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National Space Biomedical Research Institute

This report summarizes the activities of the National Space Biomedical Research Institute (NSBRI) during FY 1999, the second full year of existence of the NSBRI's research program, and is prepared in accordance with Cooperative Agreement NCC9-58 between NASA's Lyndon B. Johnson Space Center and Baylor College of Medicine (NSBRI). The report consists of progress reports on projects related to the effects of microgravity and space on physiology. The research is broken up in nine areas: (1) Bone loss, (2) Cardiovascular alterations, (3) human performance, (3) immunology, infection and hematology, (4) muscle alterations and atrophy,(5) Neurovestibular adaptation, radiation effects, (6) technology development, and (7) synergy projects.

Source record↗

Liquid Cooling/Warming Garment

The NASA liquid cooling/ventilating garment (LCVG) currently in use was developed over 40 years ago. With the commencement of a greater number of extra-vehicular activity (EVA) procedures with the construction of the International Space Station, problems of astronaut comfort, as well as the reduction of the consumption of energy, became more salient. A shortened liquid cooling/warming garment (SLCWG) has been developed based on physiological principles comparing the efficacy of heat transfer of different body zones; the capability of blood to deliver heat; individual muscle and fat body composition as a basis for individual thermal profiles to customize the zonal sections of the garment; and the development of shunts to minimize or redirect the cooling/warming loop for different environmental conditions, physical activity levels, and emergency situations. The SLCWG has been designed and completed, based on extensive testing in rest, exercise, and antiorthostatic conditions. It is more energy efficient than the LCVG currently used by NASA. The total length of tubing in the SLCWG is approximately 35 percent less and the weight decreased by 20 percent compared to the LCVG. The novel features of the innovation are: 1. The efficiency of the SLCWG to maintain thermal status under extreme changes in body surface temperatures while using significantly less tubing than the LCVG. 2. The construction of the garment based on physiological principles of heat transfer. 3. The identification of the body areas that are most efficient in heat transfer. 4. The inclusion of a hood as part of the garment. 5. The lesser consumption of energy.

Koscheyev, Victor S.↗

Noninvasive Sensor for Measuring Muscle Metabolism During Exercise

The measurement of oxygen uptake (VO2) and lactate threshold (LT) are utilized to assess changes in aerobic capacity and the efficacy of exercise countermeasures in astronauts. During extravehicular activity (EVA), real-time knowledge of VO2 and relative work intensity can be used to monitor crew activity levels and organize tasks to reduce the cumulative effects of fatigue. Currently VO2 and LT are determined with complicated measurement techniques that require sampling of expired ventilatory gases, which may not be accurate in enclosed, oxygen-rich environments such as the EVA suit. The UMMS team has developed a novel near infrared spectroscopic (NIRS) system which noninvasively, simultaneously and continuously measures muscle oxygen tension, oxygen saturation, pH (pHm), and hematocrit from a small sensor placed on the leg. This system is unique in that it allows accurate, absolute measurement of these parameters in the thigh muscle by correcting spectra for the interference from skin pigment and fat. These parameters can be used to estimate VO2 and LT. A preliminary evaluation of the system s capabilities was performed in the NASA JSC Exercise Physiology Lab.

Soller, B. R.↗

Fatigue mechanisms in patients with cancer: effects of tumor necrosis factor and exercise on skeletal muscle

Fatigue is a common adverse effect of cancer and its therapy. However, the specific mechanisms underlying cancer fatigue are unclear. One physiologic mechanism may involve changes in skeletal muscle protein stores or metabolite concentration. A reduction in skeletal muscle protein stores may result from endogenous tumor necrosis factor (TNF) or from TNF administered as antineoplastic therapy. This muscle wasting would require patients to exert an unusually high amount of effort to generate adequate contractile force during exercise performance or during extended periods of sitting or standing. This additional effort could result in the onset of fatigue. Additionally, cancer fatigue may develop or become exacerbated during exercise as a consequence of changes in the concentration of skeletal muscle metabolites. These biochemical alterations may interfere with force that is produced by the muscle contractile proteins. These physiologic changes may play a role in the decision to include exercise in the rehabilitation plans of patients with cancer. They also may affect ideas about fatigue.

