Safety evaluation of carbon tetrafluoride as an inert hyperbaric breathing gas in Sprague-Dawley rats.

Carbon tetrafluoride (CF4) is an inert gas with higher molecular weight and lower water solubility than commonly used hyperbaric breathing gases. These inert gas properties decrease time required to decompress and avoid decompression sickness after deep dives. To assess CF4 toxicity, Sprague-Dawley rats were exposed to 8 atm absolute (ATA) air (10 males, 10 females) or 8 ATA 79% CF4/21% O2 (25 males, 25 females). Exposures were 30 min daily for 5 days. Rat behavior was normal throughout the testing period. There were no gross or microscopic pathology abnormalities following repeat dose exposure. Male body weight trends were similar between groups. Female body weight trends were 0.5 ± 0.8% day-1 for hyperbaric air exposure and - 0.2 ± 0.8% day-1 for hyperbaric CF4 exposure (P = 0.01) but remained within literature cited norms. Organ weights and hematologic indices remained within or near literature normal ranges. Clinical chemistry panels showed no signs of toxicity in renal or hepatic biomarkers. Polychromatic erythrocyte micronucleus frequency showed no chromosomal damage. Comet assay showed no DNA damage in lung tissue. Females exposed to CF4 had 2.5 times greater percent tail DNA in liver tissue than controls (P = 0.009). However this result remained within the normal range of local negative controls. A bacterial reverse mutation assay with exposure to 1 ATA 79% CF4/21% O2 for 72 h was nonmutagenic in four strains of Salmonella typhimurium and one strain of Escherichia coli. Overall, there was no evidence that CF4 caused organ toxicity or genetic toxicity.

Urinary Calcium for Tracking Bone Loss and Kidney Stone Risk in Space.

INTRODUCTION: Urinary calcium (Uca) levels in space reflect bone loss and kidney stone risk and could be measured using portable devices. This project evaluated the repeatability of Uca measurements to assess how many repeated measurements would be needed to detect significant urinary calcium elevations in space.METHODS: A total of six subjects collected 24-h urine samples weekly for 8 wk and took 500 mg of oral calcium carbonate and 400 IU of vitamin D daily in week 7 and 8. Uca concentration was analyzed using a calcein-based system. The effect of the intake of calcium and vitamin D on Uca levels and the correlation between first void concentration and 24-h mass were assessed with linear mixed effect models. The reproducibility coefficient (RPC) for Uca was determined using Bland-Altman analysis on pairs of measurements at different time points.RESULTS: Oral supplementation did not significantly affect 24-h mass. First void concentration correlated with 24-h mass. The 24-h mass RPCs were 167.0, 116.8, and 108.1 mg for 1-, 2-, and 3-wk average measurements. First void concentration RPCs were 90.6, 76.6, and 72.8 mg L1. Skylab astronauts 24-h mass increased by 88.9 76.0, 123.5 58.3, 142.2 56.5, and 159.9 83.4 mg after 1, 2, 3, and 4 wk in flight.DISCUSSION: Averaging multiple Uca measurements reduced variability effectively and allowed increases likely to be seen in space to be detected. Consecutive Uca measurements could be tracked over time in space to assess the effectiveness of the countermeasure program. First void concentration could potentially be used rather than 24-h collections.Ren J, Stankovic AS, Knaus DA, Phillips SD, Kynor DB, Buckey JC. Urinary calcium for tracking bone loss and kidney stone risk in space. Aerosp Med Hum Perform. 2020; 91(9):689696.

Ocular changes over 60 min in supine and prone postures.

Some astronauts are returning from long-duration spaceflight with structural ocular and visual changes. We investigated both the transient and sustained effects of changes in the direction of the gravity vector acting on the eye using changes in body posture. Intraocular pressure (IOP; measured by Perkins tonometer), ocular geometry (axial length, corneal thickness, and aqueous depth-noncontact biometer), and the choroid (volume and subfoveal thickness optical coherence tomography) were measured in 10 subjects (5 males and 5 females). Measures were taken over the course of 60 min and analyzed with repeated-measures analysis of covariance to assess the effects of posture and time. In the supine position, choroidal volume increased significantly with time (average value at <5 min = 8.8 ± 2.3 mm3, 60 min = 9.0 ± 2.4 mm3, P = 0.03). In the prone position, IOP and axial length increased with time (IOP at <5 min 15 ± 2.7 mmHg, 60 min = 19.8 ± 4.1 mmHg, P < 0.0001; axial length at <5 min = 24.29 ± 0.77 mm, 60 min = 24.31 ± 0.76 mm, P = 0.002). Each increased exponentially, with time constants of 5.3 and 14 min, respectively. Prone corneal thickness also increased with time (<5 min = 528 ± 35 µm, 60 min = 537 ± 35 µm3, P < 0.001). Aqueous depth was shortened in the prone position (baseline = 3.22 ± 0.31 mm, 60 min = 3.18 ± 0.32 mm, P < 0.0001) but did not change with time. The data show that changes in the gravity vector have pronounced transient and sustained effects on the geometry and physiology of the eye.NEW & NOTEWORTHY We show that gravity has pronounced transient and sustained effects on the eye by making detailed ocular measurements over 60 min in the supine and prone postures. These data inform our understanding of how gravitational forces can affect ocular structures, which is essential for hypothesizing how ocular changes could occur with microgravity exposure.

