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INTRODUCTION: A ccessible spaceflight may seem a distant concept. As part of a diverse European Space Agency funded Topical Team, we are working on the physiological feasibility of space missions being undertaken by people with physical disabilities. Here, the first activity of this team is presented in the form of key lessons learned from aviation to inform new work on space missions. DISCUSSION: The first lesson is agreeing on realistic expectations about impairments, their severity, and the possibility of flying independently. This is important in terms of astronaut recruitment and societal expectations. The second lesson relates to training and adjustments for people with disabilities. Flexibility is important while maintaining safety for everyone involved. The third lesson is about managing unconscious bias from the different stakeholders. We conclude by arguing that engagement with people from different backgrounds is essential for the success of the first space mission with people with physical disabilities. [ABSTRACT FROM AUTHOR]

Physiological and premature aging are frequently associated with an accumulation of prelamin A, a precursor of lamin A, in the nuclear envelope of various cell types. Here, we aimed to underpin the hitherto unknown mechanisms by which prelamin A alters myonuclear organization and muscle fiber function. By experimentally studying membrane-permeabilized myofibers from various transgenic mouse lines, our results indicate that, in the presence of prelamin A, the abundance of nuclei and myosin content is markedly reduced within muscle fibers. This leads to a concept by which the remaining myonuclei are very distant from each other and are pushed to function beyond their maximum cytoplasmic capacity, ultimately inducing muscle fiber weakness.

Facioscapulohumeral muscular dystrophy (FSHD) involves sporadic expression of DUX4, which inhibits myogenesis and is pro-apoptotic. To identify target genes, we over-expressed DUX4 in myoblasts and found that the receptor tyrosine kinase Ret was significantly up-regulated, suggesting a role in FSHD. RET is dynamically expressed during myogenic progression in mouse and human myoblasts. Constitutive expression of either RET9 or RET51 increased myoblast proliferation, whereas siRNA-mediated knockdown of Ret induced myogenic differentiation. Suppressing RET activity using Sunitinib, a clinically-approved tyrosine kinase inhibitor, rescued differentiation in both DUX4-expressing murine myoblasts and in FSHD patient-derived myoblasts. Importantly, Sunitinib also increased engraftment and differentiation of FSHD myoblasts in regenerating mouse muscle. Thus, DUX4-mediated activation of Ret prevents myogenic differentiation and could contribute to FSHD pathology by preventing satellite cell-mediated repair. Rescue of DUX4-induced pathology by Sunitinib highlights the therapeutic potential of tyrosine kinase inhibitors for treatment of FSHD.

Studies suggest that inducing gut microbiota changes may alter both muscle physiology and cognitive behaviour. Gut microbiota may play a role in both anabolic resistance of older muscle, and cognition. In this placebo controlled double blinded randomised controlled trial of 36 twin pairs (72 individuals), aged ≥60, each twin pair are block randomised to receive either placebo or prebiotic daily for 12 weeks. Resistance exercise and branched chain amino acid (BCAA) supplementation is prescribed to all participants. Outcomes are physical function and cognition. The trial is carried out remotely using video visits, online questionnaires and cognitive testing, and posting of equipment and biological samples. The prebiotic supplement is well tolerated and results in a changed gut microbiome [e.g., increased relative Bifidobacterium abundance]. There is no significant difference between prebiotic and placebo for the primary outcome of chair rise time (β = 0.579; 95% CI -1.080-2.239 p = 0.494). The prebiotic improves cognition (factor score versus placebo (β = -0.482; 95% CI,-0.813, -0.141; p = 0.014)). Our results demonstrate that cheap and readily available gut microbiome interventions may improve cognition in our ageing population. We illustrate the feasibility of remotely delivered trials for older people, which could reduce under-representation of older people in clinical trials. [ABSTRACT FROM AUTHOR]

