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At least 379 records · Page 21

Metabolic Adaptation to Muscle Ischemia

Although all tissues in the body can adapt to varying physiological/pathological conditions, muscle is the most adaptable. To understand the significance of cellular events and their role in controlling metabolic adaptations in complex physiological systems, it is necessary to link cellular and system levels by means of mechanistic computational models. The main objective of this work is to improve understanding of the regulation of energy metabolism during skeletal/cardiac muscle ischemia by combining in vivo experiments and quantitative models of metabolism. Our main focus is to investigate factors affecting lactate metabolism (e.g., NADH/NAD) and the inter-regulation between carbohydrate and fatty acid metabolism during a reduction in regional blood flow. A mechanistic mathematical model of energy metabolism has been developed to link cellular metabolic processes and their control mechanisms to tissue (skeletal muscle) and organ (heart) physiological responses. We applied this model to simulate the relationship between tissue oxygenation, redox state, and lactate metabolism in skeletal muscle. The model was validated using human data from published occlusion studies. Currently, we are investigating the difference in the responses to sudden vs. gradual onset ischemia in swine by combining in vivo experimental studies with computational models of myocardial energy metabolism during normal and ischemic conditions.

Cabrera, Marco E.↗

Effects of diet and exposure to hindlimb suspension on estrous cycling in Sprague-Dawley rats

Various factors can disrupt the female reproductive cycle resulting in subfertility. The primary objective of this study was to determine whether physiological changes associated with exposure to hypogravity disrupt reproductive cycles. The hindlimb suspension (HLS) model was used to simulate the major physiological effects of hypogravity in female Sprague-Dawley rats. Also, to determine whether diet may influence reproductive results, rats were fed purified American Institute of Nutrition (AIN)-93G or chow diet. Rats (n = 9-11/group) subjected to HLS had lengthened estrous cycles due to prolonged diestrus, indicating hypoestrogenism. Interestingly, HLS rats fed AIN-93G but not chow diet had significantly reduced time spent in estrus and decreased plasma estradiol. Attenuation of hypoestrogenism in the chow-fed rats suggested that diet provided an exogenous source of estrogen. The mechanism involved in the disruption of estrous cycling remains to be determined. HLS increased urinary corticosterone (CORT) levels during the initial 4 days of HLS, suggesting that physiological responses to acute stress may be a potential mechanism in the disruption of estrous cycles. Higher basal urinary CORT was observed in rats fed chow vs. AIN-93G diet. HLS resulted in increased urinary CORT. However, two-way ANOVA indicated a significant HLS effect (P < 0.001) but no effect of HLS x diet effect on urinary CORT levels, suggesting that estrogenic activity associated with the chow diet did not enhance the stress response. The results of this study indicate that HLS, diet, and the combination of HLS and diet influence estrous cycling. This has important implications for future reproductive success in the hypogravity environment of space.

Estrous Cycle/physiology↗

Hydrogen peroxide homeostasis: activation of plant catalase by calcium/calmodulin

Environmental stimuli such as UV, pathogen attack, and gravity can induce rapid changes in hydrogen peroxide (H(2)O(2)) levels, leading to a variety of physiological responses in plants. Catalase, which is involved in the degradation of H(2)O(2) into water and oxygen, is the major H(2)O(2)-scavenging enzyme in all aerobic organisms. A close interaction exists between intracellular H(2)O(2) and cytosolic calcium in response to biotic and abiotic stresses. Studies indicate that an increase in cytosolic calcium boosts the generation of H(2)O(2). Here we report that calmodulin (CaM), a ubiquitous calcium-binding protein, binds to and activates some plant catalases in the presence of calcium, but calcium/CaM does not have any effect on bacterial, fungal, bovine, or human catalase. These results document that calcium/CaM can down-regulate H(2)O(2) levels in plants by stimulating the catalytic activity of plant catalase. Furthermore, these results provide evidence indicating that calcium has dual functions in regulating H(2)O(2) homeostasis, which in turn influences redox signaling in response to environmental signals in plants.

