggest that the effects of CAM on medical management of cardiovascular disease may be overlooked and that patient-physician communication need to be strengthened. 2013-02-11T03:21:17.068Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:24133 Chronic urinary tract infection is a familiar cause of chronic kidney disease. Phimosis, with high incidence in boys may cause recurrent urinary tract infection, which will do harm to the kidney. We presented a case of a patient with phimosis-associated chronic pyelonephritis, who finally developed end stage renal disease followed by a review of literature. It was concluded that phimosis might be a cause of chronic kidney disease, proper treatment on which may be necessary to reduce the damage to kidney. 2013-02-11T03:21:06.649Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:24145 Background: Diabetes mellitus is associated with micro-and macrovascular complications and increased cardiovascular risk. Elevated levels of serum asymmetric dimethylarginine (ADMA) may be responsible for endothelial dysfunction associated with diabetes-induced vascular impairment. Vitamin D may have potential protective effects against arterial stiffening. This study aimed to examine both the effects of diabetes on the functional/structural properties of the aorta and the endothelial function and the effects of vitamin D supplementation. Methods: Male Wistar rats (n = 30) were randomly assigned to control untreated, diabetic untreated, and diabetic + cholecalciferol groups. Diabetes was induced by intraperitoneal injection of streptozotocin, followed by oral administration of cholecalciferol (500 IU/kg) for 10 weeks in the treatment group. Aortic pulse wave velocity (PWV) was recorded over a mean arterial pressure (MAP) range of 50 to 200 mmHg using a dual pressure sensor catheter. Intravenous infusion of phenylephrine and nitroglycerine was used to increase and decrease MAP, respectively. Serum 25-hydroxyvitamin D [25(OH) D] levels were measured using a radioimmune assay. ADMA levels in serum were measured by enzyme-linked immunoassay. Aortic samples were collected for histomorphometrical analysis. Results: PWV up to MAP 170 mmHg did not reveal any significant differences between all groups, but in diabetic rats, PWV was significantly elevated across MAP range between 170 and 200 mmHg. Isobaric PWV was similar between the treated and untreated diabetic groups, despite significant differences in the levels of serum 25(OH) D (493 +/- 125 nmol/L vs 108 +/- 38 nmol/L, respectively). Serum levels of ADMA were similarly increased in the treated and untreated diabetic groups, compared to the control group. The concentration and integrity of the elastic lamellae in the medial layer of the aorta was impaired in untreated diabetic rats and improved by vitamin D supplementation. Conclusion: PWV profile determined under isobaric conditions demonstrated differential effects of uncontrolled diabetes on aortic stiffness. Diabetes was also associated with elevated serum levels of ADMA. Vitamin D supplementation did not improve the functional indices of aortic stiffness or endothelial function, but prevented the fragmentation of elastic fibers in the aortic media. 2013-02-11T03:20:36.209Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:24147 The effects of hyoscine-N-butylbromide (hyoscine) and propantheline-bromide (propantheline) on heart rate (HR), HR variability (HRV) and gastrointestinal tract (GIT) contractions in the normal horse were determined. Five adult horses had ECG recordings for 180. min after treatment with propantheline (100 mg), hyoscine (120 mg) or saline. Both propantheline and hyoscine reduced GIT sounds, with propantheline having a longer duration of effect (≥120 min). Both drugs elevated HR relative to the control baseline period (P< 0.05), with the effects of propantheline again being of longer duration. HRV analysis indicated that propantheline suppressed Total Power (P< 0.05), and both the high frequency (HF) and low frequency (LF) components of the power spectral analysis for up to 60-90 min post treatment. Hyoscine had no effect on HRV Total Power but reduced the HF component for 30 min after drug injection. Time domain variables correlated with Total Power and HF data (P< 0.01). The marked effect of these compounds on parasympathetic control of cardiac and GIT function in normal horses should be taken into consideration when evaluating a clinical response to these agents. 2013-02-11T03:20:35.431Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:24150 The ocular circulation provides readily visible information about the state of the systemic circulation, as well as being potentially of relevance to the pathogenesis of ocular disorders such as glaucoma. The interaction between intraocular pressure, retinal vessels and cerebrospinal fluid pressure located at the retrolaminar portion of the eye has been of great interest for both ophthalmic and neurological clinicians and researchers. Understanding the relationship between these physiological parameters can explain phenomena such as spontaneous retinal venous pulsatility, and characterize the effects of the translaminar pressure gradient. It may be feasible to use measurable changes in venous pulsatility to enhance clinical assessment in different diseases. In this article we review recent findings on ocular hemodynamics and the relevance of these parameters in the diagnosis of ophthalmic and neurological diseases. 