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Item Metadata only 360His polymorphism of the apolipoproteinA-IV gene and plasma lipid response to energy restricted diets in overweight subjects(Elsevier Sci Ireland Ltd, 2000) Heilbronn, L.; Noakes, M.; Coates, A.; Kind, K.; Clifton, P.Obesity is commonly associated with high rates of cardiovascular disease (CVD). Weight loss in obese subjects reduces risk factors for CVD but this response is not uniform. Genetic factors could be involved in this variability. The 360His polymorphism of apolipoproteinA-IV (apoA-IV) influences the lipid response to fat intake, but it is unclear whether this polymorphism could contribute to lipid variability during weight loss. Therefore, we assessed the effects of an energy restricted diet (6.3 MJ) for 12 weeks on weight loss and plasma lipids according to apoA-IV genotype in 186 overweight/obese subjects (BMI mean 33+/-4.3, range 25.0-48.0 kg/m(2)). The frequency of the 360His allele was 0.083. Energy restriction for 12 weeks resulted in an average weight loss of 8. 25+/-0.28 kg. HDL-C increased 5.4% in subjects with the apoA-IV-1/1 genotype with weight loss compared to a 2.6% decrease in apoA-IV-1/2 subjects (P=0.035). This was more apparent when only the subjects with type 2 diabetes (n=57) were analyzed (P=0.003). ApoA-IV genotype was not related to change in total cholesterol, LDL-C or triglyceride concentrations. Therefore, weight loss as a treatment to reduce CVD risk factors may be more effective in subjects with the apoA-IV-1/1 variant as compared to those with the apoA-IV-1/2 variant, especially in subjects with type 2 diabetes.Item Metadata only 5-Fluorouracil Induces an Acute Reduction in Neurogenesis and Persistent Neuroinflammation in a Mouse Model of the Neuropsychological Complications of Chemotherapy(Springer Nature, 2022) Subramaniam, C.B.; Wardill, H.R.; Davies, M.R.; Heng, V.; Gladman, M.A.; Bowen, J.M.The neuropsychological symptoms associated with chemotherapy treatment remain a major challenge with their prevention hampered by insufcient understanding of pathophysiology. While long-term neuroimmune changes have been identifed as a hallmark feature shared by neurological symptoms, the exact timeline of mechanistic events preceding neuroinfammation, and the relationship between the glial cells driving this neuroinfammatory response, remain unclear. We therefore aimed to longitudinally characterize the neuroimmunological changes following systemic 5-fuorouracil (5-FU) treatment to gain insight into the timeline of events preceding the well-documented chronic neuroinfammation seen following chemotherapy. Eighteen female C57Bl/6 mice received a single intraperitoneal dose of 5-FU and groups were killed at days 1 and 2 (acute timepoint), days 4 and 8 (subacute timepoint), and days 16 and 32 (chronic timepoint). A further six mice were administered with vehicle control with tissues collected from three mice on day 1 and day 32 of the study. The expression of key genes of interest, BCL2, BDNF, TIMP1, MMP-9, MMP-2, TNFα, IL-1β, and IL-6R were assessed using real time polymerase chain reaction. Levels of neurogenesis were determined through immunofuorescent staining of doublecortin (DCX). The density of microglia and astrocytes were assessed using immunofuorescence staining of Iba1 and GFAP respectively. 5-FU treatment caused signifcant decreases to DCX staining at acute timepoints (p=0.0030) which was positively correlated with BCL2 expression levels. An increase to microglial density was observed in the prefrontal cortex (p=0.0256), CA3 region (p=0.0283), and dentate gyrus (p=0.0052) of the hippocampus at acute timepoints. 5-FU caused increases to astrocyte density, across multiple brains regions, at subacute and chronic timepoints which were positively correlated with TNFα, TIMP-1, MMP-2, and IL-6R expression. This study has identified acute objective neuroinflammatory changes suggesting that the role of early intervention should be explored to prevent the development of neuropsychological deficits in the longer term following chemotherapy.Item Metadata only A comparison of cross-correlation and surface EMG techniques used to quantify motor unit synchronization in humans(ELSEVIER SCIENCE BV, 1999) Semmler, J.; Nordstrom, M.Two methods used to estimate the strength of motor unit (MU) synchronization in a muscle are the direct cross-correlation of MU discharge times, and averaging of the surface electromyogram (SEMG) with respect to discharge of a reference MU. Although indirect, the latter approach has the advantage that a global estimate of MU