NASA Discipline Plant Biology↗

Expression of the high capacity calcium-binding domain of calreticulin increases bioavailable calcium stores in plants

Modulation of cytosolic calcium levels in both plants and animals is achieved by a system of Ca2+-transport and storage pathways that include Ca2+ buffering proteins in the lumen of intracellular compartments. To date, most research has focused on the role of transporters in regulating cytosolic calcium. We used a reverse genetics approach to modulate calcium stores in the lumen of the endoplasmic reticulum. Our goals were two-fold: to use the low affinity, high capacity Ca2+ binding characteristics of the C-domain of calreticulin to selectively increase Ca2+ storage in the endoplasmic reticulum, and to determine if those alterations affected plant physiological responses to stress. The C-domain of calreticulin is a highly acidic region that binds 20-50 moles of Ca2+ per mole of protein and has been shown to be the major site of Ca2+ storage within the endoplasmic reticulum of plant cells. A 377-bp fragment encoding the C-domain and ER retention signal from the maize calreticulin gene was fused to a gene for the green fluorescent protein and expressed in Arabidopsis under the control of a heat shock promoter. Following induction on normal medium, the C-domain transformants showed delayed loss of chlorophyll after transfer to calcium depleted medium when compared to seedlings transformed with green fluorescent protein alone. Total calcium measurements showed a 9-35% increase for induced C-domain transformants compared to controls. The data suggest that ectopic expression of the calreticulin C-domain increases Ca2+ stores, and that this Ca2+ reserve can be used by the plant in times of stress.

NASA Discipline Plant Biology↗

Neuroprotection for the new millennium. Matchmaking pharmacology and technology

A major theme of the 1990s in the pathophysiology of nervous system injury has been the multifactorial etiology of irreversible injury. Multiple causes imply multiple opportunities for therapeutic intervention--hence the abandonment of the "magic bullet" single pharmacologic agent for neuroprotection in favor of pharmacologic "cocktails". A second theme of the 1990s has been the progress in technology for neuroprotection, minimally- or non-invasive monitoring as well as treatment. Cardiac stenting has eliminated the need, in many cases, for open heart surgery; deep brain stimulation for Parkinson's disease has offered significant improvement in quality of life for many who had exhausted cocktail drug treatment for their disease. Deep brain stimulation of the subthalamic nucleus offers a novel treatment for Parkinson's disease where a technological advance may actually be an intervention with effects that are normally expected from pharmacologic agents. Rather than merely "jamming" the nervous system circuits involved in Parkinson's disease, deep brain stimulation of the subthalamic nucleus appears to improve the neurotransmitter imbalance that lies at the heart of Parkinson's disease. It may also slow the progression of the disease. Given the example of deep brain stimulation of the subthalamic nucleus for Parkinson's disease, in future one may expect other technological or "hardware" interventions to influence the programming or "software" of the nervous system's physiologic response in certain disease states.

Review Literature↗

Suppression of antigen-specific lymphocyte activation in modeled microgravity

Various parameters of immune suppression are observed in lymphocytes from astronauts during and after a space flight. It is difficult to ascribe this suppression to microgravity effects on immune cells in crew specimens, due to the complex physiological response to space flight and the resultant effect on in vitro immune performance. Use of isolated immune cells in true and modeled microgravity in immune performance tests, suggests a direct effect of microgravity on in vitro cellular function. Specifically, polyclonal activation of T-cells is severely suppressed in true and modeled microgravity. These recent findings suggest a potential suppression of oligoclonal antigen-specific lymphocyte activation in microgravity. We utilized rotating wall vessel (RWV) bioreactors as an analog of microgravity for cell cultures to analyze three models of antigen-specific activation. A mixed-lymphocyte reaction, as a model for a primary immune response, a tetanus toxoid response and a Borrelia burgdorferi response, as models of a secondary immune response, were all suppressed in the RWV bioreactor. Our findings confirm that the suppression of activation observed with polyclonal models also encompasses oligoclonal antigen-specific activation.

