Dynamic transcriptomic responses to divergent acute exercise stimuli in young adults.

Acute exercise elicits dynamic transcriptional changes that, when repeated, form the fundamental basis of health, resilience, and performance adaptations. While moderate-intensity endurance training combined with conventional resistance training (traditional, TRAD) is often prescribed and recommended by public health guidance, high-intensity training combining maximal-effort intervals with intensive, limited-rest resistance training is a time-efficient alternative that may be used tactically (HITT) to confer similar benefits. Mechanisms of action of these distinct stimuli are incompletely characterized and have not been directly compared. We assessed transcriptome-wide responses in skeletal muscle and circulating extracellular vesicles (EVs) to a single exercise bout in young adults randomized to TRAD (n = 21, 12 M/9 F, 22 ± 3 yr) or HITT (n = 19, 11 M/8 F, 22 ± 2 yr). Next-generation sequencing captured small, long, and circular RNA in muscle and EVs. Analysis identified differentially expressed transcripts (|log2FC|>1, FDR ≤ 0.05) immediately (h0, EVs only), h3, and h24 postexercise within and between exercise protocols. In aaddition, all apparently responsive transcripts (FDR < 0.2) underwent singular value decomposition to summarize data structures into latent variables (LVs) to deconvolve molecular expression circuits and interregulatory relationships. LVs were compared across time and exercise protocol. TRAD, a longer but less intense stimulus, generally elicited a stronger transcriptional response than HITT, but considerable overlap and key differences existed. Findings reveal shared and unique molecular responses to the exercise stimuli and lay groundwork toward establishing relationships between protein-coding genes and lesser-understood transcripts that serve regulatory roles following exercise. Future work should advance the understanding of these circuits and whether they repeat in other populations or following other types of exercise/stress.NEW & NOTEWORTHY We examined small and long transcriptomics in skeletal muscle and serum-derived extracellular vesicles before and after a single exposure to traditional combined exercise (TRAD) and high-intensity tactical training (HITT). Across 40 young adults, we found more consistent protein-coding gene responses to TRAD, whereas HITT elicited differential expression of microRNA enriched in brain regions. Follow-up analysis revealed relationships and temporal dynamics across transcript networks, highlighting potential avenues for research into mechanisms of exercise response and adaptation.

δ13C methane source signatures from tropical wetland and rice field emissions.

The atmospheric methane (CH4) burden is rising sharply, but the causes are still not well understood. One factor of uncertainty is the importance of tropical CH4 emissions into the global mix. Isotopic signatures of major sources remain poorly constrained, despite their usefulness in constraining the global methane budget. Here, a collection of new δ13CCH4 signatures is presented for a range of tropical wetlands and rice fields determined from air samples collected during campaigns from 2016 to 2020. Long-term monitoring of δ13CCH4 in ambient air has been conducted at the Chacaltaya observatory, Bolivia and Southern Botswana. Both long-term records are dominated by biogenic CH4 sources, with isotopic signatures expected from wetland sources. From the longer-term Bolivian record, a seasonal isotopic shift is observed corresponding to wetland extent suggesting that there is input of relatively isotopically light CH4 to the atmosphere during periods of reduced wetland extent. This new data expands the geographical extent and range of measurements of tropical wetland and rice δ13CCH4 sources and hints at significant seasonal variation in tropical wetland δ13CCH4 signatures which may be important to capture in future global and regional models. This article is part of a discussion meeting issue 'Rising methane: is warming feeding warming? (part 2)'.

Mechanisms of exercise as a preventative measure to muscle wasting.

Skeletal muscle is the most abundant tissue in healthy individuals and it has important roles in health beyond voluntary movement. The overall mass and energy requirements of skeletal muscle require it to be metabolically active and flexible to multiple energy substrates. The tissue has evolved to be largely load dependent and it readily adapts in a number of positive ways to repetitive overload, such as various forms of exercise training. However, unloading from extended bed rest and/or metabolic derangements in response to trauma, acute illness, or severe pathology, commonly results in rapid muscle wasting. Decline in muscle mass contributes to multimorbidity, reduces function, and exerts a substantial, negative impact on the quality of life. The principal mechanisms controlling muscle mass have been well described and these cellular processes are intricately regulated by exercise. Accordingly, exercise has shown great promise and efficacy in preventing or slowing muscle wasting through changes in molecular physiology, organelle function, cell signaling pathways, and epigenetic regulation. In this review, we focus on the role of exercise in altering the molecular landscape of skeletal muscle in a manner that improves or maintains its health and function in the presence of unloading or disease.epigenetics; exercise; muscle wasting; resistance training; skeletal muscle.

