Metabolic cost and mechanical work of walking in a virtual reality emulator.

PURPOSE: The purpose of this study was to investigate the metabolic cost (C), mechanical work, and kinematics of walking on a multidirectional treadmill designed for locomotion in virtual reality. METHODS: Ten participants (5 females, body mass 67.2 ± 8.1 kg, height 1.71 ± 0.07 m, age 23.6 ± 1.9 years, mean ± SD) walked on a Virtuix Omni multidirectional treadmill at four imposed stride frequencies: 0.70, 0.85, 1.00, and 1.15 Hz. A portable metabolic system measured oxygen uptake, enabling calculation of C and the metabolic equivalent of task (MET). Gait kinematics and external, internal, and total mechanical work (WTOT) were calculated by an optoelectronic system. Efficiency was calculated either as WTOT/C or by summing WTOT to the work against sliding frictions. Results were compared with normal walking, running, and skipping. RESULTS: C was higher for walking on the multidirectional treadmill than for normal walking, running, and skipping, and decreased with speed (best-fit equation: C = 20.2-27.5·speed + 15.8·speed2); the average MET was 4.6 ± 1.4. Mechanical work was higher at lower speeds, but similar to that of normal walking at higher speeds, with lower pendular energy recovery and efficiency; differences in efficiency were explained by the additional work against sliding frictions. At paired speeds, participants showed a more forward-leaned trunk and higher ankle dorsiflexion, stride frequency, and duty factor than normal walking. CONCLUSION: Walking on a multidirectional treadmill requires a higher metabolic cost and different mechanical work and kinematics than normal walking. This raises questions on its use for gait rehabilitation but highlights its potential for high-intensity exercise and physical activity promotion.

Mechanical work as a (key) determinant of energy cost in human locomotion: recent findings and future directions.

NEW FINDINGS: What is the topic of this review? This narrative review explores past and recent findings on the mechanical determinants of energy cost during human locomotion, obtained by using a mechanical approach based on König's theorem (Fenn's approach). What advances does it highlight? Developments in analytical methods and their applications allow a better understanding of the mechanical-bioenergetic interaction. Recent advances include the determination of 'frictional' internal work; the association between tendon work and apparent efficiency; a better understanding of the role of energy recovery and internal work in pathological gait (amputees, stroke and obesity); and a comprehensive analysis of human locomotion in (simulated) low gravity conditions. ABSTRACT: During locomotion, muscles use metabolic energy to produce mechanical work (in a more or less efficient way), and energetics and mechanics can be considered as two sides of the same coin, the latter being investigated to understand the former. A mechanical approach based on König's theorem (Fenn's approach) has proved to be a useful tool to elucidate the determinants of the energy cost of locomotion (e.g., the pendulum-like model of walking and the bouncing model of running) and has resulted in many advances in this field. During the past 60 years, this approach has been refined and applied to explore the determinants of energy cost and efficiency in a variety of conditions (e.g., low gravity, unsteady speed). This narrative review aims to summarize current knowledge of the role that mechanical work has played in our understanding of energy cost to date, and to underline how recent developments in analytical methods and their applications in specific locomotion modalities (on a gradient, at low gravity and in unsteady conditions) and in pathological gaits (asymmetric gait pathologies, obese subjects and in the elderly) could continue to push this understanding further. The recent in vivo quantification of new aspects that should be included in the assessment of mechanical work (e.g., frictional internal work and elastic contribution) deserves future research that would improve our knowledge of the mechanical-bioenergetic interaction during human locomotion, as well as in sport science and space exploration.

Superior Properties of N-Acetylcysteine Ethyl Ester over N-Acetyl Cysteine to Prevent Retinal Pigment Epithelial Cells Oxidative Damage.

