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250 records · Page 14

Motor and cognitive testing of bone marrow transplant patients after chemoradiotherapy

Assessment of cognitive and motor performance of bone marrow transplant patients prior to, during, and following intensive toxic chemoradiotherapy may provide an important adjunct to measures of physiological and medical status. The present study is an attempt to assess whether, as side-effects, these aggressive treatments result in cognitive performance deficits, and if so, whether such changes recover posttreatment. Measurement of cognitive ability in this situation presents special problems not encountered with one-time tests intended for healthy adults. Such tests must be sensitive to changes within a single individual, which emphasizes the crucial importance of high reliability, stability across repeated-measures, and resistance to confounding factors such as motivation and fatigue. The present research makes use of a microbased portable test battery developed to have reliable and sensitive tests which were adapted to study the special requirements of transplant patients who may suffer cognitive deficits as a result of treatment. The results showed slight but significant changes in neuropsychological capacity when compared to baseline levels and controls, particularly near the beginning of treatment. The sensitivity of the battery in detecting such subtle temporary changes is discussed in terms of past research showing effects of other stressors, such as stimulated high altitude and ingestion of alcohol, on these measures.

Non-NASA Center↗

Relationship between body and leg VO2 during maximal cycle ergometry

It is not known whether the asymptotic behavior of whole body O2 consumption (VO2) at maximal work rates (WR) is explained by similar behavior of VO2 in the exercising legs. To resolve this question, simultaneous measurements of body and leg VO2 were made at submaximal and maximal levels of effort breathing normoxic and hypoxic gases in seven trained male cyclists (maximal VO2, 64.7 +/- 2.7 ml O2.min-1.kg-1), each of whom demonstrated a reproducible VO2-WR asymptote during fatiguing incremental cycle ergometry. Left leg blood flow was measured by constant-infusion thermodilution, and total leg VO2 was calculated as the product of twice leg flow and radial arterial-femoral venous O2 concentration difference. The VO2-WR relationships determined at submaximal WR's were extrapolated to maximal WR as a basis for assessing the body and leg VO2 responses. The differences between measured and extrapolated maximal VO2 were 235 +/- 45 (body) and 203 +/- 70 (leg) ml O2/min (not significantly different). Plateauing of leg VO2 was associated with, and explained by, plateauing of both leg blood flow and O2 extraction and hence of leg VO2. We conclude that the asymptotic behavior of whole body VO2 at maximal WRs is a direct reflection of the VO2 profile at the exercising legs.

NASA Discipline Cardiopulmonary↗

Resistance exercise countermeasures for space flight: implications of training specificity

While resistance exercise should be a logical choice for prevention of strength loss during unloading, the principle of training specificity cannot be overlooked. Our purpose was to explore training specificity in describing the effect of our constant load exercise countermeasure on isokinetic strength performance. Twelve healthy men (mean +/- SD: 28.0 +/- 5.2 years, 179.4 +/- 3.9 cm, 77.5 +/- 13.6 kg) were randomly assigned to no exercise or resistance exercise (REX) during 14 days of bed rest. REX performed five sets of leg press exercise to volitional fatigue (6-10 repetitions) every other day. Unilateral isokinetic concentric-eccentric knee extension testing performed before and on day 15 prior to reambulation included torque-velocity and power-velocity relationships at four velocities (0.52, 1.75, 2.97, and 4.19 rad s-1), torque-position relationship, and contractile work capacity (10 repetitions at 1.05 rad s-1). Two (group) x 2 (time) ANOVA revealed no group x time interactions; thus, groups were combined. Across velocities, angle-specific torque fell 18% and average power fell 20% (p < 0.05). No velocity x time or mode (concentric/eccentric) x time interactions were noted. Torque x position decreased on average 24% (p < 0.05). Total contractile work dropped 27% (p < 0.05). Results indicate bed rest induces rapid and marked reductions in strength and our constant load resistance training protocol did not prevent isokinetic strength losses. Differences between closed-chain training and open-chain testing may explain the lack of protection.