Human Immune Cell Epigenomic Signatures in Response to Infectious Diseases and Chemical Exposures.

Variations in DNA methylation patterns in human tissues have been linked to various environmental exposures and infections. Here, we identified the DNA methylation signatures associated with multiple exposures in nine major immune cell types derived from peripheral blood mononuclear cells (PBMCs) at single-cell resolution. We performed methylome sequencing on 111,180 immune cells obtained from 112 individuals who were exposed to different viruses, bacteria, or chemicals. Our analysis revealed 790,662 differentially methylated regions (DMRs) associated with these exposures, which are mostly individual CpG sites. Additionally, we integrated methylation and ATAC-seq data from same samples and found strong correlations between the two modalities. However, the epigenomic remodeling in these two modalities are complementary. Finally, we identified the minimum set of DMRs that can predict exposures. Overall, our study provides the first comprehensive dataset of single immune cell methylation profiles, along with unique methylation biomarkers for various biological and chemical exposures.

Prophylactic surgery prior to extended-duration space flight: is the benefit worth the risk?

This article explores the potential benefits and defined risks associated with prophylactic surgical procedures for astronauts before extended-duration space flight. This includes, but is not limited to, appendectomy and cholecystesctomy. Furthermore, discussion of treatment during space flight, potential impact of an acute illness on a defined mission and the ethical issues surrounding this concept are debated in detail.

Resting-state heart rate variability after stressful events as a measure of stress tolerance among elite performers.

Introduction: A common trait of elite performers is their ability to perform well when stressed by strong emotions such as fear. Developing objective measures of stress response that reliably predict performance under stress could have far-reaching implications in selection and training of elite individuals and teams. Prior data suggests that (i) Heart rate and heart rate variability (HR/HRV) are associated with stress reaction, (ii) Higher basal sympathetic tone prior to stressful events is associated with higher performance, and (iii) Elite performers tend to exhibit greater increase in parasympathetic tone after a stressful event. Methods: The current study assesses the predictive utility of post-stressful event HR/HRV measures, an under-studied time point in HR/HRV research, in the context of military personnel selection. Specifically, we examined the relationship between a comprehensive set of HR/HRV measures and established questionnaires related to stress tolerance, experimental evaluation of executive function during stress induction, and ecologically valid selection assessment data from a week-long Special Operations Forces selection course (N = 30). Results: We found that post-stressful event HR/HRV measures generally had strong correlations with the neuroticism facet of the NEO personality inventory as well as the general and distress facets of the defensive reactivity questionnaire. HR/HRV measures correlated reliably with a change in executive function measured as a decrease in verbal fluency with exposure to a well-validated stressor. Finally, we observed a divergent pattern of correlation among elite and non-elite SOF candidates. Specifically, among elite candidates, parasympathetic nervous system (PNS) measures correlated positively and sympathetic nervous system (SNS) measures correlated negatively with evaluation of stress tolerance by experts and peers. This pattern was not present in non-elite candidates. Discussion: Our findings demonstrate that post-stressful event HR/HRV data provide an objective non-invasive method to measure the recovery and arousal state in direct reaction to the stressful event and can be used as metrics of stress tolerance that could enhance selection of elite individuals and teams.

Human Health during Space Travel: State-of-the-Art Review.