2013-02-11T03:20:26.899Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:24157 BACKGROUND AND OBJECTIVE: To document cases of sustained elevation of intraocular pressure (IOP) while receiving intravitreal anti-vascular endothelial growth factor (VEGF) agents and subsequent management. PATIENTS AND METHODS: A retrospective series of all cases managed by the authors and colleagues was performed. RESULTS: Six patients developed sustained elevated IOP; five received ranibizumab and one bevacizumab. Four received unilateral and two received bilateral injections. Two had preexisting primary open-angle glaucoma and one had pseudoexfoliative glaucoma, all with stable IOP prior to anti-VEGF treatment. Angles were open in all cases. Peak IOP averaged 43 mm Hg (range: 34 to 60 mm Hg). The mean number of injections preceding the IOP increase was 10 (range: 1 to 20). Four patients required trabeculectomy, one selective laser trabeculoplasty, and one multiple topical medications. CONCLUSION: A sustained increase in IOP requiring glaucoma filtering surgery is a rare but important treatment complication for patients receiving intravitreal anti-VEGF therapy, especially those with preexisting glaucoma or glaucoma risk factors. 2013-02-11T03:20:09.505Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:23646 In this paper, we present a compact PIFA antenna (11mm×13mm×5.6mm) operating at 900 MHz Australian ISM band, custom designed for implantation under the skin of a rat. The antenna bandwidth is enhanced by partially connecting the antenna ground plane with the RFID circuit ground plane, leaving an optimized slot between them. The antenna operating environment is modeled and included when the antenna is simulated and optimized. Our results show that directivity of the antenna also improves with the ground connection. The purpose of this research is to modify an RFID-based telemetry device, which operates well in free space, for implantation into the body of an experimental rat. 2013-01-31T04:53:28.550Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:24023 2 page(s) 2013-01-31T04:50:18.455Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:23800 Platelets restrict the growth of intraerythrocytic malaria parasites by binding to parasitized cells and killing the parasite within. Here, we show that the platelet molecule platelet factor 4 (PF4 or CXCL4) and the erythrocyte Duffy-antigen receptor (Fy) are necessary for platelet-mediated killing of Plasmodium falciparum parasites. PF4 is released by platelets on contact with parasitized red cells, and the protein directly kills intraerythrocytic parasites. This function for PF4 is critically dependent on Fy, which binds PF4. Genetic disruption of Fy expression inhibits binding of PF4 to parasitized cells and concomitantly prevents parasite killing by both human platelets and recombinant human PF4. The protective function afforded by platelets during a malarial infection may therefore be compromised in Duffy-negative individuals, who do not express Fy. 2013-01-24T03:22:00.644Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:23816 The expression of c-Fos defines brain regions activated by the stressors hypotension and glucoprivation however, whether this identifies all brain sites involved is unknown. Furthermore, the neurochemicals that delineate these regions, or are utilized in them when responding to these stressors remain undefined. Conscious rats were subjected to hypotension, glucoprivation or vehicle for 30, 60 or 120 min and changes in the phosphorylation of serine residues 19, 31 and 40 in the biosynthetic enzyme, tyrosine hydroxylase (TH), the activity of TH and/or, the expression of c-Fos were determined, in up to ten brain regions simultaneously that contain catecholaminergic cell bodies and/or terminals: A1, A2, caudal C1, rostral C1, A6, A8/9, A10, nucleus accumbens, dorsal striatum and medial prefrontal cortex. Glucoprivation evoked phosphorylation changes in A1, caudal C1, rostral C1 and nucleus accumbens whereas hypotension evoked changes A1, caudal C1, rostral C1, A6, A8/9, A10 and medial prefrontal cortex 30 min post stimulus whereas few changes were evident at 60 min. Although increases in pSer19, indicative of depolarization, were seen in sites where c-Fos was evoked, phosphorylation changes were a sensitive measure of activation in A8/9 and A10 regions that did not express c-Fos and in the prefrontal cortex that contains only catecholaminergic terminals. Specific patterns of serine residue phosphorylation were detected, dependent upon the stimulus and brain region, suggesting activation of distinct signaling cascades. Hypotension evoked a reduction in phosphorylation in A1 suggestive of reduced kinase activity. TH activity was increased, indicating synthesis of TH, in regions where pSer31 alone was increased (prefrontal cortex) or in conjunction with pSer40 (caudal C1). Thus, changes in phosphorylation of serine residues in TH provide a highly sensitive measure of activity, cellular signaling and catecholamine utilization in catecholaminergic brain regions, in the short term, in response to hypotension and glucoprivation. 