Randomized Controlled Trial↗

Skeletal muscle fiber type composition and performance during repeated bouts of maximal, concentric contractions

Force output and fatigue and recovery patterns were studied during intermittent short-term exercise. 27 men performed three bouts of 30 maximal unilateral knee extensions on 2 different occasions. Blood flow was maintained or occluded during recovery periods (60 s). Blood flow was restricted by inflating a pneumatic cuff placed around the proximal thigh. Muscle biopsies from vastus lateralis were analyzed for identification of fast twitch (FT) and slow twitch (ST) fibers and relative FT area. Peak torque decreased during each bout of exercise and more when blood flow was restricted during recovery. Initial peak torque (IPT) and average peak torque (APT) decreased over the three exercise bouts. This response was 3 fold greater without than with blood flow during recovery. IPT and APT decreased more in individuals with mainly FT fibers than in those with mainly ST fibers. It is suggested that performance during repeated bouts of maximal concentric contractions differs between individuals with different fiber type composition. Specifically, in high intensity, intermittent exercise with emphasis on anaerobic energy release a high FT composition may not necessarily be advantageous for performance.

Muscle Contraction↗

Restoration of plasma volume after 16 days of head-down tilt induced by a single bout of maximal exercise

Seven healthy men performed maximal exercise 24 h before the end of 16 days exposure to 6 degrees head-down tilt (HDT) to test the hypothesis that such an exercise technique could restore plasma volume (PV) at the end of a simulated space mission. Exercise consisted of supine cycling with graded work rates increasing by 16 W/min to volitional fatigue and required an average of 16 min. The experimental protocol was a standard cross-over design in which the order of treatment (exercise or control) was counterbalanced across all seven subjects. PV, fluid intake (ad libitum), urine output, renal function, and hormones associated with fluid homeostasis were measured before HDT, 24 h before the end of HDT just prior to exercise, and at the end of HDT 24 h after exercise. HDT reduced PV by 16% in both control and exercise conditions. Maximal exercise completely restored plasma volume within 24 h to 3.9 +/- 3.2% of pre-HDT levels despite continued HDT. Compared with control, exercise induced a 660-ml larger positive fluid balance because of greater fluid intake and reduced urine volume during the 24 h after exercise. These results suggest that one bout of maximal leg exercise before return from 16 days of spaceflight may be completely effective in stimulating thirst and restoring plasma volume to preflight levels.