The field of human space travel is in the midst of a dramatic revolution. Upcoming missions are looking to push the boundaries of space travel, with plans to travel for longer distances and durations than ever before. Both the National Aeronautics and Space Administration (NASA) and several commercial space companies (e.g., Blue Origin, SpaceX, Virgin Galactic) have already started the process of preparing for long-distance, long-duration space exploration and currently plan to explore inner solar planets (e.g., Mars) by the 2030s. With the emergence of space tourism, space travel has materialized as a potential new, exciting frontier of business, hospitality, medicine, and technology in the coming years. However, current evidence regarding human health in space is very limited, particularly pertaining to short-term and long-term space travel. This review synthesizes developments across the continuum of space health including prior studies and unpublished data from NASA related to each individual organ system, and medical screening prior to space travel. We categorized the extraterrestrial environment into exogenous (e.g., space radiation and microgravity) and endogenous processes (e.g., alteration of humans' natural circadian rhythm and mental health due to confinement, isolation, immobilization, and lack of social interaction) and their various effects on human health. The aim of this review is to explore the potential health challenges associated with space travel and how they may be overcome in order to enable new paradigms for space health, as well as the use of emerging Artificial Intelligence based (AI) technology to propel future space health research.

Limited value of haptics in virtual reality laparoscopic cholecystectomy training.

BACKGROUND: Haptics is an expensive addition to virtual reality (VR) simulators, and the added value to training has not been proven. This study evaluated the benefit of haptics in VR laparoscopic surgery training for novices. METHODS: The Simbionix LapMentor II haptic VR simulator was used in the study. Randomly, 33 laparoscopic novice students were placed in one of three groups: control, haptics-trained, or nonhaptics-trained group. The control group performed nine basic laparoscopy tasks and four cholecystectomy procedural tasks one time with haptics engaged at the default setting. The haptics group was trained to proficiency in the basic tasks and then performed each of the procedural tasks one time with haptics engaged. The nonhaptics group used the same training protocol except that haptics was disengaged. The proficiency values used were previously published expert values. Each group was assessed in the performance of 10 laparoscopic cholecystectomies (alternating with and without haptics). Performance was measured via automatically collected simulator data. RESULTS: The three groups exhibited no differences in terms of sex, education level, hand dominance, video game experience, surgical experience, and nonsurgical simulator experience. The number of attempts required to reach proficiency did not differ between the haptics- and nonhaptics-training groups. The haptics and nonhaptics groups exhibited no difference in performance. Both training groups outperformed the control group in number of movements as well as path length of the left instrument. In addition, the nonhaptics group outperformed the control group in total time. CONCLUSION: Haptics does not improve the efficiency or effectiveness of LapMentor II VR laparoscopic surgery training. The limited benefit and the significant cost of haptics suggest that haptics should not be included routinely in VR laparoscopic surgery training.

Intra-abdominal pressure effects on porcine thoracic compliance in weightlessness: implications for physiologic tolerance of laparoscopic surgery in space.

OBJECTIVE: Laparoscopic surgery (LS) is envisioned as an option for spaceflight, but requires intra-abdominal hypertension (IAH) to create the surgical domain. Prolonged weightlessness induces physiologic deconditioning that questions the ability of ill or injured astronauts to tolerate IAH. On earth, IAH results in marked ventilatory embarrassment. As there has been no previous study of physiologic changes related to LS in weightlessness, we studied anesthetized pigs in parabolic flight. DESIGN: Parabolic flight research laboratory. SUBJECTS: Five anesthetized Yorkshire pigs. INTERVENTIONS: Subjects were transported from an animal care facility and secured aboard an aircraft capable of generating hypergravity and weightlessness. Mechanical ventilation was performed using pressure control and positive end-expiratory pressure at 15 and 2 cm H2O, respectively; rate 12 breaths/min. Three abdominal conditions were used during LS: insufflation to produce IAH, abdominal wall retraction (AWR), and no abdominal wall manipulation (baseline). During each parabola breath by breath-tidal volumes (Vt) were recorded by a transport ventilator (HT-50 Newport Medical). MEASUREMENTS AND MAIN RESULTS: Least square means (LS-means) of weight corrected Vt (milliliter per kilogram) by gravity (g) and abdominal condition were determined using a mixed effects model for repeated measures analysis. Increasing gravity (g) consistently reduced Vt (p = 0.0011) as did insufflation (p < 0.0001). In 1g, Vt (LS-mean 13.7, 95% confidence interval [CI]: 12.4-15.0) was relatively unaffected by AWR (LS-mean 12.8, 95% CI: 11.5-14.00), but markedly decreased by IAH (LS-mean 10.00, 95% CI: 8.9-11.1), an effect accentuated in hypergravity (LS-mean 8.1, 95% CI: 6.4-9.8). In weightlessness, Vt reduction during insufflation was near obviated (LS-mean 12.3, 95% CI: 10.6-14.1), and AWR regularly but inconsistently increased the Vt above 1g baseline (LS-mean 13.7, 95% CI: 11.7-15.8). CONCLUSIONS: Weightlessness protects against thoracic compliance changes that are inherent in IAH during induced pneumoperitoneum in gravity. The technique-related physiologic cost of performing LS in space deconditioned astronauts should be incorporated into design concepts for space surgery systems.

