Hypoxic pulmonary vasoconstriction does not limit maximal exercise capacity in healthy volunteers breathing 12% oxygen at sea level.

Maximal exercise capacity is reduced at altitude or during hypoxia at sea level. It has been suggested that this might reflect increased right ventricular afterload due to hypoxic pulmonary vasoconstriction. We have shown previously that the pulmonary vascular sensitivity to hypoxia is enhanced by sustained isocapnic hypoxia, and inhibited by intravenous iron. In this study, we tested the hypothesis that elevated pulmonary artery pressure contributes to exercise limitation during acute hypoxia. Twelve healthy volunteers performed incremental exercise tests to exhaustion breathing 12% oxygen, before and after sustained (8-h) isocapnic hypoxia at sea level. Intravenous iron sucrose (n = 6) or saline placebo (n = 6) was administered immediately before the sustained hypoxia. In the placebo group, there was a substantial (12.6 ± 1.5 mmHg) rise in systolic pulmonary artery pressure (SPAP) during sustained hypoxia, but no associated fall in maximal exercise capacity breathing 12% oxygen. In the iron group, the rise in SPAP during sustained hypoxia was markedly reduced (3.4 ± 1.0 mmHg). There was a small rise in maximal exercise capacity following sustained hypoxia within the iron group, but no overall effect of iron, compared with saline. These results do not support the hypothesis that elevated SPAP inhibits maximal exercise capacity during acute hypoxia in healthy volunteers.

Ileal Interposition for Ureteral Reconstruction Following Treatment for Abdominopelvic Malignancy: Complications and Outcomes From a Comprehensive Cancer Center.

OBJECTIVE: To characterize the outcomes of ileal interposition for the management of ureteral obstruction from tumor and ureteral stricture following treatment for abdominopelvic malignancy. MATERIALS AND METHODS: A retrospective database analysis was performed for all cases of ileal interposition performed by 5 surgeons from January 2013 to December 2020. Patients were ≥18 years of age and included if undergoing ileal interposition in either the primary setting of a surgical procedure for tumor extirpation or in the delayed setting. RESULTS: In total, 23 patients who underwent repair of 27 ureteral units were included. The mean age was 60.2 years. Median follow-up was 21.6 months. The most common primary diagnoses were urothelial (35%), colorectal (31%), and cervical (22%) cancer. The etiologies of ureteral obstruction were malignant in 48% and ureteral stricture in 52%. Types of repairs included unilateral interposition in 13 patients, bilateral interposition in 1 patient, interposition to an ileal conduit in 3 patients, and interposition with cystoplasty in 6 patients. There was a statistically significant difference between the mean preoperative (Creatinine 1.05 mg/dL, Estimated Glomerular Filtration Rate 77 ml/min/1.73 m2) renal function and postoperative (Creatinine 1.26 mg/dL, Estimated Glomerular Filtration Rate 67 mL/min/1.73 m2) renal function at the most recent follow-up (P = .024). Eight minor (grade 1-2) and 6 major (grade ≥3) complications developed for a minor and major complication rate of 35% and 26%, respectively. CONCLUSION: Ileal interposition is successfully utilized as a reconstructive technique at the time of enbloc resection involving the ureter and to address ureteral stricture in the delayed setting.

Early Human Pathophysiological Responses to Exertional Hypobaric Decompression Stress.