synchrony can be obtained quickly and easily. The two methods are generally regarded as providing equivalent information on the extent of MU synchronization in a muscle, but this proposition has not previously been tested quantitatively. In the present study, we used both the SEMG technique (189 MUs) and cross-correlation of MU discharge (498 MU pairs) to estimate MU synchrony in 28 first dorsal interosseus (FDI) muscles from 16 subjects. Despite considerable overlap in the identity of MUs used to quantify synchrony with each method, linear regression revealed no significant correlation between the estimates of MU synchronization in FDI muscles obtained with the two techniques (r2= 0.04, n = 28). This discrepancy was not due to insufficient sampling of the MU population with the cross-correlation method, although we found evidence for a non-uniform tendency for synchronous discharge in two of 13 motor units providing sufficient data for the analysis. The most likely explanation for the discrepancy between the estimates of MU synchrony is that methodological problems with the SEMG technique limit its accuracy. These problems are difficult to avoid under normal experimental conditions, and we conclude that the SEMG method is not reliable for quantitative comparisons of MU synchrony between muscles and subjects.Item Metadata only A new method to measure aquaporin-facilitated membrane diffusion of hydrogen peroxide and cations in plant suspension cells(Wiley, 2024) Ahmed, J.; Ismail, A.; Ding, L.; Yool, A.J.; Chaumont, F.Plant aquaporins (AQPs) facilitate the membrane diffusion of water and small solutes, including hydrogen peroxide (H2 O2 ) and, possibly, cations, essential signalling molecules in many physiological processes. While the determination of the channel activity generally depends on heterologous expression of AQPs in Xenopus oocytes or yeast cells, we established a genetic tool to determine whether they facilitate the diffusion of H2 O2 through the plasma membrane in living plant cells. We designed genetic constructs to co-express the fluorescent H2 O2 sensor HyPer and AQPs, with expression controlled by a heat shock-inducible promoter in Nicotiana tabacum BY-2 suspension cells. After induction of ZmPIP2;5 AQP expression, a HyPer signal was recorded when the cells were incubated with H2 O2 , suggesting that ZmPIP2;5 facilitates H2 O2 transmembrane diffusion; in contrast, the ZmPIP2;5W85A mutated protein was inactive as a water or H2 O2 channel. ZmPIP2;1, ZmPIP2;4 and AtPIP2;1 also facilitated H2 O2 diffusion. Incubation with abscisic acid and the elicitor flg22 peptide induced the intracellular H2 O2 accumulation in BY-2 cells expressing ZmPIP2;5. We also monitored cation channel activity of ZmPIP2;5 using a novel fluorescent photo-switchable Li+ sensor in BY-2 cells. BY-2 suspension cells engineered for inducible expression of AQPs as well as HyPer expression and the use of Li+ sensors constitute a powerful toolkit for evaluating the transport activity and the molecular determinants of PIPs in living plant cells.Item Metadata only A new quantitative method of real time reverse transcription polymerase chain reaction assay based on simulation of polymerase chain reaction kinetics(Academic Press Inc, 2002) Liu, W.; Saint, D.Real-time reverse transcription (RT) PCR is currently the most sensitive method for the detection of low-abundance mRNAs. Two relative quantitative methods have been adopted: the standard curve method and the comparative CT method. The latter is used when the amplification efficiency of a reference gene is equal to that of the target gene; otherwise the standard curve method is applied. Based on the simulation of kinetic process of real-time PCR, we have developed a new method for quantitation and normalization of gene transcripts. In our method, the amplification efficiency for each individual reaction is calculated from the kinetic curve, and the initial amount of gene transcript is derived and normalized. Simulation demonstrated that our method is more accurate than the comparative CT method and would save more time than the relative standard curve method. We have used the new method to quantify gene expression levels of nine two-pore potassium channels. The relative levels of gene expression revealed by our quantitative method were broadly consistent with those estimated by routine RT-PCR, but the results also showed that amplification efficiencies varied from gene to gene and from sample to sample. Our method provides a simple and accurate approach to quantifying gene expression level with the advantages that neither