Review, Tutorial↗

Musculoskeletal Modeling Component of the NASA Digital Astronaut Project

The NASA Digital Astronaut Project s (DAP) objective is to provide computational tools that support research of the physiological response to low gravity environments and analyses of how changes cause health and safety risks to the astronauts and to the success of the mission. The spaceflight risk associated with muscle atrophy is impaired performance due to reduced muscle mass, strength and endurance. Risks of early onset of osteoporosis and bone fracture are among the spaceflight risks associated with loss of bone mineral density. METHODS: Tools under development include a neuromuscular model, a biomechanical model and a bone remodeling model. The neuromuscular model will include models of neuromuscular drive, muscle atrophy, fiber morphology and metabolic processes as a function of time in space. Human movement will be modeled with the biomechanical model, using muscle and bone model parameters at various states. The bone remodeling model will allow analysis of bone turnover, loss and adaptation. A comprehensive trade study was completed to identify the current state of the art in musculoskeletal modeling. The DAP musculoskeletal models will be developed using a combination of existing commercial software and academic research codes identified in the study, which will be modified for use in human spaceflight research. These individual models are highly dependent upon each other and will be integrated together once they reach sufficient levels of maturity. ANALYSES: The analyses performed with these models will include comparison of different countermeasure exercises for optimizing effectiveness and comparison of task requirements and the state of strength and endurance of a crew member at a particular time in a mission. DISCUSSION: The DAP musculoskeletal model has the potential to complement research conducted on spaceflight induced changes to the musculoskeletal system. It can help with hypothesis formation, identification of causative mechanisms and supplementing small data samples.

Lewandowski, B. E.↗

Issues of exploration: human health and wellbeing during a mission to Mars

Today, the tools are in our hands to enable us to travel away from our home planet and become citizens of the solar system. Even now, we are seriously beginning to develop the robust infrastructure that will make the 21st century the Century of Space Travel. But this bold step must be taken with due concern for the health, safety and wellbeing of future space explorers. Our long experience with space biomedical research convinces us that, if we are to deal effectively with the medical and biomedical issues of exploration, then dramatic and bold steps are also necessary in this field. We can no longer treat the human body as if it were composed of muscles, bones, heart and brain acting independently. Instead, we must lead the effort to develop a fully integrated view of the body, with all parts connected and fully interacting in a realistic way. This paper will present the status of current (2000) plans by the National Space Biomedical Research Institute to initiate research in this area of integrative physiology and medicine. Specifically, three example projects are discussed as potential stepping stones towards the ultimate goal of producing a digital human. These projects relate to developing a functional model of the human musculoskeletal system and the heart. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

NASA Discipline General Space Life Sciences↗

Biomechanical Analysis of Treadmill Locomotion on the International Space Station

Treadmill locomotion exercise is an important aspect of ISS exercise countermeasures. It is widely believed that an optimized treadmill exercise protocol could offer benefits to cardiovascular and bone health. If training heart rate is high enough, treadmill exercise is expected to lead to improvements in aerobic fitness. If impact or bone loading forces are high enough, treadmill exercise may be expected to contribute to improved bone outcomes. Ground-based research suggests that joint loads increase with increased running speed. However, it is unknown if increases in locomotion speed results in similar increases in joint loads in microgravity. Although data exist regarding the biomechanics of running and walking in microgravity, a majority were collected during parabolic flight or during investigations utilizing a microgravity analog. The Second Generation Treadmill (T2) has been in use on the International Space Station (ISS) and records the ground reaction forces (GRF) produced by crewmembers during exercise. Biomechanical analyses will aid in understanding potential differences in typical gait motion and allow for modeling of the human body to determine joint and muscle forces during exercise. By understanding these mechanisms, more appropriate exercise prescriptions can be developed that address deficiencies. The objective of this evaluation is to collect biomechanical data from crewmembers during treadmill exercise prior to and during flight. The goal is to determine if locomotive biomechanics differ between normal and microgravity environments and to determine how combinations of subject load and speed influence joint loading during in-flight treadmill exercise. Further, the data will be used to characterize any differences in specific bone and muscle loading during locomotion in these two gravitational conditions. This project maps to the HRP Integrated Research Plan risks including Risk of Bone Fracture (Gap B15), Risk of Early Onset Osteoporosis Due to Spaceflight (Gap B15), Risk of Impaired Performance Due to Reduced Muscle Mass, Strength, and Endurance (Gaps M3, M4, M6, Ml, M8, M9) and Risk of reduced Physical Performance Capabilities Due to Reduce Aerobic Capacity (Gaps M7, M8, M9).

