The intestine is a major contributor to circulating succinate in mice.

The tricarboxylic acid (TCA) cycle is the epicenter of cellular aerobic metabolism. TCA cycle intermediates facilitate energy production and provide anabolic precursors, but also function as intra- and extracellular metabolic signals regulating pleiotropic biological processes. Despite the importance of circulating TCA cycle metabolites as signaling molecules, the source of circulating TCA cycle intermediates remains uncertain. We observe that in mice, the concentration of TCA cycle intermediates in the portal blood exceeds that in tail blood indicating that the gut is a major contributor to circulating TCA cycle metabolites. With a focus on succinate as a representative of a TCA cycle intermediate with signaling activities and using a combination of gut microbiota depletion mouse models and isotopomer tracing, we demonstrate that intestinal microbiota is not a major contributor to circulating succinate. Moreover, we demonstrate that endogenous succinate production is markedly higher than intestinal succinate absorption in normal physiological conditions. Altogether, these results indicate that endogenous succinate production within the intestinal tissue is a major physiological source of circulating succinate. These results provide a foundation for an investigation into the role of the intestine in regulating circulating TCA cycle metabolites and their potential signaling effects on health and disease.

Evaluation of Optic Disc Edema in Long-Duration Spaceflight Crewmembers Using Retinal Photography.

BACKGROUND: Long-duration spaceflight crewmembers are at risk for spaceflight-associated neuro-ocular syndrome (SANS). One of the earliest manifestations of SANS is optic disc edema (ODE), which could be missed using the subjective Frisén scale. The primary objective of this study is to determine the inter-rater and intrarater reliability of Frisén grade for SANS-induced ODE among a trained observer cohort. The secondary objective is to propose a standardized evaluation process for SANS-induced ODE across International Space Station Partner Agencies. METHODS: Retrospective, double-blinded diagnostic study. Preflight and postflight fundus photographs were presented to subject matter experts who identified and graded ODE. Pairs of images were also compared side-by-side for disc ranking. Grader concordance was assessed for Frisén grading and disc ranking. RESULTS: Expert graders identified Grade 1 ODE in 17.35% of images from 62 crewmembers (9 female, mean [SD] age, 47.81 [5.19] years). Grades 2 and 3 were identified less than 2% of the time. Concordance in Frisén grades among pairs of graders was 70.99%. Graders identified a difference in preflight and postflight fundus photographs 17.21% of the time when using disc ranking. Pairs of graders had complete concordance in disc ranking 79.79% of the time. Perfect intrarater agreement between Frisén grade and disc ranking occurred 77.7% of the time. CONCLUSIONS: These findings demonstrate intergrader and intragrader variability when using the Frisén scale to identify SANS-induced ODE, which is typically milder in presentation than terrestrial cases of idiopathic intracranial hypertension. It is possible to miss early ODE on fundoscopy alone, making it insufficient as a sole criterion for the diagnosis of SANS. A more sensitive and objective method of surveillance is necessary to monitor international crewmembers for ODE, perhaps using a multimodal approach that includes technology such as optical coherence tomography.

Surveillance for jugular venous thrombosis in astronauts.

BACKGROUND: Thrombosis of the left internal jugular vein in an astronaut aboard the International Space Station was recently described, incidentally discovered during a research study of blood flow in neck veins in microgravity. Given this event, and the high incidence of flow abnormalities, the National Aeronautics and Space Administration (NASA) instituted an occupational surveillance program to evaluate astronauts for venous thrombosis. METHODS: Duplex ultrasound of the bilateral internal jugular veins was conducted on all NASA astronauts terrestrially, and at three points during spaceflight. Respiratory maneuvers were performed. Images were analyzed for thrombosis and certain hemodynamic characteristics, including peak velocity and degree of echogenicity. RESULTS: Eleven astronauts were evaluated with matching terrestrial and in-flight ultrasounds. No thrombosis was detected. Compared to terrestrial ultrasound measurements, in-flight peak velocity was reduced and lowest in the left. Six of 11 astronauts had mild-moderate echogenicity in the left internal jugular vein during spaceflight, but none had more than mild echogenicity in the right internal jugular vein. Two astronauts developed retrograde blood flow in the left internal jugular vein. CONCLUSION: Abnormal flow characteristics in microgravity, most prominent in the left internal jugular vein, may signal an increased risk for thrombus formation in some individuals.

