Neurovascular dysfunction associated with erectile dysfunction persists after long-term recovery from simulations of weightlessness and deep space irradiation.

There has been growing interest within the space industry for long-duration manned expeditions to the Moon and Mars. During deep space missions, astronauts are exposed to high levels of galactic cosmic radiation (GCR) and microgravity which are associated with increased risk of oxidative stress and endothelial dysfunction. Oxidative stress and endothelial dysfunction are causative factors in the pathogenesis of erectile dysfunction, although the effects of spaceflight on erectile function have been unexplored. Therefore, the purpose of this study was to investigate the effects of simulated spaceflight and long-term recovery on tissues critical for erectile function, the distal internal pudendal artery (dIPA), and the corpus cavernosum (CC). Eighty-six adult male Fisher-344 rats were randomized into six groups and exposed to 4-weeks of hindlimb unloading (HLU) or weight-bearing control, and sham (0Gy), 0.75 Gy, or 1.5 Gy of simulated GCR at the ground-based GCR simulator at the NASA Space Radiation Laboratory. Following a 12-13-month recovery, ex vivo physiological analysis of the dIPA and CC tissue segments revealed differential impacts of HLU and GCR on endothelium-dependent and -independent relaxation that was tissue type specific. GCR impaired non-adrenergic non-cholinergic (NANC) nerve-mediated relaxation in the dIPA and CC, while follow-up experiments of the CC showed restoration of NANC-mediated relaxation of GCR tissues following acute incubation with the antioxidants mito-TEMPO and TEMPOL, as well as inhibitors of xanthine oxidase and arginase. These findings indicate that simulated spaceflight exerts a long-term impairment of neurovascular erectile function, which exposes a new health risk to consider with deep space exploration.

Contemporary biomedical engineering perspective on volitional evolution for human radiotolerance enhancement beyond low-earth orbit.

A primary objective of the National Aeronautics and Space Administration (NASA) is expansion of humankind's presence outside low-Earth orbit, culminating in permanent interplanetary travel and habitation. Having no inherent means of physiological detection or protection against ionizing radiation, humans incur capricious risk when journeying beyond low-Earth orbit for long periods. NASA has made large investments to analyze pathologies from space radiation exposure, emphasizing the importance of characterizing radiation's physiological effects. Because natural evolution would require many generations to confer resistance against space radiation, immediately pragmatic approaches should be considered. Volitional evolution, defined as humans steering their own heredity, may inevitably retrofit the genome to mitigate resultant pathologies from space radiation exposure. Recently, uniquely radioprotective genes have been identified, conferring local or systemic radiotolerance when overexpressed in vitro and in vivo. Aiding in this process, the CRISPR/Cas9 technique is an inexpensive and reproducible instrument capable of making limited additions and deletions to the genome. Although cohorts can be identified and engineered to protect against radiation, alternative and supplemental strategies should be seriously considered. Advanced propulsion and mild synthetic torpor are perhaps the most likely to be integrated. Interfacing artificial intelligence with genetic engineering using predefined boundary conditions may enable the computational modeling of otherwise overly complex biological networks. The ethical context and boundaries of introducing genetically pioneered humans are considered.

Bench to Bedside: Animal Models of Radiation Induced Musculoskeletal Toxicity.

Ionizing radiation is a critical aspect of current cancer therapy. While classically mature bone was thought to be relatively radio-resistant, more recent data have shown this to not be the case. Radiation therapy (RT)-induced bone loss leading to fracture is a source of substantial morbidity. The mechanisms of RT likely involve multiple pathways, including changes in angiogenesis and bone vasculature, osteoblast damage/suppression, and increased osteoclast activity. The majority of bone loss appears to occur rapidly after exposure to ionizing RT, with significant changes in cortical thickness being detectable on computed tomography (CT) within three to four months. Additionally, there is a dose-response relationship. Cortical thinning is especially notable in areas of bone that receive >40 gray (Gy). Methods to mitigate toxicity due to RT-induced bone loss is an area of active investigation. There is an accruing clinical trial investigating the use of risderonate, a bisphosphonate, to prevent rib bone loss in patients undergoing lung stereotactic body radiation therapy (SBRT). Additionally, several other promising therapeutic/preventative approaches are being explored in preclinical studies, including parathyroid hormone (PTH), amifostine, and mechanical loading of irradiated bones.