Human Physiology During Exposure to the Cave Environment: A Systematic Review With Implications for Aerospace Medicine

Background: Successful long-duration missions outside low-Earth orbit will depend on technical and physiological challenges under abnormal environmental conditions. Caves, characterized by absence of light, confinement, three-dimensional human movement and long-duration isolation, are identifiably one of the earliest examples of scientific enquiry into space analogs. However, little is known about the holistic human physiological response during cave exploration or prolonged habitation.Objectives: The aim of our review was to conduct a systematic bibliographic research review of the effects of short and prolonged exposure to a cave environment on human physiology, with a view to extend the results to implications for human planetary exploration missions.Methods: A systematic search was conducted following the structured PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for electronic databases.Results: The search retrieved 1,519 studies. There were 50 articles selected for further consideration, of which 31 met our inclusion criteria. Short-term cave exposure studies have investigated visual dysfunction, cardiovascular, endocrine-metabolic, immunologic-hematological and muscular responses in humans. Augmentations of heart rate, muscular damage, initial anticipatory stress reaction and inflammatory responses were reported during caving activity. Prolonged exposure studies mainly investigated whether biological rhythms persist or desist in the absence of standard environmental conditions. Changes were evident in estimated vs. actual rest-activity cycle periods and external desynchronization, body temperature, performance reaction time and heart rate cycles. All studies have shown a marked methodological heterogeneity and lack reproduction under controlled conditions.Conclusions: This review facilitates a further comparison of the proposed physiological impact of a subterranean space analog environment, with existing knowledge in related disciplines pertaining to human operative preparation under challenging environmental conditions. This comprehensive overview should stimulate more reproducible research on this topic and offer the opportunity to advance study design and focus future human research in the cave environment on noteworthy, reproducible projects

Exercise training alone or in combination with high-protein diet in patients with late onset Pompe disease: results of a cross over study

15noBACKGROUND: Late onset Pompe disease (LOPD) is a lysosomal neuromuscular disorder which can progressively impair the patients' exercise tolerance, motor and respiratory functions, and quality of life. The available enzyme replacement therapy (ERT) does not completely counteract disease progression. We investigated the effect of exercise training alone, or associated with a high-protein diet, on the exercise tolerance, muscle and pulmonary functions, and quality of life of LOPD patients on long term ERT. METHODS: The patients were asked to participate to a crossover randomized study comprehending a control period (free diet, no exercise) followed by 2 intervention periods: exercise or exercise + diet, each lasting 26 weeks and separated by 13 weeks washout periods. Exercise training included moderate-intensity aerobic exercise on a cycle ergometer, stretching and balance exercises, strength training. The diet was composed by 25-30% protein, 30-35% carbohydrate and 35-40% fat. Before and after each period patients were assessed for: exercise tolerance test on a cycle-ergometer, serum muscle enzymes, pulmonary function tests and SF36 questionnaire for quality of life. Compliance was evaluated by training and dietary diaries. Patients were contacted weekly by researchers to optimize adherence to treatments. RESULTS: Thirteen LOPD patients, median age 49 ± 11 years, under chronic ERT (median 6.0 ± 4.0 years) were recruited. Peak aerobic power (peak pulmonary O2 uptake) decreased after control, whereas it increased after exercise, and more markedlyafter exercise + diet. Serum levels of lactate dehydrogenase (LDH) significantly decreased after exercise + diet; both creatine kinase (CK) and LDH levels were significantly reduced after exercise + diet compared to exercise. Pulmonary function showed no changes after control and exercise, whereas a significant improvement of forced expiratory volume in 1 sec (FEV1) was observed after exercise + diet. SF36 showed a slight improvement in the "mental component" scale after exercise, and a significant improvement in "general health" and "vitality" after exercise + diet. The compliance to prescriptions was higher than 70% for both diet and exercise. CONCLUSIONS: Exercise tolerance (as evaluated by peak aerobic power) showed a tendency to decrease in LOPD patients on long term ERT. Exercise training, particularly if combined with high-protein diet, could reverse this decrease and result in an improvement, which was accompanied by improved quality of life. The association of the two lifestyle interventions resulted also in a reduction of muscle enzyme levels and improved pulmonary function.openopenSechi A.; Zuccarelli L.; Grassi B.; Frangiamore R.; De Amicis R.; Marzorati M.; Porcelli S.; Tullio A.; Bacco A.; Bertoli S.; Dardis A.; Biasutti L.; Pasanisi M.B.; Devigili G.; Bembi B.Sechi, A.; Zuccarelli, L.; Grassi, B.; Frangiamore, R.; De Amicis, R.; Marzorati, M.; Porcelli, S.; Tullio, A.; Bacco, A.; Bertoli, S.; Dardis, A.; Biasutti, L.; Pasanisi, M. B.; Devigili, G.; Bembi, B

Expedition Cognition: A Review and Prospective of Subterranean Neuroscience With Spaceflight Applications