Persistent Globe Flattening in Astronauts following Long-Duration Spaceflight.

Posterior globe flattening has been well-documented in astronauts both during and after long-duration space flight (LDSF) and has been observed as early as 10 days into a mission on the International Space Station. Globe flattening (GF) is thought to be caused by the disc centred anterior forces created by elevated volume and/or pressure within the optic nerve sheath (ONS). This might be the result of increased intracranial pressure, increased intraorbital ONS pressure from compartmentalisation or a combination of these mechanisms. We report posterior GF in three astronauts that has persisted for 7 years or more following their return from LDSFs suggesting that permanent scleral remodelling may have occurred.

Intracranial Effects of Microgravity: A Prospective Longitudinal MRI Study.

Background Astronauts on long-duration spaceflight missions may develop changes in ocular structure and function, which can persist for years after the return to normal gravity. Chronic exposure to elevated intracranial pressure during spaceflight is hypothesized to be a contributing factor, however, the etiologic causes remain unknown. Purpose To investigate the intracranial effects of microgravity by measuring combined changes in intracranial volumetric parameters, pituitary morphologic structure, and aqueductal cerebrospinal fluid (CSF) hydrodynamics relative to spaceflight and to establish a comprehensive model of recovery after return to Earth. Materials and Methods This prospective longitudinal MRI study enrolled astronauts with planned long-duration spaceflight. Measures were conducted before spaceflight followed by 1, 30, 90, 180, and 360 days after landing. Intracranial volumetry and aqueductal CSF hydrodynamics (CSF peak-to-peak velocity amplitude and aqueductal stroke volume) were quantified for each phase. Qualitative and quantitative changes in pre- to postflight (day 1) pituitary morphologic structure were determined. Statistical analysis included separate mixed-effects models per dependent variable with repeated observations over time. Results Eleven astronauts (mean age, 45 years ± 5 [standard deviation]; 10 men) showed increased mean volumes in the brain (28 mL; P < .001), white matter (26 mL; P < .001), mean lateral ventricles (2.2 mL; P < .001), and mean summated brain and CSF (33 mL; P < .001) at postflight day 1 with corresponding increases in mean aqueductal stroke volume (14.6 µL; P = .045) and mean CSF peak-to-peak velocity magnitude (2.2 cm/sec; P = .01). Summated mean brain and CSF volumes remained increased at 360 days after spaceflight (28 mL; P < .001). Qualitatively, six of 11 (55%) astronauts developed or showed exacerbated pituitary dome depression compared with baseline. Average midline pituitary height decreased from 5.9 to 5.3 mm (P < .001). Conclusion Long-duration spaceflight was associated with increased pituitary deformation, augmented aqueductal cerebrospinal fluid (CSF) hydrodynamics, and expansion of summated brain and CSF volumes. Summated brain and CSF volumetric expansion persisted up to 1 year into recovery, suggesting permanent alteration. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Lev in this issue.

Regulation of Glucose Production in the Pathogenesis of Type 2 Diabetes.

PURPOSE OF REVIEW: Increased glucose production associated with hepatic insulin resistance contributes to the development of hyperglycemia in T2D. The molecular mechanisms accounting for increased glucose production remain controversial. Our aims were to review recent literature concerning molecular mechanisms regulating glucose production and to discuss these mechanisms in the context of physiological experiments and observations in humans and large animal models. RECENT FINDINGS: Genetic intervention studies in rodents demonstrate that insulin can control hepatic glucose production through both direct effects on the liver, and through indirect effects to inhibit adipose tissue lipolysis and limit gluconeogenic substrate delivery. However, recent experiments in canine models indicate that the direct effects of insulin on the liver are dominant over the indirect effects to regulate glucose production. Recent molecular studies have also identified insulin-independent mechanisms by which hepatocytes sense intrahepatic carbohydrate levels to regulate carbohydrate disposal. Dysregulation of hepatic carbohydrate sensing systems may participate in increased glucose production in the development of diabetes.

