Fundamental Biological Features of Spaceflight: Advancing the Field to Enable Deep-Space Exploration.

Research on astronaut health and model organisms have revealed six features of spaceflight biology that guide our current understanding of fundamental molecular changes that occur during space travel. The features include oxidative stress, DNA damage, mitochondrial dysregulation, epigenetic changes (including gene regulation), telomere length alterations, and microbiome shifts. Here we review the known hazards of human spaceflight, how spaceflight affects living systems through these six fundamental features, and the associated health risks of space exploration. We also discuss the essential issues related to the health and safety of astronauts involved in future missions, especially planned long-duration and Martian missions.

Six-day dry immersion leads to downregulation of slow-fiber type and mitochondria-related genes expression.

The soleus muscle in humans is responsible for maintaining an upright posture and participating in walking and running. Under muscle disuse, it undergoes molecular signaling changes that result in altered force and work capacity. The triggering mechanisms and pathways of these changes are not yet fully understood. In this article, we aimed to detect the molecular pathways that are involved in the unloading-induced alterations in the human soleus muscle under 6-days of dry immersion. A 6-day dry immersion led to the downregulation of mitochondrial biogenesis and dynamics markers, upregulation of calcium-dependent CaMK II phosphorylation, enhanced PGC1α promoter region methylation, and altered muscle micro-RNA expression, without affecting p-AMPK content or fiber-type transformation.NEW & NOTEWORTHY Dry immersion dysregulates mitochondrial genes expression, affects mi-RNA expression and PGC1 promoter methylation.

The State of the Organs of the Female Reproductive System after a 5-Day "Dry" Immersion.

The impact of weightlessness on the female reproductive system remains poorly understood, although deep space exploration is impossible without the development of effective measures to protect women's health. The purpose of this work was to study the effect of a 5-day "dry" immersion on the state of the reproductive system of female subjects. On the fourth day of the menstrual cycle after immersion, we observed an increase in inhibin B of 35% (p < 0.05) and a decrease in luteinizing hormone of 12% (p < 0.05) and progesterone of 52% (p < 0.05) compared with the same day before immersion. The size of the uterus and the thickness of the endometrium did not change. On the ninth day of the menstrual cycle after immersion, the average diameters of the antral follicles and the dominant follicle were, respectively, 14% and 22% (p < 0.05) higher than before. The duration of the menstrual cycle did not change. The obtained results may indicate that the stay in the 5-day "dry" immersion, on the one hand, can stimulate the growth of the dominant follicle, but, on the other hand, can cause functional insufficiency of the corpus lutea.

Transcatheter and ministernotomy aortic valve replacement after bioprosthetic valve failure.

BACKGROUND: Transcatheter valve-in-valve implantation (TViV) and minimally invasive reoperative aortic valve replacement (MIrAVR) have rapidly increased as alternatives to conventional reoperative surgical AVR. This study reports a single-center experience of patients undergoing TViV and MIrAVR after bioprosthetic valve failure. METHODS: In this retrospective review between March 2009 and October 2018, 68 patients without reoperative full sternotomies, concomitant procedures, active endocarditis, and prior homografts or coronary artery bypass grafting underwent isolated AVR for degenerated aortic bioprostheses. Society of Thoracic Surgeons (STS) risk scores and age are reported as median (interquartile range [IQR]) and length of stay is reported as mean (standard deviation [SD]) due to their characteristics of the distribution. RESULTS: Forty-one (60.3%) patients underwent TViV, and 27 (39.7%) patients underwent MIrAVR. Median [IQR] STS risk scores were 5.7 [4.0-7.8] and 2.0 [1.5-3.4] for TViV and MIrAVR, respectively (p ≤ .001). The median [IQR] age for TViV patients was higher (78 [71-84] vs. 66 [53-72] years, p ≤ 0.001). More permanent pacemakers were implanted (22.2% vs. 9.8%) following MIrAVR. The MIrAVR group had a higher rate of atrial fibrillation (18.5% vs. 9.8%, p = .466). Average (SD) length of stay was less in TViV (5.3 days, SD: 3.4 vs. 8.6 days, SD: 7.4, p = .001). Survival at 1 year was not significantly different for TViV and MIrAVR (94.9% [95% confidence interval [CI]: 81.0%, 98.7%] and 86.9% [95% CI: 64.0%, 95.7%], respectively [p = .969]). CONCLUSIONS: Despite being at higher-risk, patients undergoing TViV had reduced rates of permanent pacemaker implantations and atrial fibrillation, and a shorter hospital stay as compared to MIrAVR. Survival at 1-year was similar between the two groups.