Non-NASA Center↗

High Performance EVA Glove Collaboration: Glove Injury Data Mining Effort

Human hands play a significant role during Extravehicular Activity (EVA) missions and Neutral Buoyancy Lab (NBL) training events, as they are needed for translating and performing tasks in the weightless environment. Because of this high frequency usage, hand and arm related injuries are known to occur during EVA and EVA training in the NBL. The primary objectives of this investigation were to: 1) document all known EVA glove related injuries and circumstances of these incidents, 2) determine likely risk factors, and 3) recommend interventions where possible that could be implemented in the current and future glove designs. METHODS: The investigation focused on the discomforts and injuries of U.S. crewmembers who had worn the pressurized Extravehicular Mobility Unit (EMU) spacesuit and experienced 4000 Series or Phase VI glove related incidents during 1981 to 2010 for either EVA ground training or in-orbit flight. We conducted an observational retrospective case-control investigation using 1) a literature review of known injuries, 2) data mining of crew injury, glove sizing, and hand anthropometry databases, 3) descriptive statistical analyses, and finally 4) statistical risk correlation and predictor analyses to better understand injury prevalence and potential causation. Specific predictor statistical analyses included use of principal component analyses (PCA), multiple logistic regression, and survival analyses (Cox proportional hazards regression). Results of these analyses were computed risk variables in the forms of odds ratios (likelihood of an injury occurring given the magnitude of a risk variable) and hazard ratios (likelihood of time to injury occurrence). Due to the exploratory nature of this investigation, we selected predictor variables significant at p≤0.15. RESULTS: Through 2010, there have been a total of 330 NASA crewmembers, from which 96 crewmembers performed 322 EVAs during 1981-2010, resulting in 50 crewmembers being injured inflight and 44 injured during 11,704 ground EVA training events. Of the 196 glove related injury incidents, 106 related to EVA and 90 to EVA training. Over these 196 incidents, 277 total injuries (126 flight; 151 training) were reported and were then grouped into 23 types of injuries. Of EVA flight injuries, 65% were commonly reported to the hand (in general), metacarpophalangeal (MCP) joint, and finger (not including thumb) with fatigue, abrasion, and paresthesia being the most common injury types (44% of total flight injuries). Training injuries totaled to more than 70% being distributed to the fingernail, MCP joint, and finger crotch with 88% of the specific injuries listed as pain, erythema, and onycholysis. Of these training injuries, when reporting pain or erythema, the most common location was the index finger, but when reporting onycholysis, it was the middle finger. Predictor variables specific to increased risk of onycholysis included: female sex (OR=2.622), older age (OR=1.065), increased duration in hours of the flight or training event (OR=1.570), middle finger length differences in inches between the finger and the EVA glove (OR=7.709), and use of the Phase VI glove (OR=8.535). Differentiation between training and flight and injury reporting during 2002-2004 were significant control variables. For likelihood of time to first onycholysis injury, there was a 24% reduction in rate of reporting for each year increase in age. Also, more experienced crewmembers, based on number of EVA flight or training events completed, were less likely to report an onycholysis injury (3% less for every event). Longer duration events also found reporting rates to occur 2.37 times faster for every hour of length. Crewmembers with larger hand size reported onycholysis 23% faster than those with smaller hand size. Finally, for every 1/10th of an inch increase in difference between the middle finger length and the glove, the rate of reporting increased by 60%. DISCUSSION: One key finding was that the Series 4000 glove had a lower injury risk than the Phase VI, which provides a platform for further evaluation. General interventions that reduce hand overexertion and repetitive use exposure through tool development, procedural changes and shorter exposures may be one mitigation path, but due to the way the training event times were reported, we cannot provide a guideline for a specific event duration change. When the finger length was different from the glove length, the risk of injury increased indicating that the use of larger finger take-ups could be contributing to injury and therefore may not be recommended. Prior to this investigation, there was one previous investigation indicating hand anthropometry may be related to onycholysis. We found different hand anthropometry variables indicated by this investigation as compared to the prior, specifically differences in middle finger length compared to glove finger length, which point more towards a sizing issue than a specific anthropometry issue. Additionally, although this investigation has identified sizing as an issue, the force and environmental-related variables of the EVA glove that could also cause injury were not accounted for.

Reid, C. R.↗

An overview of the issues: physiological effects of bed rest and restricted physical activity

Reduction of exercise capacity with confinement to bed rest is well recognized. Underlying physiological mechanisms include dramatic reductions in maximal stroke volume, cardiac output, and oxygen uptake. However, bed rest by itself does not appear to contribute to cardiac dysfunction. Increased muscle fatigue is associated with reduced muscle blood flow, red cell volume, capillarization and oxidative enzymes. Loss of muscle mass and bone density may be reflected by reduced muscle strength and higher risk for injury to bones and joints. The resultant deconditioning caused by bed rest can be independent of the primary disease and physically debilitating in patients who attempt to reambulate to normal active living and working. A challenge to clinicians and health care specialists has been the identification of appropriate and effective methods to restore physical capacity of patients during or after restricted physical activity associated with prolonged bed rest. The examination of physiological responses to bed rest deconditioning and exercise training in healthy subjects has provided significant information to develop effective rehabilitation treatments. The successful application of acute exercise to enhance orthostatic stability, daily endurance exercise to maintain aerobic capacity, or specific resistance exercises to maintain musculoskeletal integrity rather than the use of surgical, pharmacological, and other medical treatments for clinical conditions has been enhanced by investigation and understanding of underlying mechanisms that distinguish physical deconditioning from the disease. This symposium presents an overview of cardiovascular and musculoskeletal deconditioning associated with reduced physical work capacity following prolonged bed rest and exercise training regimens that have proven successful in ameliorating or reversing these adverse effects.