Endothelial Cell Autophagy Maintains Shear Stress-Induced Nitric Oxide Generation via Glycolysis-Dependent Purinergic Signaling to Endothelial Nitric Oxide Synthase.

OBJECTIVE: Impaired endothelial cell (EC) autophagy compromises shear stress-induced nitric oxide (NO) generation. We determined the responsible mechanism. APPROACH AND RESULTS: On autophagy compromise in bovine aortic ECs exposed to shear stress, a decrease in glucose uptake and EC glycolysis attenuated ATP production. We hypothesized that decreased glycolysis-dependent purinergic signaling via P2Y1 (P2Y purinoceptor 1) receptors, secondary to impaired autophagy in ECs, prevents shear-induced phosphorylation of eNOS (endothelial nitric oxide synthase) at its positive regulatory site S1117 (p-eNOSS1177) and NO generation. Maneuvers that restore glucose transport and glycolysis (eg, overexpression of GLUT1 [glucose transporter 1]) or purinergic signaling (eg, addition of exogenous ADP) rescue shear-induced p-eNOSS1177 and NO production in ECs with impaired autophagy. Conversely, inhibiting glucose transport via GLUT1 small interfering RNA, blocking purinergic signaling via ectonucleotidase-mediated ATP/ADP degradation (eg, apyrase), or inhibiting P2Y1 receptors using pharmacological (eg, MRS2179 [2'-deoxy-N6-methyladenosine 3',5'-bisphosphate tetrasodium salt]) or genetic (eg, P2Y1-receptor small interfering RNA) procedures inhibit shear-induced p-eNOSS1177 and NO generation in ECs with intact autophagy. Supporting a central role for PKCδT505 (protein kinase C delta T505) in relaying the autophagy-dependent purinergic-mediated signal to eNOS, we find that (1) shear stress-induced activating phosphorylation of PKCδT505 is negated by inhibiting autophagy, (2) shear-induced p-eNOSS1177 and NO generation are restored in autophagy-impaired ECs via pharmacological (eg, bryostatin) or genetic (eg, constitutively active PKCδ) activation of PKCδT505, and (3) pharmacological (eg, rottlerin) and genetic (eg, PKCδ small interfering RNA) PKCδ inhibition prevents shear-induced p-eNOSS1177 and NO generation in ECs with intact autophagy. Key nodes of dysregulation in this pathway on autophagy compromise were revealed in human arterial ECs. CONCLUSIONS: Targeted reactivation of purinergic signaling and PKCδ has strategic potential to restore compromised NO generation in pathologies associated with suppressed EC autophagy.

Real-time Ultrasound Assessment of Astronaut Spinal Anatomy and Disorders on the International Space Station.

OBJECTIVES: Back pain is one of the most common conditions of astronauts during spaceflight and is hypothesized to be attributed to pathologic anatomic changes. Ultrasound (US) represents the only available imaging modality on the International Space Station, but a formal US protocol for imaging the structures of the spinal column does not exist. This investigation developed a method of acquiring diagnostic-quality images of the anterior lumbar and cervical regions of the spine during long-duration spaceflight. METHODS: Comprehensive spinal US examinations were conducted on 7 long-duration spaceflight astronauts before flight, in flight, and after flight and compared to preflight and postflight magnetic resonance imaging data. In-flight scans were conducted after just-in-time training assisted by remote expert tele-US guidance. RESULTS: Novice users were able to obtain diagnostic-quality spinal images with a 92.5% success rate. Thirty-three anomalous or pathologic findings were identified during the preflight US analysis, and at least 14 new findings or progressions were identified during the postflight US analysis. Common findings included disk desiccation, osteophytes, and qualitative changes in the intervertebral disk height and angle. CONCLUSIONS: Ultrasound has proven efficacy as a portable and versatile diagnostic imaging modality under austere conditions. We demonstrated a potential role for US to evaluate spinal integrity and alterations in the extreme environment of space on the International Space Station. Further investigations should be performed to corroborate this imaging technique and to create a larger database related to in-flight spinal conditions during long-duration spaceflight.