INTRODUCTION: G tolerance has been widely assessed using Peripheral Light Loss (PLL), but this approach has several limitations and may lack sensitivity. The aim of this study was to investigate the use of a foveal visual endpoint for centrifuge research (Grating Loss; GL) and assess its repeatability, reliability, and usability with PLL as a reference. METHODS: A total of 11 subjects undertook centrifuge assessment. Gradual onset sessions (GOR; 0.1G · s−1) measured both endpoints simultaneously and were performed twice, consisting of six determinations with anti-G suits activated (GOR-On) and six without (GOR-Off). Four determinations of each endpoint were also taken during rapid onset runs (ROR; 3G · s−1). Usability was scored subjectively. RESULTS: The GL endpoint was reached 0.3–0.5 Gz lower than PLL with each endpoint correlating strongly in GOR-Off (r = 0.93), GOR-On (r = 0.95), and ROR (r = 0.86). The GL had excellent test–retest repeatability (intraclass correlation coefficient: GOR-Off/On = 0.99, ROR = 0.92) and low within-subject variability. Between-subject variance equaled PLL in all conditions. Subjective usability endpoint ratings were equal for all conditions. DISCUSSION: For the 11 individuals tested, the GL was a reliable, repeatable, and usable endpoint, with similar performance to PLL. GL may prove useful as a supplementary endpoint for human centrifuge research as a secondary data point or to reduce fatigue in repeated measurements. The foveal GL stimulus was lost before PLL, contrary to popular models of visual changes under +Gz. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Muscle mass is maintained through a balance between muscle protein synthesis (MPS) and breakdown (MPB). The loss of skeletal mass is one of the major challenges of prolonged exposure to micro-gravity (μG). The present study utilised two tracer approaches with the aim of investigating the effects of 7-days of whole body unloading using a novel ground-based μG analogue on muscle loss and rates of MPS and MPB in young healthy males. METHODS: Twelve healthy male subjects (27.3±4.2 years) completed the study. Six weeks prior to unloading each subject underwent a one-week control period. For the unloading intervention period the subjects were asked to lie supine on a hyper buoyancy floatation bed (HBF) for 7 days. For a maximum of 15 mins per day, they were off the HBF (for personal hygiene etc) and were fed a controlled diet during both the control and intervention periods. The deuterium oxide (D2O) tracer technique with analysis of muscle biopsies taken from the quadriceps was used to study changes in MPS (n=10) over the control and unloading periods. The 3-methylhistidine (3-MH) technique was used to measure MPB (n=12) across the whole body and changes in muscle mass of the upper part of the lower limb were measured using Magnetic Resonance Imaging (n=12). RESULTS: Muscle mass of the upper leg was reduced by 3.4% (10.4±1.8 vs 10.0±1.8 kg; p<0.01, mean±SD; paired t-test) after the unloading period. MPS (expressed as myofibrillar fractional synthetic rate) was significantly lower after the unloading compared to the control period (1.21±0.18 vs1.41±0.21%•d-1; p<0.01). The rate of MPB was also significantly lower for the unloading period compared to the control period (0.043±0.031 vs 0.062±0.23 h-1; p<0.05). DISCUSSION: The finding that unloading induced a reduction in muscle mass and MPS is not unexpected in the light of results from previous studies. However, the observation that MPB was also reduced is a novel observation which provides new insights into the processes driving unloading-induced muscle atrophy in healthy humans. Learning Objectives 1. The audience will learn about the effects of micro gravity and unloading on human skeletal muscle mass. 2. The audience will learn about the use of tracer techniques to measure rates of muscle protein synthesis and breakdown in humans. 3. The audience will learn that 7 days of whole body unloading, which induces a loss of muscle mass, is accompanied by a reduction in muscle protein synthesis and also, somewhat surprisingly, by a reduction in muscle protein breakdown. [ABSTRACT FROM AUTHOR]

Background. Regular and vigorous exercisers appear to be the logical choice for studying the inherent aging process as they tire essentially free from the complications of disuse. Cross-sectional studies of aging tend to depict an essentially smooth and progressive decrement of physiological function with increasing chronological age. On closer examination of such data, it is seen that although the young have high functional values and the very old low, between these limits, values are widely scattered. Methods. We have reevaluated published data from a recta-analysis of 242 studies on men and from a similar study on women. From both data sets, where [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] was plotted against chronological age. we stratified the [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] values into bandwidth intervals of 5 ml/kg/minute and then allocated data points to their respective bandwidth irrespective of chronological age. Results. When replotted into bandwidths of functional equivalence, these data show that at the extremes of function, the young are separated from the old. Between these values, each functional bandwidth accommodates a wide age range. The decrement in function with chronological age is not smooth or well defined. Conclusions. We suggest that participants for research into healthy aging should be initially segregated into bands of functionally equivalent [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] values irrespective of their chronological age. Subsequently, other physiological measurements should be made on every participant in the band in order to begin to define the physiological profile of the participants. By conducting longitudinal studies on every individual, it will be possible to chart the physiological history of each participant through various ages. Segregating participants into cohorts of functional equivalence with data handling blinded to chronological age may be of great utility in increasing our understanding of the inherent aging process. Key Words: Exercise--aging--[MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII]. doi: 10.1093/gerona/glq016

