Update and extension of the 'equivalent slope' of speed-changing level locomotion in humans : a computational model for shuttle running

Controlled experimental protocols for metabolic cost assessment of speed-changing locomotion are quite complex to design and manage. The use of the 'equivalent slope', i.e. the gradient locomotion at constant speed metabolically equivalent to a level progression in acceleration, has proved valuable in the estimation of the metabolic cost of speed-changing gaits. However, its use with steep slopes requires extrapolation of the experimental cost versus gradient function for constant running speed, resulting in less-reliable estimates. The present study extended the model to also work with deceleration, and revised the predictive equation to enable it to be applied to much higher levels of speed change. Shuttle running at different distances (from 5+5 to 20+20\u2005m) was then investigated using the novel approach and software, and the predictions in terms of metabolic cost and efficiency compare well with the experimental data

ASPECTS OF THE ENERGETICS AND THE MECHANICS OF HUMAN LOCOMOTION

The relationship between the mechanical work performed by the muscles during locomotion and the corresponding metabolic energy consumption is still not completely understood beside the methodological problems and the inherent assumptions in the calculation of both mechanical work and metabolic energy it seems that many factors can affect this relationship. They can be of very different nature depending on muscle structure and composition, body dimension. kinetic and kinematic parameters. The analysis of the mechanical work, in terms of its two component, external work !that done to lift and to accelerate the centre of mass at each step) and internal work (that of accelerating the limbs relative to the body centre of mass), together with the measurement of the metabolic energy consumption, appears a useful approach to better understand the determinants of many characteristics of human locomotion. The relevance of the external and of the internal work has been inferred by altering them separately in particular conditions as in uphill and downhill walking and running or in loaded locomotion (adding 'weight to the trunk or to the limbs).Optimization processes that seem to set the normal speed of walking of unrestrained subjects, the speed of spontaneous transition from walking to running. the frequency freely adopted at a given gait and speed seem better explained on these bases Yet, from the results so far obtained, it appears that neither mechanical work and energy cost are the sole determinants of many aspects of human locomotion

A "wearable" test for maximum aerobic power : real-time analysis of a 60-m sprint performance and heart rate off-kinetics

Maximum aerobic power (V.O2peak) as an indicator of body fitness is today a very well-known concept not just for athletes but also for the layman. Unfortunately, the accurate measurement of that variable has remained a complex and exhaustive laboratory procedure, which makes it inaccessible to many active people. In this paper we propose a quick estimate of it, mainly based on the heart rate off-kinetics immediately after an all-out 60-m sprint run. The design of this test took into account the recent availability of wrist wearable, heart band free, multi-sensor smart devices, which could also inertially detect the different phases of the sprint and check the distance run. 25 subjects undertook the 60-m test outdoor and a V.O2peak test on the laboratory treadmill. Running average speed, HR excursion during the sprint and the time constant (t) of HR exponential decay in the off-kinetics were fed into a multiple regression, with measured V.O2peak as the dependent variable. Statistics revealed that within the investigated range (25-55 ml O2/(kg min)), despite a tendency to overestimate low values and underestimate high values, the three predictors confidently estimate individual V.O2peak (R2= 0.65, p < 0.001). The same analysis has been performed on a 5-s averaged time course of the same measured HR off-kinetics, as these are the most time resolved data for HR provided by many modern smart watches. Results indicate that despite of the substantial reduction in sample size, predicted V.O2peak still explain 59% of the variability of the measured V.O2peak

On the estimation accuracy of the 3D body center of mass trajectory during human locomotion: Inverse vs. forward dynamics

The dynamics of body center of mass (BCoM) 3D trajectory during locomotion is crucial to the mechanical understanding of the different gaits. Forward Dynamics (FD) obtains BCoM motion from ground reaction forces while Inverse Dynamics (ID) estimates BCoM position and speed from motion capture of body segments. These two techniques are widely used by the literature on the estimation of BCoM. Despite the specific pros and cons of both methods, FD is less biased and considered as the golden standard, while ID estimates strongly depend on the segmental model adopted to schematically represent the moving body. In these experiments a single subject walked, ran, (uni- and bi-laterally) skipped, and race-walked at a wide range of speeds on a treadmill with force sensors underneath. In all conditions a simultaneous motion capture (8 cameras, 36 markers) took place. 3D BCoM trajectories computed according to five marker set models of ID have been compared to the one obtained by FD on the same (about 2,700) strides. Such a comparison aims to check the validity of the investigated models to capture the "true" dynamics of gaits in terms of distance between paths, mechanical external work and energy recovery. Results allow to conclude that: (1) among gaits, race walking is the most critical in being described by ID, (2) among the investigated segmental models, those capturing the motion of four limbs and trunk more closely reproduce the subtle temporal and spatial changes of BCoM trajectory within the strides of most gaits, (3) FD-ID discrepancy in external work is speed dependent within a gait in the most unsuccessful models, and (4) the internal work is not affected by the difference in BCoM estimates

Anatomically asymmetrical runners move more asymmetrically at the same metabolic cost.