construction of standard curve nor validation experiments are needed.Item Metadata only A novel germ cell protein, SPIF (sperm PKA interacting factor), is essential for the formation of a PKA/TCP11 complex that undergoes conformational and phosphorylation changes upon capacitation(FASEB, 2016) Stanger, S.; Law, E.; Jamsai, D.; O'Bryan, M.; Nixon, B.; McLaughlin, E.; Aitken, R.; Roman, S.Spermatozoa require the process of capacitation to enable them to fertilize an egg. PKA is crucial to capacitation and the development of hyperactivated motility. Sperm PKA is activated by cAMP generated by the germ cell-enriched adenylyl cyclase encoded by Adcy10 Male mice lacking Adcy10 are sterile, because their spermatozoa are immotile. The current study was designed to identify binding partners of the sperm-specific (Cα2) catalytic subunit of PKA (PRKACA) by using it as the "bait" in a yeast 2-hybrid system. This approach was used to identify a novel germ cell-enriched protein, sperm PKA interacting factor (SPIF), in 25% of the positive clones. Homozygous Spif-null mice were embryonically lethal. SPIF was coexpressed and coregulated with PRKACA and with t-complex protein (TCP)-11, a protein associated with PKA signaling. We established that these 3 proteins form part of a novel complex in mouse spermatozoa. Upon capacitation, the SPIF protein becomes tyrosine phosphorylated in >95% of sperm. An apparent molecular rearrangement in the complex occurs, bringing PRKACA and TCP11 into proximity. Taken together, these results suggest a role for the novel complex of SPIF, PRKACA, and TCP11 during sperm capacitation, fertilization, and embryogenesis.-Stanger, S. J., Law, E. A., Jamsai, D., O'Bryan, M. K., Nixon, B., McLaughlin, E. A., Aitken, R. J., Roman, S. D. A novel germ cell protein, SPIF (sperm PKA interacting factor), is essential for the formation of a PKA/TCP11 complex that undergoes conformational and phosphorylation changes upon capacitation.Item Open Access A predictive focus of gain modulation encodes target trajectories in insect vision(eLife Sciences Publications, 2017) Wiederman, S.; Fabian, J.; Dunbier, J.; O Carroll, D.When a human catches a ball, they estimate future target location based on the current trajectory. How animals, small and large, encode such predictive processes at the single neuron level is unknown. Here we describe small target-selective neurons in predatory dragonflies that exhibit localized enhanced sensitivity for targets displaced to new locations just ahead of the prior path, with suppression elsewhere in the surround. This focused region of gain modulation is driven by predictive mechanisms, with the direction tuning shifting selectively to match the target's prior path. It involves a large local increase in contrast gain which spreads forward after a delay (e.g. an occlusion) and can even transfer between brain hemispheres, predicting trajectories moved towards the visual midline from the other eye. The tractable nature of dragonflies for physiological experiments makes this a useful model for studying the neuronal mechanisms underlying the brain's remarkable ability to anticipate moving stimuli.Item Metadata only A premature increase in circulating cortisol suppresses expression of 11β hydroxysteroid dehydrogenase type 2 messenger ribonucleic acid in the adrenal of the fetal sheep(Oxford University Press, 2000) Ross, J.T.; McMillen, I.C.; Adams, M.B.; Coulter, C.L.We have investigated the effect of intrafetal cortisol administration, before the normal prepartum cortisol surge, on the expression of 11beta hydroxysteroid dehydrogenase (11betaHSD) type 2 mRNA in the fetal adrenal. We also determined whether increased fetal cortisol concentrations can stimulate growth of the fetal adrenal gland or increase expression of adrenal steroidogenic enzymes. Cortisol (hydrocortisone succinate: 2.0-3.0 mg in 4.4 ml/24 h) was infused into fetal sheep between 109 and 116 days of gestation (cortisol infused; n = 12), and saline was administered to control fetuses (saline infused; n = 13) at the same age. There was no effect of cortisol infusion on the fetal adrenal:body weight ratio (cortisol: 101.7 +/- 5.3 mg/kg; saline: 108.2 +/- 4.3 mg/kg). The ratio of adrenal 11betaHSD-2 mRNA to 18S rRNA expression was significantly lower, however, in the cortisol-infused group (0.75 +/- 0.02) compared with the group receiving saline (1.65 +/- 0.14). There was no significant effect of intrafetal cortisol on the relative abundance of adrenal CYP11A1, CYP17, CYP21A1, and 3betaHSD mRNA. A premature elevation in fetal cortisol therefore resulted in a suppression