NASA Program Space Physiology and Countermeasures↗

Effects of Acute Exposures to Carbon Dioxide Upon Cognitive Functions

Large quantities of carbon dioxide (CO2) originate from human metabolism and typically, within spacecraft, remain about 10-fold higher in concentration than at the earth's surface. There have been recurring complaints by crew members of episodes of "mental viscosity" adversely affecting their performance, and there is evidence from the International Space Station (ISS) that associates CO2 levels with reports of headaches by crewmembers. Additionally, there is concern that CO2 may contribute to vision impairment and intracranial pressure that has been observed in some crewmembers. Consequently, flight rules have been employed to control the level of CO2 below 4 mm Hg, which is well below the existing Spacecraft Maximum Allowable Concentration (SMAC) of 10 mm Hg for 24-hour exposures, and 5.3 mm Hg for exposures of 7 to 180 days. However, the flight rule imposed limit, which places additional demands upon resources and current technology, still exceeds the lower bound of the threshold range for reportable headaches (2 - 5 mm Hg). Headaches, while sometime debilitating themselves, are also symptoms that can provide evidence that physiological defense mechanisms have been breached. The causes of the headaches may elicit other subtle adverse effects that occur at CO2 levels well below that for headaches. The concern that CO2 may have effects at levels below the threshold for headaches appears to be substantiated in unexpected findings that CO2 at concentrations below 2 mm Hg substantially reduced some cognitive functions that are associated with the ability to make complex decisions in conditions that are characterized by volatility, uncertainty, complexity, ambiguity, and delayed feedback. These are conditions that could be encountered by crews in off-nominal situations or during the first missions beyond low earth orbit. If findings of the earlier study are confirmed in crew-like subjects, our findings would provide additional evidence that CO2 may need to be controlled at levels that are well below current spacecraft limits. Our study will extend the earlier study to determine if crew-like subjects are similarly effected by CO2. In addition to employing the Strategic Management Simulation tool, we will use the Cognition battery of psychometric measures that are being utilized aboard the ISS. It will be important to learn, by using Cognition, if additional cognitive domains are sensitive to concentrations of CO2 at or below limits currently controlled by flight rules. While spaceflight Cognition data will greatly enhance the knowledge base related to inflight behavioral health and performance, some of the measures may be influenced by fatigue (related to sleep deprivation and or workload) and changes in circadian rhythms. Therefore our use of this battery of tests in a well-controlled, ground-based study that is free of these potential confounding influences will establish a baseline terrestrial data set against which Cognition data collected in flight may be assessed. The findings from this study will be useful to the NASA Toxicology Office and the National Research Council Committee on Toxicology, which assists NASA in setting environmental standards, for revision of the SMAC for CO2, and for designing further studies on effects of CO2 upon cognitive functions.