Acute effects of changes to the gravitational vector on the eye.

Intraocular pressure (IOP) initially increases when an individual enters microgravity compared with baseline values when an individual is in a seated position. This has been attributed to a headward fluid shift that increases venous pressures in the head. The change in IOP exceeds changes measured immediately after moving from seated to supine postures on Earth, when a similar fluid shift is produced. Furthermore, central venous and cerebrospinal fluid pressures are at or below supine position levels when measured initially upon entering microgravity, unlike when moving from seated to supine postures on Earth, when these pressures increase. To investigate the effects of altering gravitational forces on the eye, we made ocular measurements on 24 subjects (13 men, 11 women) in the seated, supine, and prone positions in the laboratory, and upon entering microgravity during parabolic flight. IOP in microgravity (16.3 ± 2.7 mmHg) was significantly elevated above values in the seated (11.5 ± 2.0 mmHg) and supine (13.7 ± 3.0 mmHg) positions, and was significantly less than pressure in the prone position (20.3 ± 2.6 mmHg). In all measurements,P< 0.001. Choroidal area was significantly increased in subjects in a microgravity environment (P< 0.007) compared with values from subjects in seated (increase of 0.09 ± 0.1 mm(2)) and supine (increase of 0.06 ± 0.09 mm(2)) positions. IOP results are consistent with the hypothesis that hydrostatic gradients affect IOP, and may explain how IOP can increase beyond supine values in microgravity when central venous and intracranial pressure do not. Understanding gravitational effects on the eye may help develop hypotheses for how microgravity-induced visual changes develop.

Laparoscopic surface scanning and subsurface targeting: implications for image-guided laparoscopic liver surgery.

Segmental liver resection and locoregional ablative therapies are dependent upon accurate tumor localization to ensure safety as well as acceptable oncologic results. Because of the liver's limited external landmarks and complex internal anatomy, such tumor localization poses a technical challenge. Image guided therapies (IGT) address this problem by mapping the real-time, intraoperative position of surgical instruments onto preoperative tomographic imaging through a process called registration. Accuracy is critical to IGT and is a function of: 1) the registration technique, 2) the tissue characteristics, and 3) imaging techniques. The purpose of this study is to validate a novel method of registration using an endoscopic Laser Range Scanner (eLRS) and demonstrate its applicability to laparoscopic liver surgery. Six radiopaque targets were inserted into an ex-vivo bovine liver and a computed tomography (CT) scan was obtained. Using the eLRS, the liver surface was scanned and a surface-based registration was constructed to predict the position of the intraparenchymal targets. The target registration error (TRE) achieved using our surface-based registration was 2.4 +/- 1.0 mm. A comparable TRE using traditional fiducial-based registration was 2.6 +/- 1.7 mm. Compared to traditional fiducial-based registration, laparoscopic surface scanning is able to predict the location of intraparenchymal liver targets with similar accuracy and rate of data acquisition.

Dual-frequency ultrasound for detecting and sizing bubbles.

ISS construction and Mars exploration require extensive extravehicular activity (EVA), exposing crewmembers to increased decompression sickness risk. Improved bubble detection technologies could help increase EVA efficiency and safety. Creare Inc. has developed a bubble detection and sizing instrument using dual-frequency ultrasound. The device emits "pump" and "image" signals at two frequencies. The low-frequency pump signal causes an appropriately-sized bubble to resonate. When the image frequency hits a resonating bubble, mixing signals are returned at the sum and difference of the two frequencies. To test the feasibility of transcutaneous intravascular detection, intravascular bubbles in anesthetized swine were produced using agitated saline and decompression stress. Ultrasonic transducers on the chest provided the two frequencies. Mixing signals were detected transthoracically in the right atrium using both methods. A histogram of estimated bubble sizes could be constructed. Bubbles can be detected and sized transthoracically in the right atrium using dual-frequency ultrasound.