Drosophila melanogaster Sperm under Simulated Microgravity and a Hypomagnetic Field: Motility and Cell Respiration.

The role of the Earth's gravitational and magnetic fields in the evolution and maintenance of normal processes of various animal species remains unclear. The aim of this work was to determine the effect of simulated microgravity and hypomagnetic conditions for 1, 3, and 6 h on the sperm motility of the fruit fly Drosophila melanogaster. In addition to the usual diet, the groups were administered oral essential phospholipids at a dosage of 500 mg/kg in medium. The speed of the sperm tails was determined by video recording and analysis of the obtained video files, protein content by western blotting, and cell respiration by polarography. The results indicated an increase in the speed of movement of the sperm tails after 6 h in simulated microgravity. The levels of proteins that form the axoneme of the sperm tail did not change, but cellular respiration was altered. A similar effect occurred with the administration of essential phospholipids. These results may be due to a change in the level of phosphorylation of motor proteins. Exposure to hypomagnetic conditions led to a decrease in motility after 6 h against a background of a decrease in the rate of cellular respiration due to complex I of the respiratory chain. This effect was not observed in the flies that received essential phospholipids. However, after 1 h under hypomagnetic conditions, the rate of cellular respiration also increased due to complex I, including that in the sperm of flies receiving essential phospholipids.

Rapid changes in transcriptomic profile and mitochondrial function in human soleus muscle after 3-day dry immersion.

We aimed to explore the effect of the 3-day dry immersion, a model of physical unloading, on mitochondrial function, transcriptomic and proteomic profiles in a slow-twitch soleus muscle of six healthy females. We registered that a marked reduction (25-34%) in the ADP-stimulated respiration in permeabilized muscle fibers was not accompanied by a decrease in the content of mitochondrial enzymes (mass spectrometry-based quantitative proteomics), hence, it is related to the disruption in regulation of respiration. We detected a widespread change in the transcriptomic profile (RNA-seq) upon dry immersion. Downregulated mRNAs were strongly associated with mitochondrial function, as well as with lipid metabolism, glycolysis, insulin signaling, and various transporters. Despite the substantial transcriptomic response, we found no effect on the content of highly abundant proteins (sarcomeric, mitochondrial, chaperon, and extracellular matrix-related, etc.) that may be explained by long half-life of these proteins. We suggest that during short-term disuse the content of some regulatory (and usually low abundant) proteins such as cytokines, receptors, transporters, and transcription regulators is largely determined by their mRNA concentration. These mRNAs revealed in our work may serve as putative targets for future studies aimed at developing approaches for the prevention of muscle deconditioning induced by disuse.NEW & NOTEWORTHY Three-day dry immersion (a model of physical unloading) substantially changes the transcriptomic profile in the human soleus muscle, a muscle with predominantly slow-twitch fibers and strong postural function; despite this, we found no effect on the muscle proteome (highly abundant proteins). Dry immersion markedly reduces ADP-stimulated respiration; this decline is not accompanied by a decrease in the content of mitochondrial proteins/respiratory enzymes, indicating the disruption in regulation of cellular respiration.

How We Perform a David Procedure With an Upper Hemisternotomy Approach.