Volumetric Ophthalmic Ultrasound for Inflight Monitoring of Visual Impairment and Intracranial Pressure.

OBJECTIVE: The objective is enhanced ophthalmic ultrasound imaging to monitor ocular structure and intracranial dynamics changes related to visual impairment and intracranial pressure (ICP) induced by microgravity. The goals are to improve the ease of use and reduce operator variability by automatically rendering improved views of the anatomy and deriving new metrics of the morphology and dynamics. MATERIALS AND METHODS: A prototype three-dimensional (3-D) probe was integrated onto a portable ultrasound scanner. Image analysis algorithms were developed to automatically detect the ocular anatomy and simultaneously render views of the optic nerve with improved sheath definition. Curvature metrics were calculated from 3-D retinal surfaces to quantify posterior globe flattening, and tissue velocity waveforms of the optic nerve were analyzed to assess intracranial dynamics. RESULTS: New 3-D structural measurements were evaluated in a head-down tilt study. The response of optic nerve sheath and globe flattening metrics were quantified in 11 healthy volunteers from baseline to moderately elevated ICP. The optic nerve measurements showed good correlation with existing two-dimensional (2-D) methods and an acute response to increased ICP, while globe flattening did not show an acute response. The tissue velocities were evaluated in a porcine model from baseline to significantly elevated ICP and correlated with invasive ICP readings in four animals. CONCLUSIONS: Volumetric ophthalmic imaging was demonstrated on a portable ultrasound system and structural measurements validated with existing methods. New 3-D structural measurements and dynamic measurements were evaluation during in vivo studies. Further investigations are needed to evaluate improvements in performance for non-experts and application to clinically relevant conditions.

Persistent Asymmetric Optic Disc Swelling After Long-Duration Space Flight: Implications for Pathogenesis.

BACKGROUND: Several ophthalmic findings including optic disc swelling, globe flattening and choroidal folds have been observed in astronauts following long-duration space flight. The authors now report asymmetric choroidal expansion, disc swelling and optic disc morphologic changes in a 45-year-old astronaut which occurred during long-duration space flight and persisted following his space mission. METHODS: Case study of ocular findings in an astronaut documented during and after a long-duration space flight of approximately 6 months. Before, during and after his spaceflight, he underwent complete eye examination, including fundus photography, ultrasound, and optical coherence tomography. RESULTS: We documented asymmetric choroidal expansion inflight that largely resolved by 30 days postflight, asymmetric disc swelling observed inflight that persisted for over 180 days postflight, asymmetric optic disc morphologic changes documented inflight by OCT that persisted for 630 days postflight and asymmetric globe flattening that began inflight and continued 660 days postflight. Lumbar puncture opening pressures obtained at 7 and 365 days post-mission were 22 and 16 cm H20 respectively. CONCLUSION: The persistent asymmetric findings noted above, coupled with the lumbar puncture opening pressures, suggest that prolonged microgravity exposure may have produced asymmetric pressure changes within the perioptic subarachnoid space.

MR-derived cerebral spinal fluid hydrodynamics as a marker and a risk factor for intracranial hypertension in astronauts exposed to microgravity.

