Influence of Exercise Modality on Cerebral-Ocular Hemodynamics and Pressures

Background: Moderate and high intensity aerobic or resistance exercise has clearly identified benefits for cardiac, muscle, and bone health. However, the impact of such exercise - either as a mitigating or an exacerbating factor - on the development of the visual impairment and intracranial pressure syndrome (VIIP) is unknown. Accordingly, our aim was to characterize the effect of an acute bout of resistance (RE), moderate-intensity continuous (CE), and high-intensity interval exercise (IE) during a cephalad fluid shift on cerebral-ocular hemodynamics and pressures. Methods: 10 male subjects (36 plus or minus 9 years) completed 4 testing days in a 15 degree head-down tilt (HDT): (1) assessment of maximum volume of O (sub 2), (2) RE session (4 sets of 12 repetition maximum leg press exercise), (3) CE session (30 minutes of cycling at 60 percent maximum volume of O (sub 2)), and (4) IE session (4 by 4-minute intervals of exercise at 85 percent maximum volume of O (sub 2) with 3-minute active rest periods). During each session, blood flow (Vivid-e, GE Healthcare) in extracranial arteries (common carotid artery, CCA; internal carotid artery, ICA; external carotid artery, ECA and vertebral artery, VA), and mean blood flow velocity in middle cerebral artery (MCA), internal jugular pressure (IJP; VeinPress), and intraocular pressure (IOP; Icare PRO) were measured at rest, at the end of each resistance or interval set, and every 5 minutes during continuous exercise. Translaminar pressure gradient (TLPG) was estimated by subtracting IJP from IOP. Results: There were no differences across days in pre-exercise resting blood flows or pressures. IOP decreased slightly from HDT rest (20.2 plus or minus 2.3 millimeters of mercury) to exercise (RE: 19.2 plus or minus 2.8 millimeters of mercury; CE: 18.9 plus or minus 3.2 millimeters of mercury; IE: 20.1 plus or minus 2.8 millimeters of mercury), while IJP decreased during CE (31.6 plus or minus 9.5 millimeters of mercury) and RE (32.0 plus or minus 8.1 millimeters of mercury), and increased during IE (35.1 plus or minus 9.5 millimeters of mercury) from HDT rest (33.3 plus or minus 6.5 millimeters of mercury). Estimated TLPG was increased during IE only. Compared to RE and CE, IE resulted in the greatest increase in MCA blood flow velocity and extracranial artery blood flow. Conclusions: These preliminary results suggest that high-intensity IE acutely increases cerebral blood flow, IJP, and TLPG. Alterations in TLPG is one mechanism that may contribute to optic nerve sheath edema in astronauts. Accordingly, acutely raising IOP and/or orbital pressure during exercise could optimize cerebral-ocular pressures during spaceflight

Predicting postoperative troponin in patients undergoing elective hip or knee arthroplasty: A comparison of five cardiac risk prediction tools

BACKGROUND: Elderly patients undergoing hip or knee arthroplasty are at a risk for myocardial injury after noncardiac surgery (MINS). We evaluated the ability of five common cardiac risk scores, alone or combined with baseline high-sensitivity cardiac troponin I (hs-cTnI), in predicting MINS and postoperative day 2 (POD2) hs-cTnI levels in patients undergoing elective total hip or knee arthroplasty. METHODS: This study is ancillary to the Genetics-InFormatics Trial (GIFT) of Warfarin Therapy to Prevent Deep Venous Thrombosis, which enrolled patients 65 years and older undergoing elective total hip or knee arthroplasty. The five cardiac risk scores evaluated were the atherosclerotic cardiovascular disease calculator (ASCVD), the Framingham risk score (FRS), the American College of Surgeon\u27s National Surgical Quality Improvement Program (ACS-NSQIP) calculator, the revised cardiac risk index (RCRI), and the reconstructed RCRI (R-RCRI). RESULTS: None of the scores predicted MINS in women. Among men, the ASCVD ( CONCLUSION: In elderly patients undergoing elective hip or knee arthroplasty, several of the scores modestly predicted MINS in men and correlated with POD2 hs-cTnI