INTRODUCTION: Consistent blood biomarkers of hypobaric (altitude) decompression stress remain elusive. Recent laboratory investigation of decompression sickness risk at 25,000 ft (7620 m) enabled evaluation of early pathophysiological responses to exertional decompression stress.METHODS: In this study, 15 healthy men, aged 20-50 yr, undertook 2 consecutive (same-day) ascents to 25,000 ft (7620 m) for 60 and 90 min, breathing 100% oxygen, each following 1 h of prior denitrogenation. Venous blood was sampled at baseline (T0), immediately after the second ascent (T8), and next morning (T24). Analyses encompassed whole blood hematology, endothelial microparticles, and soluble markers of cytokine response, endothelial function, inflammation, coagulopathy, oxidative stress, and brain insult, plus cortisol and creatine kinase.RESULTS: Acute hematological effects on neutrophils (mean 72% increase), eosinophils (40% decrease), monocytes (37% increase), and platelets (7% increase) normalized by T24. Consistent elevation (mean five-fold) of the cytokine interleukin-6 (IL-6) at T8 was proinflammatory and associated with venous gas emboli (microbubble) load. Levels of C-reactive protein and complement peptide C5a were persistently elevated at T24, the former by 100% over baseline. Additionally, glial fibrillary acidic protein, a sensitive marker of traumatic brain injury, increased by a mean 10% at T24.CONCLUSIONS: This complex composite environmental stress, comprising the triad of hyperoxia, decompression, and moderate exertion at altitude, provoked pathophysiological changes consistent with an IL-6 cytokine-mediated inflammatory response. Multiple persistent biomarker disturbances at T24 imply incomplete recovery the day after exposure. The elevation of glial fibrillary acidic protein similarly implies incomplete resolution following recent neurological insult.Connolly DM, Madden LA, Edwards VC, D'Oyly TJ, Harridge SDR, Smith TG, Lee VM. Early human pathophysiological responses to exertional hypobaric decompression stress. Aerosp Med Hum Perform. 2023; 94(10):738-749.

Decompression Sickness Risk in Parachutist Dispatchers Exposed Repeatedly to High Altitude.

INTRODUCTION: Occurrences of severe decompression sickness (DCS) in military parachutist dispatchers at 25,000 ft (7620 m) prompted revision of exposure guidelines for high altitude parachuting. This study investigated residual risks to dispatchers and explored the potential for safely conducting repeat exposures in a single duty period.METHODS: In this study, 15 healthy men, ages 20-50 yr, undertook 2 profiles of repeated hypobaric chamber decompression conducting activities representative of dispatcher duties. Phase 1 comprised two ascents to 25,000 ft (7620 m) for 60 and then 90 min. Phase 2 included three ascents first to 25,000 ft for 60 min, followed by two ascents to 22,000 ft (6706 m) for 90 min. Denitrogenation was undertaken at 15,000 ft (4572 m) with successive ascents separated by 1-h air breaks at ground level.RESULTS: At 25,000 ft (7620 m), five cases of limb (knee) pain DCS developed, the earliest at 29 min. Additionally, multiple minor knee "niggles" occurred with activity but disappeared when seated at rest. No DCS and few niggles occurred at 22,000 ft (6706 m). Early, heavy, and sustained bubble loads were common at 25,000 ft, particularly in older subjects, but lighter and later loads followed repeat exposure, especially at 22,000 ft.DISCUSSION: Parachutist dispatchers are at high risk of DCS at 25,000 ft (7620 m) commensurate with their heavy level of exertion. However, the potential exists for repeated safe ascents to 22,000 ft (6706 m), in the same duty period, if turn-around times breathing air at ground level are brief. Older dispatchers (>40 yr) with functional right-to-left (intracardiac or pulmonary) vascular shunts will be at risk of arterialization of microbubbles.Connolly DM, D'Oyly TJ, Harridge SDR, Smith TG, Lee VM. Decompression sickness risk in parachutist dispatchers exposed repeatedly to high altitude. Aerosp Med Hum Perform. 2023; 94(9):666-677.

Fluorous Liquids for Magnetic Resonance-Based Thermometry with Enhanced Responsiveness and Environmental Degradation.