PURPOSE: To quantify the change in cerebral spinal fluid (CSF) production rate and maximum systolic velocity in astronauts before and after exposure to microgravity and identify any physiologic trend and/or risk factor related to intracranial hypertension. MATERIALS AND METHODS: Following Institutional Review Board (IRB) approval, with waiver of informed consent, a retrospective review of 27 astronauts imaged at 3T was done. Qualitative analysis was performed on T2 -weighted axial images through the orbits for degree of flattening of the posterior globe according to the following grades: 0 = none, 1 = mild, 2 = moderate, and 3 = severe. One grade level change postflight was considered significant for exposure to intracranial hypertension. CSF production rate and maximum systolic velocity was calculated from cine phase-contrast magnetic resonance imaging and compared to seven healthy controls. RESULTS: Fourteen astronauts were studied. The preflight CSF production rate in astronauts was similar to controls (P = 0.83). Six astronauts with significant posterior globe flattening demonstrated a 70% increase in CSF production rate postflight compared to baseline (P = 0.01). There was a significant increase in CSF maximum systolic velocity in the subgroup without posterior globe flattening (P = 0.01). CONCLUSION: The increased postflight CSF production rate in astronauts with positive flattening is compatible with the hypothesis of microgravity-induced intracranial hypertension inferring downregulation in CSF production in microgravity that is upregulated upon return to normal gravity. Increased postflight CSF maximum systolic velocity in astronauts with negative flattening suggests increased craniospinal compliance and a potential negative risk factor to microgravity-induced intracranial hypertension.

Liver retinol transporter and receptor for serum retinol-binding protein (RBP4).

Vitamin A (retinol) is absorbed in the small intestine, stored in liver, and secreted into circulation bound to serum retinol-binding protein (RBP4). Circulating retinol may be taken up by extrahepatic tissues or recycled back to liver multiple times before it is finally metabolized or degraded. Liver exhibits high affinity binding sites for RBP4, but specific receptors have not been identified. The only known high affinity receptor for RBP4, Stra6, is not expressed in the liver. Here we report discovery of RBP4 receptor-2 (RBPR2), a novel retinol transporter expressed primarily in liver and intestine and induced in adipose tissue of obese mice. RBPR2 is structurally related to Stra6 and highly conserved in vertebrates, including humans. Expression of RBPR2 in cultured cells confers high affinity RBP4 binding and retinol transport, and RBPR2 knockdown reduces RBP4 binding/retinol transport. RBPR2 expression is suppressed by retinol and retinoic acid and correlates inversely with liver retinol stores in vivo. We conclude that RBPR2 is a novel retinol transporter that potentially regulates retinol homeostasis in liver and other tissues. In addition, expression of RBPR2 in liver and fat suggests a possible role in mediating established metabolic actions of RBP4 in those tissues.

Impairment of autophagy in endothelial cells prevents shear-stress-induced increases in nitric oxide bioavailability.

Autophagy is a lysosomal catabolic process by which cells degrade or recycle their contents to maintain cellular homeostasis, adapt to stress, and respond to disease. Impairment of autophagy in endothelial cells studied under static conditions results in oxidant stress and impaired nitric oxide (NO) bioavailability. We tested the hypothesis that vascular autophagy is also important for induction of NO production caused by exposure of endothelial cells to shear stress (i.e., 3 h × ≈20 dyn/cm(2)). Atg3 is a requisite autophagy pathway mediator. Control cells treated with non-targeting control siRNA showed increased autophagy, reactive oxygen species (ROS) production, endothelial NO synthase (eNOS) phosphorylation, and NO production upon exposure to shear stress (p < 0.05 for all). In contrast, cells with >85% knockdown of Atg3 protein expression (via Atg3 siRNA) exhibited a profound impairment of eNOS phosphorylation, and were incapable of increasing NO in response to shear stress. Moreover, ROS accumulation and inflammatory cytokine production (MCP-1 and IL-8) were exaggerated (all p < 0.05) in response to shear stress. These findings reveal that autophagy not only plays a critical role in maintaining NO bioavailability, but may also be a key regulator of oxidant-antioxidant balance and inflammatory-anti-inflammatory balance that ultimately regulate endothelial cell responses to shear stress.

New heights in ultrasound: first report of spinal ultrasound from the international space station.