Oxidative stress plays a key role in the pathophysiology of retinal diseases, including age-related macular degeneration (AMD) and diabetic retinopathy, which are the major causes of irreversible blindness in developed countries. An excess of reactive oxygen species (ROS) can directly cause functional and morphological impairments in retinal pigment epithelium (RPE), endothelial cells, and retinal ganglion cells. Antioxidants may represent a preventive/therapeutic strategy and reduce the risk of progression of AMD. Among antioxidants, N-acetyl-L-cysteine (NAC) is widely studied and has been proposed to have therapeutic benefit in treating AMD by mitigating oxidative damage in RPE. Here, we demonstrate that N-acetyl-L-cysteine ethyl ester (NACET), a lipophilic cell-permeable cysteine derivative, increases the viability in oxidative stressed RPE cells more efficiently than NAC by reacting directly and more rapidly with oxidizing agents, and that NACET, but not NAC, pretreatment predisposes RPE cells to oxidative stress resistance and increases the intracellular reduced glutathione (GSH) pool available to act as natural antioxidant defense. Moreover, we demonstrate the ability of NACET to increase GSH levels in rats' eyes after oral administration. In conclusion, even if experiments in AMD animal models are still needed, our data suggest that NACET may play an important role in preventing and treating retinal diseases associated with oxidative stress, and may represent a valid and more efficient alternative to NAC in therapeutic protocols in which NAC has already shown promising results.

Frictional internal work of damped limbs oscillation in human locomotion.

Joint friction has never previously been considered in the computation of mechanical and metabolic energy balance of human and animal (loco)motion, which heretofore included just muscle work to move the body centre of mass (external work) and body segments with respect to it. This happened mainly because, having been previously measured ex vivo, friction was considered to be almost negligible. Present evidences of in vivo damping of limb oscillations, motion captured and processed by a suited mathematical model, show that: (a) the time course is exponential, suggesting a viscous friction operated by the all biological tissues involved; (b) during the swing phase, upper limbs report a friction close to one-sixth of the lower limbs; (c) when lower limbs are loaded, in an upside-down body posture allowing to investigate the hip joint subjected to compressive forces as during the stance phase, friction is much higher and load dependent; and (d) the friction of the four limbs during locomotion leads to an additional internal work that is a remarkable fraction of the mechanical external work. These unprecedented results redefine the partitioning of the energy balance of locomotion, the internal work components, muscle and transmission efficiency, and potentially readjust the mechanical paradigm of the different gaits.

A slow V̇O2 on-response allows to comfortably adopt aerobically unaffordable walking and running speeds in short stairs ascending.

The aim of this paper is to investigate the mechanical and metabolic reasons of the spontaneous gait/speed choice of ascending short flight of stairs, where walking on every step or running on every other step are frequently interchangeable options. Twenty-four subjects' kinematics, oxygen uptake (V̇O2), ventilation and heart rate were sampled during climbing one and two flights of stairs while using the two gaits. Although motor acts were very short in time (5-22 s), metabolic kinetics, extending in the successive 250 s after the end of climbing, consistently reflected the (equivalent of the) needed mechanical energy and allowed to compare the two ascent choices: despite a 250% higher mechanical power associated to running, measured V̇O2, ventilation and heart rate peaked only at +25% with respect to walking, and in both gaits at a much lower values than V̇O2max despite of predictions based on previous gradient locomotion studies. Mechanical work and metabolic cost of transport, as expected, showed similar increase (+25%) in running. For stairs up to 4.8 m tall (30 steps at 53% gradient), running makes us consuming slightly more calories than walking, and in both gaits at no discomfort at all. The cardio-respiratory-metabolic responses similarly delay and damp the replenishing of phosphocreatine stores, which were much faster depleted during the impulsive, highly powered mechanical event, with almost overlapping time courses. Such a discrepancy between mechanical and metabolic dynamics allows to afford almost-to-very anaerobic climbs and to interchangeably decide whether to walk or run up a short flight of stairs.

A slow V̇O2 on-response allows comfortable adoption of aerobically unaffordable walking and running speeds on short stair ascents.