2013-01-21T01:10:14.547Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:23795 3 page(s) 2013-01-17T07:30:21.174Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:23728 Question: Can information literacy (IL) be embedded into the curriculum and clinical environment to facilitate patient care and lifelong learning? Setting: The Australian School of Advanced Medicine (ASAM) provides competence-based programs incorporating patient-centred care and lifelong learning. ASAM librarians use outcomes-based educational theory to embed and assess IL into ASAM's educational and clinical environments. Methods: A competence-based IL program was developed where learning outcomes were linked to current patients and assessed with checklists. Weekly case presentations included clinicians' literature search strategies, results, and conclusions. Librarians provided support to clinicians' literature searches and assessed their presentations using a checklist. Main Results: Outcome data showed clinicians' searching skills improved over time; however, advanced MEDLINE searching remained challenging for some. Recommendations are provided. Conclusion: IL learning that takes place in context using measurable outcomes is more meaningful, is enduring, and likely contributes to patient care. Competence-based assessment drives learning in this environment. 2013-01-13T22:00:15.142Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:23682 Morphological integration and modularity within semi-autonomous modules are essential mechanisms for the evolution of morphological traits. However, the genetic makeup responsible for the control of variational modularity is still relatively unknown. In our study, we tested the hypothesis that the genetic variation for mandible shape clustered into two morphogenetic components: the alveolar group and the ascending ramus. We used the mouse as a model system to investigate genetics determinants of mandible shape. To do this, we used a combination of geometric morphometric tools and a set of 18 interspecific recombinant congenic strains (IRCS) derived from the distantly related species, Mus spretus SEG/Pas and Mus musculus C57BL/6. Quantitative trait loci (QTL) analysis comparing mandible morphometry between the C57BL/6 and the IRCSs identified 42 putative SEG/Pas segments responsible for the genetic variation. The magnitude of the QTL effects was dependent on the proportion of SEG/Pas genome inherited. Using a multivariate correlation coefficient adapted for modularity assessment and a two-block partial least squares analysis to explore the morphological integration, we found that these QTL clustered into two well-integrated morphogenetic groups, corresponding to the ascending ramus and the alveolar region. Together, these results provide evidence that the mouse mandible is subjected to genetic coordination in a modular manner. 2013-01-11T03:51:15.648Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:23711 (Associated video file can be found at: http://dx.doi.org/10.3791/4158) Photochemical tissue bonding (PTB) is a sutureless technique for tissue repair, which is achieved by applying a solution of rose bengal (RB) between two tissue edges¹,². These are then irradiated by a laser that is selectively absorbed by the RB. The resulting photochemical reactions supposedly crosslink the collagen fibers in the tissue with minimal heat production³. In this report, RB has been incorporated in thin chitosan films to fabricate a novel tissue adhesive that is laser-activated. Adhesive films, based on chitosan and containing ~0.1 wt% RB, are fabricated and bonded to calf intestine and rat tibial nerves by a solid state laser (λ=532 nm, Fluence~110 J/cm², spot size~0.5 cm). A single-column tensiometer, interfaced with a personal computer, is used to test the bonding strength. The RB-chitosan adhesive bonds firmly to the intestine with a strength of 15 ± 6 kPa, (n=30). The adhesion strength drops to 2 ± 2 kPa (n=30) when the laser is not applied to the adhesive. The anastomosis of tibial nerves can be also completed without the use of sutures. A novel chitosan adhesive has been fabricated that bonds photochemically to tissue and does not require sutures. 