BACKGROUND: Changes in the lumbar and sacral spine occur with exposure to microgravity in astronauts; monitoring these alterations without radiographic capabilities on the International Space Station (ISS) requires novel diagnostic solutions to be developed. STUDY OBJECTIVES: We evaluated the ability of point-of-care ultrasound, performed by nonexpert-operator astronauts, to provide accurate anatomic information about the spine in long-duration crewmembers in space. METHODS: Astronauts received brief ultrasound instruction on the ground and performed in-flight cervical and lumbosacral ultrasound examinations using just-in-time training and remote expert tele-ultrasound guidance. Ultrasound examinations on the ISS used a portable ultrasound device with real-time communication/guidance with ground experts in Mission Control. RESULTS: The crewmembers were able to obtain diagnostic-quality examinations of the cervical and lumbar spine that would provide essential information about acute or chronic changes to the spine. CONCLUSIONS: Spinal ultrasound provides essential anatomic information in the cervical and lumbosacral spine; this technique may be extensible to point-of-care situations in emergency departments or resource-challenged areas without direct access to additional radiologic capabilities.

Invasive and ultrasound based monitoring of the intracranial pressure in an experimental model of epidural hematoma progressing towards brain tamponade on rabbits.

INTRODUCTION: An experimental epidural hematoma model was used to study the relation of ultrasound indices, namely, transcranial color-coded-Doppler (TCCD) derived pulsatility index (PI), optic nerve sheath diameter (ONSD), and pupil constriction velocity (V) which was derived from a consensual sonographic pupillary light reflex (PLR) test with invasive intracranial pressure (ICP) measurements. MATERIAL AND METHODS: Twenty rabbits participated in the study. An intraparenchymal ICP catheter and a 5F Swan-Ganz catheter (SG) for the hematoma reproduction were used. We successively introduced 0.1 mL increments of autologous blood into the SG until the Cushing reaction occurred. Synchronous ICP and ultrasound measurements were performed accordingly. RESULTS: A constant increase of PI and ONSD and a decrease of V values were observed with increased ICP values. The relationship between the ultrasound variables and ICP was exponential; thus curved prediction equations of ICP were used. PI, ONSD, and V were significantly correlated with ICP (r² = 0.84 ± 0.076, r² = 0.62 ± 0.119, and r² = 0.78 ± 0.09, resp. (all P < 0.001)). CONCLUSION: Although statistically significant prediction models of ICP were derived from ultrasound indices, the exponential relationship between the parameters underpins that results should be interpreted with caution and in the current experimental context.

Doppler ultrasound of the central retinal artery in microgravity.

BACKGROUND: Ocular changes have been noted during long-duration spaceflight; we studied central retinal artery (CRA) blood flow using Doppler before, during, and after long-term microgravity exposure in astronauts compared with data from a control group of nonastronauts subjected to head-down tilt (HDT). METHODS: Available Doppler spectra of International Space Station (ISS) crewmembers were obtained from the NASA Lifetime Surveillance of Astronaut Health database, along with 2D ultrasound-derived measurements of the optic nerve sheath diameter (ONSD). CRA Doppler spectra and optic nerve sheath images were also obtained from healthy test subjects in an acute HDT experiment at 20 min of exposure (the ground-based analogue). RESULTS: HDT CRA peak systolic velocity in the ground-based analogue group increased by an average of 3 cm -s(-1) (33%) relative to seated values. ONSD at 300 of HDT increased by 0.5 mm relative to supine values. CRA Doppler spectra obtained on orbit were of excellent quality and demonstrated in-flight changes of +5 cm x s(-1) (50%) compared to preflight. ONSD increased in ISS crewmembers during flight relative to before flight, with some reversal postflight. DISCUSSION: A significant ONSD response to acute postural change and to spaceflight was demonstrated in this preliminary study. Increases in Doppler peak flow velocities correlated with increases in ONSD. Further investigations are warranted to corroborate the relationship between ONSD, intracranial pressure, and central retinal blood flow for occupational surveillance and research purposes.

Optic nerve sheath diameter measurement techniques: examination using a novel ex-vivo porcine model.