The aim of this study was to investigate the mechanical and metabolic reasons for the spontaneous gait/speed choice when ascending a short flight of stairs, where walking on every step or running on every other step are frequently interchangeable options. The kinematics, oxygen uptake (V̇O2 ), ventilation and heart rate of 24 subjects were sampled during climbing one and two flights of stairs while using the two gaits. Although motor acts were very short in time (5-22 s), metabolic kinetics, extending into the 250 s after the end of climbing, consistently reflected the (metabolic equivalent of the) required mechanical energy and allowed comparison of the two ascent choices: despite a 250% higher mechanical power associated with running, measured [Formula: see text], ventilation and heart rate peaked at only +25% with respect to walking, and in both gaits at much lower values than [Formula: see text] despite predictions based on previous gradient locomotion studies. Mechanical work and metabolic cost of transport, as expected, showed a similar increase (+25%) in running. For stairs up to a height of 4.8 m (30 steps at 53% gradient), running makes us consume slightly more calories than walking, and in both gaits with no discomfort at all. The cardio-respiratory-metabolic responses similarly delay and dampen the replenishment of phosphocreatine stores, which were depleted much faster during the impulsive, highly powered mechanical event, with almost overlapping time courses. This discrepancy between mechanical and metabolic dynamics allows us to afford climbs ranging from almost to very anaerobic, and to interchangeably decide whether to walk or run up a short flight of stairs.

Comprehensive mechanical power analysis in sprint running acceleration.

Sprint running is a common feature of many sport activities. The ability of an athlete to cover a distance in the shortest time relies on his/her power production. The aim of this study was to provide an exhaustive description of the mechanical determinants of power output in sprint running acceleration and to check whether a predictive equation for internal power designed for steady locomotion is applicable to sprint running acceleration. Eighteen subjects performed two 20 m sprints in a gym. A 35-camera motion capture system recorded the 3D motion of the body segments and the body center of mass (BCoM) trajectory was computed. The mechanical power to accelerate and rise BCoM (external power, Pext ) and to accelerate the segments with respect to BCoM (internal power, Pint ) was calculated. In a 20 m sprint, the power to accelerate the body forward accounts for 50% of total power; Pint accounts for 41% and the power to rise BCoM accounts for 9% of total power. All the components of total mechanical power increase linearly with mean sprint velocity. A published equation for Pint prediction in steady locomotion has been adapted (the compound factor q accounting for the limbs' inertia decreases as a function of the distance within the sprint, differently from steady locomotion) and is still able to predict experimental Pint in a 20 m sprint with a bias of 0.70 ± 0.93 W kg-1 . This equation can be used to include Pint also in other methods that estimate external horizontal power only.

Energy cost of ambulation in trans-tibial amputees using a dynamic-response foot with hydraulic versus rigid 'ankle': insights from body centre of mass dynamics.

BACKGROUND: Previous research has shown that use of a dynamic-response prosthetic foot (DRF) that incorporates a small passive hydraulic ankle device (hyA-F), provides certain biomechanical benefits over using a DRF that has no ankle mechanism (rigA-F). This study investigated whether use of a hyA-F in unilateral trans-tibial amputees (UTA) additionally provides metabolic energy expenditure savings and increases the symmetry in walking kinematics, compared to rigA-F. METHODS: Nine active UTA completed treadmill walking trials at zero gradient (at 0.8, 1.0, 1.2, 1.4, and 1.6 of customary walking speed) and for customary walking speed only, at two angles of decline (5° and 10°). The metabolic cost of locomotion was determined using respirometry. To gain insights into the source of any metabolic savings, 3D motion capture was used to determine segment kinematics, allowing body centre of mass dynamics (BCoM), differences in inter-limb symmetry and potential for energy recovery through pendulum-like motion to be quantified for each foot type. RESULTS: During both level and decline walking, use of a hyA-F compared to rigA-F significantly reduced the total mechanical work and increased the interchange between the mechanical energies of the BCoM (recovery index), leading to a significant reduction in the metabolic energy cost of locomotion, and hence an associated increase in locomotor efficiency (p < 0.001). It also increased inter-limb symmetry (medio-lateral and progression axes, particularly when walking on a 10° decline), highlighting the improvements in gait were related to a lessening of the kinematic compensations evident when using the rigA-F. CONCLUSIONS: Findings suggest that use of a DRF that incorporates a small passive hydraulic ankle device will deliver improvements in metabolic energy expenditure and kinematics and thus should provide clinically meaningful benefits to UTAs' everyday locomotion, particularly for those who are able to walk at a range of speeds and over different terrains.

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 m) 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.