De Witt, J. K.↗

Methodologies to determine forces on bones and muscles of body segments during exercise, employing compact sensors suitable for use in crowded space vehicles

Work under this grant was carried out by the author and by a graduate research assistant. An instrumented bicycle ergometer was implemented focusing on the stated objective: to estimate the forces exerted by each muscle of the feet, calf, and thigh of an individual while bicycling. The sensors used were light and compact. These were probes to measure muscle EMG activity, miniature accelerometers, miniature load sensors, and small encoders to measure angular positions of the pedal. A methodology was developed and implemented to completely describe the kinematics of the limbs using data from the sensors. This work has been published as a Master's Thesis by the Graduate student supported by the grant. The instrumented ergometer along with the sensors and instrumentation were tested during a KC-135 Zero-Gravity flight in July, 1994. A complete description of the system and the tests performed have been published as a report submitted to NASA Johnson Space Center. The data collected during the KC-135 flight is currently being processed so that a kinematic description of the bicycling experiment will be soon determined. A methodology to estimate the muscle forces has been formulated based on previous work. The methodology involves the use of optimization concepts so that the individual muscle forces that represent variables in dynamic equations of motion may be estimated. Optimization of a criteria (goal) function such as minimization of energy will be used along with constraint equations defined by rigid body equations of motion. Use of optimization principles is necessary, because the equations of motion alone constitute an indeterminate system of equations with respect to the large amount of muscle forces which constitute the variables in these equations. The number of variables is reduced somewhat by using forces measured by the load cells installed on the pedal. These load cells measure pressure and shear forces on the foot. The author and his collaborators at NASA and at the University of Alabama, Tuscaloosa, are continuing the work of reducing the experimental data from the KC-135 flight, and the implementation of the optimization methods to estimate muscle forces. As soon as results from these efforts are available, they will be published in reputable journals. Results of this work will impact studies addressing bone density loss and development of countermeasures to minimize bone loss in zero gravity conditions. By analyzing muscle forces on Earth and in Space during exercise, scientists could eventually formulate new exercises and machines to help maintain bone density. On Earth, this work will impact studies concerning arthritis, and will provide the means to study possible exercise countermeasures to minimize arthritis problems.

Figueroa, Fernando↗

Molecular Signaling in Muscle Plasticity

Extended spaceflight under microgravity conditions leads to significant atrophy of weight-bearing muscles. Atrophy and hypertrophy are the extreme outcomes of the high degree of plasticity exhibited by skeletal muscle. Stimuli which control muscle plasticity include neuronal, hormonal, nutritional, and mechanical inputs. The mechanical stimulus for muscle is directly related to the work or exercise against a load performed. Little or no work is performed by weight-bearing muscles under microgravity conditions. A major hypothesis is that focal adhesion kinase (FAK) which is associated with integrin at the adherens junctions and costa meres of all skeletal muscles is an integral part of the major mechanism for molecular signaling upon mechanical stimulation in all muscle fibers. Additionally, we propose that myotonic protein kinase (DMPK) and dystrophin (DYSTR) also participate in distinct mechanically stimulated molecular signaling pathways that are most critical in type I and type II muscle fibers, respectively. To test these hypotheses, we will use the paradigms of hindlimb unloading and overloading in mice as models for microgravity conditions and a potential exercise countermeasure, respectively, in mice. We expect that FAK loss-of-function will impair hypertrophy and enhance atrophy in all skeletal muscle fibers whereas DYSTR and DMPK loss-of-function will have similar but more selective effects on Type IT and Type I fibers, respectively. Gene expression will be monitored by muscle-specific creatine kinase M promoter-reporter construct activity and specific MRNA and protein accumulation in the soleus (type I primarily) and plantaris (type 11 primarily) muscles. With these paradigms and assays, the following Specific Project Aims will be tested in genetically altered mice: 1) identify the roles of DYSTR and its pathway; 2) evaluate the roles of the DMPK and its pathway; 3) characterize the roles of FAK and its pathway and 4) genetically analyze the mechanisms and interactions between the FAK, DYSTR, and DMPK-associated pathways in single and specific combinations of mutants. The identification of potential signaling mechanisms may permit future development of pharmacological countermeasures for amelioration and prevention of the microgravity-induced atrophy in extended spaceflight, and the analysis of both overloading and unloading paradigms may provide further support for development of exercise-based countermeasures. Understanding the basic mechanisms of molecular signaling in muscle plasticity may aid our understanding and treatment of skeletal muscle atrophy not only in spaceflight but in similar problems of the aging population, in prolonged bed rest, and in cachexia associated with chronic disease.

