Nutrient provision increases signalling and protein synthesis in human skeletal muscle after repeated sprints

The effect of nutrient availability on the acute molecular responses following repeated sprint exercise is unknown. The aim of this study was to determine skeletal muscle cellular and protein synthetic responses following repeated sprint exercise with nutrient provision. Eight healthy young male subjects undertook two sprint cycling sessions (10 × 6 s, 0.75 N m torque kg -1, 54 s recovery) with either pre-exercise nutrient (24 g whey, 4.8 g leucine, 50 g maltodextrin) or non-caloric placebo ingestion. Muscle biopsies were taken from vastus lateralis at rest, and after 15 and 240 min post-exercise recovery to determine muscle cell signalling responses and protein synthesis by primed constant infusion of L-[ring- 13C 6] phenylalanine. Peak and mean power outputs were similar between nutrient and placebo trials. Post-exercise myofibrillar protein synthetic rate was greater with nutrient ingestion compared with placebo ( ? 48%, P<0.05) but the rate of mitochondrial protein synthesis was similar between treatments. The increased myofibrillar protein synthesis following sprints with nutrient ingestion was associated with coordinated increases in Akt-mTOR-S6KrpS6 phosphorylation 15 min post-exercise (?200-600%, P<0.05), while there was no effect on these signalling molecules when exercise was undertaken in the fasted state. For the first time we report a beneficial effect of nutrient provision on anabolic signalling and muscle myofibrillar protein synthesis following repeated sprint exercise. Ingestion of protein/carbohydrate in close proximity to high-intensity sprint exercise provides an environment that increases cell signalling and protein synthesis.

High rates of muscle glycogen resynthesis after exhaustive exercise when carbohydrate is coingested with caffeine

We determined the effect of coingestion of caffeine (Caff) with carbohydrate (CHO) on rates of muscle glycogen resynthesis during recovery from exhaustive exercise in seven trained subjects who completed two experimental trials in a randomized, double-blind crossover design. The evening before an experiment subjects performed intermittent exhaustive cycling and then consumed a low-CHO meal. The next morning subjects rode until volitional fatigue. On completion of this ride subjects consumed either CHO [4 g/kg body mass (BM)] or the same amount of CHO + Caff (8 mg/kg BM) during 4 h of passive recovery. Muscle biopsies and blood samples were taken at regular intervals throughout recovery. Muscle glycogen levels were similar at exhaustion [?75 mmol/kg dry wt (dw)] and increased by a similar amount (?80%) after 1 h of recovery (133 ± 37.8 vs. 149 ± 48 mmol/kg dw for CHO and Caff, respectively). After 4 h of recovery Caff resulted in higher glycogen accumulation (313 ± 69 vs. 234 ± 50 mmol/kg dw, P < 0.001). Accordingly, the overall rate of resynthesis for the 4-h recovery period was 66% higher in Caff compared with CHO (57.7 ± 18.5 vs. 38.0 ± 7.7 mmol·kg dw-1·h-1, P < 0.05). After 1 h of recovery plasma Caff levels had increased to 31 ± 11 ?M (P < 0.001) and at the end of the recovery reached 77 ± 11 ?M (P < 0.001) with Caff. Phosphorylation of CaMKThr286 was similar after exercise and after 1 h of recovery, but after 4 h CaMKThr286 phosphorylation was higher in Caff than CHO (P < 0.05). Phosphorylation of AMP-activated protein kinase (AMPK)Thr172 and AktSer473 was similar for both treatments at all time points. We provide the first evidence that in trained subjects coingestion of large amounts of Caff (8 mg/kg BM) with CHO has an additive effect on rates of postexercise muscle glycogen accumulation compared with consumption of CHO alone.