Examining the Relationship between Community Orientation and Hospital Financial Performance

A community orientation strategy may be a socially responsible way for hospitals to simultaneously improve financial performance and community health, in accordance with the Affordable Care Act. Using data from the AHA Annual Survey, AHRF, and CMS Cost Reports, this study examined the association between hospital community orientation and three measures of financial performance, and whether that relationship differs for some types of hospitals. The analysis revealed that hospital community orientation was positively associated with total margin and that not-for-profit hospitals engaging in higher levels of community orientation experienced lower operating margins, on average, relative to for-profit hospital

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

Defining the Relationship Between Biomarkers of Oxidative and Inflammatory Stress and the Risk for Atherosclerosis in Astronauts During and After Long-Duration Spaceflight

Future human space travel will primarily consist of long-duration missions aboard the International Space Station (ISS) or exploration class missions to Mars, its moons, or nearby asteroids. These missions will expose astronauts to increased risk of oxidative and inflammatory damage primarily from radiation, but also from psychological stress, reduced physical activity, diminished nutritional status, and, in the case of extravehicular activity, hyperoxic exposure. There is evidence that increased oxidative damage and inflammation can accelerate the development of atherosclerosis. PURPOSE The purpose of this proposal is to identify biomarkers of oxidative and inflammatory stress and to correlate them to indices of atherosclerosis risk before, during, and after long-duration spaceflight. METHODS To meet the objectives of the study, we will study astronauts before, during, and up to 5 years after long-duration missions aboard ISS. Biomarkers of oxidative and inflammatory stress, some of which we have previously shown to be elevated with spaceflight, will be measured before, during, and after spaceflight. Arterial structure will be monitored using ultrasound to measure carotid intima-medial thickness before, during, and after weightlessness. Carotid intima-medial thickness has been shown to be a better indicator than Framingham Risk scores for prediction of atherosclerosis. Arterial function will be monitored using brachial flow-mediated dilation before flight and after landing. Brachial flow-mediated dilation is a good index of endothelium-dependent vasodilation, which is a sensitive predictor of atherosclerotic risk. This is the first study to propose assessing atherosclerotic risk using biochemical, structural, and functional measures before, during, and immediately after spaceflight and structural functional measures for up to 5 years after landing. EXPECTED RESULTS We hypothesize that these biomarkers of oxidative and inflammatory stress will be increased with spaceflight and will correlate with increased carotid intima-medial thickness in- and postflight and with decreased flow-mediated dilation after the mission. Furthermore, we hypothesize that measures of oxidative stress will return to baseline after flight, but that biomarkers of inflammatory stress and vascular indices of atherosclerosis risk will remain elevated

Top Quark Physics at the Tevatron

The discovery of the top quark in 1995, by the CDF and D0 collaborations at the Fermilab Tevatron, marked the dawn of a new era in particle physics. Since then, enormous efforts have been made to study the properties of this remarkable particle, especially its mass and production cross section. In this article, we review the status of top quark physics as studied by the two collaborations using the p-pbar collider data at sqrt(s) = 1.8 TeV. The combined measurement of the top quark mass, m_t = 173.8 +- 5.0 GeV/c^2, makes it known to a fractional precision better than any other quark mass. The production cross sections are measured as sigma (t-tbar) = 7.6 -1.5 +1.8 pb by CDF and sigma (t-tbar) = 5.5 +- 1.8 pb by D0. Further investigations of t-tbar decays and future prospects are briefly discussed.Comment: 119 pages, 59 figures, 17 tables Submitted to Int. J. Mod. Phys. A Fixed some minor error

T-cell activation is enhanced by targeting IL-10 cytokine production in toll-like receptor-stimulated macrophages