Epstein, Henry F.↗

Tissue-engineered human bioartificial muscles expressing a foreign recombinant protein for gene therapy

Murine skeletal muscle cells transduced with foreign genes and tissue engineered in vitro into bioartificial muscles (BAMs) are capable of long-term delivery of soluble growth factors when implanted into syngeneic mice (Vandenburgh et al., 1996b). With the goal of developing a therapeutic cell-based protein delivery system for humans, similar genetic tissue-engineering techniques were designed for human skeletal muscle stem cells. Stem cell myoblasts were isolated, cloned, and expanded in vitro from biopsied healthy adult (mean age, 42 +/- 2 years), and elderly congestive heart failure patient (mean age, 76 +/- 1 years) skeletal muscle. Total cell yield varied widely between biopsies (50 to 672 per 100 mg of tissue, N = 10), but was not significantly different between the two patient groups. Percent myoblasts per biopsy (73 +/- 6%), number of myoblast doublings prior to senescence in vitro (37 +/- 2), and myoblast doubling time (27 +/- 1 hr) were also not significantly different between the two patient groups. Fusion kinetics of the myoblasts were similar for the two groups after 20-22 doublings (74 +/- 2% myoblast fusion) when the biopsy samples had been expanded to 1 to 2 billion muscle cells, a number acceptable for human gene therapy use. The myoblasts from the two groups could be equally transduced ex vivo with replication-deficient retroviral expression vectors to secrete 0.5 to 2 microg of a foreign protein (recombinant human growth hormone, rhGH)/10(6) cells/day, and tissue engineered into human BAMs containing parallel arrays of differentiated, postmitotic myofibers. This work suggests that autologous human skeletal myoblasts from a potential patient population can be isolated, genetically modified to secrete foreign proteins, and tissue engineered into implantable living protein secretory devices for therapeutic use.

Non-NASA Center↗

Formation of ectopic osteogenesis in weightlessness

An ectopic osteogenesis experiment aboard the Cosmos-936 biosatellite is described. Decalcified, lyophilized femur and tibia were implanted under the fascia or in the anterior wall of the abdomen in rats. Bone formation before and after the tests is described and illustrated. The extent of formation of ectopic bone in weightlessness did not differ significantly from that in the ground controls, but the bone marrow of the ectopic bone of the flight rats consisted exclusively of fat cells. The deficit of support-muscle loading was considered to cause the disturbance in skeletal bone tissue development.

Source record↗

Changes of the body functions during long-term hypokinesia

Prolonged hypokinesis (100-170 days) studied in 2000 rats kept in cages limiting their mobility provoked considerable changes in the gaseous and energetic metabolism: an elevation of the total gaseous metabolism and of the rate of O2 requirement by the muscles (in the late periods of hypokinesis) and a change in the intensity of tissue respiration of the liver and myocardium. There also proved to be a reduction in the level of phosphorylation and separation of oxidative phosphorylation in the myocardium, liver, and partially in the skeletal muscle. Prolonged hypokinesia led to changes in tissue metabolism: a disturbance of development of the animals, a marked delay and an increase in the weight of the organism and the muscular system, and disturbances of the mineral and protein metabolism. Prolonged hypokinesis also lead to exhaustion of the hypothalamus-hypophysis-adrenal cortex system.

Kovalenko, Y. A.↗

Computational problems in autoregressive moving average (ARMA) models

The choice of the sampling interval and the selection of the order of the model in time series analysis are considered. Band limited (up to 15 Hz) random torque perturbations are applied to the human ankle joint. The applied torque input, the angular rotation output, and the electromyographic activity using surface electrodes from the extensor and flexor muscles of the ankle joint are recorded. Autoregressive moving average models are developed. A parameter constraining technique is applied to develop more reliable models. The asymptotic behavior of the system must be taken into account during parameter optimization to develop predictive models.

