Acute acetaminophen ingestion improves performance and muscle activation during maximal intermittent knee extensor exercise

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.AIM: Acetaminophen is a commonly used medicine for pain relief and emerging evidence suggests that it may improve endurance exercise performance. This study investigated some of the physiological mechanisms by which acute acetaminophen ingestion might blunt muscle fatigue development. METHODS: Thirteen active males completed 60 × 3 s maximum voluntary contractions (MVC) of the knee extensors with each contraction separated by a 2 s passive recovery period. This protocol was completed 60 min after ingesting 1 g of maltodextrin (placebo) or 1 g of acetaminophen on two separate visits. Peripheral nerve stimulation was administered every 6th contraction for assessment of neuromuscular fatigue development, with the critical torque (CT), which reflects the maximal sustainable rate of oxidative metabolism, taken as the mean torque over the last 12 contractions. Surface electromyography was recorded continuously as a measure of muscle activation. RESULTS: Mean torque (61 ± 11 vs. 58 ± 14% pre-exercise MVC) and CT (44 ± 13 vs. 40 ± 15% pre-exercise MVC) were greater in the acetaminophen trial compared to placebo (both P  0.05). However, the decline in electromyography amplitude was attenuated in the acetaminophen trial, with electromyography amplitude being greater compared to placebo from 210 s onwards (P < 0.05). CONCLUSION: These findings indicate that acute acetaminophen ingestion might be ergogenic by increasing CT and preserving muscle activation during high-intensity exercise.This research was not sponsored by any funding body external to University of Exete

Contralateral fatigue during severe-intensity single-leg exercise: influence of acute acetaminophen ingestion.

This is the author accepted manuscript. The final version is available from American Physiological Society via the DOI in this recordExhaustive single-leg exercise has been suggested to reduce time to task failure (Tlim) during subsequent exercise in the contralateral leg by exacerbating central fatigue development. We investigated the influence of acetaminophen (ACT), an analgesic which may blunt central fatigue development, on Tlim- during single-leg exercise completed both with, and without, prior fatiguing exercise of the contralateral leg. Fourteen recreationally-active men performed single-leg, severe-intensity knee extensor exercise to Tlim on the left (Leg1) and right (Leg2) legs without prior contralateral fatigue, and on Leg2 immediately following Leg1 (Leg2-CONTRA). The tests were completed following ingestion of 1 g ACT or maltodextrin (placebo) capsules. Intramuscular phosphorous-containing metabolites and substrates, and muscle activation, were assessed using 31P-MRS and electromyography, respectively. Tlim was not different between the Leg1ACT and Leg1PL conditions (402 ± 101 vs. 390 ± 106 s; P=0.11). There was also no difference in Tlim between Leg2ACT-CONTRA and Leg2PL-CONTRA (324 ± 85 vs. 311 ± 92 s; P=0.10), but Tlim was shorter in these tests compared to Leg2CON (385 ± 104 s; both P0.05). These findings suggest that levels of metabolic perturbation and muscle activation are not different at task failure during single-leg severe-intensity knee extensor exercise completed with or without prior fatiguing exercise of the contralateral leg. Despite the existence of contralateral fatigue, ACT ingestion did not alter neuromuscular responses or exercise performance.NIH

Acute ibuprofen ingestion does not attenuate fatigue during maximal intermittent knee extensor or all-out cycling exercise