2013-01-11T03:50:20.664Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:23714 (Background) Recently, the number of the external valvular stenting (EVS) at the saphenofemoral junction (SFJ) for varicose veins has been increasing markedly in America, Europe and Australia because of its several advantages, such as minimal invasive surgery, low recurrence rate and preservation of the great saphenous vein. However, there are only a few reports on EVS with hand-made material in Japan. This paper introduces my surgical experience of the EVS in Sydney. (Materials and Method) Eighteen limbs (12 females, 3 males) underwent EVS surgery at the sapheno-femoral junction for varicose veins with the Venocuff II which is a small and thin Dacron-reinforced Silicone cuff between December 2006 and March 2008 in collaboration with Professor Rodney J Lane, creator of the Venocuff II. (Results) No complications, such as infection, superficial clots or deep vein thrombosis occurred. Moreover, duplex scanning revealed that the blood flow in sapheno-femoral junction returned to a physiologically normal level in all the patients 3 months after surgery. In addition, all the patients were much satisfied with the results of the operation. (Conclusion) Vascular diseases have been markedly increasing in Japan, such as coronary and peripheral artery diseases due to changes in life style and Westernization of diet. Therefore, preservation of the great saphenous vein will be important for bypass surgery. EVS using the Venocuff II may be widely performed in the future in Japan. 2013-01-11T03:50:05.265Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:23632 Spontaneous retinal venous pulsations (SRVP) are assessed as a clinical marker for patients with ophthalmic or neurological disorders. The pulsations are influenced by intraocular pressure (IOP), cerebrospinal fluid pressure (CSFp), and retinal venous pressure (RVP). However, little is known about the effect of cyanosis with polycythemia, a common finding in adults with complex congenital heart disease (CHD), on SRVP. This study investigated 11 subjects with long-standing cyanosis secondary to CHD and 11 control subjects to determine if there were measurable differences in resting pulsatility for a given IOP level. Intraocular pressure was measured using Goldman tonometry, and dynamic SRVP was recorded noninvasively using a retinal vessel imaging system. Peak amplitude of SRVP at each cardiac cycle was measured and compared with IOP. Heart rate was also monitored during the tests. Results show that for a similar baseline IOP, SRVP amplitudes are significantly lower in cyanotic patients compared with normal subjects (P < 0.0001). This may be explained by an increased RVP or high CSFp in these patients. Mean venous diameter is also significantly higher in cyanotic patients (P < 0.01), but no significant relationship was found between SRVP or diameter with blood parameters. 2013-01-09T18:31:27.612Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:23589 Object Noncommunicating canalicular syringomyelia occurs in up to 65% of patients with Chiari malformation Type I. The pathogenesis of this type of syringomyelia is poorly understood and treatment is not always effective. Although it is generally thought that syringomyelia is simply an accumulation of CSF from the subarachnoid space, the pathogenesis is likely to be more complex and may involve cellular and molecular processes. Aquaporin-4 (AQP4) has been implicated in numerous CNS pathological conditions involving fluid accumulation, including spinal cord edema. There is evidence that AQP4 facilitates the removal of extracellular water following vasogenic edema. The aim of this study was to investigate AQP4 expression and the structural and functional integrity of the blood-spinal cord barrier (BSCB) in a model of noncommunicating canalicular syringomyelia. Methods A kaolin-induced model of canalicular syringomyelia was used to investigate BSCB permeability and AQP4 expression in 27 adult male Sprague-Dawley rats. Control groups consisted of nonoperated, laminectomy-only, and saline-injected animals. The structural integrity of the BSCB was assessed using immunoreactivity to endothelial barrier antigen. Functional integrity of the BSCB was assessed by extravasation of systemically injected horseradish peroxidase (HRP) at 1, 3, 6, or 12 weeks after surgery. Immunofluorescence was used to assess AQP4 and glial fibrillary acidic protein (GFAP) expression at 12 weeks following syrinx induction. Results Extravasation of HRP was evident surrounding the central canal in 11 of 15 animals injected with kaolin, and in 2 of the 5 sham-injected animals. No disruption of the BSCB was observed in laminectomy-only controls. At 12 weeks the tracer leakage was widespread, occurring at every level rostral to the kaolin injection. At this time point there was a decrease in EBA expression in the gray matter surrounding the central canal from C-5 to C-7. Aquaporin-4 was expressed in gray- and white-matter astrocytes, predominantly at the glia limitans interna and externa, and to a lesser extent around neurons and blood vessels, in both control and syrinx animals. Expression of GFAP and APQ4 directly surrounding the central canal in kaolin-injected animals was variable and not significantly different from expression in controls. Conclusions This study demonstrated a prolonged disruption of the BSCB directly surrounding the central canal in the experimental model of noncommunicating canalicular syringomyelia. The disruption was widespread at 12 weeks, when central canal dilation was most marked. Loss of integrity of the barrier with fluid entering the interstitial space of the spinal parenchyma may contribute to enlargement of the canal and progression of syringomyelia. Significant changes in AQP4 expression were not observed in this model of canalicular syringomyelia. Further investigation is needed to elucidate whether subtle changes in AQP4 expression occur in canalicular syringomyelia. 