NASA Discipline Cell Biology↗

Physical examination during space flight

OBJECTIVE: To develop techniques for conducting a physical examination in microgravity and to describe and document the physiologic changes noted with use of a modified basic physical examination. DESIGN: On the basis of data gathered from physical examinations on KC-135 flights, three physical variables were assessed serially in astronauts during two shuttle missions (of 8- and 10-day duration, respectively). Preflight, in-flight, and postflight examinations were conducted by trained physician-astronauts or flight surgeons, who used this modified examination. MATERIAL AND METHODS: Five male and two female crewmembers participated in the "hands-on" physical examination of all physiologic systems except the genitourinary system. Level of edema, intensity of bowel sounds, and peripheral reflexes were assessed and graded. RESULTS: This investigation identified unique elements of a physical examination performed during space flight that will assist in the development of standard methods for conducting examinations of astronauts in weightlessness. In addition, demonstrable changes induced by microgravity were noted in most physiologic systems examined. CONCLUSION: The data support the hypothesis that the microgravity examination differs from that conducted on earth or in a 1g environment. In addition, alterations in the physiologic response can be detected with use of hands-on technique. These data are invaluable in the development of optimal medical care for humans in space.

STS Shuttle Project↗

The Flora Mission for Ecosystem Composition, Disturbance and Productivity

Global land use and climate variability alter ecosystem conditions - including structure, function, and biological diversity - at a pace that requires unambiguous observations from satellite vantage points. Current global measurements are limited to general land cover, some disturbances, vegetation leaf area index, and canopy energy absorption. Flora is a pathfinding mission that provides new measurements of ecosystem structure, function, and diversity to understand the spatial and temporal dynamics of human and natural disturbances, and the biogeochemical and physiological responses of ecosystems to disturbance. The mission relies upon high-fidelity imaging spectroscopy to deliver full optical spectrum measurements (400-2500 nm) of the global land surface on a monthly time step at 45 meter spatial resolution for three years. The Flora measurement objectives are: (i) fractional cover of biological materials, (ii) canopy water content, (iii) vegetation pigments and light-use efficiency, (iv) plant functional types, (v) fire fuel load and fuel moisture content, and (vi) disturbance occurrence, type and intensity. These measurements are made using a multi-parameter, spectroscopic analysis approach afforded by observation of the full optical spectrum. Combining these measurements, along with additional observations from multispectral sensors, Flora will far advance global studies and models of ecosystem dynamics and change.

Asner, Gregory P.↗

The Apollo Medical Operations Project: Recommendations to Improve Crew Health and Performance for Future Exploration Missions and Lunar Surface Operations

Medical requirements for the future Crew Exploration Vehicle (CEV), Lunar Surface Access Module (LSAM), advanced Extravehicular Activity (EVA) suits and Lunar habitat are currently being developed. Crews returning to the lunar surface will construct the lunar habitat and conduct scientific research. Inherent in aggressive surface activities is the potential risk of injury to crewmembers. Physiological responses to and the operational environment of short forays during the Apollo lunar missions were studied and documented. Little is known about the operational environment in which crews will live and work and the hardware that will be used for long-duration lunar surface operations.Additional information is needed regarding productivity and the events that affect crew function such as a compressed timeline. The Space Medicine Division at the NASA Johnson Space Center (JSC) requested a study in December 2005 to identify Apollo mission issues relevant to medical operations that had impact to crew health and/or performance. The operationally oriented goals of this project were to develop or modify medical requirements for new exploration vehicles and habitats, create a centralized database for future access, and share relevant Apollo information with the multiple entities at NASA and abroad participating in the exploration effort.