Scully, R. R.↗

Familial orthostatic tachycardia due to norepinephrine transporter deficiency

Orthostatic intolerance (OI) or postural tachycardia syndrome (POTS) is a syndrome primarily affecting young females, and is characterized by lightheadedness, palpitations, fatigue, altered mentation, and syncope primarily occurring with upright posture and being relieved by lying down. There is typically tachycardia and raised plasma norepinephrine levels on upright posture, but little or no orthostatic hypotension. The pathophysiology of OI is believed to be very heterogeneous. Most studies of the syndrome have focused on abnormalities in norepinephrine release. Here the hypothesis that abnormal norepinephrine transporter (NET) function might contribute to the pathophysiology in some patients with OI was tested. In a proband with significant orthostatic symptoms and tachycardia, disproportionately elevated plasma norepinephrine with standing, impaired systemic, and local clearance of infused tritiated norepinephrine, impaired tyramine responsiveness, and a dissociation between stimulated plasma norepinephrine and DHPG elevation were found. Studies of NET gene structure in the proband revealed a coding mutation that converts a highly conserved transmembrane domain Ala residue to Pro. Analysis of the protein produced by the mutant cDNA in transfected cells demonstrated greater than 98% reduction in activity relative to normal. NE, DHPG/NE, and heart rate correlated with the mutant allele in this family. CONCLUSION: These results represent the first identification of a specific genetic defect in OI and the first disease linked to a coding alteration in a Na+/Cl(-)-dependent neurotransmitter transporter. Identification of this mechanism may facilitate our understanding of genetic causes of OI and lead to the development of more effective therapeutic modalities.

Review, Tutorial↗

Hypovolemia in syncope and orthostatic intolerance role of the renin-angiotensin system

PURPOSE: Orthostatic intolerance is the cause of significant disability in otherwise normal patients. Orthostatic tachycardia is usually the dominant hemodynamic abnormality, but symptoms may include dizziness, visual changes, discomfort in the head or neck, poor concentration, fatigue, palpitations, tremulousness, anxiety and, in some cases, syncope. It is the most common disorder of blood pressure regulation after essential hypertension. There is a predilection for younger rather than older adults and for women more than men. Its cause is unknown; partial sympathetic denervation or hypovolemia has been proposed. METHODS AND MATERIALS: We tested the hypothesis that reduced plasma renin activity, perhaps from defects in sympathetic innervation of the kidney, could underlie a hypovolemia, giving rise to these clinical symptoms. Sixteen patients (14 female, 2 male) ranging in age from 16 to 44 years were studied. Patients were enrolled in the study if they had orthostatic intolerance, together with a raised upright plasma norepinephrine (> or = 600 pg/mL). Patients underwent a battery of autonomic tests and biochemical determinations. RESULTS: There was a strong positive correlation between the blood volume and plasma renin activity (r = 0.84, P = 0.001). The tachycardic response to upright posture correlated with the severity of the hypovolemia. There was also a correlation between the plasma renin activity measured in these patients and their concomitant plasma aldosterone level. CONCLUSIONS: Hypovolemia occurs commonly in orthostatic intolerance. It is accompanied by an inappropriately low level of plasma renin activity. The degree of abnormality of blood volume correlates closely with the degree of abnormality in plasma renin activity. Taken together, these observations suggest that reduced plasma renin activity may be an important pathophysiologic component of the syndrome of orthostatic intolerance.

Non-NASA Center↗

Forearm training attenuates sympathetic responses to prolonged rhythmic forearm exercise

We previously demonstrated that nonfatiguing rhythmic forearm exercise at 25% maximal voluntary contraction (12 2-s contractions/min) evokes sympathoexcitation without significant engagement of metabolite-sensitive muscle afferents (B.A. Batman, J.C. Hardy, U.A. Leuenberger, M.B. Smith, Q.X. Yang and L.I. Sinoway. J. Appl. Physiol. 76: 1077-1081, 1994). This is in contrast to the sympathetic nervous system responses observed during fatiguing static forearm exercise where metabolite-sensitive afferents are the key determinants of sympathetic activation. In this report we examined whether forearm exercise training would attenuate sympathetic nervous system responses to rhythmic forearm exercise. We measured heart rate, mean arterial blood pressure (MAP), muscle sympathetic nerve activity (microneurography), plasma norepinephrine (NE), and NE spillover and clearance (tritiated NE kinetics) during nonfatiguing rhythmic forearm exercise before and after a 4-wk unilateral forearm training paradigm. Training had no effect on forearm mass, maximal voluntary contraction, or heart rate but did attenuate the increase in MAP (increase in MAP: from 15.2 +/- 1.8 before training to 11.4 +/- 1.4 mmHg after training; P < 0.017), muscle sympathetic nerve activity (increase in bursts: from 10.8 +/- 1.4 before training to 6.2 +/- 1.1 bursts/min after training; P < 0.030), and the NE spillover (increases in arterial spillover: from 1.3 +/- 0.2 before training to 0.6 +/- 0.2 nmol.min-1.m-2 after training, P < 0.014; increase in venous spillover: from 2.0 +/- 0.6 before training to 1.0 +/- 0.5 nmol.min-1.m-2 after training, P < 0.037) seen in response to exercise performed by the trained forearm. Thus forearm training reduces sympathetic responses during a nonfatiguing rhythmic handgrip paradigm that does not engage muscle metaboreceptors. We speculate that this effect is due to a conditioning-induced reduction in mechanically sensitive muscle afferent discharge.