2013-01-07T09:52:18.878Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:23591 To demonstrate the value of recording air-conducted ocular Vestibular Evoked Myogenic Potentials (oVEMP) in a patient with bilaterally enlarged vestibular aqueducts. : Cervical VEMP and oVEMP were recorded from a patient presenting with bilateral hearing loss and imbalance, attributable to large vestibular aqueduct syndrome. The stimuli were air-conducted tone bursts at octave frequencies from 250 to 2000 Hz. Amplitudes and thresholds were measured and compared with the normal response range of 32 healthy control subjects. : oVEMP reflexes demonstrated pathologically increased amplitudes and reduced thresholds for low-frequency tone bursts. Cervical VEMP amplitudes and thresholds were within normal limits for both ears across all frequencies of stimulation. : This study is the first to describe the augmentation of AC oVEMPs in an adult with large vestibular aqueduct syndrome. 2013-01-07T09:52:11.667Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:23595 Background: To compare the structure/function relationship in glaucoma cases at different levels of severity, and with different disc sizes, between the Heidelberg Retinal Tomography and Spectralis spectral domain optical coherence tomography. Design: Retrospective study of glaucoma patients attending a Sydney-based private practice. Participants: 169 eyes of 169 patients with a clinical diagnosis of glaucoma. Methods: Patients were divided on visual field criteria into early (mean deviation > -4 dB), moderate (-4 dB < mean deviation < -10 dB) and severe (mean deviation < -10 dB) disease. Bivariate correlation (Spearman's rho) between mean threshold scores for each area and the corresponding mean retinal nerve fibre layer thickness sectoral measurement were calculated. Main Outcome Measures: Correlation, as measured by Spearman's rho, between retinal nerve fibre layer measurements and mean threshold scores. Comparison of correlation strengths between the two scanning modalities with analysis of the effect of disease severity and disc size. Results: Both imaging techniques showed only moderate correlations at best. Spectral domain optical coherence tomography (global retinal nerve fibre layer Spearman's rho = 0.670, P < 0.01) had higher correlation coefficients compared with Heidelberg Retinal Tomography rim area (Spearman's rho = 0.449, P < 0.01) and retinal nerve fibre layer (Spearman's rho = 0.421, P < 0.01). Disc size did not have a significant influence on the structure/function relationship. Conclusions: Spectral domain optical coherence tomography retinal nerve fibre layer measurements demonstrated closer correlations to visual field threshold reductions using a structure/function model in varying stages of glaucoma. 2013-01-07T09:51:38.044Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:23597 Background: The reduction in smoking in Australia in the past 30 years has established the conditions in which elimination of smoking should now be considered. This is sometimes referred to as the 'tobacco endgame'. A range of approaches can be considered and any that are implemented would build on current actions such as plain packaging. Objective: This article outlines possible public health and policy approaches with the goal of leading to the elimination of smoking, and discusses a potential target date for the elimination of smoking in Australia. Discussion: The most effective strategy for eliminating smoking in Australia is likely to be one that reverses the tolerable, addictive nature of modern tobacco by the elimination of all additives and by specifying a very low level of true nicotine delivery. Use of an unsatisfying, costly and toxic product would naturally, and rapidly, decline. 2013-01-07T09:51:31.275Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:23598 Increasingly, important areas of medical therapy and research rely on the donation and use of human embryos. Yet their use is commonly determined by community tolerance and ethico-legal regulation. The aim of this study was to explore the views of an Australian community about what an embryo is, how it should be used and who should make disposition decisions. The findings of a large representative population survey showed that most participants thought of an embryo as human or potentially human but that this did not affect a majority community view that embryos should be used rather than discarded. This study also found divergent views about what the community perceived to be acceptable uses of embryos. The majority perceived the couple as having the authority to make a disposition decision. Women held different views to men across all three questions. The way an embryo was perceived related significantly to how it should be used and who should decide its disposition. These differences and