of adrenal 11betaHSD-2. Increased intra-adrenal exposure to cortisol at this stage of gestation is, however, not sufficient to promote adrenal growth or steroidogenic enzyme gene expression.Item Metadata only A progressive assessment strategy improves student learning and perceived course quality in undergraduate physiology(American Physiological Society, 2015) Saint, D.; Horton, D.; Yool, A.; Elliott, A.In 2010, second-year physiology (n = 165) had a traditional single 3-h end-of-semester exam. To provide diagnostic feedback earlier, for students enrolled in 2011 (n = 128), we incorporated an in-class exam at 3 wk in addition to the final exam. Based on initial analysis and positive student comments, for the 2012 cohort (n = 148), we expanded this to incorporate four 1-h in-class exams every 3 wk plus a short final integrative exam. Average scores from exams and questionnaires (student evaluations of learning and teaching, 10 questions) were compared among 2010, 2011, and 2012 cohorts. We also compared scores in the practical component of the course, which had a constant format for all cohorts. Data are given as means ± SD; statistical analyses were done with unpaired two-way Students t-tests. From 2010 to 2012, there was a significant improvement in total exam scores (59.7 ± 15.8 vs. 68.6 ± 14.2, P < 0.001) but no significant change in total practical scores (72.3 ± 9.0 vs. 74.4 ± 10.2, P = 0.05), indicating that the rise in exam score was not due to higher academic abilities of the 2012 cohort. Overall mean student evaluation of learning and teaching responses (4.9 ± 0.4 vs. 5.3 ± 0.3, P = 0.015) and overall percent broad agreement (66.0 ± 8.0 vs. 79.2 ± 7.5, P = 0.003) indicated a significant improvement in student satisfaction. In conclusion, both learning outcome and perceived course quality were enhanced by the increased frequency of examinations, possibly by promoting consistent student study habits.Item Metadata only A randomized controlled trial of continuous positive airway pressure in mild obstructive sleep apnea(American Thoracic Society, 2002) Barnes, M.; Houston, D.; Worsnop, C.; Neill, A.; Mykytyn, I.; Kay, A.; Trinder, J.; Saunders, N.; McEvoy, R.; Pierce, R.A common clinical dilemma faced by sleep physicians is in deciding the level of severity at which patients with obstructive sleep apnea (OSA) should be treated. There is particular uncertainty about the need for, and the effectiveness of, treatment in mild cases. To help define the role of nasal continuous positive airway pressure (CPAP) treatment in mild OSA we undertook a randomized controlled cross-over trial of CPAP in patients with an apnea- hypopnea index (AHI) of 5 - 30 (mean, 12.9 +/- 6.3 SD). Twenty-four-hour blood pressure and neurobehavioral function were measured at baseline, after 8 wk of treatment with CPAP, and after 8 wk of treatment with an oral placebo tablet. Twenty-eight of 42 patients enrolled in the study completed both treatment arms. Baseline characteristics were not different between those who completed the study and those who did not complete the study. Patients used CPAP for a mean (SD) of 3.53 (2.13) h per night and the mean AHI on the night of CPAP implementation was 4.24 (2.9). Nasal CPAP improved self-reported symptoms of OSA, including snoring, restless sleep, daytime sleepiness, and irritability (in-house questionnaire), more than did placebo, but did not improve objective (Multiple Sleep Latency Test) or subjective (Epworth Sleepiness Scale) measures of daytime sleepiness. We found no benefit of CPAP over placebo in any tests of neurobehavioral function, generic SF-36 (36-item Short Form Medical Outcomes Survey) or sleep-specific (Functional Outcomes of Sleep Questionnaire) quality of life questionnaires, mood score (Profile of Moods States and Beck Depression Index), or 24-h blood pressure. However, the placebo tablet resulted in a significant improvement in a wide range of functional variables compared with baseline. This placebo effect may account for some of the treatment responses to CPAP observed previously in patients with mild OSA.Item Metadata only A rotating light cycle promotes weight gain and hepatic lipid storage in mice(American Physiological Society, 2018) Christie, S.; Vincent, A.; Li, H.; Frisby, C.; Kentish, S.; O'Rielly, R.; Wittert, G.; Page, A.Processes involved in regulation of energy balance and intermediary metabolism are aligned to the light-dark cycle. Shift-work and high-fat diet (HFD)-induced obesity disrupt circadian rhythmicity and are associated with increased risk of nonalcoholic fatty liver disease. This study