Agarwal, G. C.↗

Reliability of Strength Testing using the Advanced Resistive Exercise Device and Free Weights

The Advanced Resistive Exercise Device (ARED) was developed for use on the International Space Station as a countermeasure against muscle atrophy and decreased strength. This investigation examined the reliability of one-repetition maximum (1RM) strength testing using ARED and traditional free weight (FW) exercise. Methods: Six males (180.8 +/- 4.3 cm, 83.6 +/- 6.4 kg, 36 +/- 8 y, mean +/- SD) who had not engaged in resistive exercise for at least six months volunteered to participate in this project. Subjects completed four 1RM testing sessions each for FW and ARED (eight total sessions) using a balanced, randomized, crossover design. All testing using one device was completed before progressing to the other. During each session, 1RM was measured for the squat, heel raise, and deadlift exercises. Generalizability (G) and intraclass correlation coefficients (ICC) were calculated for each exercise on each device and were used to predict the number of sessions needed to obtain a reliable 1RM measurement (G . 0.90). Interclass reliability coefficients and Pearson's correlation coefficients (R) also were calculated for the highest 1RM value (1RM9sub peak)) obtained for each exercise on each device to quantify 1RM relationships between devices.

English, Kirk L.↗

Magnetic resonance imaging after exposure to microgravity

A number of physiological changes were demonstrated in bone, muscle, and blood from exposure of humans and animals to microgravity. Determining mechanisms and the development of effective countermeasures for long-duration space missions is an important NASA goal. Historically, NASA has had to rely on tape measures, x-ray, and metabolic balance studies with collection of excreta and blood specimens to obtain this information. The development of magnetic resonance imaging (MRI) offers the possibility of greatly extending these early studies in ways not previously possible; MRI is also non-invasive and safe; i.e., no radiation exposure. MRI provides both superb anatomical images for volume measurements of individual structures and quantification of chemical/physical changes induced in the examined tissues. This investigation will apply MRI technology to measure muscle, intervertebral disc, and bone marrow changes resulting from exposure to microgravity.

Leblanc, Adrian↗

Functional Sensory-Motor Performance Following Long Term Space Flight: The First Results of "Field Test" Experiment

The effect that extended-duration space flights may have on human space travelers, including exploration missions, is widely discussed at the present time. Specifically, there is an increasing amount of evidence showing that the physical capacity of cosmonauts is significantly reduced after long-duration space flights. It is evident that the most impaired functions are those that rely on gravity, particularly up right posture and gait. Because of the sensorimotor disturbances manifested in the neurology of the posture and gait space flight and postflight changes may also be observed in debilitating motion sickness. While the severity of particular symptoms varies, disturbances in spatial orientation and alterations in the accuracy of voluntary movements are persistently observed after long-duration space flights. At this time most of the currently available data are primarily descriptive and not yet suitable for predicting operational impacts of most sensorimotor decrements observed upon landing on planetary surfaces or asteroids. In particular there are no existing data on the recovery dynamics or functionality of neurological, cardiovascular or muscle performance making it difficult to model or simulate the cosmonauts' activity after landing and develop the appropriate countermeasure that will ensure the rapid and safe recovery of crewmembers immediately after landing in what could be hostile environments. However and as a starting position, the videos we have acquired during recent data collection following the long duration flights of cosmonauts and astronauts walking and performing other tasks shortly after return from space flight speak volumes about their level of deconditioning. A joint Russian-American team has developed a new study specifically to address the changes in crewmembers performance and the recovery of performance with the intent of filling the missing data gaps. The first (pilot) phase of this study includes recording body kinematics and quantifying the coordination and timing of relatively simple basic movements - transition from seated and prone positions to standing, walking, stepping over obstacles, tandem walking, muscle compliance, as well as characteristics of postural sway and orthostatic tolerance. Testing for changes in these parameters have been initiated in the medical tent at the landing site. The first set of experiments showed that during the first hour after landing, cosmonauts and astronauts were able to execute (although slower and with more effort than preflight) simple movements such as egress from a seated or prone position and also to remain standing for 3.5 minutes without exhibiting pronounced cardiovascular changes. More challenging tests, however, demonstrated a prominent reduction in coordination - the obstacle task, for example, was performed at much slower speed and with a marked overestimation of the obstacle height and tandem walking was greatly degraded suggesting significant changes in proprioception, brainstem and vestibular function. There is some speculation that the neural changes, either from the bottom-up or top down may be long lasting; requiring compensatory responses that will modify or mask the adverse responses we have observed. Furthermore, these compensatory responses may actually be beneficial, helping achieve a more rapid adaptation to both weightlessness and a return to earth.