Accurate temperature measurement via magnetic resonance is valuable for both in vitro and in vivo analysis of local tissue for evaluating disease pathology and medical interventions. 1H MRI-based thermometry is used clinically but is susceptible to error from magnetic field drift and low sensitivity in fatty tissue and requires a reference for absolute temperature determination. As an alternative, perfluorotributylamine (PFTBA), a perfluorocarbon liquid for 19F MRI thermometry, is based on chemical shift responsiveness and approaches the sensitivity of 1H MRI thermometry agents; however, environmental persistence, greenhouse gas concerns, and multiple resonances which can lead to MRI artifacts indicate a need for alternative sensors. Using a 19F NMR-based structure-property study of synthetic organofluorine molecules, this research develops new organofluorine liquids with improved temperature responsiveness, high signal, and reduced nonmagnetically equivalent fluorine resonances. Environmental degradation analysis using reverse-phase HPLC and quantitative 19F NMR demonstrates a rapid degradation profile mediated via the aryl fluorine core of temperature sensors. Our findings show that our lead liquid temperature sensor, DD-1, can be made in high yield in a single step and possesses an improved responsiveness over our prior work and an 83% increase in aqueous thermal responsiveness over PFTBA. Degradation studies indicate robust degradation with half-lives of less than two hours under photolysis conditions for the parent compound and formation of other fluorinated products. The improved performance of DD-1 and its susceptibility to environmental degradation highlight a new lead fluorous liquid for thermometry applications.

Measuring Arterial Oxygen Saturation Using Wearable Devices Under Varying Conditions.

INTRODUCTION: Recently developed wearable monitoring devices can provide arterial oxygen saturation (Spo2) measurements, offering potential for use in aerospace operations. Pilots and passengers are already using these technologies, but their performance has not yet been established under conditions experienced in the flight environment such as environmental hypoxia and concurrent body motion.METHODS: An initial evaluation was conducted in 10 healthy subjects who were studied in a normobaric chamber during normoxia and at a simulated altitude of 15,000 ft (4572 m; 11.8% oxygen). Spo2 was measured simultaneously using a standard pulse oximeter and four wearable devices: Apple Watch Series 6; Garmin Fenix 6 watch; Cosinusso Two in-ear sensor; and Oxitone 1000M wrist-worn pulse oximeter. Measurements were made while stationary at rest, during very slight body motion (induced by very low intensity cycling at 30 W on an ergometer), and during moderate body motion (induced by moderate intensity cycling at 150 W).RESULTS: Missed readings, defined as failure to record an Spo2 value within 1 min, occurred commonly with all wearables. Even with only very slight body motion, most devices missed most readings (range of 12-82% missed readings) and the rate was higher with greater body motion (range 18-92%). One device tended to under-report Spo2, while the other devices tended to over-report Spo2. Performance decreased across the devices when oxygenation was reduced.DISCUSSION: In this preliminary evaluation, the wearable devices studied did not perform to the same standard as a traditional pulse oximeter. These limitations may restrict their utility in flight and require further investigation.Hearn EL, Byford J, Wolfe C, Agyei C, Hodkinson PD, Pollock RD, Smith TG. Measuring arterial oxygen saturation using wearable devices under varying conditions. Aerosp Med Hum Perform. 2023; 94(1):42-47.

Cardiorespiratory Responses to Voluntary Hyperventilation During Normobaric Hypoxia.