Evaluation of teleoperated surgical robots in an enclosed undersea environment.

The ability to support surgical care in an extreme environment is a significant issue for both military medicine and space medicine. Telemanipulation systems, those that can be remotely operated from a distant site, have been used extensively by the National Aeronautics and Space Administration (NASA) for a number of years. These systems, often called telerobots, have successfully been applied to surgical interventions. A further extension is to operate these robotic systems over data communication networks where robotic slave and master are separated by a great distance. NASA utilizes the National Oceanographic and Atmospheric Administration (NOAA) Aquarius underwater habitat as an analog environment for research and technology evaluation missions, known as NASA Extreme Environment Mission Operations (NEEMO). Three NEEMO missions have provided an opportunity to evaluate teleoperated surgical robotics by astronauts and surgeons. Three robotic systems were deployed to the habitat for evaluation during NEEMO 7, 9, and 12. These systems were linked via a telecommunications link to various sites for remote manipulation. Researchers in the habitat conducted a variety of tests to evaluate performance and applicability in extreme environments. Over three different NEEMO missions, components of the Automated Endoscopic System for Optimal Positioning (AESOP), the M7 Surgical System, and the RAVEN were deployed and evaluated. A number of factors were evaluated, including communication latency and semiautonomous functions. The M7 was modified to permit a remote surgeon the ability to insert a needle into simulated tissue with ultrasound guidance, resulting in the world's first semi-autonomous supervisory-controlled medical task. The deployment and operation of teleoperated surgical systems and semi-autonomous, supervisory-controlled tasks were successfully conducted.

Evaluation of unmanned airborne vehicles and mobile robotic telesurgery in an extreme environment.

As unmanned extraction vehicles become a reality in the military theater, opportunities to augment medical operations with telesurgical robotics become more plausible. This project demonstrated an experimental surgical robot using an unmanned airborne vehicle (UAV) as a network topology. Because battlefield operations are dynamic and geographically challenging, the installation of wireless networks is not a feasible option at this point. However, to utilize telesurgical robotics to assist in the urgent medical care of wounded soldiers, a robust, high bandwidth, low latency network is requisite. For the first time, a mobile surgical robotic system was deployed to an austere environment and surgeons were able to remotely operate the systems wirelessly using a UAV. Two University of Cincinnati surgeons were able to remotely drive the University of Washington's RAVEN robot's end effectors. The network topology demonstrated a highly portable, quickly deployable, bandwidth-sufficient and low latency wireless network required for battlefield use.

Manual suturing quality at acceleration levels equivalent to spaceflight and a lunar base.

INTRODUCTION: Cutaneous wounds, either from injuries or as a result of surgical incisions, are a likely possibility that future space medicine specialists will need to address. While there has been some prior study of manual suturing in microgravity (0 G), there has been no study of manual suturing in reduced gravity consistent with that of the Moon. METHODS: Six separate operators with varying degrees of surgical experience (four trained surgeons, and two non-surgeons) attempted to manually suture wound phantoms during the reduced gravity phases of parabolic flight simulating either 0 G or lunar gravity (0.16 G). Each operator subjectively evaluated the difficulty and relative speed in performing the same task in different environments, serving as their own internal control. There were 20-s periods of 1 G that were carefully timed for each surgeon to compare to the approximately 20 s available for each parabola of either 0 G or 0.16 G. RESULTS: Six periods of 1 G were used as controls to perform manual suturing of the phantoms. There were 51 parabolas of 0 G and 67 parabolas of 0.16 G performed by the six operators. As judged subjectively by the operators themselves and by group inspection of the sutured phantoms, there was no qualitative difference in the adequacy of wound closure as judged by suture placement accuracy and wound coaptation. There was consensus, though, that suturing in microgravity was significantly slower, as has been noted in more complex surgical studies. DISCUSSION: The technical aspects of wound management during exploration-class missions in prolonged microgravity or lunar missions with reduced gravity (0.16 G) will likely not present challenges beyond those faced in addressing the tremendous logistical and training obstacles to providing experienced and equipped surgeons on-board such a mission.