NASA Discipline Musculoskeletal↗

Daytime Cognitive Performance in Response to Sunlight or Fluorescent Light Controlling for Sleep Duration

Light is the primary synchronizer of the human circadian rhythm and also has acute alerting effects. Our study involves and comparing the alertness, performance and sleep of participants in the NASA Ames Sustainability Base, which uses sunlight as its primary light source, to in a traditional office building which uses overhead florescent lighting and varying exposure to natural light. The purpose of this study is to determine whether the use of natural lighting as a primary light source improves daytime cognitive function and promotes nighttime sleep. Participants from the Sustainability Base will be matched by gender and age to individuals working in other NASA buildings. In a prior study we found no differences in performance between those working in the Sustainability Base and those working in other buildings. Unexpectedly, we found that the average sleep duration among participants in both buildings was short, which likely obscured our ability to detect a difference the effect of light exposure on alertness. Given that such sleep deprivation has negative effects on cognitive performance, in this iteration of the study we are asking the participants to maintain a regular schedule with eight hours in bed each night in order to control for the effect of self-selected sleep restriction. Over the course of one week, we will ask the participants to wear actiwatches continuously, complete a psychomotor vigilance task (PVT) and digit symbol substitution task (DSST) three times per day, and keep daily sleepwork diaries. We hope that this study will provide data to support the idea that natural lighting and green architectural design are optimal to enhance healthy nighttime sleep patterns and daytime cognitive performance.

cognitive performance↗

Reduced levels of skeletal muscle Na+K+ -ATPase in McArdle disease

We evaluated the hypothesis that impaired sarcolemmal function associated with exaggerated potassium release, impaired potassium uptake, or both may contribute to exertional fatigue and abnormal circulatory responses to exercise in McArdle disease (MD). The cellular mechanism of exertional fatigue and muscle injury in MD is unknown but likely involves impaired function of the ATPases that couple ATP hydrolysis to cellular work, including the muscle sodium potassium pump (Na+K+-ATPase). However, the concentration of muscle Na+K+ pumps in MD is not known, and no studies have related exercise increases in blood potassium concentrations to muscle Na+K+ pump levels. We measured muscle Na+K+ pumps (3H-ouabain binding) and plasma K+ in response to 20 minutes of cycle exercise in six patients with MD and in six sex-, age-, and weight-matched sedentary individuals. MD patients had lower levels of 3H-ouabain binding (231 +/- 18 pmol/g w.w., mean +/- SD, range, 210 to 251) than control subjects (317 +/- 37, range, 266 to 371, p < 0.0004), higher peak increases in plasma potassium in response to 45 +/- 7 W cycle exercise (MD, 1.00 +/- 0.15 mmol/L; control subjects, 0.48 +/- 0.09; p < 0.0001), and mean exercise heart rate responses to exercise that were 45 +/- 12 bpm greater than control subjects. Our results indicate that Na+K+ pump levels are low in MD patients compared with healthy subjects and identify a limitation of potassium reuptake that could result in sarcolemmal failure during peak rates of membrane activation and may promote exaggerated potassium-activated circulatory responses to submaximal exercise. The mechanism of the low Na+K+ pump concentrations in MD is unknown but may relate to deconditioning or to disruption of a close functional relationship between membrane ion transport and glycolysis.