BACKGROUND: Unexplained physiological events (PE), possibly related to hypoxia and hyperventilation, are a concern for some air forces. Physiological monitoring could aid research into PEs, with measurement of arterial oxygen saturation (Spo2) often suggested despite potential limitations in its use. Given similar physiological responses to hypoxia and hyperventilation, the present study characterized the cardiovascular and respiratory responses to each.METHODS: Ten healthy subjects were exposed to 55 mins of normobaric hypoxia simulating altitudes of 0, 8000, and 12,000 ft (0, 2438, and 3658 m) while breathing normally and voluntarily hyperventilating (doubling minute ventilation). Respiratory gas analysis and spirometry measured end-tidal gases (PETo2 and PETco2) and minute ventilation. Spo2 was assessed using finger pulse oximetry. Mean arterial, systolic, and diastolic blood pressure were measured noninvasively. Cognitive impairment was assessed using the Stroop test.RESULTS: Voluntary hyperventilation resulted in a doubling of minute ventilation and lowered PETco2, while altitude had no effect on these. PETo2 and Spo2 declined with increasing altitude. However, despite a significant drop in PETo2 of 15.2 mmHg from 8000 to 12,000 ft, Spo2 was similar when hyperventilating (94.7 ± 2.3% vs. 93.4 ± 4.3%, respectively). The only cardiovascular response was an increase in heart rate while hyperventilating. Altitude had no effect on cognitive impairment, but hyperventilation did.DISCUSSION: For many cardiovascular and respiratory variables, there is minimal difference in responses to hypoxia and hyperventilation, making these challenging to differentiate. Spo2 is not a reliable marker of environmental hypoxia in the presence of hyperventilation and should not be used as such without additional monitoring of minute ventilation and end-tidal gases.Haddon A, Kanhai J, Nako O, Smith TG, Hodkinson PD, Pollock RD. Cardiorespiratory responses to voluntary hyperventilation during normobaric hypoxia. Aerosp Med Hum Perform. 2023; 94(2):59-65.

Leveraging the HMBC to Facilitate Metabolite Identification.

The accuracy and ease of metabolite assignments from a complex mixture are expected to be facilitated by employing a multispectral approach. The two-dimensional (2D) 1H-13C heteronuclear single quantum coherence (HSQC) and 2D 1H-1H-total correlation spectroscopy (TOCSY) are the experiments commonly used for metabolite assignments. The 2D 1H-13C HSQC-TOCSY and 2D 1H-13C heteronuclear multiple-bond correlation (HMBC) are routinely used by natural products chemists but have seen minimal usage in metabolomics despite the unique information, the nearly complete 1H-1H and 1H-13C and spin systems provided by these experiments that may improve the accuracy and reliability of metabolite assignments. The use of a 13C-labeled feedstock such as glucose is a routine practice in metabolomics to improve sensitivity and to emphasize the detection of specific metabolites but causes severe artifacts and an increase in spectral complexity in the HMBC experiment. To address this issue, the standard HMBC pulse sequence was modified to include carbon decoupling. Nonuniform sampling was also employed for rapid data collection. A dataset of reference 2D 1H-13C HMBC spectra was collected for 94 common metabolites. 13C-13C spin connectivity was then obtained by generating a covariance pseudo-spectrum from the carbon-decoupled HMBC and the 1H-13C HSQC-TOCSY spectra. The resulting 13C-13C pseudo-spectrum provides a connectivity map of the entire carbon backbone that uniquely describes each metabolite and would enable automated metabolite identification.

Cyclic ADP ribose isomers: Production, chemical structures, and immune signaling.

Cyclic adenosine diphosphate (ADP)-ribose (cADPR) isomers are signaling molecules produced by bacterial and plant Toll/interleukin-1 receptor (TIR) domains via nicotinamide adenine dinucleotide (oxidized form) (NAD+) hydrolysis. We show that v-cADPR (2'cADPR) and v2-cADPR (3'cADPR) isomers are cyclized by O-glycosidic bond formation between the ribose moieties in ADPR. Structures of 2'cADPR-producing TIR domains reveal conformational changes that lead to an active assembly that resembles those of Toll-like receptor adaptor TIR domains. Mutagenesis reveals a conserved tryptophan that is essential for cyclization. We show that 3'cADPR is an activator of ThsA effector proteins from the bacterial antiphage defense system termed Thoeris and a suppressor of plant immunity when produced by the effector HopAM1. Collectively, our results reveal the molecular basis of cADPR isomer production and establish 3'cADPR in bacteria as an antiviral and plant immunity-suppressing signaling molecule.

The "Fragile" Urethra as a Predictor of Early Artificial Urinary Sphincter Erosion.