Evaluation of surgical skills in microgravity using force sensing.

INTRODUCTION: Force measurements can be used to characterize surgical maneuvers in microgravity. METHODS: : A series of surgical tasks was performed by a group of 20 participants (n=20) both in 1g on the ground and in 0 g aboard NASA's KC-135 aircraft in parabolic flight. The group included astronauts, a flight surgeon, surgeons, physicians, Ph.D.-scientists, and technical personnel. The interaction forces between the surgical instruments and the mock tissue were measured for a clip-applying, suturing, grasping, and cutting. Seven evaluations in 1g and a single evaluation in 0 g were performed by each of the participants. RESULTS: The data from a single participant are examined in detail. Statistical results for the group of 20 participants do not show significant differences in the average or peak forces during clip-applying or in the average forces applied during suturing in 0 g versus in 1g. However, the results do show statistically greater (43% higher) peak forces during suturing in microgravity. DISCUSSION: These data show the usefulness of analyzing force information to assess surgical task performance in microgravity. Although peak suturing forces were statistically higher in microgravity, their clinical relevance is unknown, but likely would not result in a change in clinical outcome. Overall, the data suggest that forces exerted during surgical tasks will not pose a significant barrier to effective surgery in microgravity.

Simulated hand-assisted laparoscopic surgery (HALS) in microgravity.

INTRODUCTION: Previous simulation and porcine experiments aboard the reduced gravity program KC-135 turbojet have demonstrated that microgravity surgery is feasible. Ideally, surgical care in spaceflight will incorporate recent advances in care while remaining easy enough for a crew medical officer (CMO) lacking surgical proficiency or extensive surgical experience to perform. As a minimally invasive surgical technique, hand-assisted laparoscopic surgery (HALS) benefits the patient via smaller incisions, less pain, and faster recovery than traditional open surgery. HALS also helps less experienced laparoscopic surgeons perform laparoscopic surgery. METHODS: An inexpensive inanimate surgical simulator was constructed to evaluate the usefulness of HALS in microgravity. This simulator was utilized during brief periods of microgravity provided by parabolic flight on the KC-135. The simulator was successfully used by both a physician-astronaut and an experienced laparoscopic surgeon. Task completion included simulated surgery with exploration of the intestines and ligation of the appendix. RESULTS: Simulated HALS was successfully performed in microgravity. HALS effectively contained operative equipment and small amounts of introduced fluids within the simulated abdominal cavity. Astronaut and surgeon experience suggest that HALS could facilitate minimally invasive surgery (MIS) in microgravity. DISCUSSION: HALS holds promise as a surgical approach in microgravity, particularly as space travel extends beyond low earth orbit. HALS provides the benefits of MIS, facilitates MIS surgery by less surgically proficient or experienced CMOs, and contains equipment and fluid within the operative field. Simulation provides an easy, cost-effective platform to evaluate medical technology for space flight as well as a method to train CMOs on-orbit.

Assessment of simulated surgical skills in parabolic microgravity.

BACKGROUND: During spaceflight crew health is paramount in the success of flight missions. The delivery of healthcare during flight requires crew readiness for medical and surgical response. METHODS: There were 20 participants who were evaluated for accurate performance of 4 basic laparoscopic surgical skills (clip applying, cutting, grasping, and suturing) during parabolic weightlessness using an inanimate workstation aboard the NASA KC-135 aircraft. RESULTS: Data indicate that motor skill performance decreased within the parabolic microgravity flight environment. Performance in parabolic microgravity flight included futile effort with an increase in number of tasks attempted and a decrease in tasks completed successfully. CONCLUSIONS: There is a decreased frequency of accurate task completion in parabolic microgravity flight, but it is not an obstacle to implementation of effective training for providing in-flight medical care. The data reveal that individuals perform basic laparoscopic surgical simulation with greater effort in microgravity following simulation training.