OBJECTIVE: Valve-sparing aortic root replacement (David procedure) is the technique of choice in appropriately selected patients with aortic root aneurysms. These procedures are seldom performed in a minimally invasive fashion. We describe our systematic approach to the David procedure using an upper hemisternotomy (UHS). Methods: Our method involves a J-type UHS exiting the right third or fourth intercostal space. Ascending aortic and femoral venous cannulation are performed using the Seldinger technique under transesophageal echocardiographic guidance. Between August 2005 and August 2014, 27 patients underwent an isolated elective David procedure using a full sternotomy (FS). Sixteen underwent an isolated elective UHS David procedure from May 2015 to February 2019. Perioperative safety outcomes were compared between the 2 cohorts. Results: The UHS and FS David cohorts were primarily male (87.5% and 85.2%, respectively) and 51 and 50 years old on average, respectively. Custodiol-histidine-tryptophan-ketoglutarate cardioplegia (93.8% vs 37.0%, P < 0.001) and Cor-Knot (100% vs 0%, P < 0.001) were used significantly more in the UHS David cohort. There were no significant differences in cardiopulmonary bypass (200 [183-208] vs 212 [183-223] min, P = 0.309) and aortic cross-clamp (169 [155-179] vs 188 [155-199] min, P = 0.128) times in the UHS and FS cohorts. There were no instances of hospital or 30-day mortality in either cohort. Intensive care unit and hospital stays were comparable between the 2 cohorts. Conclusions: The David procedure via UHS is a safe and reproducible technique for aortic root replacement.

Sleep in 21-Day Dry Immersion. Are Cardiovascular Adjustments Rapid Eye Movement Sleep-Dependent?

Introduction: A decrease in sleep quality and duration during space missions has repeatedly been reported. However, the exact causes that underlie this effect remain unclear. In space, sleep might be impacted by weightlessness and its influence on cardiovascular function. In this study, we aimed at exploring the changes of night sleep architecture during prolonged, 21-day Dry Immersion (DI) as one of the ground-based models for microgravity studies and comparing them with adaptive changes in the cardiovascular system. Methods: Ten healthy young men were exposed to DI for 21 days. The day before (baseline, B-1), on the 3rd (DI3), 10th (DI10), and 19th (DI19) day of DI, as well as in the recovery period, 1 day after the end of DI (R + 1), they were subjected to overnight polysomnography (PSG) and ambulatory blood pressure monitoring. Results: On DI3, when the most severe back pain occurred due to the effects of DI on the spine and back muscles, the PSG data showed dramatically disorganized sleep architecture. Sleep latency, the number of awakenings, and the duration of wake after sleep onset (WASO) were significantly increased compared with the B-1. Furthermore, the sleep efficiency, duration of rapid eye movement sleep (REM), and duration of non-rapid eye movement stage 2 decreased. On DI10, subjective pain ratings declined to 0 and sleep architecture returned to the baseline values. On DI19, the REM duration increased and continued to rise on R + 1. An increase in REM was accompanied by rising in a nighttime heart rate (HR), which also shows the most significant changes after the end of DI. On DI19 and R + 1, the REM duration showed opposite correlations with the BP parameters: on DI19 it was negatively associated with the systolic BP (SBP), and on R + 1 it was positively correlated with the diastolic BP (DBP). Conclusion: An increase in REM at the end of DI and in recovery might be associated with regulatory changes in the cardiovascular system, in particular, with the reorganization of the peripheral and central blood flow in response to environmental changes.

Hybrid Aortic Arch Repair Using a Ministernotomy.

Hybrid thoracic endovascular aortic repair with surgical arch debranching is an accepted method for total arch reconstruction. Although off-pump arch debranching is increasingly used as a prophylactic adjunct to endovascular arch repair extending into landing zone 0, this technique is seldom performed with a ministernotomy due to a steep learning curve among surgeons. Herein, we report our standard technique for off-pump hybrid total aortic arch repair using a ministernotomy.

Total Arch Replacement with Hypothermic Circulatory Arrest, Antegrade Cerebral Perfusion and the Y-graft.