Recumbent vs. upright bicycles: 3D trajectory of body centre of mass, limb mechanical work, and operative range of propulsive muscles.

Recumbent bicycles (RB) are high performance, human-powered vehicles. In comparison to normal/upright bicycles (NB) the RB may allow individuals to reach higher speeds due to aerodynamic advantages. The purpose of this investigation was to compare the non-aerodynamic factors that may potentially influence the performance of the two bicycles. 3D body centre of mass (BCoM) trajectory, its symmetries, and the components of the total mechanical work necessary to sustain cycling were assessed through 3D kinematics and computer simulations. Data collected at 50, 70, 90 110 rpm during stationary cycling were used to drive musculoskeletal modelling simulation and estimate muscle-tendon length. Results demonstrated that BCoM trajectory, confined in a 15-mm side cube, changed its orientation, maintaining a similar pattern across all cadences in both bicycles. RB displayed a reduced additional mechanical external power (16.1 ± 9.7 W on RB vs. 20.3 ± 8.8 W on NB), a greater symmetry on the progression axis, and no differences in the internal mechanical power compared to NB. Simulated muscle activity revealed small significant differences for only selected muscles. On the RB, quadriceps and gluteus demonstrated greater shortening, while biceps femoris, iliacus, and psoas exhibited greater stretch; however, aerodynamics still remains the principal benefit.

Mechanical work and efficiency of 5 + 5 m shuttle running.

PURPOSE: Acceleration and deceleration phases characterise shuttle running (SR) compared to constant speed running (CR); mechanical work is thus expected to be larger in the former compared to the latter, at the same average speed (v mean). The aim of this study was to measure total mechanical work (W tot (+) , J kg(-1) m(-1)) during SR as the sum of internal (W int (+) ) and external (W ext (+) ) work and to calculate the efficiency of SR. METHODS: Twenty males were requested to perform shuttle runs over a distance of 5 + 5 m at different speeds (slow, moderate and fast) to record kinematic data. Metabolic data were also recorded (at fast speed only) to calculate energy cost (C, J kg(-1) m(-1)) and mechanical efficiency (eff(+) = W tot (+) C (-1)) of SR. RESULTS: Work parameters significantly increased with speed (P < 0.001): W ext (+)  = 1.388 + 0.337 v mean; W int (+)  = -1.002 + 0.853 v mean; W tot (+)  = 1.329 v mean. At the fastest speed C was 27.4 ± 2.6 J kg(-1) m(-1) (i.e. about 7 times larger than in CR) and eff(+) was 16.2 ± 2.0 %. CONCLUSIONS: W ext (+) is larger in SR than in CR (2.5 vs. 1.4 J kg(-1) m(-1) in the range of investigated speeds: 2-3.5 m s(-1)) and W int (+) , at fast speed, is about half of W tot (+) . eff(+) is lower in SR (16 %) than in CR (50-60 % at comparable speeds) and this can be attributed to a lower elastic energy reutilization due to the acceleration/deceleration phases over this short shuttle distance.

Shoulder 3D range of motion and humerus rotation in two volleyball spike techniques: injury prevention and performance.

Repetitive stresses and movements on the shoulder in the volleyball spike expose this joint to overuse injuries, bringing athletes to a career threatening injury. Assuming that specific spike techniques play an important role in injury risk, we compared the kinematic of the traditional (TT) and the alternative (AT) techniques in 21 elite athletes, evaluating their safety with respect to performance. Glenohumeral joint was set as the centre of an imaginary sphere, intersected by the distal end of the humerus at different angles. Shoulder range of motion and angular velocities were calculated and compared to the joint limits. Ball speed and jump height were also assessed. Results indicated the trajectory of the humerus to be different for the TT, with maximal flexion of the shoulder reduced by 10 degrees, and horizontal abduction 15 degrees higher. No difference was found for external rotation angles, while axial rotation velocities were significantly higher in AT, with a 5% higher ball speed. Results suggest AT as a potential preventive solution to shoulder chronic pathologies, reducing shoulder flexion during spiking. The proposed method allows visualisation of risks associated with different overhead manoeuvres, by depicting humerus angles and velocities with respect to joint limits in the same 3D space.