aimed to determine the effect of simulating shift work on hepatic lipid accumulation in lean and HFD mice. C57BL/6 mice fed a standard laboratory diet (SLD) or HFD for 4 wk were further allocated to a normal light (NL) cycle (lights on: 0600–1800) or rotating light (RL) cycle [3 days NL and 4 days reversed (lights on: 1800–0600) repeated] for 8 wk. Tissue was collected every 3 h beginning at 0600. HFD mice gained more weight than SLD mice, and RL mice gained more weight than NL mice. SLD-NL and HFD-NL mice, but not RL mice, were more active, had higher respiratory quotients, and consumed/expended more energy during the dark phase compared with the light phase. Blood glucose and plasma cholesterol and triglyceride concentrations were elevated in HFD and SLD-RL compared with SLD-NL mice. Hepatic glycogen was elevated in HFD compared with SLD mice. Hepatic triglycerides were elevated in SLD-RL and HFD mice compared with SLD-NL. Circadian rhythmicity of hepatic acetyl-CoA carboxylase (ACACA) mRNA was phase shifted in SLD-RL and HFD-NL and lost in HFD-RL mice. Hepatic ACACA protein was reduced in SLD-RL and HFD mice compared with SLD-NL mice. Hepatic adipose triglyceride lipase was elevated in HFD-NL compared with SLD-NL but lower in RL mice compared with NL mice irrespective of diet. In conclusion, an RL cycle model of shift work promotes weight gain and hepatic lipid storage even in lean conditions.Item Metadata only A simple and inexpensive system for monitoring jaw movements in ambulatory humans(Elsevier Sci Ltd, 2002) Flavel, S.; Nordstrom, M.; Miles, T.A simple and inexpensive method for recording vertical movements of the human mandible relative to the maxilla is presented. Measurements are made from accelerometers and a Hall-effect device temporarily glued to the upper and lower anterior teeth. The accelerometer signals are integrated once to give velocity and a second time to give position. Movements of the mandible relative to the maxilla are obtained by integrating the difference between the two accelerometer signals. The (relative) velocity and position records derived in this way are linear, but subject to drift when the jaw is stationary. Steady mandibular position is obtained from the Hall-effect system, but this signal must be corrected for its inherent non-linearity. This device can record rapid movements of the mandible even when the head is unrestrained, and interferes minimally with normal jaw movements.Item Metadata only A simplified model of screening questionnaire and home monitoring for obstructive sleep apnoea in primary care(British Med Journal Publ Group, 2011) Chai-Coetzer, C.; Antic, N.; Rowland, L.; Catcheside, P.; Esterman, A.; Reed, R.; Williams, H.; Dunn, S.; McEvoy, R.Background: To address the growing burden of disease and long waiting lists for sleep services, a simplified two-stage model was developed and validated for identifying obstructive sleep apnoea (OSA) in primary care using a screening questionnaire followed by home sleep monitoring. Methods: 157 patients aged 25–70 years attending their primary care physician for any reason at six primary care clinics in rural and metropolitan regions of South Australia participated. The first 79 patients formed the development group and the next 78 patients the validation group. A screening questionnaire was developed from factors identified from sleep surveys, demographic and anthropometric data to be predictive of moderate to severe OSA. Receiver operating characteristic (ROC) curve analysis was used to validate the two-channel ApneaLink device against full polysomnography. The diagnostic accuracy of the overall two-stage model was then evaluated. Results: Snoring, waist circumference, witnessed apnoeas and age were predictive of OSA and incorporated into a screening questionnaire (ROC area under curve (AUC) 0.84, 95% CI 0.75 to 0.94, p<0.001). ApneaLink oximetry with a 3% dip rate was highly predictive of OSA (AUC 0.96, 95% CI 0.91 to 1.0, p<0.001). The two-stage diagnostic model showed a sensitivity of 0.97 (95% CI 0.81 to 1.00) and specificity of 0.87 (95% CI 0.74 to 0.95) in the development group, and a sensitivity of 0.88 (95% CI 0.60 to 0.98) and specificity of 0.82 (95% CI 0.70 to 0.90) in the validation group. Conclusion: A two-stage model of screening questionnaire followed by home oximetry can accurately identify patients with OSA in primary care and has the potential to expedite care for patients with this common sleep disorder.Item Metadata only A single 4 mg dose of nicotine decreases heart rate variability in healthy nonsmokers: Implications for smoking