Space Flight-Induced Intracranial Hypertension: An Ophthalmic Review

Background: Although physiologic and pathologic changes associated with microgravity exposure have been studied extensively, the effect of this environment on the eye is largely unknown. Over the last several years, NASA s Space Medicine Division has documented astronauts presenting with varying degrees of disc edema, globe flattening, choroidal folds, cotton wool spots, and hyperopic shifts after long-duration space flight. Methods: Before and after long-duration space flight, six astronauts underwent complete eye examinations to include cycloplegic and/or manifest refraction and fundus photography. Five of these astronauts had Optical Coherence Tomography (OCT) and Magnetic Resonance Imaging (MRI) performed following their missions. Results: Following exposure to space flight of approximately 6-months duration, six astronauts had neuro-ophthalmic findings. These consisted of disc edema in four astronauts, globe flattening in four astronauts, choroidal folds in four astronauts, cotton wool spots in three astronauts, nerve fiber layer thickening by OCT in five astronauts, and decreased near vision in five astronauts. Four of the astronauts with near vision complaints had a hyperopic shift equal to or greater than + 0.50D between pre- and post-mission spherical equivalent refraction in one or both eyes (range +0.50D to +1.50D). These same four had globe flattening by MRI. Conclusions: The findings we describe may have resulted from a rise in intracranial pressure caused by microgravity fluid shifts, and could represent parts of a spectrum of ocular and cerebral responses to extended microgravity

Vision Changes after Space Flight Are Related to Alterations in Folate-Dependent One-Carbon Metabolism

About 20% of astronauts on International Space Station missions have developed measurable ophthalmic changes after flight. This study was conducted to determine whether the folate-dependent 1-carbon pathway is altered in these individuals. Data were modeled to evaluate differences between individuals with ophthalmic changes (n=5) and those without them (n=15). We also correlated mean preflight serum concentrations of the 1-carbon metabolites with changes in measured refraction after flight. Serum homocysteine (HCy), cystathionine, 2-methylcitric acid, and methylmalonic acid concentrations were 25%-45% higher (P<0.001) in astronauts with ophthalmic changes than in those without them. These differences existed before, during, and after flight. Preflight serum HCy and cystathionine, and in-flight serum folate, were significantly (P<0.05) correlated with postflight change in refraction, and preflight serum concentrations of 2-methylcitric acid tended to be associated (P=0.06) with ophthalmic changes. The biochemical differences observed in those with vision issues strongly suggests impairment of the folate-dependent 1-carbon transfer pathway. Impairment of this pathway, by polymorphisms, diet or other means, may interact with components of the microgravity environment to influence these pathophysiologic changes. This study was funded by the NASA Human Research Program

Microbial load of rinsed and unrinsed body cavities of roe deer (Capreolus capreolus) on the killing day and after cold storage: A preliminary investigation

Ensuring good game meat hygiene is a challenge in the hunting supply chain. Game carcasses can be soiled with intestinal contents or other substances from the environment due to hunting and handling practices. This soiling can increase the microbial load (ML) of the carcass and the resulting game meat. The aim of this study was to investigate whether rinsing of soiled and unsoiled body cavities with drinking water can reduce the ML of carcasses. Carcasses of 23 roe deer (Capreolus capreolus) were processed, either rinsed (n = 12) or unrinsed (n = 11), and examined for ML. Swab and muscle samples were taken from the carcasses at killing day and after 3 days of cold storage. The levels of ML were comparable for the rinsed and unrinsed roe deer carcasses with an increase of Pseudomonas spp. during cold storage. Initial ML seems to be independent of visible soiling. Other factors affecting the initial ML should be determined in future studies

Apparent non-canonical trans-splicing is generated by reverse transcriptase in vitro

Trans-splicing, the in vivo joining of two RNA molecules, is well characterized in several groups of simple organisms but was long thought absent from fungi, plants and mammals. However, recent bioinformatic analyses of expressed sequence tag (EST) databases suggested widespread trans-splicing in mammals^1-2^. Splicing, including the characterised trans-splicing systems, involves conserved sequences at the splice junctions. Our analysis of a yeast non-coding RNA revealed that around 30% of the products of reverse transcription lacked an internal region of 117 nt, suggesting that the RNA was spliced. The junction sequences lacked canonical splice-sites but were flanked by direct repeats, and further analyses indicated that the apparent splicing actually arose because reverse transcriptase can switch templates during transcription^3^. Many newly identified, apparently trans-spliced, RNAs lacked canonical splice sites but were flanked by short regions of homology, leading us to question their authenticity. Here we report that all reported categories of non-canonical splicing could be replicated using an in vitro reverse transcription system with highly purified RNA substrates. We observed the reproducible occurrence of ostensible trans-splicing, exon shuffling and sense-antisense fusions. The latter generate apparent antisense non-coding RNAs, which are also reported to be abundant in humans^4^. Different reverse transcriptases can generate different products of template switching, providing a simple diagnostic. Many reported examples of splicing in the absence of canonical splicing signals may be artefacts of cDNA preparation