Tomilovskaya, E. S.↗

Effect of spaceflight on the isotonic contractile properties of single skeletal muscle fibers in the rhesus monkey

Experiments from both Cosmos and Space Shuttle missions have shown weightlessness to result in a rapid decline in the mass and force of rat hindlimb extensor muscles. Additionally, despite an increased maximal shortening velocity, peak power was reduced in rat soleus muscle post-flight. In humans, declines in voluntary peak isometric ankle extensor torque ranging from 15-40% have been reported following long- and short-term spaceflight and prolonged bed rest. Complete understanding of the cellular events responsible for the fiber atrophy and the decline in force, as well as the development of effective countermeasures, will require detailed knowledge of how the physiological and biochemical processes of muscle function are altered by spaceflight. The specific purpose of this investigation was to determine the extent to which the isotonic contractile properties of the slow- and fast-twitch fiber types of the soleus and gastrocnemius muscles of rhesus monkeys (Macaca mulatta) were altered by a 14-day spaceflight.

Non-NASA Center↗

Implicit Formulation of Muscle Dynamics in OpenSim

Astronauts lose bone and muscle mass during spaceflight. Exercise countermeasure is the primary method for counteracting bone and muscle mass loss in space. New spacecraft exercise device concepts are currently being developed for the NASAs new crew exploration vehicle. The NASA Digital Astronaut Project (DAP) uses computational modeling to help determine if the new exercise devices will be effective as countermeasures. The NASA Digital Astronaut Project is developing the ability to utilize predictive simulation to provide insight into the change in kinematics and kinetics with a change in device and gravitational environment (1-g versus 0-g). For example, in space exercise the subject's body weight is applied in addition to the loads prescribed for musculoskeletal maintenance. How and where these loads are applied obviously directly impacts bone and tissue loads. Additionally, due to space vehicle structural requirements, exercise devices are often placed on vibration isolation systems. This changes the apparent impedance or stiffness of the device as seen by the user. Data collection under these conditions is often impractical and limited. Predictive modeling provides a means to have a virtual subject to test hypotheses. Predictive simulation provides a virtual subject for which we are able to perform studies such as sensitivity to device loading and vibration isolation without the need for laboratory kinematic or kinetic test data.Direct Collocation optimization provides an efficient means to perform task based optimization and predictive modeling. It is relatively straight forward to structure a physical exercise task in a Direct Collocation mathematical formulation: perform a motion such that you start at an initial pose, achieve a given amount of deflection i.e a squat, return to the initial pose, and minimize muscle activation cost. Direct Collocation is advantageous in that it does not require numerical integration to evaluate the objective function. Instead, the system dynamics are transformed to discrete time and the optimizer is constrained such that the solution is not considered to be a valid unless the dynamic equations are satisfied at all time points. The simulation and optimization are effectively done simultaneously. Due to the implicit integration, time steps can be more coarse than in a differential equation solver. In a gait scenario this means that that the model constraints and cost function are evaluated at 100 nodes in the gait cycle versus 10,000 integration steps in a variable-step forward dynamic simulation. Furthermore, no time is wasted on accurate simulations of movements that are far from the optimum. Constrained optimization algorithms require a Jacobian matrix that contains the partial derivatives of each of the dynamic constraints with respect to of each of the state and control variables at all time points. This is a large but sparse matrix. An implicit dynamics formulation requires computation of the dynamic residuals f as a function of the states x and their derivatives, and controls u:f(x, dxdt, u) 0If the dynamics of musculoskeletal system are formulated implicitly, the Jacobian elements are often available analytically, eliminating the need for numerical differentiation; this is obviously computationally advantageous. Additionally, implicit formulation of musculoskeletal dynamics do not suffer from singularities from low mass bodies, zero muscle activation, or other stiff system or

physical exercise↗