Traits of fear resistance and susceptibility in an advanced intercross line

Genetic variability in the strength and precision of fear memory is hypothesised to contribute to the etiology of anxiety disorders, including post-traumatic stress disorder. We generated fear-susceptible (F-S) or fear-resistant (F-R) phenotypes from an F8 advanced intercross line (AIL) of C57BL/6J and DBA/2J inbred mice by selective breeding. We identified specific traits underlying individual variability in Pavlovian conditioned fear learning and memory. Offspring of selected lines differed in the acquisition of conditioned fear. Furthermore, F-S mice showed greater cued fear memory and generalised fear in response to a novel context than F-R mice. F-S mice showed greater basal corticosterone levels and hypothalamic corticotrophin-releasing hormone (CRH) mRNA levels than F-R mice, consistent with higher hypothalamic-pituitary-adrenal (HPA) axis drive. Hypothalamic mineralocorticoid receptor and CRH receptor 1 mRNA levels were decreased in F-S mice as compared with F-R mice. Manganese-enhanced magnetic resonance imaging (MEMRI) was used to investigate basal levels of brain activity. MEMRI identified a pattern of increased brain activity in F-S mice that was driven primarily by the hippocampus and amygdala, indicating excessive limbic circuit activity in F-S mice as compared with F-R mice. Thus, selection pressure applied to the AIL population leads to the accumulation of heritable trait-relevant characteristics within each line, whereas non-behaviorally relevant traits remain distributed. Selected lines therefore minimise false-positive associations between behavioral phenotypes and physiology. We demonstrate that intrinsic differences in HPA axis function and limbic excitability contribute to phenotypic differences in the acquisition and consolidation of associative fear memory. Identification of system-wide traits predisposing to variability in fear memory may help in the direction of more targeted and efficacious treatments for fear-related pathology. Through short-term selection in a B6D2 advanced intercross line we created mouse populations divergent for the retention of Pavlovian fear memory. Trait distinctions in HPA-axis drive and fear network circuitry could be made between naïve animals in the two lines. These data demonstrate underlying physiological and neurological differences between Fear-Susceptible and Fear-Resistant animals in a natural population. F-S and F-R mice may therefore be relevant to a spectrum of disorders including depression, anxiety disorders and PTSD for which altered fear processing occurs.

Fully Bayesian experimental design for pharmacokinetic studies

Utility functions in Bayesian experimental design are usually based on the posterior distribution. When the posterior is found by simulation, it must be sampled from for each future data set drawn from the prior predictive distribution. Many thousands of posterior distributions are often required. A popular technique in the Bayesian experimental design literature to rapidly obtain samples from the posterior is importance sampling, using the prior as the importance distribution. However, importance sampling will tend to break down if there is a reasonable number of experimental observations and/or the model parameter is high dimensional. In this paper we explore the use of Laplace approximations in the design setting to overcome this drawback. Furthermore, we consider using the Laplace approximation to form the importance distribution to obtain a more efficient importance distribution than the prior. The methodology is motivated by a pharmacokinetic study which investigates the effect of extracorporeal membrane oxygenation on the pharmacokinetics of antibiotics in sheep. The design problem is to find 10 near optimal plasma sampling times which produce precise estimates of pharmacokinetic model parameters/measures of interest. We consider several different utility functions of interest in these studies, which involve the posterior distribution of parameter functions.

A facile chemical screening method for the detection of stress corrosion cracking in 9 carat gold alloys

Stress corrosion cracking (SCC) is a well known form of environmental attack in low carat gold jewellery. It is desirable to have a quick, easy and cost effective way to detect SCC in alloys and prevent them from being used and later failing in their application. A facile chemical method to investigate SCC of 9 carat gold alloys is demonstrated. It involves a simple application of tensile stress to a wire sample in a corrosive environment such as 1–10 % FeCl3 which induces failure in less than 5 minutes. In this study three quaternary (Au, Ag, Cu and Zn) 9 carat gold alloy compositions were investigated for their resistance to SCC and the relationship between time to failure and processing conditions is studied. It is envisaged that the use of such a rapid and facile screening procedure at the production stage may readily identify alloy treatments that produce jewellery that will be susceptible to SCC in its lifetime.