relationships should be considered when developing clinic practices an d ethico-legal frameworks to regulate embryo use in science or treatment. Increasingly, important areas of medical therapy and research rely on the donation and use of human embryos. Yet their use is commonly determined by community tolerance and ethico-legal regulation. The aim of this study was to explore the views of an Australian community about what an embryo is, how it should be used and who should make disposition decisions. The findings of a large representative population survey showed that most participants thought of an embryo as human or potentially human but that this did not affect a majority community view that embryos should be used rather than discarded. We also found divergent views about what the community perceived to be acceptable uses of embryos. The majority perceived the couple as having the authority to make a disposition decision. Women held different views to men across all three questions. The way an embryo was perceived related significantly to how it should be used and who should decide its disposition. These differences and relationships should be considered when developing clinic practices and ethico-legal frameworks to regulate embryo use in science or treatment. 2013-01-07T09:51:27.869Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:23602 1 page(s) 2013-01-07T09:50:59.636Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:23424 Background: Inflammatory dysfunction is considered an important part of chronic rhinosinusitis (CRS). Corticosteroid therapy has been widely used in CRS. Effective topical delivery has been previously problematic. The post-endoscopic sinus surgery (ESS) corridor is essential for adequate topical drug access. Devices delivering large volume with positive pressure allow better distribution to sinus mucosa. The objective of this study is to evaluate the efficacy of postoperative topical sinonasal steroid irrigations for CRS. Methods: Patients with CRS undergoing ESS after failing previous medical therapy were recruited. Structured histopathology including markers of eosinophilia was performed. After surgery, patients received either budesonide 1 mg or betamethasone 1 mg delivered in a 240-mL squeeze bottle daily. Outcomes of the symptom score, Sino-Nasal Outcome Test 22 (SNOT-22) score, and endoscopy score were recorded. Results: A total of 111 patients (mean 50.1 ± 13.5 standard deviation [SD] years, 40.5% female) were included. Mean follow-up was 55.5 ± 33.9 weeks. Baseline and posttreatment symptom scores (2.6 ± 1.1 vs 1.2 ± 1.0), SNOT-22 scores (2.2 ± 1.1 vs 1.0 ± 0.8), and endoscopy scores (6.7 ± 3.0 vs 2.5 ± 2.0) revealed significant improvement (all, p < 0.001). Contrary to previous publications, patients with high tissue eosinophilia (>10/high power field [HPF]) had significantly more improvement on symptom score (1.9 ± 1.4 vs 1.1 ± 1.0, p = 0.04), SNOT-22 score (1.6 ± 1.3 vs 1.0 ± 0.8, p = 0.03), and endoscopy score (5.12 ± 3.4 vs 3.06 ± 3.0, p = 0.01) than those without. Conclusion: The philosophical approach to ESS in CRS is evolving. Topical therapies, when used appropriately, are highly effective for the most challenging eosinophilic patients. Although corticosteroid is a nonspecific therapy, it is effective when appropriately delivered. 2012-12-17T10:00:07.125Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:23381 Background: Tissue eosinophilia in chronic rhinosinusitis (CRS) is a marker of inflammatory disorders recalcitrant to surgical intervention. Eosinophilic chronic rhinosinusitis (ECRS) is traditionally associated with asthma, polyps, aspirin sensitivity, high serum eosinophilia, and elevated immunoglobulin E (IgE). However, patients with ECRS may not present with these associations and there is a need to establish other surrogate markers. The objective of the study was to determine the associations between the histopathology, serology, and clinical characteristics in CRS patients. Methods: A cross-sectional study was undertaken of CRS patients undergoing surgery. Tissue eosinophilia and other pathological features were compared to traditional surrogate features of ECRS, as well as to symptoms, and to radiologic and endoscopic scores. Results: A total of 51 patients were assessed (47% female, mean age 46.6 ± 4.1 years). High tissue eosinophilia (>10 per high-power field [HPF]) was more prominent in polyps (84%) (χ2 = 25.76; p < 0.01) but was also seen in nonpolyp patients (19%). Asthma was not associated with high tissue eosinophilia (p = 0.60), with 43% of nonasthmatics demonstrating high tissue eosinophilia. Serum eosinophilia predicted high tissue eosinophilia at >0.30 × 10^9/L or 4.4% of leukocytes (sensitivity 52%, specificity 87%, receiver operating characteristic [ROC] p = 0.001), with low negative predictive value. Serum IgE was nonpredictive (p = 0.08). Conclusion: The diagnosis of ECRS has unique prognostic implications. Traditional features of the ECRS phenotype are not necessarily reliable markers for the presence of tissue eosinophilia. Serum eosinophilia may be a good surrogate marker of tissue eosinophilia but of limited use. The routine use of structured histopathology reporting in CRS is suggested, to allow for the diagnosis of ECRS and to identify other prognostic markers. 