This study examines postoperative morbidity and mortality and long-term survival after total arch replacement (TAR) using deep to moderate hypothermic circulatory arrest (HCA), antegrade cerebral perfusion (ACP), and the Y-graft. Seventy-five patients underwent TAR with the Y graft. Deep to moderate HCA was initiated at 18-22°C. ACP was either initiated immediately (early ACP) or after the distal anastomosis was performed (late ACP). The arch vessels were then serially anastomosed to the individual limbs of the Y-graft. The median age was 66 years (range = 32-82). Etiology of aneurysmal dilatation included 20 (27%) patients with medial degenerations, 25 (33%) with chronic dissections, 14 (19%) with acute dissections, 9 (12%) with atherosclerosis and 2 (3%) with Marfan syndrome. In-hospital mortality was 5%. Neurologic complications occurred in 8 (11%) patients; 2 (3%) had strokes and 6 (8%) had transient neurologic deficits. Patients undergoing TAR with moderate hypothermia had a significantly higher incidence of new-onset renal insufficiency (3 [23%] vs [0%], P < 0.001) and TND (3 (23%) vs 3 (5%), P = 0.028) than the profound and deep hypothermia cohort. Excluding the 1 patient who died intraoperatively, 89% (95%CI: 79-94%) were alive at 1 year, 78% at 5 years (95%CI: 66-86%), and 73% at 10 years (95%CI: 59-82%). The combination of deep to moderate HCA, ACP, and the Y-graft is a safe and reproducible technique. Further inquiry is needed to assess if early ACP provides superior clinical outcomes.

Aortic Root Pseudoaneurysm Caused by Mycobacterium Chimaera.

Nontuberculous mycobacteria cause severe pulmonary, vascular graft, and bloodstream infections after cardiac surgery. Patient prognosis remains poor because of delays in diagnosis and treatment. Complicated aortic root infections caused by nontuberculous mycobacteria have been mostly fatal. We describe a case of a 50-year-old man who developed an invasive Mycobacterium chimaera infection with an aortic root pseudoaneurysm after a Bentall-de Bono procedure for a Stanford type A aortic dissection.

Incidence, Natural History, and Factors Associated With Paravalvular Leak Following Surgical Aortic Valve Replacement.

Objective: Our study investigates the incidence, cumulative incidence, natural history, and factors associated with intraoperative paravalvular leak (PVL) and the development of a postoperative PVL in a contemporary consecutive cohort of patients following surgical aortic valve replacement. Methods: A total of 636 patients underwent surgical aortic valve replacement from 2006 to 2016; 410 (64.5%) underwent minimally invasive aortic valve replacement and 226 (35.5%) underwent conventional aortic valve replacement. Primary outcomes were the incidence of intraoperative PVL and cumulative incidence of postoperative PVL. Secondary outcomes were the incidence of in-hospital and long-term death and need for reoperation. Results: The overall incidence of intraoperative PVL was 1.4% (95% confidence interval [CI]: 1% to 3%). All intraoperative PVLs developed in the hand-tied group. The overall incidence of postoperative PVL was 5.3% (95% CI: 4% to 7%). In the univariable and multivariable analyses, postoperative renal failure was the only factor significantly associated with the development of a postoperative PVL. Conclusions: The incidence of intraoperative PVL is low. Cumulative incidence of postoperative PVL was 3.1% (95% CI: 1.0% to 13.6%), 4.3% (95% CI: 1.3% to 16.5%), and 5.0% (95% CI: 1.4% to 17.9%) at 1, 3, and 5 years, respectively. All intraoperative PVLs occurred with hand-tied knots. A larger cohort may identify additional risk factors.

Testes and duct deferens of mice during space flight: cytoskeleton structure, sperm-specific proteins and epigenetic events.