Renewed interest in human space exploration has highlighted the gaps in knowledge needed for successful long-duration missions outside low-Earth orbit. Although the technical challenges of such missions are being systematically overcome, many of the unknowns in predicting mission success depend on human behavior and performance, knowledge of which must be either obtained through space research or extrapolated from human experience on Earth. Particularly in human neuroscience, laboratory-based research efforts are not closely connected to real environments such as human space exploration. As caves share several of the physical and psychological challenges of spaceflight, underground expeditions have recently been developed as a spaceflight analog for astronaut training purposes, suggesting that they might also be suitable for studying aspects of behavior and cognition that cannot be fully examined under laboratory conditions. Our objective is to foster a bi-directional exchange between cognitive neuroscientists and expedition experts by (1) describing the cave environment as a worthy space analog for human research, (2) reviewing work conducted on human neuroscience and cognition within caves, (3) exploring the range of topics for which the unique environment may prove valuable as well as obstacles and limitations, (4) outlining technologies and methods appropriate for cave use, and (5) suggesting how researchers might establish contact with potential expedition collaborators. We believe that cave expeditions, as well as other sorts of expeditions, offer unique possibilities for cognitive neuroscience that will complement laboratory work and help to improve human performance and safety in operational environments, both on Earth and in space

Near-infrared spectroscopy estimation of combined skeletal muscle oxidative capacity and O2 diffusion capacity in humans

The final steps of the O2 cascade during exercise depend on the product of the microvascular-tointramyocyte PO2 difference and muscle O2 diffusing capacity (DmO2). Non-invasive methods to determine DmO2 in humans are currently unavailable. Muscle oxygen uptake (mVO2) recovery rate constant (k), measured by near-infrared spectroscopy (NIRS) using intermittent arterial occlusions, is associated with muscle oxidative capacity in vivo. We reasoned that k would be limited by DmO2 when muscle oxygenation is low (kLOW), and hypothesized that: i) k in well-oxygenated muscle (kHIGH) is associated with maximal O2 flux in fiber bundles; and ii) Δk (kHIGH-kLOW) is associated with capillary density (CD). Vastus lateralis k was measured in 12 participants using NIRS after moderate exercise. The timing and duration of arterial occlusions were manipulated to maintain tissue saturation index (TSI) within a 10% range either below (LOW) or above (HIGH) half-maximal desaturation, assessed during sustained arterial occlusion. Maximal O2 flux in phosphorylating state was 37.7±10.6 pmol·s−1·mg−1 (~5.8 ml·min−1·100g−1). CD ranged 348 to 586 mm-2. kHIGH was greater than kLOW (3.15±0.45 vs 1.56±0.79 min-1, p\u3c0.001). Maximal O2 flux was correlated with kHIGH (r=0.80, p=0.002) but not kLOW (r=-0.10, p=0.755). Δk ranged -0.26 to -2.55 min-1, and correlated with CD (r=- 0.68, p=0.015). mVO2 k reflects muscle oxidative capacity only in well-oxygenated muscle. Δk, the difference in k between well- and poorly-oxygenated muscle, was associated with CD, a mediator of DmO2. Assessment of muscle k and Δk using NIRS provides a non-invasive window on muscle oxidative and O2 diffusing capacity

Pathophysiology, risk, diagnosis, and management of venous thrombosis in space: where are we now?

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

Impact of sedentarism due to the COVID-19 home confinement on neuromuscular, cardiovascular and metabolic health: Physiological and pathophysiological implications and recommendations for physical and nutritional countermeasures.

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 O2 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 medium-intensity 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.Highlights This paper describes the impact of sedentarism, caused by the COVID-19 home confinement on the neuromuscular, cardiovascular, metabolic and endocrine systems.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

Pathophysiology, risk, diagnosis, and management of venous thrombosis in space: where are we now?

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

Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice

IMPORTANCE: It is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes. OBJECTIVE: To evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a pathogenic/likely pathogenic (P/LP) variant were included in the study. Case report forms were completed by all health care professionals. EXPOSURES: Genetic test results. MAIN OUTCOMES AND MEASURES: Clinical management changes after a genetic diagnosis (ie, 1 P/LP variant in autosomal dominant and X-linked diseases; 2 P/LP variants in autosomal recessive diseases) and subsequent patient outcomes as reported by health care professionals on case report forms. RESULTS: Among 418 patients, median (IQR) age at the time of testing was 4 (1-10) years, with an age range of 0 to 52 years, and 53.8% (n = 225) were female individuals. The mean (SD) time from a genetic test order to case report form completion was 595 (368) days (range, 27-1673 days). A genetic diagnosis was associated with changes in clinical management for 208 patients (49.8%) and usually (81.7% of the time) within 3 months of receiving the result. The most common clinical management changes were the addition of a new medication (78 [21.7%]), the initiation of medication (51 [14.2%]), the referral of a patient to a specialist (48 [13.4%]), vigilance for subclinical or extraneurological disease features (46 [12.8%]), and the cessation of a medication (42 [11.7%]). Among 167 patients with follow-up clinical information available (mean [SD] time, 584 [365] days), 125 (74.9%) reported positive outcomes, 108 (64.7%) reported reduction or elimination of seizures, 37 (22.2%) had decreases in the severity of other clinical signs, and 11 (6.6%) had reduced medication adverse effects. A few patients reported worsening of outcomes, including a decline in their condition (20 [12.0%]), increased seizure frequency (6 [3.6%]), and adverse medication effects (3 [1.8%]). No clinical management changes were reported for 178 patients (42.6%). CONCLUSIONS AND RELEVANCE: Results of this cross-sectional study suggest that genetic testing of individuals with epilepsy may be materially associated with clinical decision-making and improved patient outcomes