mTOR inhibition in breast cancer

No description supplie

Time-trial performance is not impaired in either competitive athletes or untrained individuals following a prolonged cognitive task

This is the final version. Available from Springer via the DOI in this record.It has been reported that mental fatigue decreases exercise performance during high-intensity constant-work-rate exercise (CWR) and self-paced time trials (TT) in recreationally-trained individuals. The purpose of this study was to determine whether performance is impaired following a prolonged cognitive task in individuals trained for competitive sport. Ten trained competitive athletes (ATH) and ten untrained healthy men (UNT) completed a 6-min severe-intensity CWR followed by a 6-min cycling TT immediately following cognitive tasks designed to either perturb (Stroop colour-word task and N-back task; PCT) or maintain a neutral (documentary watching; CON) mental state. UNT had a higher heart rate (75 ± 9 v. 69 ± 7 bpm; P = 0.002) and a lower positive affect PANAS score (19.9 ± 7.5 v. 24.3 ± 4.6; P = 0.036) for PCT compared to CON. ATH showed no difference in heart rate, but had a higher negative affect score for PCT compared to CON (15.1 ± 3.7 v. 12.2 ± 2.7; P = 0.029). Pulmonary O 2 uptake during CWR was not different between PCT and CON for ATH or UNT. Work completed during TT was not different between PCT and CON for ATH (PCT 103 ± 12 kJ; CON 102 ± 12 kJ; P > 0.05) or UNT (PCT 75 ± 11 kJ; CON 74 ± 12 kJ; P > 0.05). Compared to CON, during PCT, UNT showed unchanged psychological stress responses, whereas ATH demonstrated increased psychological stress responses. However, regardless of this distinction, exercise performance was not affected by PCT in either competitive athletes or untrained individuals

Dynamics of the power-duration relationship during prolonged endurance exercise and influence of carbohydrate ingestion

This is the author accepted manuscript. The final version is available from the American Physiological Society via the DOI in this recordWe tested the hypotheses that the parameters of the power-duration relationship, estimated as the end-test power (EP) and work done above EP (WEP) during a 3-min all out exercise test (3MT), would be reduced progressively following 40 min, 80 min and 2 h of heavy-intensity cycling, and that carbohydrate (CHO) ingestion would attenuate the reduction in EP and WEP. Sixteen participants completed a 3MT without prior exercise (control), immediately after 40 min, 80 min and 2-h of heavy-intensity exercise while consuming a placebo beverage, and also after 2-h of heavy-intensity exercise while consuming a CHO supplement (60 g/h CHO). There was no difference in EP measured without prior exercise (260 ± 37 W) compared to EP following 40 min (268 ± 39 W) or 80 min (260 ± 40 W) of heavy-intensity exercise; however, after 2-h, EP was 9% lower compared to control (236 ± 47 W; P<0.05). There was no difference in WEP measured without prior exercise (17.9 ± 3.3 kJ) compared to after 40 min of heavy-intensity exercise (16.1 ± 3.3 kJ), but WEP was lower (P<0.05) than control after 80 min (14.7 ± 2.9 kJ) and 2-h (13.8 ± 2.7 kJ). Compared to placebo, CHO ingestion negated the reduction of EP following 2-h of heavy-intensity exercise (254 ± 49 W) but had no effect on WEP (13.5 ± 3.4 kJ). These results reveal a different time course for the deterioration of EP and WEP during prolonged endurance exercise and indicate that EP is sensitive to CHO availability

Physiological demands of running at 2-hour marathon race pace

This is the author accepted manuscript. The final version is available from the American Physiological Society via the DOI in this recordThe requirements of running a 2 hour marathon have been extensively debated but the actual physiological demands of running at ~21.1 km/h have never been reported. We therefore conducted laboratory-based physiological evaluations and measured running economy (O2 cost) while running outdoors at ~21.1 km/h, in world-class distance runners as part of Nike's 'Breaking 2' marathon project. On separate days, 16 male distance runners (age, 29 ± 4 years; height, 1.72 ± 0.04 m; mass, 58.9 ± 3.3 kg) completed an incremental treadmill test for the assessment of V̇O2peak, O2 cost of submaximal running, lactate threshold and lactate turn-point, and a track test during which they ran continuously at 21.1 km/h. The laboratory-determined V̇O2peak was 71.0 ± 5.7 ml/kg/min with lactate threshold and lactate turn-point occurring at 18.9 ± 0.4 and 20.2 ± 0.6 km/h, corresponding to 83 ± 5 % and 92 ± 3 % V̇O2peak, respectively. Seven athletes were able to attain a steady-state V̇O2 when running outdoors at 21.1 km/h. The mean O2 cost for these athletes was 191 ± 19 ml/kg/km such that running at 21.1 km/h required an absolute V̇O2 of ~4.0 L/min and represented 94 ± 3 % V̇O2peak. We report novel data on the O2 cost of running outdoors at 21.1 km/h, which enables better modelling of possible marathon performances by elite athletes. Using the value for O2 cost measured in this study, a sub-2 hour marathon would require a 59 kg runner to sustain a V̇O2 of approximately 4.0 L/min or 67 ml/kg/min.Nik

SCAMP:standardised, concentrated, additional macronutrients, parenteral nutrition in very preterm infants: a phase IV randomised, controlled exploratory study of macronutrient intake, growth and other aspects of neonatal care