OBJECTIVES: To identify predictors of early artificial sphincter (AUS) erosion among a cohort of men with erosion, who underwent AUS placement by either university or community-based surgeons. METHODS: The records of all patients with AUS erosions, including men who underwent AUS placement at outside facilities, were retrospectively reviewed. A Cox proportional-hazards model for time to erosion was performed with the predictors being the components of a fragile urethra (history of radiation, prior AUS, prior urethroplasty), androgen deprivation therapy (ADT), trans-corporal (TC), and 3.5 cm cuff, controlling for other risk factors. Kaplan-Meier survival curves and log-rank test compared "fragile" urethras with "not fragile" urethras. All statistical analysis was done using R version 3.5.2. RESULTS: Of the 156 men included, 36% had undergone AUS placement in the community. Median time to erosion was 16.0 months (1.0-240.0 months), and 122 (78%) met at least one fragility criteria. Radiation (HR 2.36, 95% CI 1.52-3.64) and prior urethroplasty (HR 2.12, 95% CI 1.18-3.80) were independently associated with earlier time to erosion. The Kaplan-Meier estimates demonstrate 1- and 5-year survival rates of 76.5% and 50.0%, respectively, for "non-fragile" and 44.1% and 14.8% for "fragile" urethras (P < .0001). CONCLUSION: In a diverse cohort of men with AUS erosion, men with "fragile" urethras eroded sooner. Radiation and prior urethroplasty were independent risk factors for earlier time to erosion, but prior AUS, ADT, TC and 3.5 cm cuff were not.

Rapid automated validation, annotation and publication of SARS-CoV-2 sequences to GenBank.

Rapid response to the current coronavirus disease 2019 (COVID-19) pandemic requires fast dissemination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic sequence data in order to align diagnostic tests and vaccines with the natural evolution of the virus as it spreads through the world. To facilitate this, the National Library of Medicine's National Center for Biotechnology Information developed an automated pipeline for the deposition and quick processing of SARS-CoV-2 genome assemblies into GenBank for the user community. The pipeline ensures the collection of contextual information about the virus source, assesses sequence quality and annotates descriptive biological features, such as protein-coding regions and mature peptides. The process promotes standardized nomenclature and creates and publishes fully processed GenBank files within minutes of deposition. The software has processed and published 982 454 annotated SARS-CoV-2 sequences, as of 21 October 2021. This development addresses the needs of the scientific community as the sequencing of SARS-CoV-2 genomes increases and will facilitate unrestricted access to and usability of SARS-CoV-2 genomic sequence data, providing important reagents for scientific and public health activities in response to the COVID-19 pandemic. Database URL https://submit.ncbi.nlm.nih.gov/sarscov2/genbank/.

Defining Success after Anterior Urethroplasty: An Argument for a Universal Definition and Surveillance Protocol.

PURPOSE: A successful urethroplasty has been defined in different ways across studies. This variety in the literature makes it difficult to compare success rates and techniques across studies. We aim to evaluate the success of anterior urethroplasty based on different definitions of success in a single cohort. MATERIALS AND METHODS: Data were collected from a multi-institutional, prospectively maintained database. We included men undergoing first-time, single-stage, anterior urethroplasty between 2006 and 2020. Exclusion criteria included lack of followup, hypospadias, extended meatotomy, perineal urethrostomy, posterior urethroplasty and staged repairs. We compared 5 different ways to define a "failed" urethroplasty: 1) stricture retreatment, 2) anatomical recurrence on cystoscopy, 3) peak flow rate <15 ml/second, 4) weak stream on questionnaire and 5) failure by any of these measures. Kaplan-Meier survival curves were generated for each of the definitions. We also compared outcomes by stricture length, location and etiology. RESULTS: A total of 712 men met inclusion criteria, including completion of all types of followup. The 1- and 5-year estimated probabilities of success were "retreatment," 94% and 75%; "cystoscopy," 88% and 71%; "uroflow," 84% and 58%; "questionnaire," 67% and 37%; and "any failure," 57% and 23%. This pattern was inconsistent across stricture length, location and etiology. CONCLUSIONS: The estimated probability of success after first-time, anterior urethroplasty is highly dependent on the way success is defined. The variability in definitions in the literature has limited our ability to compare urethroplasty outcomes across studies.