cessation programs(Oxford University Press, 2011) Sjoberg, N.; Saint, D.Introduction: The vast majority of work on the physiological effects of nicotine in humans has been done in smokers or smokers trying to quit. Such studies can be confounded by tolerance, desensitization of receptors, or withdrawal. Because of these difficulties, there is still some dispute as to whether nicotine is proparasympathetic or prosympathetic in humans. To circumvent these difficulties, we assessed the effect of nicotine on autonomic function by measuring changes in heart rate variability (HRV) in nicotine-naive healthy subjects. Methods: Twenty males and 20 females aged between 18 and 25 years received 4 mg oral nicotine lozenge or placebo. HRV was assessed in 15-min periods before, during, and after ingestion. Results: There were no significant changes in any measure after placebo administration. During and after nicotine ingestion, heart rate increased to 78 ± 2 beats per minute (bpm) from a baseline level of 75 ± 2 bpm (p < .01). Nicotine significantly increased low frequency (LF; normalized units) from 66 ± 2 at baseline to 70 ± 2 at 15–30 min postingestion (p < .01) and decreased high frequency (HF; normalized units) from 28 ± 2 to 24 ± 1 (p < .01). LF/HF ratio was therefore substantially increased from 2.9 ± 0.3 to 3.7 ± 0.3 (p < .01). Conclusions: A single dose of 4 mg oral nicotine produces a significant reduction in HRV (i.e., a proportional decrease in high-frequency variability) in healthy young nonsmokers consistent with a reduced vagal activity. This has implications for nicotine replacement treatments aimed at cessation of smoking.Item Metadata only A single bout of aerobic exercise promotes motor cortical neuroplasticity(Amer Physiological Soc, 2013) McDonnell, M.; Buckley, J.; Opie, G.; Ridding, M.; Semmler, J.Regular physical activity is associated with enhanced plasticity in the motor cortex, but the effect of a single session of aerobic exercise on neuroplasticity is unknown. The aim of this study was to compare corticospinal excitability and plasticity in the upper limb cortical representation following a single session of lower limb cycling at either low or moderate intensity, or a control condition. We recruited 25 healthy adults to take part in three experimental sessions. Cortical excitability was examined using transcranial magnetic stimulation to elicit motor-evoked potentials in the right first dorsal interosseus muscle. Levels of serum brain-derived neurotrophic factor and cortisol were assessed throughout the experiments. Following baseline testing, participants cycled on a stationary bike at a workload equivalent to 57% (low intensity, 30 min) or 77% age-predicted maximal heart rate (moderate intensity, 15 min), or a seated control condition. Neuroplasticity within the primary motor cortex was then examined using a continuous theta burst stimulation (cTBS) paradigm. We found that exercise did not alter cortical excitability. Following cTBS, there was a transient inhibition of first dorsal interosseus motor-evoked potentials during control and low-intensity conditions, but this was only significantly different following the low-intensity state. Moderate-intensity exercise alone increased serum cortisol levels, but brain-derived neurotrophic factor levels did not increase across any condition. In summary, low-intensity cycling promoted the neuroplastic response to cTBS within the motor cortex of healthy adults. These findings suggest that light exercise has the potential to enhance the effectiveness of motor learning or recovery following brain damage.Item Metadata only A systematic review of experimental treatments for mitochondrial dysfunction in sepsis and multiple organ dysfunction syndrome(Pergamon-Elsevier Science Ltd, 2009) Dare, A.; Phillips, A.; Hickey, A.; Mittal, A.; Loveday, B.; Thompson, N.; Windsor, J.Sepsis and multiple organ dysfunction syndrome (MODS) are major causes of morbidity and mortality in the intensive care unit. Recently mitochondrial dysfunction has been proposed as a key early cellular event in critical illness. A growing body of experimental evidence suggests that mitochondrial therapies are effective in sepsis and MODS. The aim of this article is to undertake a systematic review of the current experimental evidence for the use of therapies for mitochondrial dysfunction during sepsis and MODS and to classify these mitochondrial therapies. A search of the MEDLINE and PubMed databases (1950 to July 2009) and a manual review of reference lists were conducted to find experimental studies containing data on the