Natalie Strobel

Antioxidant Supplementation Reduces Skeletal Muscle Mitochondrial Biogenesis

PURPOSE Exercise increases the production of reactive oxygen species (ROS) in skeletal muscle, and athletes often consume antioxidant supplements in the belief they will attenuate ROS-related muscle damage and fatigue during exercise. However, exercise-induced ROS may regulate beneficial skeletal muscle adaptations, such as increased mitochondrial biogenesis. We therefore investigated the effects of long-term antioxidant supplementation with vitamin E and α-lipoic acid on changes in markers of mitochondrial biogenesis in the skeletal muscle of exercise-trained and sedentary rats. METHODS Male Wistar rats were divided into four groups: 1) sedentary control diet, 2) sedentary antioxidant diet, 3) exercise control diet, and 4) exercise antioxidant diet. Animals ran on a treadmill 4 d · wk at ∼ 70%VO2max for up to 90 min · d for 14 wk. RESULTS Consistent with the augmentation of skeletal muscle mitochondrial biogenesis and antioxidant defenses, after training there were significant increases in peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) messenger RNA (mRNA) and protein, cytochrome C oxidase subunit IV (COX IV) and cytochrome C protein abundance, citrate synthase activity, Nfe2l2, and SOD2 protein (P < 0.05). Antioxidant supplementation reduced PGC-1α mRNA, PGC-1α and COX IV protein, and citrate synthase enzyme activity (P < 0.05) in both sedentary and exercise-trained rats. CONCLUSIONS Vitamin E and α-lipoic acid supplementation suppresses skeletal muscle mitochondrial biogenesis, regardless of training status.

Oxidative stress biomarkers as predictors of cardiovascular disease

Evidence for the role of oxidative stress in the pathogenesis of cardiovascular disease (CVD) is primarily based on experimental and observational human studies. The aim of this review is to examine the observational longitudinal studies that have investigated the relationship between oxidative stress biomarkers and CVD. Fifty-one studies were identified with twenty-six of these measuring oxidized (Ox)-LDL, fifteen assessing myeloperoxidase, seven using lipid peroxidation measures and three quantifying protein oxidation. Results of studies using Ox-LDL have been equivocal with sixteen of the twenty-six studies reporting that this measure is predictive of cardiovascular events. These inconsistent results are not explained by differences in the study populations (primary or secondary CVD) or the type of assay used (auto or monoclonal antibodies). Six of the seven lipid peroxidation, and two of three protein oxidation studies found associations. Twelve of fifteen studies assessing the role of myeloperoxidase reported it to be predictive of CVD. However, issues surrounding the specificity of myeloperoxidase as a marker of oxidative stress and the small number of research groups reporting these results, limit this finding. In summary, the ability of oxidative stress biomarkers to predict CVD has yet to be established. Furthermore, it is important to note that the methods used to assess oxidative stress in these studies are indirect, and the evidence that the various methods actually reflect oxidative stress in vivo is limited.

The effect of consecutive days of exercise on markers of oxidative stress.

We examined the influence of 3 consecutive days of high-intensity cycling on blood and urinary markers of oxidative stress. Eight highly-trained male cyclists (VO2 max 76 +/- 4 mL.kg-1.min-1; mean +/- SD) completed an interval session (9 exercise bouts lasting 30 s each, at 150% peak power output) on day 1, followed by 2 laboratory-simulated 30 km time trials on days 2 and 3. The cyclists also completed a submaximal exercise trial matched to the interval session for oxygen consumption. Blood was collected pre- and post-exercise for the determination of malondialdehyde (MDA), total antioxidant status (TAS), vitamin E, and the antioxidant enzyme activity of superoxide dismutase and glutathione peroxidase, while urine was collected for the determination of allantoin. There were significant increases in plasma MDA concentrations (p < 0.01), plasma TAS (p < 0.01), and urinary allantoin excretion (p < 0.01) following the high-intensity interval session on day 1, whereas plasma vitamin E concentration significantly decreased (p = 0.028). Post-exercise changes in plasma MDA (p = 0.036), TAS concentrations (p = 0.039), and urinary allantoin excretion (p = 0.031) were all significantly attenuated over the 3 consecutive days of exercise, whereas resting plasma TAS concentration was elevated. There were no significant changes in plasma MDA, TAS, or allantoin excretion following submaximal exercise and there were no significant changes in antioxidant enzyme activity over consecutive days of exercise or following submaximal exercise. Consecutive days of high-intensity exercise enhanced resting plasma TAS concentration and reduced the post-exercise increase in plasma MDA concentrations.