Minimizing Antibiotic Use in Urethral Reconstruction.

PURPOSE: There are no established guidelines regarding management of antibiotics for patients specifically undergoing urethral reconstruction. Our aim was to minimize antibiotic use by following a standardized protocol in the pre-, peri- and postoperative setting, and adhere to American Urological Association antibiotic guidelines. We hypothesized that prolonged suppressive antibiotics post-urethroplasty does not prevent urinary tract infection and/or wound infection rates. MATERIALS AND METHODS: We prospectively treated 900 patients undergoing urethroplasty or perineal urethrostomy at 11 centers over 2 years. The first-year cohort A received prolonged postoperative antibiotics. Year 2, cohort B, did not receive prolonged antibiotics. A standardized protocol following the American Urological Association guidelines for perioperative antibiotics was used. The 30-day postoperative infectious complications were determined. We used chi-square analysis to compare the cohorts, and multivariate logistic regression to identify risk factors. RESULTS: The mean age of participants in both cohorts was 49.7 years old and the average stricture length was 4.09 cm. Overall, the rate of postoperative urinary tract infection and wound infection within 30 days was 5.1% (6.7% in phase 1 vs 3.9% in phase 2, p=0.064) and 3.9% (4.1% in phase 1 vs 3.7% in phase 2, p=0.772), respectively. Multivariate logistic regression analysis of patient characteristics and operative factors did not reveal any factors predictive of postoperative infections. CONCLUSIONS: The use of a standardized protocol minimized antibiotic use and demonstrated no benefit to prolonged antibiotic use. There were no identifiable risk factors when considering surgical characteristics. Given the concern of antibiotic over-prescription, we do not recommend prolonged antibiotic use after urethral reconstruction.

Urethroscopic Findings following Urethroplasty Predict the Need for Secondary Intervention in the Long Term: A Multi-Institutional Study from Trauma and Urologic Reconstructive Network of Surgeons.

PURPOSE: Postoperative surveillance urethroscopy has been shown to be an effective tool to predict reoperation within 1 year after urethroplasty. We aimed to evaluate early surveillance urethroscopy findings and long-term outcomes among urethroplasty patients in order to define the value of surveillance urethroscopy to predict failure. MATERIALS AND METHODS: We evaluated 304 patients with at least 4 years of followup after urethroplasty performed at 10 institutions across the United States and Canada. All patients were surveilled using a flexible 17Fr cystoscope and were categorized into 3 groups: 1) normal lumen, 2) large-caliber stricture (≥17Fr) defined as the ability of the cystoscope to easily pass the narrowing and 3) small-caliber stricture (<17Fr) that the cystoscope could not be passed. Failure was stricture recurrence requiring a secondary intervention. RESULTS: The median followup time was 64.4 months (range 55.3-80.6) and the time to initial surveillance urethroscopy was 3.7 months (range 3.1-4.8) following urethroplasty. Secondary interventions were performed in 29 of 194 (15%) with normal lumens, 11 of 60 (18.3%) with ≥17Fr strictures and 32 of 50 (64%) with <17Fr strictures (p <0.001). The 1-, 3- and 9-year cumulative probability of intervention was 0.01, 0.06 and 0.23 for normal, 0.05, 0.17 and 0.18 for ≥17Fr, and 0.32, 0.50 and 0.73 for <17Fr lumen groups, respectively. Patient-reported outcome measures performed poorly to differentiate the 3 groups. CONCLUSIONS: Early cystoscopic visualization of scar recurrence that narrows the lumen to <17Fr following urethroplasty is a significant long-term predictor for patients who will eventually undergo a secondary intervention.