Recent research suggests that acute consumption of pharmacological analgesics can improve exercise performance, but the ergogenic potential of ibuprofen (IBP) administration is poorly understood. This study tested the hypothesis that IBP administration would enhance maximal exercise performance. In one study, 13 physically active males completed 60 × 3-s maximal voluntary contractions (MVCs) of the knee extensors interspersed with 2-s passive recovery periods, on 2 occasions, with the critical torque (CT) estimated as the mean torque over the last 12 contractions (part A). In another study, 16 active males completed two 3-min all-out tests against a fixed resistance on an electronically braked cycle ergometer, with the critical power estimated from the mean power output over the final 30 s of the test (part B). All tests were completed 60 min after ingestion of maltodextrin (placebo, PL) or 400 mg of IBP. Peripheral nerve stimulation was administered at regular intervals and electromyography was measured throughout. For part A, mean torque (IBP: 60% ± 13% of pre-exercise MVC; PL: 58% ± 14% of pre-exercise MVC) and CT (IBP: 41% ± 16% of pre-exercise MVC; PL: 40% ± 15% of pre-exercise MVC) were not different between conditions (P > 0.05). For part B, end-test power output (IBP: 292 ± 28 W; PL: 288 ± 31 W) and work done (IBP: 65.9 ± 5.9 kJ; PL: 65.4 ± 6.4 kJ) during the 3-min all-out cycling tests were not different between conditions (all P > 0.05). For both studies, neuromuscular fatigue declined at a similar rate in both conditions (P > 0.05). In conclusion, acute ingestion of 400 mg of IBP does not improve single-leg or maximal cycling performance in healthy humans

A comparison of user testing and heuristic evaluation methods for identifying website usability problems

This study compared the effectiveness and efficiency of two usability testing methods, user testing and heuristic evaluation. Thirty two participants took part in the study, sixteen for each of the two methods. Four measures were used to compare their performance: number of problems identified, severity of problems, type of problems and time taken to find problems. It was found that heuristic evaluation found nearly 5 times more individual problems than user testing, so could be seen as more effective. However, user testing found on average slightly more severe problems and took less time to complete than heuristic evaluation. Heuristic evaluation had a faster problem identification rate (number of seconds per problem found), so could also be seen as more efficient. While each method had advantages in the test both methods are seen as complementary to each other in practice

Accuracy of five algorithms to diagnose gambiense human African trypanosomiasis.

Algorithms to diagnose gambiense human African trypanosomiasis (HAT, sleeping sickness) are often complex due to the unsatisfactory sensitivity and/or specificity of available tests, and typically include a screening (serological), confirmation (parasitological) and staging component. There is insufficient evidence on the relative accuracy of these algorithms. This paper presents estimates of the accuracy of five algorithms used by past Médecins Sans Frontières programmes in the Republic of Congo, Southern Sudan and Uganda

Combined effects of time spent in physical activity, sedentary behaviors and sleep on obesity and cardio-metabolic health markers: a novel compositional data analysis approach

<div><p>The associations between time spent in sleep, sedentary behaviors (SB) and physical activity with health are usually studied without taking into account that time is finite during the day, so time spent in each of these behaviors are codependent. Therefore, little is known about the combined effect of time spent in sleep, SB and physical activity, that together constitute a composite whole, on obesity and cardio-metabolic health markers. Cross-sectional analysis of NHANES 2005–6 cycle on N = 1937 adults, was undertaken using a compositional analysis paradigm, which accounts for this intrinsic codependence. Time spent in SB, light intensity (LIPA) and moderate to vigorous activity (MVPA) was determined from accelerometry and combined with self-reported sleep time to obtain the 24 hour time budget composition. The distribution of time spent in sleep, SB, LIPA and MVPA is significantly associated with BMI, waist circumference, triglycerides, plasma glucose, plasma insulin (all p<0.001), and systolic (p<0.001) and diastolic blood pressure (p<0.003), but not HDL or LDL. Within the composition, the strongest positive effect is found for the proportion of time spent in MVPA. Strikingly, the effects of MVPA replacing another behavior and of MVPA being displaced by another behavior are asymmetric. For example, re-allocating 10 minutes of SB to MVPA was associated with a lower waist circumference by 0.001% but if 10 minutes of MVPA is displaced by SB this was associated with a 0.84% higher waist circumference. The proportion of time spent in LIPA and SB were detrimentally associated with obesity and cardiovascular disease markers, but the association with SB was stronger. For diabetes risk markers, replacing SB with LIPA was associated with more favorable outcomes. Time spent in MVPA is an important target for intervention and preventing transfer of time from LIPA to SB might lessen the negative effects of physical inactivity.</p></div