Altering the redox state of skeletal muscle by glutathione depletion increases the exercise‐activation of PGC‐1α

We investigated the relationship between markers of mitochondrial biogenesis, cell signaling, and antioxidant enzymes by depleting skeletal muscle glutathione with diethyl maleate (DEM) which resulted in a demonstrable increase in oxidative stress during exercise. Animals were divided into six groups: (1) sedentary control rats; (2) sedentary rats + DEM; (3) exercise control rats euthanized immediately after exercise; (4) exercise rats + DEM; (5) exercise control rats euthanized 4 h after exercise; and (6) exercise rats + DEM euthanized 4 h after exercise. Exercising animals ran on the treadmill at a 10% gradient at 20 m/min for the first 30 min. The speed was then increased every 10 min by 1.6 m/min until exhaustion. There was a reduction in total glutathione in the skeletal muscle of DEM treated animals compared to the control animals (P < 0.05). Within the control group, total glutathione was higher in the sedentary group compared to after exercise (P < 0.05). DEM treatment also significantly increased oxidative stress, as measured by increased plasma F2–isoprostanes (P < 0.05). Exercising animals given DEM showed a significantly greater increase in peroxisome proliferator activated receptor γ coactivator‐1α (PGC–1α) mRNA compared to the control animals that were exercised (P < 0.05). This study provides novel evidence that by lowering the endogenous antioxidant glutathione in skeletal muscle and inducing oxidative stress through exercise, PGC‐1α gene expression was augmented. These findings further highlight the important role of exercise induced oxidative stress in the regulation of mitochondrial biogenesis.

Discriminant validity of the Hospital Anxiety and Depression Scale, Beck Depression Inventory (II) and Beck Anxiety Inventory to confirmed clinical diagnosis of depression and anxiety in patients with chronic obstructive pulmonary disease.

The objective of this study was to investigate the discriminant validity of commonly used depression and anxiety screening tools in order to determine the most suitable tool for patients with chronic obstructive pulmonary disease (COPD). COPD patients (n = 56) completed the Hospital Anxiety and Depression Scale (HADS), Beck Depression Inventory (BDI-II) and Beck Anxiety Inventory (BAI). These scores were compared to confirmed clinical diagnoses of depression and anxiety using the Mini Neuropsychiatric Interview. HADS depression subscale (HADS-D) sensitivity/specificity was 78/81%; BDI-II 89/77%; HADS anxiety subscale (HADS-A) 71/81%; and BAI 89/62%. HADS-D sensitivity/specificity was improved (100/83%) with the removal of Q4 ‘I feel as if I am slowed down’ and adjusted cut-off (≥5). Removal of BDI-II Q21 ‘Loss of interest in sex’ with adjusted cut-off ≥12 resulted in similar improvement (100/79%). No problematic items were identified for HADS-A or BAI. Previously reported low sensitivity/specificity of the HADS for COPD patients was not replicated. Furthermore, simple modifications of the HADS-D markedly improved sensitivity/specificity for depression. BDI-II, HADS-A and BAI produced acceptable sensitivity/specificity unmodified. Pending further research for COPD patients we recommend continued use of the HADS-A with standard cut-off (≥8) and removal of Q4 of the HADS-D with lower cut-off ≥5.

Performance benefits of rehydration with intravenous fluid and oral glycerol.

PURPOSE Intravenous (IV) saline has been used by athletes attempting to accelerate rehydration procedures. The diuresis from IV rehydration may be circumvented through the concomitant use of oral glycerol. We aimed to examine the effects of rehydrating with four different regimens of IV fluid and oral glycerol on subsequent 40-km cycling time trial performance. METHODS Nine endurance-trained men were dehydrated by 4% bodyweight via exercise in the heat. They then rehydrated with 150% of the fluid lost via four protocols using a randomized crossover design: 1) oral = sports drink and water; 2) oral glycerol = sports drink, water, and glycerol; 3) IV = half as normal saline, half of sports drink, and water; and 4) IV with oral glycerol = half as normal saline, half as sports drink, water, and glycerol. After this, they completed a 40-km cycling performance test in the heat. RESULTS Compared with oral rehydration, there were significant performance benefits (P < 0.05) when rehydrating with oral glycerol (improved time to complete 40 km by 3.7%), IV (3.5%), and IV with oral glycerol (4.1%). Plasma volume restoration was highest in IV with oral glycerol, then IV, then oral glycerol, then oral (P < 0.01 for all of these comparisons). There were no differences in HR, tympanic/skin temperatures, sweat rate, blood lactate concentration, thermal stress, or RPE between groups. CONCLUSIONS Combining IV fluid with oral glycerol resulted in the greatest fluid retention; however, it did not improve exercise performance compared with either modality alone.