To analyze the effect of gravity on the structure of germinal tissues, we examined tissues of the testes and duct deferens of mice that were exposed to space flight conditions for 21-24 days (experiment Rodent Research-4, SpaceX-10 mission, February 2017, USA). We evaluated the levels of cytoskeletal proteins, sperm-specific proteins, and epigenetic events; in particular, we evaluated levels of 5-hydroxymethylcytosine and of enzymes that regulate DNA methylation/demethylation. We did not detect changes in the levels of cytoskeletal proteins, sperm-specific proteins, DNA-methylases, DNA demethylases, DNA acetylases, or histone deacetylases. However, there were changes at the gene expression level. In particular, there was an increase in the demethylase Tet2 and a decrease in the histone deacetylase Hdac1. These gene expression changes may be of key importance during the early period of readaptation since they could lead to an increase in the expression of target genes.

Ministernotomy aortic valve surgery in patients with prior patent mammary artery grafts after coronary artery bypass grafting.

OBJECTIVES: Patients with patent internal thoracic artery (ITA) grafts after prior coronary artery bypass grafting surgery who require aortic valve replacement (AVR) pose unique technical challenges for safe and optimal myocardial protection. The purpose of this study is to review our short- and long-term outcomes with redo minimally invasive AVR in patients with patent in situ ITA grafts. METHODS: From 2008 to 2016, 48 patients with at least 1 patent in situ mammary artery graft underwent minimally invasive AVR. Preoperative computed tomography was performed in all patients to evaluate the relationship of patent grafts to the sternum. Retrograde coronary sinus and pulmonary vent catheters were placed via the right internal jugular vein. The in situ ITA grafts were not clamped during AVR. Transverse aortotomy, taking care to avoid the grafts arising from the aorta, was performed to expose the aortic valve. RESULTS: The median age of the patients was 78 years [Quartile 1 (Q1)-Quartile 3 (Q3): 71-81]. Thirty-nine (81%) patients were men, and 46 (96%) patients had aortic stenosis. The median cardiopulmonary bypass and cross-clamp times were 124 (Q1-Q3: 108-164) and 92 (Q1-Q3: 83-116) min, respectively. Moderate hypothermia at 28-30°C was used in all patients. Most patients received cold blood cardioplegia with antegrade induction and continuous retrograde delivery. Four patients received only retrograde delivery due to some degree of aortic insufficiency. Thirty-day mortality was 4% (2 of 48 patients). There was no conversion to full sternotomy, and no reoperations were performed for postoperative bleeding or sternal wound infection. Excluding the 2 patients who died in the hospital, the median postoperative length of stay was 7 days (Q1-Q3: 5-8). Overall survival at 1, 5 and 10 years was 94%, 87% and 44%, respectively. CONCLUSIONS: Percutaneous retrograde cardioplegia combined with antegrade cardioplegia and moderate hypothermia, without interruption of ITA flow, is a safe and reliable strategy in patients with patent ITA grafts undergoing aortic valve replacement. This strategy combined with a minimally invasive approach may reduce surgical trauma, and is a safe and effective technique in these challenging patients.

Telemedicine and spaceflight.

Medical assessment and treatment of crews during spaceflight is primarily perfomed by the Earth-based medical staff analyzing information received by telemetry and onboard preventive and medical treatment facilities. In the coming decades, the building of the International Space Station (ISS) will be the most important near-Earth space exploration project. Remote monitoring and distance support of the crewmembers by the Earth-based clinical medicine specialists will become increasely important. The international nature of the ISS will require integrating medical support systems of the participating countries. Consideration must also be given to biomedical ethics and the confidentiality of the medical information exchanged. In Russia, the construction of the telemedicine network for the Russian node of the ISS has been completed. It is evident that during interplanetary flight biomedical problems will be much more difficult than during orbital flights of the same duration. Such a long-duration flight will require development of a special telemedical support system, as well as onboard facilities, which will present many new challenges. This new system will involve the integration of information technologies with biology, as well as physics and chemistry, representing a new interdisciplinary technological breakthrough.

Evolution of telemedicine in Russia: the influence of the space program on modern telemedicine programs.

Telemedicine education and application throughout Russia has its roots in Russia's space program. The concepts of telemedicine have evolved during the course of 40 years of space exploration. This paper reviews the evolution of telemedicine and the achievements of the Soviet/Russian Space Program.