Non-NASA Center↗

Circadian rhythms of women with fibromyalgia

Fibromyalgia syndrome is a chronic and debilitating disorder characterized by widespread nonarticular musculoskeletal pain whose etiology is unknown. Many of the symptoms of this syndrome, including difficulty sleeping, fatigue, malaise, myalgias, gastrointestinal complaints, and decreased cognitive function, are similar to those observed in individuals whose circadian pacemaker is abnormally aligned with their sleep-wake schedule or with local environmental time. Abnormalities in melatonin and cortisol, two hormones whose secretion is strongly influenced by the circadian pacemaker, have been reported in women with fibromyalgia. We studied the circadian rhythms of 10 women with fibromyalgia and 12 control healthy women. The protocol controlled factors known to affect markers of the circadian system, including light levels, posture, sleep-wake state, meals, and activity. The timing of the events in the protocol were calculated relative to the habitual sleep-wake schedule of each individual subject. Under these conditions, we found no significant difference between the women with fibromyalgia and control women in the circadian amplitude or phase of rhythms of melatonin, cortisol, and core body temperature. The average circadian phases expressed in hours posthabitual bedtime for women with and without fibromyalgia were 3:43 +/- 0:19 and 3:46 +/- 0:13, respectively, for melatonin; 10:13 +/- 0:23 and 10:32 +/- 0:20, respectively for cortisol; and 5:19 +/- 0:19 and 4:57 +/- 0:33, respectively, for core body temperature phases. Both groups of women had similar circadian rhythms in self-reported alertness. Although pain and stiffness were significantly increased in women with fibromyalgia compared with healthy women, there were no circadian rhythms in either parameter. We suggest that abnormalities in circadian rhythmicity are not a primary cause of fibromyalgia or its symptoms.

Non-NASA Center↗

Orthostatic intolerance and tachycardia associated with norepinephrine-transporter deficiency

BACKGROUND: Orthostatic intolerance is a syndrome characterized by lightheadedness, fatigue, altered mentation, and syncope and associated with postural tachycardia and plasma norepinephrine concentrations that are disproportionately high in relation to sympathetic outflow. We tested the hypothesis that impaired functioning of the norepinephrine transporter contributes to the pathophysiologic mechanism of orthostatic intolerance. METHODS: In a patient with orthostatic intolerance and her relatives, we measured postural blood pressure, heart rate, plasma catecholamines, and systemic norepinephrine spillover and clearance, and we sequenced the norepinephrine-transporter gene and evaluated its function. RESULTS: The patient had a high mean plasma norepinephrine concentration while standing, as compared with the mean (+/-SD) concentration in normal subjects (923 vs. 439+/-129 pg per milliliter [5.46 vs. 2.59+/-0.76 nmol per liter]), reduced systemic norepinephrine clearance (1.56 vs. 2.42+/-0.71 liters per minute), impairment in the increase in the plasma norepinephrine concentration after the administration of tyramine (12 vs. 56+/-63 pg per milliliter [0.07 vs. 0.33+/-0.37 pmol per liter]), and a disproportionate increase in the concentration of plasma norepinephrine relative to that of dihydroxyphenylglycol. Analysis of the norepinephrine-transporter gene revealed that the proband was heterozygous for a mutation in exon 9 (encoding a change from guanine to cytosine at position 237) that resulted in more than a 98 percent loss of function as compared with that of the wild-type gene. Impairment of synaptic norepinephrine clearance may result in a syndrome characterized by excessive sympathetic activation in response to physiologic stimuli. The mutant allele in the proband's family segregated with the postural heart rate and abnormal plasma catecholamine homeostasis. CONCLUSIONS: Genetic or acquired deficits in norepinephrine inactivation may underlie hyperadrenergic states that lead to orthostatic intolerance.

