Inadequate Loading Stimulus on ISS Results in Bone and Muscle Loss

INTRODUCTION Exercise has been the primary countermeasure to combat musculoskeletal changes during International Space Station (ISS) missions. However, these countermeasures have not been successful in preventing loss of bone mineral density (BMD) or muscle volume in crew members. METHODS We examined lower extremity loading during typical days on-orbit and on Earth for four ISS crew members. In-shoe forces were monitored using force-measuring insoles placed inside the shoes. BMD (by DXA), muscle volumes (by MRI), and strength were measured before and after long-duration spaceflight (181 +/- 15 days). RESULTS The peak forces measured during ISS activity were significantly less than those measured in 1g for the same activities. Typical single-leg loads on-orbit during walking and running were 0.89 +/- 0.17 body weights (BW) and 1.28 +/- 0.18 BW compared to 1.18 +/- 0.11 BW and 2.36 +/- .22 BW in 1g, respectively [2]. Crew members were only loaded for an average of 43.17 +/- 14.96 min a day while performing exercise on-orbit even though 146.8 min were assigned for exercise each day. Areal BMD decreased in the femoral neck and total hip by 0.71 +/- 0.34% and 0.81 +/- 0.21% per month, respectively. Changes in muscle volume were observed in the lower extremity (-10 to -16% calf; -4 to -7% thigh) but there were no changes in the upper extremity (+0.4 to -0.8%). Decrements in isometric and isokinetic strength at the knee (range: -10.4 to -24.1%), ankle (range: -4 to -22.3%), and elbow (range: -7.5 to - 16.7%) were also observed. Knee extension endurance tests showed an overall decline in total work (-14%) but an increased resistance to fatigue post-flight. DISCUSSION AND CONCLUSIONS Our findings support the conclusion that the measured exercise durations and/or loading stimuli were insufficient to protect bone and muscle health

Foot Reaction Forces during Long Duration Space Flight

Musculoskeletal changes, particularly in the lower extremities, are an established consequence of long-duration space flight despite exercise countermeasures. It is widely believed that disuse and reduction in load bearing are key to these physiological changes, but no quantitative data characterizing the on-orbit movement environments currently exist. Here we present data from the Foot Experiment (E318) regarding astronaut activity on the ground and on-orbit during typical days from 4 International Space Station (ISS) crew members who flew during increments 6, 8, 11, and 12

Using the Enhanced Daily Load Stimulus Model to Quantify the Mechanical Load and Bone Mineral Density Changes Experienced by Crew Members on the International Space Station

Despite the use of exercise countermeasures during long-duration space missions, bone mineral density (BMD) and predicted bone strength of astronauts continue to show decreases in the lower extremities and spine. This site-specific bone adaptation is most likely caused by the effects of microgravity on the mechanical loading environment of the crew member. There is, therefore, a need to quantify the mechanical loading experienced on Earth and on-orbit to define the effect of a given "dose" of loading on bone homeostasis. Gene et al. recently proposed an enhanced DLS (EDLS) model that, when used with entire days of in-shoe forces, takes into account recently developed theories on the importance of factors such as saturation, recovery, and standing and their effects on the osteogenic response of bone to daily physical activity. This algorithm can also quantify the tinting and type of activity (sit/unload, stand, walk, run or other loaded activity) performed throughout the day. The purpose of the current study was to use in-shoe force measurements from entire typical work days on Earth and on-orbit in order to quantify the type and amount of loading experienced by crew members. The specific aim was to use these measurements as inputs into the EDLS model to determine activity timing/type and the mechanical "dose" imparted on the musculoskeletal system of crew members and relate this dose to changes in bone homeostasis

Convalescent human IgG, but not IgM, from COVID-19 survivors confers dose-dependent protection against SARS-CoV-2 replication and disease in hamsters

IntroductionAntibody therapeutic strategies have served an important role during the COVID-19 pandemic, even as their effectiveness has waned with the emergence of escape variants. Here we sought to determine the concentration of convalescent immunoglobulin required to protect against disease from SARS-CoV-2 in a Syrian golden hamster model.MethodsTotal IgG and IgM were isolated from plasma of SARS-CoV-2 convalescent donors. Dose titrations of IgG and IgM were infused into hamsters 1 day prior to challenge with SARS-CoV-2 Wuhan-1.ResultsThe IgM preparation was found to have ~25-fold greater neutralization potency than IgG. IgG infusion protected hamsters from disease in a dose-dependent manner, with detectable serum neutralizing titers correlating with protection. Despite a higher in vitro neutralizing potency, IgM failed to protect against disease when transferred into hamsters.DiscussionThis study adds to the growing body of literature that demonstrates neutralizing IgG antibodies are important for protection from SARS-CoV-2 disease, and confirms that polyclonal IgG in sera can be an effective preventative strategy if the neutralizing titers are sufficiently high. In the context of new variants, against which existing vaccines or monoclonal antibodies have reduced efficacy, sera from individuals who have recovered from infection with the emerging variant may potentially remain an efficacious tool

A SARS-CoV-2 Spike Ferritin Nanoparticle Vaccine Is Protective and Promotes a Strong Immunological Response in the Cynomolgus Macaque Coronavirus Disease 2019 (COVID-19) Model

The COVID-19 pandemic has had a staggering impact on social, economic, and public health systems worldwide. Vaccine development and mobilization against SARS-CoV-2 (the etiologic agent of COVID-19) has been rapid. However, novel strategies are still necessary to slow the pandemic, and this includes new approaches to vaccine development and/or delivery that will improve vaccination compliance and demonstrate efficacy against emerging variants. Here, we report on the immunogenicity and efficacy of a SARS-CoV-2 vaccine comprising stabilized, pre-fusion spike protein trimers displayed on a ferritin nanoparticle (SpFN) adjuvanted with either conventional aluminum hydroxide or the Army Liposomal Formulation QS-21 (ALFQ) in a cynomolgus macaque COVID-19 model. Vaccination resulted in robust cell-mediated and humoral responses and a significant reduction in lung lesions following SARS-CoV-2 infection. The strength of the immune response suggests that dose sparing through reduced or single dosing in primates may be possible with this vaccine. Overall, the data support further evaluation of SpFN as a SARS-CoV-2 protein-based vaccine candidate with attention to fractional dosing and schedule optimization