The work to swing limbs in humans versus chimpanzees and its relation to the metabolic cost of walking.

Compared to their closest ape relatives, humans walk bipedally with lower metabolic cost (C) and less mechanical work to move their body center of mass (external mechanical work, WEXT). However, differences in WEXT are not large enough to explain the observed lower C: humans may also do less work to move limbs relative to their body center of mass (internal kinetic mechanical work, WINT,k). From published data, we estimated differences in WINT,k, total mechanical work (WTOT), and efficiency between humans and chimpanzees walking bipedally. Estimated WINT,k is ~ 60% lower in humans due to changes in limb mass distribution, lower stride frequency and duty factor. When summing WINT,k to WEXT, between-species differences in efficiency are smaller than those in C; variations in WTOT correlate with between-species, but not within-species, differences in C. These results partially support the hypothesis that the low cost of human walking is due to the concerted low WINT,k and WEXT.

Horizontal running inside circular walls of Moon settlements: a comprehensive countermeasure for low-gravity deconditioning?

Long-lasting exposure to low gravity, such as in lunar settlements planned by the ongoing Artemis Program, elicits muscle hypotrophy, bone demineralization, cardio-respiratory and neuro-control deconditioning, against which optimal countermeasures are still to be designed. Rather than training selected muscle groups only, 'whole-body' activities such as locomotion seem better candidates, but at Moon gravity both 'pendular' walking and bouncing gaits like running exhibit abnormal dynamics at faster speeds. We theoretically and experimentally show that much greater self-generated artificial gravities can be experienced on the Moon by running horizontally inside a static 4.7 m radius cylinder (motorcyclists' 'Wall of Death' of amusement parks) at speeds preventing downward skidding. To emulate lunar gravity, 83% of body weight was unloaded by pre-tensed (36 m) bungee jumping bands. Participants unprecedentedly maintained horizontal fast running (5.4-6.5 m s-1) for a few circular laps, with intense metabolism (estimated as 54-74 mlO2 kg-1 min-1) and peak forces during foot contact, inferred by motion analysis, of 2-3 Earth body weight (corresponding to terrestrial running at 3-4 m s-1), high enough to prevent bone calcium resorption. A training regime of a few laps a day promises to be a viable countermeasure for astronauts to quickly combat whole-body deconditioning, for further missions and home return.

A novel computational framework for the estimation of internal musculoskeletal loading and muscle adaptation in hypogravity.

Introduction: Spaceflight is associated with substantial and variable musculoskeletal (MSK) adaptations. Characterisation of muscle and joint loading profiles can provide key information to better align exercise prescription to astronaut MSK adaptations upon return-to-Earth. A case-study is presented of single-leg hopping in hypogravity to demonstrate the additional benefit computational MSK modelling has when estimating lower-limb MSK loading. Methods: A single male participant performed single-leg vertical hopping whilst attached to a body weight support system to replicate five gravity conditions (0.17, 0.25, 0.37, 0.50, 1 g). Experimental joint kinematics, joint kinetics and ground reaction forces were tracked in a data-tracking direct collocation simulation framework. Ground reaction forces, sagittal plane hip, knee and ankle net joint moments, quadriceps muscle forces (Rectus Femoris and three Vasti muscles), and hip, knee and ankle joint reaction forces were extracted for analysis. Estimated quadriceps muscle forces were input into a muscle adaptation model to predict a meaningful increase in muscle cross-sectional area, defined in (DeFreitas et al., 2011). Results: Two distinct strategies were observed to cope with the increase in ground reaction forces as gravity increased. Hypogravity was associated with an ankle dominant strategy with increased range of motion and net plantarflexor moment that was not seen at the hip or knee, and the Rectus Femoris being the primary contributor to quadriceps muscle force. At 1 g, all three joints had increased range of motion and net extensor moments relative to 0.50 g, with the Vasti muscles becoming the main muscles contributing to quadriceps muscle force. Additionally, hip joint reaction force did not increase substantially as gravity increased, whereas the other two joints increased monotonically with gravity. The predicted volume of exercise needed to counteract muscle adaptations decreased substantially with gravity. Despite the ankle dominant strategy in hypogravity, the loading on the knee muscles and joint also increased, demonstrating this provided more information about MSK loading. Discussion: This approach, supplemented with muscle-adaptation models, can be used to compare MSK loading between exercises to enhance astronaut exercise prescription.