A combined scanning electron micrograph and electrochemical study of the effect of chemical interaction on the cyclability of lithium electrodes in an ionic liquid electrolyte

The effect of storage time on the cyclability of lithium electrodes in an ionic liquid electrolyte, namely 0.5 m LiBF4 in N-methyl-N-propyl pyrrolidinium bis(fluorosulfonyl)imide, [C3mpyr+][FSI–], was investigated. A chemical interaction was observed which is time dependent and results in a morphology change of the Li surface due to build up of passivation products over a 12-day period. The formation of this layer significantly impacts on the Li electrode resistance before cycling and the charging/discharging process for symmetrical Li|0.5 m LiBF4 in [C3mpyr+][FSI–]|Li coin cells. Indeed it was found that introducing a rest period between cycling, and thereby allowing the chemical interaction between the Li electrode and electrolyte to take place, also impacted on the charging/discharging process. For all Li surface treatments the electrode resistance decreased after cycling and was due to significant structural rearrangement of the surface layer. These results suggest that careful electrode pretreatment in a real battery system will be required before operation.

Decoration of active sites to create bimetallic surfaces and its implication for electrochemical processes

The creation of electrocatalysts based on noble metals has received a significant amount of research interest due to their extensive use as fuel cell catalysts and electrochemical sensors. There have been many attempts to improve the activity of these metals through creating nanostructures, as well as post-synthesis treatments based on chemical, electrochemical, sonochemical and thermal approaches. In many instances these methods result in a material with active surface states, which can be considered to be adatoms or clusters of atoms on the surface that have a low lattice co-ordination number making them more prone to electrochemical oxidation at a wide range of potentials that are significantly less positive than those of their bulk metal counterparts. This phenomenon has been termed pre-monolayer oxidation and has been reported to occur on a range of metallic surfaces. In this work we present findings on the presence of active sites on Pd that has been: evaporated as a thin film; electrodeposited as nanostructures; as well as commercially available Pd nanoparticles supported on carbon. Significantly, advantage is taken of the low oxidation potential of these active sites whereby bimetallic surfaces are created by the spontaneous deposition of Ag from AgNO3 to generate Pd/Ag surfaces. Interestingly this approach does not increase the surface area of the original metal but has significant implications for its further use as an electrode material. It results in the inhibition or promotion of electrocatalytic activity which is highly dependent on the reaction of interest. As a general approach the decoration of active catalytic materials with less active metals for a particular reaction also opens up the possibility of investigating the role of the initially present active sites on the surface and identifying the degree to which they are responsible for electrocatalytic activity.

Review : "Quality of life: the assessment, analysis and interpretation of patient-reported outcomes (2nd Ed.)" by Peter M. Fayers & David Machin

An updated version, this excellent text is a timely addition to the library of any nurse researching in oncology or other settings where individuals’ quality of life must be understood. Health-related quality of life should be a central aspect of studies concerned with health and illness. Indeed, considerable evidence has recently emerged in oncology and other research settings that selfreported quality of life is of great prognostic significance and may be the most reliable predictor of subsequent morbidity and mortality. From a nursing perspective, it is also gratifying to note that novel therapy and other oncology studies increasingly recognize the importance of understanding patients’ subjective experiences of an intervention over time and to ascertain whether patients perceive that a new intervention makes a difference to their quality of life and treatment outcomes. Measurements of quality of life are now routine in clinical trials of chemotherapy drugs and are often considered the prime outcome of interest in the cost/benefit analyses of these treatments. The authors have extensive experience in qualityof- life assessment in cancer clinical trials, where most of the pioneering work into quality of life has been conducted. That said, many of the health-related qualityof- life issues discussed are common to many illnesses, and researchers outside of cancer should find the book equally helpful.

