Vestibular and Cardiovascular Responses After Long-Duration Spaceflight.

BACKGROUND: The vestibulo-sympathetic reflex operates during orthostatically challenging movements to initiate cardiovascular responses in advance of a baroreceptor-mediated response. The objective of this study was to determine whether there was an association between changes in vestibular function and cardiovascular responses during a prone-to-stand movement in astronauts after return from long-duration spaceflight.METHODS: Thirteen crewmembers who participated in International Space Station missions were tested before spaceflight and 1 d after landing. Vestibular function was evaluated by computerized dynamic posturography while their head was erect and while they performed dynamic head tilts. Heart rate and mean arterial blood pressure were measured while the subjects were in prone and standing positions.RESULTS: The 21.4% increase in the astronauts' heart rate during the prone to stand maneuver after spaceflight correlated significantly with their spaceflight-induced 48.7% decrease in postural stability during dynamic head tilts. The larger mean arterial pressure in the prone position after spaceflight compared to preflight (+7%) also correlated with the postflight decrease in postural stability during dynamic head tilts.CONCLUSION: These results indicate that an appropriate vestibular function is important to evoke optimum vestibulo-sympathetic response during orthostatically challenging voluntary movements performed after spaceflight. They also suggest that there may be a greater need to generate an anticipatory cardiovascular response after spaceflight.Deshpande N, Laurie SS, Lee SMC, Miller CA, Mulavara AP, Peters BT,Reschke MF, Stenger MB, Taylor LC, Wood SJ, Clément GR, Bloomberg JJ. Vestibular and cardiovascular responses after long-duration spaceflight. Aerosp Med Hum Perform. 2020; 91(8):621-627.

Functional Task and Balance Performance in Bed Rest Subjects and Astronauts.

INTRODUCTION: The purpose of this study was to determine how short- and long-duration spaceflight affects astronauts' performance on functional tests that challenge the balance control system (Seated Egress and Walk; Object Translation; Recovery from Fall/Stand; and Jump Down) and on clinical tests of balance function (Computerized Dynamic Posturography and Tandem Walk). In addition, we examined how exercise affects functional performance after long-term axial body unloading during 70 d of bed rest at 6° head-down tilt. METHODS: Data were collected twice during the 2-mo period before spaceflight or during the 2-wk period before bed rest, and four times after flight or bed rest: on the day of landing or the day bed rest ended, 1 d and 6 d later, and a final session 12 d after bed rest or 30 d after spaceflight. RESULTS: For bed rest subjects, long-term axial unloading alone caused functional performance deficits immediately after bed rest. However, the addition of an exercise regimen did not significantly improve median functional performance immediately after this axial unloading. For spaceflight subjects, the length of the space mission was directly related to the severity of functional performance deficits within 1 d of landing and during the subsequent recovery period after flight. DISCUSSION: The performance data suggest that an additional sensorimotor-based countermeasure may be necessary to maintain functional performance at preflight levels immediately after spaceflight.Miller CA, Kofman IS, Brady RR, May-Phillips TR, Batson CD, Lawrence EL, Taylor LC, Peters BT, Mulavara AP, Feiveson AH, Reschke MF, Bloomberg JJ. Functional task and balance performance in bed rest subjects and astronauts. Aerosp Med Hum Perform. 2018; 89(9):805-815.

Physiological and Functional Alterations after Spaceflight and Bed Rest.