We hypothesized that, as occurring in cars, body structural asymmetries could generate asymmetry in the kinematics/dynamics of locomotion, ending up in a higher metabolic cost of transport, i.e. more 'fuel' needed to travel a given distance. Previous studies found the asymmetries in horses' body negatively correlated with galloping performance. In this investigation, we analyzed anatomical differences between the left and right lower limbs as a whole by performing 3D cross-correlation of Magnetic Resonance Images of 19 male runners, clustered as Untrained Runners, Occasional Runners and Skilled Runners. Running kinematics of their body centre of mass were obtained from the body segments coordinates measured by a 3D motion capture system at incremental running velocities on a treadmill. A recent mathematical procedure quantified the asymmetry of the body centre of mass trajectory between the left and right steps. During the same sessions, runners' metabolic consumption was measured and the cost of transport was calculated. No correlations were found between anatomical/kinematic variables and the metabolic cost of transport, regardless of the training experience. However, anatomical symmetry significant correlated to the kinematic symmetry, and the most trained subjects showed the highest level of kinematic symmetry during running. Results suggest that despite the significant effects of anatomical asymmetry on kinematics, either those changes are too small to affect economy or some plastic compensation in the locomotor system mitigates the hypothesized change in energy expenditure of running

Evaluation of presumably disease causing SCN1A variants in a cohort of common epilepsy syndromes

Objective: The SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high-throughput next-generation sequencing, clinical laboratories are generating an ever-increasing catalogue of SCN1A variants. Variants are more likely to be classified as pathogenic if they have already been identified previously in a patient with epilepsy. Here, we critically re-evaluate the pathogenicity of this class of variants in a cohort of patients with common epilepsy syndromes and subsequently ask whether a significant fraction of benign variants have been misclassified as pathogenic. Methods: We screened a discovery cohort of 448 patients with a broad range of common genetic epilepsies and 734 controls for previously reported SCN1A mutations that were assumed to be disease causing. We re-evaluated the evidence for pathogenicity of the identified variants using in silico predictions, segregation, original reports, available functional data and assessment of allele frequencies in healthy individuals as well as in a follow up cohort of 777 patients. Results and Interpretation: We identified 8 known missense mutations, previously reported as path

Movement in low gravity environments (MoLo) programme The Molo-L.O.O.P. study protocol

The aim of this paper is to define an experimental protocol and methodology suitable to estimate in high-fidelity hypogravity conditions the lower limb internal joint reaction forces. State-of-the-art movement kinetics, kinematics, muscle activation and muscle-tendon unit behaviour during locomotor and plyometric movements will be collected and used as inputs (Objective 1), with musculoskeletal modelling and an optimisation framework used to estimate lower limb internal joint loading (Objective

A novel missense variant in ATP11C is associated with reduced red blood cell phosphatidylserine flippase activity and mild hereditary hemolytic anemia

Adenosine Triphosphatase (ATPase) Phospholipid Transporting 11C gene (ATP11C) encodes the major phosphatidylserine (PS) flippase in human red blood cells (RBCs). Flippases actively transport phospholipids (e.g., PS) from the outer to the inner leaflet to establish and maintain phospholipid asymmetry of the lipid bilayer of cell membranes. This asymmetry is crucial for survival since externalized PS triggers phagocytosis by splenic macrophages. Here we report on pathophysiological consequences of decreased flippase activity, prompted by a patient with hemolytic anemia and hemizygosity for a novel c.2365C > T p.(Leu789Phe) missense variant in ATP11C. ATP11C protein expression was strongly reduced by 58% in patient-derived RBC ghosts. Furthermore, functional characterization showed only 26% PS flippase activity. These results were confirmed by recombinant mutant ATP11C protein expression in HEK293T cells, which was decreased to 27% compared to wild type, whereas PS-stimulated ATPase activity was decreased by 57%. Patient RBCs showed a mild increase in PS surface exposure when compared to control RBCs, which further increased in the most dense RBCs after RBC storage stress. The increase in PS was not due to higher global membrane content of PS or other phospholipids. In contrast, membrane lipid lateral distribution showed increased abundance of cholesterol-enriched domains in RBC low curvature areas. Finally, more dense RBCs and subtle changes in RBC morphology under flow hint toward alterations in flow behavior of ATP11C-deficient RBCs. Altogether, ATP11C deficiency is the likely cause of hemolytic anemia in our patient, thereby underlining the physiological role and relevance of this flippase in human RBCs