INTRODUCTION: Military rotary-wing operations require sustained levels of cognitive and psychomotor performance from aircrew to ensure safety and operational effectiveness. Significant flight-related neck pain (SFRNP) is common amongst rotary-wing aircrew, potentially affecting their performance. This study aimed to examine the effect of SFRNP on psychomotor and cognitive performance in a cohort of military rotarywing aircrew in the operational flight environment. METHODOLOGY: A field study was conducted using a dual-task paradigm with 40 military operational CH-47 rear crew (39 male, 1 female). The primary outcome variable was the Dual Task Effect (DTE) (% change between single and dual task conditions) for cognitive and psychomotor performance on a novel simulated flight-task test battery. These data were stratified post-hoc for those with or without SFRNP. This study received favourable opinion from the UK Ministry of Defence Research Ethics Committee (MODREC). RESULTS: 65% (n=26) of participants reported SFRNP during the test flights. Mean intensity of SFRNP was 2.5 on the Numerical Pain Rating Scale. Pre-flight, there was a significantly greater deterioration in psychomotor performance under dual task conditions for the SFRNP group (DTE -15.8), compared to the non-neck pain group (DTE 1.5) (p=.01). Deterioration in dual-task performance (DTE) for both the cognitive and psychomotor conditions was slightly worse following the operational flight sortie; however, no significant differences were observed after the operational flight sortie in either the SFRNP or non-neck pain group (p=>.05). DISCUSSION: SFRNP was found to be present amongst this sample of military rotary-wing aircrew. There was a detectable change in the cognitive and psychomotor performance of the aircrew using the dual-task paradigm. Whilst there was evidence that SFRNP was associated with reduced psychomotor dual-task performance, operational flight exposure did not affect aircrew performance in this study. Future research could consider the relationship between the pain intensity and its effect on performance. Learning Objectives 1. Psychomotor dual-task performance was reduced in military rotarywing rear crew with significant flight-related neck pain. 2. Operational flight exposure was not associated with reduced dual-task performance in aircrew with or without significant flight-related neck pain in this study. [ABSTRACT FROM AUTHOR]

BACKGROUND: One in 5 people worldwide lives with a disability, frequently facing challenges in aviation. This makes accessible space flight seem like a distant dream. Recently, ESA selected the first astronaut with a physical disability. Our ESA Topical Team supports this opportunity by reviewing the existing literature and lived experience in the field, to investigate the physical and physiological challenges and also the potential advantages of astronauts with disabilities. OVERVIEW: Given the overlap between the medical standards required for pilot medical certification and those for astronaut selection, we started by examining the experience of a disabled flying charity, Aerobility. Three key lessons were learned from this review which will support the collaboration between stakeholders when working with astronauts with physical impairments.The first lesson was to recognise that not everyone will meet the standards for aeromedical certification. Astronauts face similar requirements and a transparent approach to assessment is required. However, these criteria can evolve over time, as advancements in both medical and technological fields may mitigate the impact of physical impairments on an individual's ability to participate in space missions. The second lesson was that people with disabilities can meet the requirements for flying with adapted training and technical modifications. In this context, flexibility and open discussions are needed to understand individual needs and find optimal solutions. Likewise, considering astronauts, dedicated efforts are required to adapt systems and procedures, ensuring accessibility. The third lesson highlighted the significance of involving different stakeholders when reviewing recruitment, training, adaptations, and operations. Unconscious bias remains a challenge in the field. Without scientific evidence demonstrating the suitability of candidates with physical disabilities, space accessibility would remain partial. DISCUSSION: We reviewed the experience of a leading flying charity to define key lessons from aviation that could be translated and adapted for space flight. Our overarching goal is to evaluate the physiological considerations for people with physical disabilities in order to support ESA's team and space missions. This work will become even more relevant with the emergence of space tourism, and the need for accommodating a diverse array of candidates for both short-term and extended space flights. Learning Objectives 1. To discuss the requirements and adjustments for people with disabilities in aviation and how they can inform space missions. 2. To identify the needs and adjustments for astronauts with a physical disability. [ABSTRACT FROM AUTHOR]