efficacy of mitochondrial therapies in sepsis and sepsis-related MODS. Fifty-one studies were included in this review. Five categories of mitochondrial therapies were defined-substrate provision, cofactor provision, mitochondrial antioxidants, mitochondrial reactive oxygen species scavengers, and membrane stabilizers. Administration of mitochondrial therapies during sepsis was associated with improvements in mitochondrial electron transport system function, oxidative phosphorylation, and ATP production and a reduction in cellular markers of oxidative stress. Amelioration of proinflammatory cytokines, caspase activation, and prevention of the membrane permeability transition were reported. Restoration of mitochondrial bioenergetics was associated with improvements in hemodynamic parameters, organ function, and overall survival. A substantial body of evidence from experimental studies at both the cellular and the organ level suggests a beneficial role for the administration of mitochondrial therapies in sepsis and MODS. We expect that mitochondrial therapies will have an increasingly important role in the management of sepsis and MODS. Clinical trials are now required.Item Metadata only A whey-derived growth factor extract suppresses an indicator of disease activity in the dextran sulphate sodium model of colitis(1997) Porter, S.; Howarth, G.; Butler, R.Item Metadata only Abdominal compression increases upper airway collapsibility during sleep in obese male obstructive sleep apnea patients(Amer Academy Sleep Medicine, 2009) Stadler, D.; McEvoy, R.; Sprecher, K.; Thomson, K.; Ryan, M.; Thompson, C.; Catcheside, P.Study objectives
Abdominal obesity, particularly common in centrally obese males, may have a negative impact on upper airway (UA) function during sleep. For example, cranial displacement of the diaphragm with raised intra-abdominal pressure may reduce axial tension exerted on the UA by intrathoracic structures and increase UA collapsibility during sleep.Design
This study aimed to examine the effect of abdominal compression on UA function during sleep in obese male obstructive sleep apnea patients.Setting
Participants slept in a sound-insulated room with physiologic measurements controlled from an adjacent room.Participants
Fifteen obese (body mass index: 34.5 +/- 1.1 kg/m2) male obstructive sleep apnea patients (apnea-hypopnea index: 58.1 +/- 6.8 events/h) aged 50 +/- 2.6 years participated.Interventions
Gastric (PGA) and transdiaphragmatic pressures (P(DI)), UA closing pressure (UACP), UA airflow resistance (R(UA)), and changes in end-expiratory lung volume (EELV) were determined during stable stage 2 sleep with and without abdominal compression, achieved via inflation of a pneumatic cuff placed around the abdomen. UACP was assessed during brief mask occlusions.Measurements and results
Abdominal compression significantly decreased EELV by 0.53 +/- 0.24 L (P=0.045) and increased PGA (16.2 +/- 0.8 versus 10.8 +/- 0.7 cm H2O, P < 0.001), P(DI) (11.7 +/- 0.9 versus 7.6 +/- 1.2 cm H2O, P < 0.001) and UACP (1.4 +/- 0.8 versus 0.9 +/- 0.9 cm H2O, P = 0.039) but not R(UA)(6.5 +/- 1.4 versus 6.9 +/- 1.4 cm H2O x L/s, P=0.585).Conclusions
Abdominal compression negatively impacts on UA collapsibility during sleep and this effect may help explain strong associations between central obesity and obstructive sleep apnea.Item Metadata only Accuracy of two pulse oximeters during maximal cycling exercise(1997) Wood, R. J.; Gore, Christopher J.; Hahn, Allan G.; Norton, K. I.; Scroop, Garry Campbell; Campbell, D. P.; Watson, D. B.; Emonson, D. L.Item Metadata only Accuracy of velocity estimation by Reichardt correlators(Optical Soc Amer, 2001) Dror, R.; O'Carroll, D.; Laughlin, S.Although a great deal of experimental evidence supports the notion of a Reichardt correlator as a mechanism for biological motion detection, the correlator does not signal true image velocity. This study examines the accuracy with which realistic Reichardt correlators can provide velocity estimates in an organism's natural visual environment. The predictable statistics of natural images imply a consistent correspondence between mean correlator response and velocity, allowing the otherwise ambiguous Reichardt correlator to act as a practical velocity estimator. Analysis and simulations suggest that processes commonly found in visual systems, such as prefiltering, response compression, integration, and adaptation, improve the reliability of velocity estimation and expand the range of velocities coded. Experimental recordings confirm our predictions of correlator response to broadband images.