Estimating Surface Area in Early Hominins

Height and weight-based methods of estimating surface area have played an important role in the development of the current consensus regarding the role of thermoregulation in human evolution. However, such methods may not be reliable when applied to early hominins because their limb proportions differ markedly from those of humans. Here, we report a study in which this possibility was evaluated by comparing surface area estimates generated with the best-known height and weight-based method to estimates generated with a method that is sensitive to proportional differences. We found that the two methods yield indistinguishable estimates when applied to taxa whose limb proportions are similar to those of humans, but significantly different results when applied to taxa whose proportions differ from those of humans. We also found that the discrepancy between the estimates generated by the two methods is almost entirely attributable to inter-taxa differences in limb proportions. One corollary of these findings is that we need to reassess hypotheses about the role of thermoregulation in human evolution that have been developed with the aid of height and weight-based methods of estimating body surface area. Another is that we need to use other methods in future work on fossil hominin body surface areas

Tetrahydrobiopterin modulates ubiquitin conjugation to UBC13/UBE2N and proteasome activity by S-nitrosation

Nitric Oxide (NO) is an intracellular signalling mediator, which affects many biological processes via the posttranslational modification of proteins through S-nitrosation. The availability of NO and NOS-derived reactive oxygen species (ROS) from enzymatic uncoupling are determined by the NO synthase cofactor Tetrahydrobiopterin (BH4). Here, using a global proteomics “biotin-switch” approach, we identified components of the ubiquitin-proteasome system to be altered via BH4-dependent NO signalling by protein S-nitrosation. We show S-nitrosation of ubiquitin conjugating E2 enzymes, in particular the catalytic residue C87 of UBC13/UBE2N, leading to impaired polyubiquitylation by interfering with the formation of UBC13~Ub thioester intermediates. In addition, proteasome cleavage activity in cells also seems to be altered by S-nitrosation, correlating with the modification of cysteine residues within the 19S regulatory particle and catalytic subunits of the 20S complex. Our results highlight the widespread impact of BH4 on downstream cellular signalling as evidenced by the effect of a perturbed BH4-dependent NO-Redox balance on critical processes within the ubiquitin-proteasome system (UPS). These studies thereby uncover a novel aspect of NO associated modulation of cellular homeostasis

Use of machine learning to shorten observation-based screening and diagnosis of autism

The Autism Diagnostic Observation Schedule-Generic (ADOS) is one of the most widely used instruments for behavioral evaluation of autism spectrum disorders. It is composed of four modules, each tailored for a specific group of individuals based on their language and developmental level. On average, a module takes between 30 and 60 min to deliver. We used a series of machine-learning algorithms to study the complete set of scores from Module 1 of the ADOS available at the Autism Genetic Resource Exchange (AGRE) for 612 individuals with a classification of autism and 15 non-spectrum individuals from both AGRE and the Boston Autism Consortium (AC). Our analysis indicated that 8 of the 29 items contained in Module 1 of the ADOS were sufficient to classify autism with 100% accuracy. We further validated the accuracy of this eight-item classifier against complete sets of scores from two independent sources, a collection of 110 individuals with autism from AC and a collection of 336 individuals with autism from the Simons Foundation. In both cases, our classifier performed with nearly 100% sensitivity, correctly classifying all but two of the individuals from these two resources with a diagnosis of autism, and with 94% specificity on a collection of observed and simulated non-spectrum controls. The classifier contained several elements found in the ADOS algorithm, demonstrating high test validity, and also resulted in a quantitative score that measures classification confidence and extremeness of the phenotype. With incidence rates rising, the ability to classify autism effectively and quickly requires careful design of assessment and diagnostic tools. Given the brevity, accuracy and quantitative nature of the classifier, results from this study may prove valuable in the development of mobile tools for preliminary evaluation and clinical prioritization—in particular those focused on assessment of short home videos of children—that speed the pace of initial evaluation and broaden the reach to a significantly larger percentage of the population at risk