Cause and Effect Analysis between Influencing Factors Related to Environmental Conditions, Hunting and Handling Practices and the Initial Microbial Load of Game Carcasses

Environmental, hunting and handling factors affect the microbial load of hunted game and the resulting meat products. The aim of this study was to systematically investigate the influence of several factors on the initial microbial load (IML) of game carcasses during the early hunting chain. Eviscerated roe deer body cavities (n = 24) were investigated in terms of total viable count and the levels of Pseudomonas spp., Lactobacillus spp., Enterobacteriaceae and Escherichia coli (E. coli). Furthermore, a risk analysis based on the obtained original IML data, literature search and a Failure Mode and Effects Analysis (FMEA) was performed. The IML could be explained in a regression model by factors including the higher body weight (BW), damaged gastrointestinal tract by the shot, ambient temperature or rain. The levels of Lactobacillus spp. (p = 0.0472), Enterobacteriaceae (p = 0.0070) and E. coli (p = 0.0015) were lower on the belly flap surface when gloves were used during evisceration. The literature search revealed that studies examining influencing factors (IF) on the IML of game carcasses found contradictory effects of the comparable IF on IML. Potential handling failures may lead to a higher IML of game carcasses during the early hunting chain ranked by FMEA. Several handling practices for game carcasses are recommended, such as ensuring efficient cooling of heavier BW carcasses to limit bacterial growth or eviscerating heavier carcasses before lighter ones

Evidence Report: Risk of Spaceflight Associated Neuro-ocular Syndrome (SANS)

A subset of astronauts develop neuro-ocular structural and functional changes during prolonged periods of spaceflight that may lead to additional neurologic and ocular consequences upon return to Earth

The HIPASS Catalogue - II. Completeness, Reliability, and Parameter Accuracy

The HI Parkes All Sky Survey (HIPASS) is a blind extragalactic HI 21-cm emission line survey covering the whole southern sky from declination -90 to +25. The HIPASS catalogue (HICAT), containing 4315 HI-selected galaxies from the region south of declination +2, is presented in Meyer et al. (2004a, Paper I). This paper describes in detail the completeness and reliability of HICAT, which are calculated from the recovery rate of synthetic sources and follow-up observations, respectively. HICAT is found to be 99 per cent complete at a peak flux of 84 mJy and an integrated flux of 9.4 Jy km/s. The overall reliability is 95 per cent, but rises to 99 per cent for sources with peak fluxes >58 mJy or integrated flux > 8.2 Jy km/s. Expressions are derived for the uncertainties on the most important HICAT parameters: peak flux, integrated flux, velocity width, and recessional velocity. The errors on HICAT parameters are dominated by the noise in the HIPASS data, rather than by the parametrization procedure.Comment: Accepted for publication in MNRAS. 12 pages, 11 figures. Paper with higher resolution figures can be downloaded from http://hipass.aus-vo.or