Scheuring, Richard A.↗

The Apollo Medical Operations Project: Recommendations to Improve Crew Health and Performance for Future Exploration Missions and Lunar Surface Operations

Medical requirements for the future Crew Exploration Vehicle (CEV), Lunar Surface Access Module (LSAM), advanced Extravehicular Activity (EVA) suits and Lunar habitat are currently being developed. Crews returning to the lunar surface will construct the lunar habitat and conduct scientific research. Inherent in aggressive surface activities is the potential risk of injury to crewmembers. Physiological responses and the operational environment for short forays during the Apollo lunar missions were studied and documented. Little is known about the operational environment in which crews will live and work and the hardware will be used for long-duration lunar surface operations. Additional information is needed regarding productivity and the events that affect crew function such as a compressed timeline. The Space Medicine Division at the NASA Johnson Space Center (JSC) requested a study in December 2005 to identify Apollo mission issues relevant to medical operations that had impact to crew health and/or performance. The operationally oriented goals of this project were to develop or modify medical requirements for new exploration vehicles and habitats, create a centralized database for future access, and share relevant Apollo information with the multiple entities at NASA and abroad participating in the exploration effort.

Scheuring, Richard A.↗

The Interaction of the Space Shuttle Launch and Entry Suits and Sustained Weightless on Astronaut Egress Locomotion

The purpose of this study was to determine the consequences of extended periods of weightlessness during space missions on astronauts f ability to perform a simulated contingency egress while wearing either of the Launch and Entry suits immediately after space flight. In our previous lab-based study of simulated contingency egress, we found only 4 of 12 non-astronauts wearing the Launch and Entry Suit (LES) successfully completed the simulated egress. However, 4 of 4 of the previous failures (when tested wearing the LES), were then successful in completing the test wearing the Advanced Crew Escape Suit (ACES). Therefore, this study tested 21 Astronaut Volunteers wearing either the LES or ACES while performing a simulated egress on a treadmill (TM) onboard the Crew Transportation Vehicle immediately after space flight at either the Kennedy Space Center or Edwards AFB. Astronauts walked for 400 meters at 1.6m/sec with g-suit inflation level set to preflight testing levels, visor down, breathing from the suit emergency O2 supply. Metabolic, heartrate, and perceived exertion data were collected during these post-flight tests. Exactly the same preflight simulated egress tests on a TM were performed in the lab at NASA/JSC by each crewmember at L-60. Preflight testing found 2 of the 21 crewmembers were unable to complete the simulated contingency egress. Postflight, 9 crew (8 ACES, 1 LES) completed the simulated contingency egress of 400 meters at 1.6m/sec. and 12 failed to meet that standard (7 ACES, 5 LES). Preflight physiological response tests failed to identify crew capable of performing the egress vs. those who failed. However, 18 of the 21 crew did make at least 2.67 minutes into the postflight egress testing. At that point in time, heartrate was higher (P <=.20) for the failures compared to the finishers. These findings indicate that NASA fs switch to the ACES for space flight crews should be expedited.

Greenisen, M. C.↗

Lower Body Negative Pressure Treadmill Exercise and Resistive Exercise Countermeasures Maintain Physiologic Function in Women during Simulated Microgravity

We hypothesized that supine LBNP treadmill exercise combined with Flywheel resistive exercise maintains upright physiologic responses following 60-days of head-down tilt (HDT) bed rest (BR). METHODS: 16 healthy women (age 25-40 years) underwent 60-days HDT (-6deg.) BR. Women were assigned to either a non-exercise control group (CON, n=8) or to an exercise group (EX, n=8). EX subjects performed a 40-min, variable intensity LBNP exercise protocol at foot-ward forces between 1.0-1.1 times body weight, followed by 10- min of resting LBNP 3-4 days/week. Resistive exercise of maximal concentric and eccentric supine leg press and heel raise exercises were performed using a flywheel ergometer 2-3 days/week. IRBs approved this study with informed/written consent. RESULTS: Post-BR VO2pk was not different in EX (-3.3+/-1.2%) but decreased significantly in CON (-21.2+/-2.1%), p< 0.05. Post-BR orthostatic tolerance time (mean se) decreased significantly less in EX (19.3+/-1.3 to 14.4+/-1.5 min) than in CON (17.5+/-0.1 to 9.1+/- 1.5 min), p=0.03. Post-BR muscle strength decreased significantly in CON, but was preserved in EX. Post-BR bone resorption was greater than pre-BR in both groups (p<0.05). Bone formation markers, were significantly elevated (p<0.05) in EX than in CON. CONCLUSIONS: Supine LBNP treadmill exercise along with flywheel resistive exercise maintains upright exercise capacity, orthostatic responses and muscle strength during 60-days HDT BR.