2012-12-14T09:21:00.361Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:23356 Cerebrovascular (CVA) accidents are the second leading cause of death worldwide and their numbers are increasing. Strokes can arise from several causes, with extracranial carotid artery atherosclerosis (CAS) being one of the leading causes. CAS causes these strokes either by diminishing blood flow distal to the diseased stenotic segment of the artery or, as more recently discovered, by a thromboembolic event of material from the plaque site itself. The specific etiology of CAS is unknown, but causative factors in the formation of atherosclerotic plaque of the carotid arteries have been linked to specific morphological areas within the plaque that may be vulnerable to rupture, leading to thromboemboli into the cerebrovascular circulation. The current means for imaging and reporting CAS is through the measurement of the severity of luminal diameter stenosis caused by atherosclerotic disease. Recent developments in medical imaging techniques have expanded the role of early imaging and detection of CAS. Although current practice uses luminal narrowing as the surrogate marker to assess CAS, it has been recently discovered that plaque morphology and composition may help predict the clinical behavior of CAS and better determine the necessary medical intervention or risk of stroke. Although a single optimized imaging modality for standard CAS imaging has not been established or agreed on, various modalities can provide key elements to a successful exam. This review article will evaluate the most commonly used methods for CAS imaging along with the new and upcoming uses, advantages, and limitations for advanced CAS imaging. 2012-12-13T03:30:19.954Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:23326 1 page(s) 2012-12-12T00:00:39.617Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:23327 1 page(s) 2012-12-12T00:00:38.107Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:23331 Four aneurysms which were treated by flow diverter (FD) stents were simulated by using computational fluid dynamics (CFD). The objectives of this research were to find the characters of 2 fully successful cases among those 4 patients in terms of hemodynamic change after the FD was implanted. In CFD simulation, the FD stent mesh was represented by a porous medium layer with equivalent flow resistance. Results showed that for fully successful cases, after the FD was implanted both the blood volume flow rate and energy loss (EL) at the aneurysm were greatly reduced, but simultaneously the EL at the artery part did not appear alteration. For the unsuccessful cases, residual aneurysm was observed during the follow-up observation. For the large residual aneurysm, the EL at the aneurysm part was not decreased at the condition of high blood flow rates. On the other hand, for small residual aneurysm cases, although the flow rate and EL at the aneurysm were decreased, the EL at parent artery was increased. 2012-12-12T00:00:29.607Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:23333 We present a previously undescribed variant of the middle cerebral artery (MCA) protruding through a defect in the temporal bone, associated with a large arteriovenous malformation (AVM). The patient, a 59-year-old male, presented with a large right frontoparietal AVM with feeding aneurysms and a recent haemorrhage. Preoperative imaging demonstrated a tortuous right MCA feeder abutting the anterosuperior temporal bone in the region of the pterion. An associated temporal bone defect was visible. The patient underwent a pterional craniotomy for surgical clipping of aneurysms associated with the AVM. On reflection of the temporalis muscle, the MCA branch was transected as it coursed through a defect in the temporal bone. This patient demonstrates that the MCA may deviate from its usual anatomy and herniate through a defect in the skull. Because a pterional craniotomy is such a common surgical approach, knowledge and anticipation of such anatomic variants are essential to avoid catastrophic vascular injury during surgery. 2012-12-12T00:00:26.767Z ]]> http://www.researchonline.mq.edu.au/vital/access/manager/Repository/mq:23332 Management of cerebral aneurysms is currently done solely based on clinicians’ experience and knowledge. Computational fluid dynamics (CFD), a numerical method aims to provide data that will help in clinical decision making and in the treatment of cerebral aneurysms. A review of relevant research conducted to date was incorporated in this paper to delineate the current standing in our grasp of the various hemodynamic and morphologic parameters that might play a crucial role in the initiation, growth and rupture of cerebral aneurysms. The limitations of CFD from a hemodynamic point of view are discussed in detail. This helps us to identify the areas of future research that is essential to improve the accuracy of its clinical application. 2012-12-12T00:00:25.936Z ]]>