Physiological Effects of Centrifuge-Simulated Suborbital Spaceflight.

BACKGROUND: High-G acceleration experienced during launch and re-entry of suborbital spaceflights may present challenges for older or medically susceptible participants. A detailed understanding of the associated physiological responses would support the development of an evidence-based medical approach to commercial suborbital spaceflight.METHODS: There were 24 healthy subjects recruited into 'younger' (18-44 yr), 'intermediate' (45-64 yr) and 'older' (65-80 yr) age groups. Cardiovascular and respiratory variables were measured continuously during dynamic combinations of +Gx (chest-to-back) and +Gz (head-to-foot) acceleration that simulated suborbital G profiles for spaceplane and rocket/capsule platforms. Measurements were conducted breathing air and breathing 15% oxygen to simulate a cabin pressure altitude of 8000 ft.RESULTS: Suborbital G profiles generated highly dynamic changes in heart rate, blood pressure, and cardiac output. G-induced hypoxemia was observed, with minimum arterial oxygen saturation < 80% in a quarter of subjects. Increased age was associated with greater hypoxemia and reduced cardiac output responses but did not have detrimental cardiovascular effects. ECG changes included recurrent G-induced trigeminy in one individual. Respiratory and visual symptoms were common, with 88% of subjects reporting greyout and 29% reporting blackout. There was one episode of G-induced loss of consciousness (G-LOC).DISCUSSION: Suborbital acceleration profiles are generally well tolerated but are not physiologically inconsequential. Marked hemodynamic effects and transient respiratory compromise could interact with predisposing factors to precipitate adverse cardiopulmonary effects in a minority of participants. Medically susceptible individuals may benefit from expanded preflight centrifuge familiarization that includes targeted physiological evaluation in the form of a 'G challenge test'.Smith TG, Pollock RD, Britton JK, Green NDC, Hodkinson PD, Mitchell SJ, Stevenson AT. Physiological effects of centrifuge-simulated suborbital spaceflight. Aerosp Med Hum Perform. 2022; 93(12):830-839.

Perioperative management including dual cell salvage in a Jehovah's Witness patient undergoing major urological surgery.

Complex surgery associated with major hemorrhage presents particular risks for Jehovah's Witnesses who do not accept transfusion of blood products. Intraoperative use of two cell saver machines simultaneously can maximize the yield of salvaged blood from both the operative field and from washed surgical swabs and can potentially be life-saving.

Oh G: The x, y and z of human physiological responses to acceleration.

NEW FINDINGS: What is the topic of this review? This review focuses on the main physiological challenges associated with exposure to acceleration in the Gx, Gy and Gz directions and to microgravity. What advances does it highlight? Our current understanding of the physiology of these environments and latest strategies to protect against them are discussed in light of the limited knowledge we have in some of these areas. ABSTRACT: The desire to go higher, faster and further has taken us to environments where the accelerations placed on our bodies far exceed or are much lower than that attributable to Earth's gravity. While on the ground, racing drivers of the fastest cars are exposed to high degrees of lateral acceleration (Gy) during cornering. In the air, while within the confines of the lower reaches of Earth's atmosphere, fast jet pilots are routinely exposed to high levels of acceleration in the head-foot direction (Gz). During launch and re-entry of suborbital and orbital spacecraft, astronauts and spaceflight participants are exposed to high levels of chest-back acceleration (Gx), whereas once in space the effects of gravity are all but removed (termed microgravity, µG). Each of these environments has profound effects on the homeostatic mechanisms within the body and can have a serious impact, not only for those with underlying pathology but also for healthy individuals. This review provides an overview of the main challenges associated with these environments and our current understanding of the physiological and pathophysiological adaptations to them. Where relevant, protection strategies are discussed, with the implications of our future exposure to these environments also being considered.