Macias, B. R.↗

Did Vertigo Kill America's Forgotten Astronaut?

On November 15, 1967, U.S. Air Force test pilot Major Michael J. Adams was killed while flying the X-15 rocket-propelled research vehicle in a parabolic spaceflight profile. This flight was part of a joint effort with NASA. An electrical short in one of the experiments aboard the vehicle caused electrical transients, resulting in excessive workload by the pilot. At altitude Major Adams inappropriately initiated a flat spin that led to a series of unusual aircraft attitudes upon atmospheric re-entry, ultimately causing structural failure of the airframe. Major Adams was known to experience vertigo (i.e. spatial disorientation) while flying the X-15, but all X-15 pilots most likely experienced vertigo (i.e. somatogravic, or "Pitch-Up", illusion) as a normal physiologic response to the accelerative forces involved. Major Adams probably experienced vertigo to a greater degree than did others, since prior aeromedical testing for astronaut selection at Brooks AFB revealed that he had an unusually high degree of labyrinthine sensitivity. Subsequent analysis reveals that after engine burnout, and through the zenith of the flight profile, he likely experienced the oculoagravic ("Elevator") illusion. Nonetheless, painstaking investigation after the mishap revealed that spatial disorientation (Type II, Recognized) was NOT the cause, but rather, a contributing factor. The cause was in fact the misinterpretation of a dual-use flight instrument (i.e. Loss of Mode Awareness), resulting in confusion between yaw and roll indications, with subsequent flight control input that was inappropriate. Because of the altitude achieved on this flight, Major Adams was awarded Astronaut wings posthumously. Understanding the potential for spatial disorientation, particularly the oculoagravic illusion, associated with parabolic spaceflight profiles, and understanding the importance of maintaining mode awareness in the context of automated cockpit design, are two lessons that have direct application to the commercial space industry today.

Bendrick, Gregg A.↗

Human Adaptation to Space: Space Physiology and Countermeasures

This viewgraph presentation reviews human physiological responses to spaceflight, and the countermeasures taken to prevent adverse effects of manned space flight. The topics include: 1) Human Spaceflight Experience; 2) Human Response to Spaceflight; 3) ISS Expeditions 1-16; 4) Countermeasure; and 5) Biomedical Data;

Fogarty, Jennifer↗

Feasibility Study of a Lunar Analog Bed Rest Model

The purpose of this study was to determine the feasibility of using a 9.5deg head-up tilt bed rest model to simulate the effects of the 1/6 g load to the human body that exists on the lunar surface. The lunar analog bed rest model utilized a modified hospital bed. The modifications included mounting the mattress on a sled that rolled on bearings to provide freedom of movement. The weight of the sled was off-loaded using a counterweight system to insure that 1/6 body weight was applied along the long axis (z-axis) of the body. Force was verified through use of a force plate mounted at the foot of the bed. A seating assembly was added to the bed to permit periods of sitting. Subjects alternated between standing and sitting positions throughout the day. A total of 35% of the day was spent in the standing position and 65% was spent sitting. In an effort to achieve physiologic fluid shifts expected for a 1/6 G environment, subjects wore compression stockings and performed unloaded foot and ankle exercises. Eight subjects (3 females and 5 males) participated in this study. Subjects spent 13 days in the pre-bed rest phase, 6 days in bed rest and 3 days post bed rest. Subjects consumed a standardized diet throughout the study. To determine feasibility, measures of subject comfort, force and plasma volume were collected. Subject comfort was assessed using a Likert scale. Subjects were asked to assess level of comfort (0-100) for 11 body regions and provide an overall rating. Results indicated minimal to no discomfort as most subjects reported scores of zero. Force measures were performed for each standing position and were validated against subject s calculated 1/6 body weight (r(sup 2) = 0.993). The carbon monoxide rebreathing technique was used to assess plasma volume during pre-bed rest and on the last day of bed rest. Plasma volume results indicated a significant decrease (p = 0.001) from pre to post bed rest values. Subjects lost on average 8.3% (sd = 6.1%) during the bed rest phase. Findings from this feasibility study indicated that 1) the lunar analog bed rest model was well tolerated by subjects; 2) a 1/6 load was accurately applied to the z-axis of the body; and 3) plasma volume losses could be achieved in a head-up tilt bed rest model. Future work to refine this model should include extending the duration of bed rest to mimic longer mission durations and a comprehensive assessment of the physiological responses to this bed rest analog.