Biomechanics of human locomotion in the wind.

In laboratory settings, human locomotion encounters minimal opposition from air resistance. However, moving in nature often requires overcoming airflow. Here, the drag force exerted on the body by different headwind or tailwind speeds (between 0 and 15 m·s-1) was measured during walking at 1.5 m·s-1 and running at 4 m·s-1. To our knowledge, the biomechanical effect of drag in human locomotion has only been evaluated by simulations. Data were collected on eight male subjects using an instrumented treadmill placed in a wind tunnel. From the ground reaction forces, the drag and external work done to overcome wind resistance and to sustain the motion of the center of mass of the body were measured. Drag increased with wind speed: a 15 m·s-1 headwind exerted a drag of ∼60 N in walking and ∼50 N in running. The same tailwind exerted -55 N of drag in both gaits. At this wind speed, the work done to overcome the airflow represented ∼80% of the external work in walking and ∼50% in running. Furthermore, in the presence of fast wind speeds, subjects altered their drag area (CdA) by adapting their posture to limit the increase in air friction. Moving in the wind modified the ratio between positive and negative external work performed. The modifications observed when moving with a head- or tailwind have been compared with moving uphill or downhill. The present findings may have implications for optimizing aerodynamic performance in competitive running, whether in sprints or marathons.NEW & NOTEWORTHY This is the first study to assess the biomechanical adaptations to a wide range of wind speeds inside a wind tunnel. Humans increase their mechanical work and alter their drag area (CdA) by adapting their posture when walking and running against increasing head and tailwinds. The observed drag force applied to the subject is different between walking and running at similar headwind speeds.

NRF2 activation by cysteine as a survival mechanism for triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) is a very aggressive and heterogeneous group of tumors. In order to develop effective therapeutic strategies, it is therefore essential to identify the subtype-specific molecular mechanisms underlying disease progression and resistance to chemotherapy. TNBC cells are highly dependent on exogenous cystine, provided by overexpression of the cystine/glutamate antiporter SLC7A11/xCT, to fuel glutathione synthesis and promote an oxidative stress response consistent with their high metabolic demands. Here we show that TNBC cells of the mesenchymal stem-like subtype (MSL) utilize forced cystine uptake to induce activation of the transcription factor NRF2 and promote a glutathione-independent mechanism to defend against oxidative stress. Mechanistically, we demonstrate that NRF2 activation is mediated by direct cysteinylation of the inhibitor KEAP1. Furthermore, we show that cystine-mediated NRF2 activation induces the expression of important genes involved in oxidative stress response, but also in epithelial-to-mesenchymal transition and stem-like phenotype. Remarkably, in survival analysis, four upregulated genes (OSGIN1, RGS17, SRXN1, AKR1B10) are negative prognostic markers for TNBC. Finally, expression of exogenous OSGIN1, similarly to expression of exogenous NRF2, can prevent cystine depletion-dependent death of MSL TNBC cells. The results suggest that the cystine/NRF2/OSGIN1 axis is a potential target for effective treatment of MSL TNBCs.

Quantitative mapping of proteasome interactomes and substrates using ProteasomeID.

Proteasomes are essential molecular machines responsible for the degradation of proteins in eukaryotic cells. Altered proteasome activity has been linked to neurodegeneration, auto-immune disorders and cancer. Despite the relevance for human disease and drug development, no method currently exists to monitor proteasome composition and interactions in vivo in animal models. To fill this gap, we developed a strategy based on tagging of proteasomes with promiscuous biotin ligases and generated a new mouse model enabling the quantification of proteasome interactions by mass spectrometry. We show that biotin ligases can be incorporated in fully assembled proteasomes without negative impact on their activity. We demonstrate the utility of our method by identifying novel proteasome-interacting proteins, charting interactomes across mouse organs, and showing that proximity-labeling enables the identification of both endogenous and small-molecule-induced proteasome substrates.