The COVID-19 pandemic is an unprecedented health crisis as entire populations have been asked to self-isolate and live in home-confinement for several weeks to months, which in itself represents a physiological challenge with significant health risks. This paper describes the impact of sedentarism on the human body at the level of the muscular, cardiovascular, metabolic, endocrine and nervous systems and is based on evidence from several models of inactivity, including bed rest, unilateral limb suspension, and step-reduction. Data form these studies show that muscle wasting occurs rapidly, being detectable within two days of inactivity. This loss of muscle mass is associated with fibre denervation, neuromuscular junction damage and upregulation of protein breakdown, but is mostly explained by the suppression of muscle protein synthesis. Inactivity also affects glucose homeostasis as just few days of step reduction or bed rest, reduce insulin sensitivity, principally in muscle. Additionally, aerobic capacity is impaired at all levels of the O 2 cascade, from the cardiovascular system, including peripheral circulation, to skeletal muscle oxidative function. Positive energy balance during physical inactivity is associated with fat deposition, associated with systemic inflammation and activation of antioxidant defences, exacerbating muscle loss. Importantly, these deleterious effects of inactivity can be diminished by routine exercise practice, but the exercise dose-response relationship is currently unknown. Nevertheless, low to mediumintensity high volume resistive exercise, easily implementable in home-settings, will have positive effects, particularly if combined with a 15-25% reduction in daily energy intake. This combined regimen seems ideal for preserving neuromuscular, metabolic and cardiovascular health.. Just few days of sedentary lifestyle are sufficient to induce muscle loss, neuromuscular junction damage and fibre denervation, insulin resistance, decreased aerobic capacity, fat deposition and low-grade systemic inflammation. . Regular low/medium intensity high volume exercise, together with a 15-25% reduction in caloric intake are recommended for preserving neuromuscular, cardiovascular, metabolic and endocrine health.2 M. Narici et al.

Aerobic exercise prescription is often set at specific heart rate (HR) values. Previous studies demonstrated that during exercise carried out at a HR slightly above that corresponding to the gas exchange threshold (GET), work rate (WR) has to decrease in order to maintain HR constant. We hypothesized a greater WR decrease at a fixed HR following simulated microgravity/inactivity (bed rest, BR). Ten male volunteers (23±5 yr) were tested before (PRE) and after (POST) a 10-day horizontal BR, and performed on a cycle ergometer: a) incremental exercise; b) 15-min HRCLAMPED exercise, in which WR was continuously adjusted to maintain a constant HR, corresponding to that at 120% of GET determined in PRE; c) two moderate-intensity constant WR (MOD) exercises. Breath-by-breath VO2, HR and other variables were determined. After BR, VO2peak and GET significantly decreased, by about 10%. During HRCLAMPED (145±11 b∙min-1), the decrease in WR needed to maintain a constant HR was greater in POST vs. PRE (-39±10 vs. -29±14%, p<0.01). In 6 subjects the decreased WR switched from the heavy- to the moderate-intensity domain. The decrease in WR during HRCLAMPED, in PRE vs. POST, was significantly correlated with the VO2peak decrease (R2=0.52; p=0.02). A greater amplitude of the slow component of the HR kinetics was observed during MOD following BR. Exercise at a fixed HR is not associated with a specific WR or WR domain; the problem, affecting exercise evaluation and prescription, is greater following BR. The WR decrease during HRCLAMPED is a biomarker of exercise intolerance following BR.

The peer review history is available in the supporting information section of this article (https://doi.org/10.1113/JP281800#support-information-section).

The recent incidental discovery of an asymptomatic venous thrombosis (VT) in the internal jugular vein of an astronaut on the International Space Station prompted a necessary, immediate response from the space medicine community. The European Space Agency formed a topical team to review the pathophysiology, risk and clinical presentation of venous thrombosis and the evaluation of its prevention, diagnosis, mitigation, and management strategies in spaceflight. In this article, we discuss the findings of the ESA VT Topical Team over its 2-year term, report the key gaps as we see them in the above areas which are hindering understanding VT in space. We provide research recommendations in a stepwise manner that build upon existing resources, and highlight the initial steps required to enable further evaluation of this newly identified pertinent medical risk.

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