Toll-like receptor (TLR) agonists represent potentially useful cancer vaccine adjuvants in their ability to stimulate antigen-presenting cells (APCs) and subsequently amplify the cytotoxic T-cell response. The purpose of this study was to characterize APC responses to TLR activation and to determine the subsequent effect on lymphocyte activation. We exposed murine primary bone marrow-derived macrophages to increasing concentrations of agonists to TLRs 2, 3, 4, and 9. This resulted in a dose-dependent increase in production of not only tumor necrosis factor–alpha (TNF-α), a surrogate marker of the proinflammatory response, but also interleukin 10 (IL-10), a well-described inhibitory cytokine. Importantly, IL-10 secretion was not induced by low concentrations of TLR agonists that readily produced TNF-α. We subsequently stimulated lymphocytes with anti-CD3 antibody in the presence of media from macrophages activated with higher doses of TLR agonists and observed suppression of interferon gamma release. Use of both IL-10 knockout macrophages and IL-10 small-interfering RNA (siRNA) ablated this suppressive effect. Finally, IL-10 siRNA was successfully used to suppress CpG-induced IL-10 production in vivo. We conclude that TLR-mediated APC stimulation can induce a paradoxical inhibitory effect on T-cell activation mediated by IL-10

Vision Issues and Space Flight: Evaluation of One-Carbon Metabolism Polymorphisms

Intermediates of the one-carbon metabolic pathway are altered in astronauts who experience vision-related issues during and after space flight. Serum concentrations of homocysteine, cystathionine, 2-methylcitric acid, and methylmalonic acid were higher in astronauts with ophthalmic changes than in those without (Zwart et al., J Nutr, 2012). These differences existed before, during, and after flight. Potential confounding factors did not explain the differences. Genetic polymorphisms could contribute to these differences, and could help explain why crewmembers on the same mission do not all have ophthalmic issues, despite the same environmental factors (e.g., microgravity, exercise, diet). A follow-up study was conducted to evaluate 5 polymorphisms of enzymes in the one-carbon pathway, and to evaluate how these relate to vision and other ophthalmic changes after flight. Preliminary evaluations of the genetic data indicate that all of the crewmembers with the MTRR GG genotype had vision issues to one degree or another. However, not everyone who had vision issues had this genetic polymorphism, so the situation is more complex than the involvement of this single polymorphism. Metabolomic and further data analyses are underway to clarify these findings, but the preliminary assessments are promising

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

Increased R2* in the Caudate Nucleus of Asymptomatic Welders

Welding has been associated with neurobehavioral disorders. Welding fumes contain several metals including copper (Cu), manganese (Mn), and iron (Fe) that may interact to influence welding-related neurotoxicity. Although welding-related airborne Fe levels are about 10-fold higher than Mn, previous studies have focused on Mn and its accumulation in the basal ganglia. This study examined differences in the apparent transverse relaxation rates [R2* (1/T2*), estimate of Fe accumulation] in the basal ganglia (caudate nucleus, putamen, and globus pallidus) between welders and controls, and the dose–response relationship between estimated Fe exposure and R2* values. Occupational questionnaires estimated recent and lifetime Fe exposure, and blood Fe levels and brain magnetic resonance imaging (MRI) were obtained. Complete exposure and MRI R2* and R1 (1/T1: measure to estimate Mn accumulation) data from 42 subjects with welding exposure and 29 controls were analyzed. Welders had significantly greater exposure metrics and higher whole-blood Fe levels compared with controls. R2* in the caudate nucleus was significantly higher in welders after controlling for age, body mass index, respirator use, caudate R1, and blood metals of Cu and Mn, whereas there was no difference in R1 values in the basal ganglia between groups. The R2* in the caudate nucleus was positively correlated with whole-blood Fe concentration. This study provides the first evidence of higher R2* in the caudate nucleus of welders, which is suggestive of increased Fe accumulation in this area. Further studies are needed to replicate the findings and determine the neurobehavioral relevance