Tangled Webs : Using Bayesian Networks in the Fight Against Infection

Bayesian networks (BNs) provide a statistical modelling framework which is ideally suited for modelling the many factors and components of complex problems such as healthcare-acquired infections. The methicillin-resistant Staphylococcus aureus (MRSA) organism is particularly troublesome since it is resistant to standard treatments for Staph infections. Overcrowding and understa�ng are believed to increase infection transmission rates and also to inhibit the effectiveness of disease control measures. Clearly the mechanisms behind MRSA transmission and containment are very complicated and control strategies may only be e�ective when used in combination. BNs are growing in popularity in general and in medical sciences in particular. A recent Current Content search of the number of published BN journal articles showed a fi�ve fold increase in general and a six fold increase in medical and veterinary science from 2000 to 2009. This chapter introduces the reader to Bayesian network (BN) modelling and an iterative modelling approach to build and test the BN created to investigate the possible role of high bed occupancy on transmission of MRSA while simultaneously taking into account other risk factors.

A biological staging model for operable non-small cell lung cancer

Background Currently the best prognostic index for operable non-small cell lung cancer (NSCLC) is the TNM staging system. Molecular biology holds the promise of predicting outcome for the individual patient and identifying novel therapeutic targets. Angiogenesis, matrix metalloproteinases (MMP)-2 and -9, and the erb/HER type I tyrosine kinase receptors are all implicated in the pathogenesis of NSCLC. Methods A retrospective analysis of 167 patients with resected stage I-IIIa NSCLC and >60 days postoperative survival with a minimum follow up of 2 years was undertaken. Immunohistochemical analysis was performed on paraffin embedded sections for the microvessel marker CD34, MMP-2 and MMP-9, EGFR, and c-erbB-2 to evaluate the relationships between and impact on survival of these molecular markers. Results Tumour cell MMP-9 (HR 1.91 (1.23-2.97)), a high microvessel count (HR 1.97 (1.28-3.03)), and stage (stage II HR 1.44 (0.87-2.40), stage IIIa HR 2.21 (1.31-3.74)) were independent prognostic factors. Patients with a high microvessel count and tumour cell MMP-9 expression had a worse outcome than cases with only one (HR 1.68 (1.04-2.73)) or neither (HR 4.43 (2.29-8.57)) of these markers. EGFR expression correlated with tumour cell MMP-9 expression (p<0.001). Immunoreactivity for both of these factors within the same tumour was associated with a poor prognosis (HR 2.22 (1.45-3.41)). Conclusion Angiogenesis, EGFR, and MMP-9 expression provide prognostic information independent of TNM stage, allowing a more accurate outcome prediction for the individual patient. The development of novel anti-angiogenic agents, EGFR targeted therapies, and MMP inhibitors suggests that target specific adjuvant treatments may become a therapeutic option in patients with resected NSCLC.

Discounts and consumer search behavior : the role of framing

This paper studies the pure framing effect of price discounts, focusing on its impact on consumer search behavior. In a simple two-shop search experiment, we compare search behavior in base treatments (where both shops post net prices without discounts) to discount treatments (where either the first shop or the second shop posts gross prices with separate discount offers, keeping the net prices constant). Although the objective search problems are identical across treatments, subjects search less in discount frames, irrespective where the discount is offered. There is evidence showing that subjects only base their decisions on salient characteristics of the situation rather than on the objective price information.

The effects and interactions of GABAergic and dopaminergic agents in the prevention of form deprivation myopia by brief periods of normal vision

Intravitreal injections of GABA antagonists, dopamine agonists and brief periods of normal vision have been shown separately to inhibit form-deprivation myopia (FDM). Our study had three aims: (i) establish whether GABAergic agents modify the myopia protective effect of normal vision, (ii) investigate the receptor sub-type specificity of any observed effect, and (iii) consider an interaction with the dopamine (DA) system. Prior to the period of normal vision GABAergic agents were applied either (i) individually, (ii) in combination with other GABAergic agents (an agonist with an antagonist), or (iii) in combination with DA agonists and antagonists. Water injections were given to groups not receiving drug treatments so that all experimental eyes received intravitreal injections. As shown previously, constant form-deprivation resulted in high myopia and when diffusers were removed for 2 h per day the period of normal vision greatly reduced the FDM that developed. GABA agonists inhibited the protective effect of normal vision whereas antagonists had the opposite effect. GABAA/C agonists and D2 DA antagonists when used in combination were additive in suppressing the protective effect of normal vision. A D2 DA agonist restored some of the protective effect of normal vision that was inhibited by a GABA agonist (muscimol). The protective effect of normal vision against form-deprivation is modifiable by both the GABAergic and DAergic pathways.