<p>Abstract</p> <p>Background</p> <p>Infants born <29 weeks gestation are at high risk of neurocognitive disability. Early postnatal growth failure, particularly head growth, is an important and potentially reversible risk factor for impaired neurodevelopmental outcome. Inadequate nutrition is a major factor in this postnatal growth failure, optimal protein and calorie (macronutrient) intakes are rarely achieved, especially in the first week. Infants <29 weeks are dependent on parenteral nutrition for the bulk of their nutrient needs for the first 2-3 weeks of life to allow gut adaptation to milk digestion. The prescription, formulation and administration of neonatal parenteral nutrition is critical to achieving optimal protein and calorie intake but has received little scientific evaluation. Current neonatal parenteral nutrition regimens often rely on individualised prescription to manage the labile, unpredictable biochemical and metabolic control characteristic of the early neonatal period. Individualised prescription frequently fails to translate into optimal macronutrient delivery. We have previously shown that a standardised, concentrated neonatal parenteral nutrition regimen can optimise macronutrient intake.</p> <p>Methods</p> <p>We propose a single centre, randomised controlled exploratory trial of two standardised, concentrated neonatal parenteral nutrition regimens comparing a standard macronutrient content (maximum protein 2.8 g/kg/day; lipid 2.8 g/kg/day, dextrose 10%) with a higher macronutrient content (maximum protein 3.8 g/kg/day; lipid 3.8 g/kg/day, dextrose 12%) over the first 28 days of life. 150 infants 24-28 completed weeks gestation and birthweight <1200 g will be recruited. The primary outcome will be head growth velocity in the first 28 days of life. Secondary outcomes will include a) auxological data between birth and 36 weeks corrected gestational age b) actual macronutrient intake in first 28 days c) biomarkers of biochemical and metabolic tolerance d) infection biomarkers and other intravascular line complications e) incidence of major complications of prematurity including mortality f) neurodevelopmental outcome at 2 years corrected gestational age</p> <p>Trial registration</p> <p>Current controlled trials: <a href="http://www.controlled-trials.com/ISRCTN76597892">ISRCTN76597892</a>; EudraCT Number: 2008-008899-14</p

PINK1 Defect Causes Mitochondrial Dysfunction, Proteasomal Deficit and α-Synuclein Aggregation in Cell Culture Models of Parkinson's Disease

Mutations in PTEN induced kinase 1 (PINK1), a mitochondrial Ser/Thr kinase, cause an autosomal recessive form of Parkinson's disease (PD), PARK6. Here, we report that PINK1 exists as a dimer in mitochondrial protein complexes that co-migrate with respiratory chain complexes in sucrose gradients. PARK6 related mutations do not affect this dimerization and its associated complexes. Using in vitro cell culture systems, we found that mutant PINK1 or PINK1 knock-down caused deficits in mitochondrial respiration and ATP synthesis. Furthermore, proteasome function is impaired with a loss of PINK1. Importantly, these deficits are accompanied by increased α-synclein aggregation. Our results indicate that it will be important to delineate the relationship between mitochondrial functional deficits, proteasome dysfunction and α-synclein aggregation

Bioenergetic Consequences of PINK1 Mutations in Parkinson Disease

BACKGROUND: Mutations of the gene for PTEN-induced kinase 1 (PINK1) are a cause of familial Parkinson's disease (PD). PINK1 protein has been localised to mitochondria and PINK1 gene knockout models exhibit abnormal mitochondrial function. The purpose of this study was to determine whether cells derived from PD patients with a range of PINK1 mutations demonstrate similar defects of mitochondrial function, whether the nature and severity of the abnormalities vary between mutations and correlate with clinical features. METHODOLOGY: We investigated mitochondrial bioenergetics in live fibroblasts from PINK1 mutation patients using single cell techniques. We found that fibroblasts from PINK1 mutation patients had significant defects of bioenergetics including reduced mitochondrial membrane potential, altered redox state, a respiratory deficiency that was determined by substrate availability, and enhanced sensitivity to calcium stimulation and associated mitochondrial permeability pore opening. There was an increase in the basal rate of free radical production in the mutant cells. The pattern and severity of abnormality varied between different mutations, and the less severe defects in these cells were associated with later age of onset of PD. CONCLUSIONS: The results provide insight into the molecular pathology of PINK1 mutations in PD and also confirm the critical role of substrate availability in determining the biochemical phenotype--thereby offering the potential for novel therapeutic strategies to circumvent these abnormalities

The effects of a 6-week strength training on critical velocity, anaerobic running distance, 30-m sprint and yo-yo intermittent running test performances in male soccer players

The objectives of this study were to examine the effects of a moderate intensity strength training on changes in critical velocity (CV), anaerobic running distance (D'), sprint performance and Yo-Yo intermittent running test (Yo-Yo IR1) performances. Methods: two recreational soccer teams were divided in a soccer training only group (SO; n = 13) and a strength and soccer training group (ST; n = 13). Both groups were tested for values of CV, D', Yo-Yo IR1 distance and 30-m sprint time on two separate occasions (pre and post intervention). The ST group performed a concurrent 6-week upper and lower body strength and soccer training, whilst the SO group performed a soccer only training. Results: after the re-test of all variables, the ST demonstrated significant improvements for both, YoYo IR1 distance (p = 0.002) and CV values (p<0.001) with no significant changes in the SO group. 30-m sprint performance were slightly improved in the ST group with significantly decreased performance times identified in the SO group (p<0.001). Values for D' were slightly reduced in both groups (ST -44.5 m, 95% CI = -90.6 to 1.6; SO -42.6 m, 95% CI = -88.7 to 3.5). Conclusions: combining a 6-week moderate strength training with soccer training significantly improves CV, Yo-Yo IR1 whilst moderately improving 30-m sprint performances in non-previously resistance trained male soccer players. Critical Velocity can be recommended to coaches as an additional valid testing tool in soccer