Non-NASA Center↗

VEG-05 Tomato Crop Testing on the International Space Station

Production of fresh, nutritious, and tasty produce for astronauts during spaceflight may provide health-promoting, bioavailable nutrients, enhance the dietary experience, and reduce menu fatigue as we move into longer-duration missions. Growing and caring for plants may also reduce the psychological stresses associated with spaceflight and enhance connection to Earth. A diversity of crops will be required to provide nutrition, variety, and resiliency, however requirements for consistent growth under spaceflight environmental conditions remain unclear. VEG-05 is part of a series of experiments with pick-and-eat salad crops to better define best practices for crop production in space. VEG-05 and predecessor experiments VEG-04A and VEG-04B, grew salad crops in the Veggie vegetable production facilities on the International Space Station using different lighting treatments. In VEG-05 we grew ‘Red Robin’ dwarf cherry tomatoes under two different red: blue lighting spectra. Light can impact the growth habit, yield, nutritional composition, microbial levels, and even flavor attributes within crops, and our goal was to assess these characteristics in ‘Red Robin’ tomatoes during VEG-05. Considerable pre-flight verification testing was performed prior to launch in Nov. 2022. Prior to the flight and ground experiments, lighting in both Veggie units on ISS was measured and lights were standardized between flight and ground hardware. VEG-05 flight operations ran between December 2022 and March 2023, with a ground control initially 48 hours delayed. Due to environmental challenges of very low humidity during the first week of the experiment, seed germination was low for both flight and ground plants. The flight experiment ultimately had 4 - 5 plants per treatment out of the planned 6 plants, but the initial ground control had only three plants in one treatment and none in the other, so this ground control was restarted at the beginning of Feb. 2023 and ran through May, with successful growth of all 12 plants. Both flight and ground control ran 100 days, with harvests of fruit at day 83, day 90, and day 100. Flight plants had uneven growth, and following the early drying events, excess water was frequently observed, which led to a variety of plant stress responses including uneven plant growth, excess adventitious root formation, flower and fruit abortion, and visible microbial growth. In total, from the five surviving red-rich lighted plants, only 5 ripe fruit were produced, and from the four surviving blue-rich lighted plants, 10 fruit were produced with only 6 of these ripe by day 100. Because of the small fruit number and the unsatisfactory growth, crew members were not allowed to consume the tomatoes, and all fruit, as well as large branches with leaves, samples of the adventitious roots, two plant rooting pillows from each treatment, microbial sampling swabs, and some water samples were returned for analysis. Because of the small sample sizes and factors affecting growth on the ISS, objectives of assessing light quality effect (red: blue light treatments) will not be achieved. Revised objectives of this study include to compare stressed flight plants with normal ground plants to determine the impact of plant overwatering stress in space on food safety and the plant microbial community, to determine nutrient content changes in fruit and leaves from stressed plants, and to evaluate stress metabolism changes in returned tissue by transcriptomic analysis. Postflight analysis is underway with the following analyses being conducted: A. culturable microbiology and food safety as well as molecular microbial community analysis of 1. ripe fruit, 2. leaves, stems, and adventitious roots, 3. pillow components (roots, wicks, and substrates), 4. swabs, and 5. water samples from root mats before and after growth. B. transcriptomics of leaf tissue and adventitious roots, and C. elemental analysis of leaf tissue. If sufficient tissue remains elemental analyses will also be conducted on fruit. While not generating the desired information on spaceflight growth responses of healthy crops, our team is hopeful that these analyses will shed light on tomato responses to stress in this environment as plant overwatering stress is a mission-relevant condition that could occur in future space crop growth systems. This research was co-funded by the Human Research Program and Space Biology (MTL#1075) in the ILSRA 2015 NRA call.

Gioia D. Massa↗