Transcriptional regulation of IRS5/DOK4 expression in non-small-cell lung cancer cells

The insulin-receptor substrate family plays important roles in cellular growth, signaling, and survival. Two new members of this family have recently been isolated: IRS5/Dok4 and IRS6/Dok5. This study examines the expression of IRS5/DOK4 in a panel of lung cancer cell lines and tumor specimens. The results demonstrate that expression of IRS5/DOK4 is frequently altered with both elevated and decreased expression in non-small-cell lung cancer (NSCLC) tumor specimens. The altered expression of IRS5/DOK4 observed in tumor samples is not due to aberrant methylation. In vitro cell culture studies demonstrate that treatment of NSCLC cell lines with the histone deacetylase inhibitor trichostatin A (TSA) upregulates IRS5/DOK4. This finding indicates that expression is regulated epigenetically at the level of chromatin remodeling. Chromatin immunoprecipitation experiments confirm that the IRS5/DOK4 promoter has enhanced histone hyperacetylation following treatments with TSA. Finally, hypoxia was demonstrated to downregulate IRS5/DOK4 expression. This expression was restored by TSA. The clinical relevance of altered IRS5/DOK4 expression in NSCLC requires fur ther evaluation.

Exenatide extended-release; clinical trials, patient preference, and economic considerations

Type 2 diabetes remains an escalating world-wide problem, despite a range of treatments. The revelation that insulin secretion is under the control of a gut hormone, glucagon-like peptide 1 (GLP-1) led to a new paradigm in the management of type 2 diabetes, medicines that directly stimulate, or that prolong the actions of the endogenous GLP-1, at its receptors. Exenatide is an agonist at the GLP-1 receptors, and was initially developed as a subcutaneous twice daily medication, ExBID. The clinical trials with ExBID established a role for exenatide in the treatment of type 2 diabetes. Subsequently, once weekly exenatide (ExQW) was shown to have advantages over ExBID, and there is now more emphasis on the development of ExQW. ExQW alone reduces glycosylated haemoglobin (HbA1c) and body weight, and is well tolerated. ExQW has been compared to sitagliptin, pioglitazone and metformin, and shown to have a greater ability to reduce HbA1c than these other medicines. The only preparation of insulin, which ExQW has been compared to, is insulin glargine, and the ExQW has some favourable properties in this comparison, notably causing weight loss, compared to the gain with insulin glargine. ExQW has been compared to another GLP-1 receptor agonist, liraglutide, and ExQW is non-inferior to liraglutide in reducing HbA1c. The small amount of evidence available, shows that subjects with type 2 diabetes, prefer ExQW to ExBID, and that adherence was high to these in the clinical trial setting. Healthcare and economic modelling suggests that ExQW will reduce diabetic complications and be cost-effective, compared to other medications, with long term use. Little is known about whether subjects with type 2 diabetes prefer ExQW to other medicines, and whether adherence is good to ExQW in practice, and these important topics require further study.

Directory of World Cinema : Australia and New Zealand 2

Building on and bringing up to date the material presented in the first installment of Directory of World Cinema : Australia and New Zealand, this volume continues the exploration of the cinema produced in Australia and New Zealand since the beginning of the twentieth century. Among the additions to this volume are in-depth treatments of the locations that feature prominently in the countries' cinema. Essays by leading critics and film scholars consider the significance in films of the outback and the beach, which is evoked as a liminal space in Long Weekend and a symbol of death in Heaven's Burning, among other films. Other contributions turn the spotlight on previously unexplored genres and key filmmakers, including Jane Campion, Rolf de Heer, Charles Chauvel, and Gillian Armstrong.