Changes in the Optic Nerve Head and Choroid Over 1 Year of Spaceflight

Importance: While 6-month data are available regarding spaceflight-associated neuro-ocular syndrome, manned missions for 1 year and beyond are planned, warranting evaluation for spaceflight-associated neuro-ocular syndrome beyond 6 months. Objective: To determine if the manifestation of spaceflight-associated neuro-ocular syndrome worsens during International Space Station missions exceeding the present 4- to 6-month duration. Design, Setting, and Participants: The One-Year Mission Study used quantitative imaging modalities to investigate changes in ocular structure in 2 crew members who completed a 1-year-long spaceflight mission. This study investigated the ocular structure of crew members before, during, and after their mission on the International Space Station. Two crew members participated in this study from March 2015 to September 2016. Analysis began in March 2015 and ended in May 2020. Exposures: Crew members were tested before, during, and up to 1 year after spaceflight. Main Outcomes and Measures: This study compares ocular changes (peripapillary retinal edema, axial length, anterior chamber depth, and refraction) in two 1-year spaceflight mission crew members with cohort crew members from a 6-month mission (n = 11). Minimum rim width (the shortest distance between Bruch membrane opening and the internal limiting membrane) and peripapillary total retinal thickness were measured using optical coherence tomography. Results: Both crew members were men. Minimum rim width and total retinal thickness increased in both participants throughout the duration of spaceflight exposure to the maximal observed change from preflight (minimum rim width: participant 1, 561 [+149 from preflight] μm at flight day 270; participant 2, 539 [+56 from preflight] μm at flight day 270; total retinal thickness: participant 1, 547 [+135 from preflight] μm at flight day 90; participant 2, 528 [+45 from preflight] μm at flight day 210). Changes in peripapillary choroid engorgement, axial length, and anterior chamber depth appeared similar between the 1-year mission participants and a 6-month mission cohort. Conclusions and Relevance: This report documents the late development of mild optic disc edema in 1 crew member and the progressive development of choroidal folds and optic disc edema in another crew member over the duration of 1 year in low Earth orbit aboard the International Space Station. Previous reports characterized the ocular risk associated with 4 to 6 months of spaceflight. As future spaceflight missions are planned to increase in duration and extend beyond low Earth orbit, further observation of astronaut ocular health on spaceflight missions longer than 6 months in duration may be warranted

UBVRI Light Curves of 44 Type Ia Supernovae

We present UBVRI photometry of 44 type-Ia supernovae (SN Ia) observed from 1997 to 2001 as part of a continuing monitoring campaign at the Fred Lawrence Whipple Observatory of the Harvard-Smithsonian Center for Astrophysics. The data set comprises 2190 observations and is the largest homogeneously observed and reduced sample of SN Ia to date, nearly doubling the number of well-observed, nearby SN Ia with published multicolor CCD light curves. The large sample of U-band photometry is a unique addition, with important connections to SN Ia observed at high redshift. The decline rate of SN Ia U-band light curves correlates well with the decline rate in other bands, as does the U-B color at maximum light. However, the U-band peak magnitudes show an increased dispersion relative to other bands even after accounting for extinction and decline rate, amounting to an additional ~40% intrinsic scatter compared to B-band.Comment: 84 authors, 71 pages, 51 tables, 10 figures. Accepted for publication in the Astronomical Journal. Version with high-res figures and electronic data at http://astron.berkeley.edu/~saurabh/cfa2snIa

Pharmacokinetic Properties of Liraglutide as Adjunct to Insulin in Subjects with Type 1 Diabetes Mellitus.

BACKGROUND: The pharmacokinetic properties of liraglutide, a glucagon-like peptide-1 receptor agonist approved for the treatment of type 2 diabetes mellitus (T2D), have been established in healthy individuals and subjects with T2D. Liraglutide has been under investigation as adjunct treatment to insulin in type 1 diabetes mellitus (T1D). This single-center, double-blind, placebo-controlled, crossover, clinical pharmacology trial is the first to analyze the pharmacokinetic properties of liraglutide as add-on to insulin in T1D. METHODS: Subjects (18-64 years; body mass index 20.0-28.0 kg/m(2); glycated hemoglobin ≤9.5 %) were randomized 1:1:1 to 0.6, 1.2, or 1.8 mg liraglutide/placebo. Each group underwent two 4-week treatment periods (liraglutide then placebo or placebo then liraglutide) separated by a 2- to 3-week washout. Both trial drugs were administered subcutaneously, once daily, as adjunct to insulin. A stepwise hypoglycemic clamp was performed at the end of each treatment period (data reported previously). Pharmacokinetic endpoints were derived from liraglutide concentration-time curves after the final dose and exposure was compared with data from previous trials in healthy volunteers and subjects with T2D. RESULTS: The pharmacokinetic properties of liraglutide in T1D were comparable with those observed in healthy volunteers and subjects with T2D. Area under the steady-state concentration-time curve (AUC) and maximum plasma concentration data were consistent with dose proportionality of liraglutide. Comparison of dose-normalized liraglutide AUC suggested that exposure in T1D, when administered with insulin, is comparable with that observed in T2D. CONCLUSIONS: Liraglutide, administered as adjunct to insulin in subjects with T1D, shows comparable pharmacokinetics to those in subjects with T2D. ClinicalTrials.gov Identifier: NCT01536665