INTRODUCTION: Exposure to microgravity causes alterations in multiple physiological systems, potentially impacting the ability of astronauts to perform critical mission tasks. The goal of this study was to determine the effects of spaceflight on functional task performance and to identify the key physiological factors contributing to their deficits. METHODS: A test battery comprised of seven functional tests and 15 physiological measures was used to investigate the sensorimotor, cardiovascular, and neuromuscular adaptations to spaceflight. Astronauts were tested before and after 6-month spaceflights. Subjects were also tested before and after 70 d of 6° head-down bed rest, a spaceflight analog, to examine the role of axial body unloading on the spaceflight results. These subjects included control and exercise groups to examine the effects of exercise during bed rest. RESULTS: Spaceflight subjects showed the greatest decrement in performance during functional tasks that required the greatest demand for dynamic control of postural equilibrium which was paralleled by similar decrements in sensorimotor tests that assessed postural and dynamic gait control. Other changes included reduced lower limb muscle performance and increased HR to maintain blood pressure. Exercise performed during bed rest prevented detrimental change in neuromuscular and cardiovascular function; however, both bed rest groups experienced functional and balance deficits similar to spaceflight subjects. CONCLUSION: Bed rest data indicate that body support unloading experienced during spaceflight contributes to postflight postural control dysfunction. Further, the bed rest results in the exercise group of subjects confirm that resistance and aerobic exercises performed during spaceflight can play an integral role in maintaining neuromuscular and cardiovascular functions, which can help in reducing decrements in functional performance. These results indicate that a countermeasure to mitigate postflight postural control dysfunction is required to maintain functional performance.

Breast Cancer Neoantigens Can Induce CD8+ T-Cell Responses and Antitumor Immunity.

Next-generation sequencing technologies have provided insights into the biology and mutational landscape of cancer. Here, we evaluate the relevance of cancer neoantigens in human breast cancers. Using patient-derived xenografts from three patients with advanced breast cancer (xenografts were designated as WHIM30, WHIM35, and WHIM37), we sequenced exomes of tumor and patient-matched normal cells. We identified 2,091 (WHIM30), 354 (WHIM35), and 235 (WHIM37) nonsynonymous somatic mutations. A computational analysis identified and prioritized HLA class I-restricted candidate neoantigens expressed in the dominant tumor clone. Each candidate neoantigen was evaluated using peptide-binding assays, T-cell cultures that measure the ability of CD8+ T cells to recognize candidate neoantigens, and preclinical models in which we measured antitumor immunity. Our results demonstrate that breast cancer neoantigens can be recognized by the immune system, and that human CD8+ T cells enriched for prioritized breast cancer neoantigens were able to protect mice from tumor challenge with autologous patient-derived xenografts. We conclude that next-generation sequencing and epitope-prediction strategies can identify and prioritize candidate neoantigens for immune targeting in breast cancer. Cancer Immunol Res; 5(7); 516-23. ©2017 AACR.

Dynamic visual acuity during walking after long-duration spaceflight.

INTRODUCTION: Astronauts experience alterations in gaze control as a result of adaptive changes in eye-head coordination produced by microgravity exposure. This may lead to potential changes in postflight visual acuity during head and body motion. METHODS: We gathered dynamic visual acuity (DVA) data from 14 astronauts and cosmonauts after long-duration (approximately 6 mo) stays in space. Walking was used to induce self-motion and visual acuity was determined by sequentially presenting Landolt ring optotypes on a computer display placed 4 m in front of subjects. Acuity assessments were made while seated (static condition) and walking (dynamic condition) at 6.4 km x h(-1) on a motorized treadmill. In each condition, a psychophysical threshold detection algorithm minimized the required number of optotype presentations by maximizing the amount displayed around the subject's acuity threshold. The difference between static and dynamic acuity measures provided a metric of change in the subjects' ability to maintain gaze fixation on the visual target while walking. RESULTS: A decrement in postflight visual acuity during walking was found. A mean dynamic acuity decrement of approximately 0.75 eye-chart lines was observed 1 d after returning from space. The population mean showed a consistent improvement in DVA performance during the first postflight week. DISCUSSION: The recovery curves for individual subjects did not necessarily follow a pattern of continuous improvement with each passing day. When adjusted for previous long-duration flight experience, the population mean showed an unexpected DVA reduction in the re-adaptation curve that is similar to recovery patterns observed in prism adaptation studies.