A novel telemedicine method for viewing the open surgical field.

BACKGROUND AND PURPOSE: The surgical theater has undergone a series of transformations from an open stadium-like environment to the closed environment of minimally invasive endoscopic surgery. Paradoxically, evolution from open surgery performed under direct vision to closed surgery performed through use of video images has been accompanied by improved viewing of the operative field by student observers. The objective of these experiments was to determine if a laparoscope mounted on the operating table during open surgery would provide students a better view of the operative field than that provided while standing behind the operating surgeon or via an optimally positioned hand-held video camera. MATERIALS AND METHODS: An endoscopic video camera and telescope were attached to an operating table by an Alpha Virtual Port, which facilitates use of the laparoscope in open surgery by fixing it to the operating table in the position of interest. Additional imaging systems were set up so as to simulate viewing of the surgical field by direct vision or a hand-held video camera. Common objects were placed on the operating table in mock surgical fields of various depth-to-aperture ratios. Images of these surgical fields were obtained by each of these systems and placed in a Web-based tool. Eleven people with a wide range of medical training evaluated the images and determined that the Alpha Port-mounted surgical telescope provided optimal visibility of the mock open surgical field. RESULTS AND CONCLUSION: The benefit of use of the mounted telescope was more pronounced as the depth-to-aperture ratio of the surgical field increased. Use of the Alpha Port-mounted laparoscope in open surgical procedures improves student viewing of the open surgical field.

Training in laparoscopic suturing skills using a new computer-based virtual reality simulator (MIST-VR) provides results comparable to those with an established pelvic trainer system.

BACKGROUND: We hypothesized that the Minimally Invasive Surgery Trainer (MIST-VR; VP Medical R, London, U.K.) would be as effective as the Yale Laparoscopic Skills Course in improving laparoscopic intracorporeal suturing skills. MATERIALS AND METHODS: Each student made six attempts to tie a knot laparoscopically. Students were then randomized to train on the MIST-VR for five sessions (six skills/session) or the Yale Skills for five sessions (three skills/session) over 5 days. On completion of training, all students were evaluated by a test consisting of six attempts to tie a laparoscopic knot. RESULTS: The percentage improvement in knot tying time did not differ significantly in the pelvic trainer group (30 +/- 21%) (from 443 +/- 135 to 311 +/- 137 seconds) and the MIST-VR group (39 +/- 21%) (from 409 +/- 109 to 256 +/- 140 seconds) (P = 0.308). CONCLUSIONS: The MIST-VR is equivalent to the Yale Skills Course for training in the advanced laparoscopic skill of intracorporeal suturing.

Evaluation of operative imaging techniques in surgical education.

BACKGROUND: Certain open surgical procedures are difficult to observe, and poor visualization of the surgical field results in a compromised teaching environment for residents and medical students. In an attempt to improve the visualization of the open surgical field, we performed an open surgical procedure while viewing it via a laparoscope mounted to the side of the operating room table with an alpha port. These images were then compared in a blinded fashion with images from a boom-mounted camera positioned above the surgical field and a head-mounted camera positioned on the operating surgeon. METHODS: Participants viewed all 3 images from a remote location in a blinded, random fashion. All participants then completed a Likert questionnaire evaluating each image. RESULTS: Fourteen participants were in the study. The alpha port/laparoscope image was superior to the head-cam image in all 8 categories. The alpha port/laparoscope image was superior to the sky-cam image in 4 of 8 categories. All 14 participants felt the alpha port/laparoscope image would benefit surgical education CONCLUSIONS: Use of a laparoscope mounted via an alpha port to an operating room table provides superior images during open surgery. This provides a unique and affordable way to teach residents and medical students operative procedures that are otherwise difficult to view.