Cromwell, Ronita L.↗

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.↗

Psychophysiological Studies in Extreme Environments

This paper reviews the results from two studies that employed the methodology of multiple converging indicators (physiological measures, subjective self-reports and performance metrics) to examine individual differences in the ability of humans to adapt and function in high stress environments. The first study was a joint collaboration between researchers at the US Army Research Laboratory (ARL) and NASA Ames Research Center. Twenty-four men and women active duty soldiers volunteered as participants. Field tests were conducted in the Command and Control Vehicle (C2V), an enclosed armored vehicle, designed to support both stationary and on-the-move operations. This vehicle contains four computer workstations where crew members are expected to perform command decisions in the field under combat conditions. The study objectives were: 1) to determine the incidence of motion sickness in the C2V relative to interior seat orientation/position, and parked, moving and short-haul test conditions; and 2) to determine the impact of the above conditions on cognitive performance, mood, and physiology. Data collected during field tests included heart rate, respiration rate, skin temperature, and skin conductance, self-reports of mood and symptoms, and cognitive performance metrics that included seven subtests in the DELTA performance test battery. Results showed that during 4-hour operational tests over varied terrain motion sickness symptoms increased; performance degraded by at least 5 percent; and physiological response profiles of individuals were categorized based on good and poor cognitive performance. No differences were observed relative to seating orientation or position.

Toscano, William B.↗

Monitors Track Vital Signs for Fitness and Safety

Have you ever felt nauseous reading a book in the back seat of a car? Or woken from a deep sleep feeling disoriented, unsure which way is up? Momentary mixups like these happen when the sensory systems that track the body's orientation in space become confused. (In the case of the backseat bookworm, the conflict arises when the reader s inner ear, part of the body s vestibular system, senses the car s motion while her eyes are fixed on the stationary pages of the book.) Conditions like motion sickness are common on Earth, but they also present a significant challenge to astronauts in space. Human sensory systems use the pull of gravity to help determine orientation. In the microgravity environment onboard the International Space Station, for example, the body experiences a period of confusion before it adapts to the new circumstances. (In space, even the body s proprioceptive system, which tells the brain where the arms and legs are oriented without the need for visual confirmation, goes haywire, meaning astronauts sometimes lose track of where their limbs are when they are not moving them.) This Space Adaptation Syndrome affects a majority of astronauts, even experienced ones, causing everything from mild disorientation to nausea to severe vomiting. "It can be quite debilitating," says William Toscano, a research scientist in NASA s Ames Research Center Psychophysiology Laboratory, part of the Center s Human Systems Integration Division. "When this happens, as you can imagine, work proficiency declines considerably." Since astronauts cannot afford to be distracted or incapacitated during critical missions, NASA has explored various means for preventing and countering motion sickness in space, including a range of drug treatments. Many effective motion sickness drugs, however, cause undesirable side effects, such as drowsiness. Toscano and his NASA colleague, Patricia Cowings, have developed a different approach: Utilizing biofeedback training methods, the pair can teach astronauts, military pilots, and others susceptible to motion sickness to self-regulate their own physiological responses and suppress the unpleasant symptoms. This NASA-patented method invented by Cowings is called the Autogenic Feedback Training Exercise (ATFE), and several studies have demonstrated its promise

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