Effects of Low- Versus High-Fidelity Simulations on the Cognitive Burden and Performance of Entry-Level Paramedicine Students: A Mixed-Methods Comparison Trial Using Eye-Tracking, Continuous Heart Rate, Difficulty Rating Scales, Video Observation and Interviews.

Introduction High-fidelity simulation-based training is often avoided for early-stage students because of the assumption that while practicing newly learned skills, they are ill suited to processing multiple demands, which can lead to “cognitive overload” and poorer learning outcomes. We tested this assumption using a mixed-methods experimental design manipulating psychological immersion. Methods Thirty-nine randomly assigned first-year paramedicine students completed low- or high-environmental fidelity simulations [low–environmental fidelity simulations (LFenS) vs. high–environmental fidelity simulation (HFenS)] involving a manikin with obstructed airway (SimMan3G). Psychological immersion and cognitive burden were determined via continuous heart rate, eye tracking, self-report questionnaire (National Aeronautics and Space Administration Task Load Index), independent observation, and postsimulation interviews. Performance was assessed by successful location of obstruction and time-to-termination. Results Eye tracking confirmed that students attended to multiple, concurrent stimuli in HFenS and interviews consistently suggested that they experienced greater psychological immersion and cognitive burden than their LFenS counterparts. This was confirmed by significantly higher mean heart rate (P < 0.001) and National Aeronautics and Space Administration Task Load Index mental demand (P < 0.05). Although group allocation did not influence the proportion of students who ultimately revived the patient (58% vs. 30%, P < 0.10), the HFenS students did so significantly more quickly (P < 0.01). The LFenS students had low immersion resulting in greater assessment anxiety. Conclusions High–environmental fidelity simulation engendered immersion and a sense of urgency in students, whereas LFenS created assessment anxiety and slower performance. We conclude that once early-stage students have learned the basics of a clinical skill, throwing them in the “deep end” of high-fidelity simulation creates significant additional cognitive burden but this has considerable educational merit.

Importance of understanding pre-analytical variability in biomarker development.

that HMGB1 preconditioning may also provide a HMGB1 tolerance and cardioprotection [5,6]. Phosphoinositide 3-kinases (PI3K) and their downstream target serine/threonine kinase Akt (also known as protein kinase B) are a conserved family of signal transduction enzymes which are involved in regulating cellular activation, inflammatory responses, and apoptosis [7]. Activation of PI3K/Akt-dependent signalling has been shown to prevent cardiacmyocyte apoptosis andprotect themyocardium from I/R injury [7,8]. Recently, Ha et al. [8] showed that the PI3K/Akt signaling pathway was involved in LPS preconditioning induced myocardial protection against I/R injury, while HMGB1 preconditioning could induce LPS tolerance during hepatic I/R [5]. In this study, we found that HMGB1 preconditioning could activate Akt and the PI3K/Akt signaling pathway inhibitor could abolished the protective effect of HMGB1 preconditioning on myocardial I/R injury, suggesting that PI3K/Akt signaling pathway may be involved in cardioprotection of HMGB1 preconditioning during myocardial I/R injury. When Akt was activated by HMGB1 preconditioning, and then activated the reperfusion injury salvage kinase pathway, such as endogenous nitric oxide synthase, protein kinase C, mitochondrial potassium channel, reactive oxygen species, etc., at last could provide a cardioprotection [9]. HMGB1 preconditioning could induce HMGB1 tolerance and protect against myocardial I/R injury, which may be involved in PI3K/Akt signaling pathway. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [10].

Sustained participation in annual continuous quality improvement activities improves quality of care for Aboriginal and Torres Strait Islander children

To determine whether participation in the continuous quality improvement (CQI) Audit and Best Practice for Chronic Disease programme improved care and outcomes for Indigenous children.

Determinants of morbidity associated with infant male circumcision: community-level population-based study in rural Ghana.

Male circumcision services have expanded throughout Africa as part of a long‐term HIV prevention strategy. We assessed the effect of type of service provider (formal and informal) and hygiene practices on circumcision‐related morbidities in rural Ghana.