BACKGROUND: Ultrasound (U/S) and MRI measurements of the optic nerve sheath diameter (ONSD) have been proposed as intracranial pressure measurement surrogates, but these methods have not been fully evaluated or standardized. The purpose of this study was to develop an ex-vivo model for evaluating ONSD measurement techniques by comparing U/S and MRI measurements to physical measurements. METHODS: The left eye of post mortem juvenile pigs (N = 3) was excised and the subdural space of the optic nerve cannulated. Caliper measurements and U/S imaging measurements of the ONSD were acquired at baseline and following 1 cc saline infusion into the sheath. The samples were then embedded in 0.5% agarose and imaged in a 7 Tesla (7T) MRI. The ONSD was subsequently measured with digital calipers at locations and directions matching the U/S and direct measurements. RESULTS: Both MRI and sonographic measurements were in agreement with direct measurements. U/S data, especially axial images, exhibited a positive bias and more variance (bias: 1.318, 95% limit of agreement: 8.609) compared to MRI (bias: 0.3156, 95% limit of agreement: 2.773). In addition, U/S images were much more dependent on probe placement, distance between probe and target, and imaging plane. CONCLUSIONS: This model appears to be a valid test-bed for continued scrutiny of ONSD measurement techniques. In this model, 7T MRI was accurate and potentially useful for in-vivo measurements where direct measurements are not available. Current limitations with ultrasound imaging for ONSD measurement associated with image acquisition technique and equipment necessitate further standardization to improve its clinical utility.

Optic disc edema in an astronaut after repeat long-duration space flight.

BACKGROUND: A number of ophthalmic findings including optic disc edema, globe flattening, and choroidal folds have been observed in several astronauts after long-duration space flights. The authors report the first astronaut with previously documented postflight ophthalmic abnormalities who developed new pathological changes after a repeat long-duration mission. METHODS: A case study of an astronaut with 2 long-duration (6 months) exposures to microgravity. Before and after his first long-duration space flight, he underwent complete eye examination, including fundus photography. Before and after his second flight, 9 years later, he underwent fundus photography, optical coherence tomography, ocular ultrasonography, and brain magnetic resonance imaging, as well as in-flight fundus photography and ultrasound. RESULTS: After his first long-duration mission, the astronaut was documented to have eye findings limited to unilateral choroidal folds and a single cotton wool spot. During a subsequent 6-month mission, he developed more widespread choroidal folds and new onset of optic disc edema in the same eye. CONCLUSION: Microgravity-induced anatomical changes that occurred during the first mission may have set the stage for recurrent or additional changes when the astronaut was subjected to physiological stress of repeat space flight.

Enabling the mission through trans-atlantic remote mentored musculoskeletal ultrasound: case report of a portable hand-carried tele-ultrasound system for medical relief missions.

Modern medical practice has become extremely dependent upon diagnostic imaging technologies to confirm the results of clinical examination and to guide the response to therapies. Of the various diagnostic imaging techniques, ultrasound is the most portable modality and one that is repeatable, dynamic, relatively cheap, and safe as long as the imaging provided is accurately interpreted. It is, however, the most user-dependent, a characteristic that has prompted the development of remote guidance techniques, wherein remote experts guide distant users through the use of information technologies. Medical mission work often brings specialist physicians to less developed locations, where they wish to provide the highest levels of care but are often bereft of diagnostic imaging resources on which they depend. Furthermore, if these personnel become ill or injured, their own care received may not be to the standard they have left at home. We herein report the utilization of a compact hand-carried remote tele-ultrasound system that allowed real-time diagnosis and follow-up of an acutely torn adductor muscle by a team of ultrasonographers, surgeons, and physicians. The patient was one of the mission surgeons who was guided to self-image. The virtual network of supporting experts was located across North America, whereas the patient was in Lome, Togo, West Africa. The system consisted of a hand-carried ultrasound, the output of which was digitized and streamed to the experts within standard voice-over-Internet-protocol software with an embedded simultaneous videocamera image of the ultrasonographer's hands using a customized graphical user interface. The practical concept of a virtual tele-ultrasound support network was illustrated through the clinical guidance of multiple physicians, including National Aeronautics and Space Administration Medical Operations remote guiders, Olympic team-associated surgeons, and ultrasound-focused emergentologists.