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Purpose: We examined changes in stride temporal parameters and spring-mass model characteristics during repeated sprints following a 3-week period of "live high–train low and high" (LHTLH) altitude training in team-sport players. Methods: While residing under normobaric hypoxia (≥14 h/d; inspired oxygen fraction [FiO2] 14.5%–14.2%) for 14 days, elite field hockey players performed, in addition to their regular field hockey practice in normoxia, 6 sessions (4 × 5 × 5-s maximal sprints; 25-s passive recovery; 5-min rest) under either normobaric hypoxia (LHTLH; FiO2 ∼14.5%, n = 11) or normoxia (live high–train low; FiO2 20.9%, n = 12). A control group (live low–train low; FiO2 ∼20.9%, n = 9) residing in normoxia without additional repeated-sprint training was included. Before (Pre) and a few days (Post-1) and 3 weeks (Post-2) after the intervention, stride mechanics were assessed during an overground repeated-sprint test (8 × 20 m, 20-s recovery). Two-way repeated-measures analysis of variance (time [Pre, Post-1, and Post-2] × condition [LHTLH, live high–train low, and live low–train low]) were conducted. Results: Peak sprinting speed increased in LHTLH from Pre to Post-1 (+2.2% [2.0%]; P =.002) and Post-2 (+2.0% [2.4%]; P =.025), with no significant changes in live high–train low and live low–train low. There was no main effect of time (all P ≥.062), condition (all P ≥.771), or a significant time × condition interaction (all P ≥.230) for any stride temporal variable (contact time, flight time, stride frequency, and stride length) or spring-mass model characteristics (vertical and leg stiffness). Conclusions: Peak sprinting speed improved in elite field hockey players following LHTLH altitude training, while stride mechanical adjustments to repeated overground sprints remained unchanged for at least 3 weeks postintervention. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effects of repeated-sprint training with voluntary hypoventilation at low (RSH-VHL) and high (RS-VHH) lung volume on repeated-sprint ability (RSA) in female athletes. Methods: Over a 6-week period, 24 female soccer players completed 12 sessions of repeated 30-m running sprints with end-expiratory breath holding (RSH-VHL, n = 8), end-inspiratory breath holding (RS-VHH, n = 8), or unrestricted breathing (RS-URB, n = 8). Before and after training, a running RSA test consisting of performing 30-m all-out sprints until exhaustion was implemented. Results: From before to after training, the number of sprints completed during the RSA test was increased in both RSH-VHL (19.3 [0.9] vs 22.6 [0.9]; P <.01) and RS-VHH (19.3 [1.5] vs 20.5 [1.7]; P <.01) but not in RS-URB (19.4 [1.3] vs 19.5 [1.7]; P =.67). The mean velocity and the percentage decrement score calculated over sprints 1 to 17 were, respectively, higher (82.2% [1.8%] vs 84.6% [2.1%] of maximal velocity) and lower (23.7% [3.1%] vs 19.4% [3.2%]) in RSH-VHL (P <.01), whereas they remained unchanged in RS-VHH and RS-URB. The mean arterial oxygen saturation recorded during training at the end of the sprints was lower in RSH-VHL (92.1% [0.4%]) than in RS-VHH (97.3% [0.1%]) and RS-URB (97.8% [0.1%]). Conclusions: This study shows that female athletes can benefit from the RSH-VHL intervention to improve RSA. The performance gains may have been limited by the short sprinting distance with end-expiratory breath holding, which provoked only moderate hypoxemia. The increase in the number of sprints in RS-VHH seems to show that factors other than hypoxia may have played a role in RSA improvement. [ABSTRACT FROM AUTHOR]

Purpose: We examined the effects of increasing hypoxia severity on oxygenation kinetics in the vastus lateralis muscle during repeated treadmill sprints, using statistical parametric mapping (SPM). Methods: Ten physically active males completed 8 sprints of 5 seconds each (recovery = 25 s) on a motorized sprint treadmill in normoxia (sea level; inspired oxygen fraction = 0.21), moderate hypoxia (inspired oxygen fraction = 0.17), and severe hypoxia (SH; inspired oxygen fraction = 0.13). Continuous assessment of tissue saturation index (TSI) in the vastus lateralis muscle was conducted using near-infrared spectroscopy. Subsequently, TSI data were averaged for the sprint–recovery cycle of all sprints and compared between conditions. Results: The SPM analysis revealed no discernible difference in TSI signal amplitude between conditions during the actual 5-second sprint phase. However, during the latter portion of the 25-second recovery phase, TSI values were lower in SH compared with both sea level (from 22 to 30 s; P =.003) and moderate hypoxia (from 16 to 30 s; P =.001). The mean distance covered at sea level (22.9 [1.0] m) was greater than for both moderate hypoxia (22.5 [1.2] m; P =.045) and SH (22.3 [1.4] m; P =.043). Conclusions: The application of SPM demonstrated that only SH reduced muscle oxygenation levels during the late portion of the passive (recovery) phase and not the active (sprint) phase during repeated treadmill sprints. These findings underscore the usefulness of SPM for assessing muscle oxygenation differences due to hypoxic exposure and the importance of the duration of the between-sprints recovery period. [ABSTRACT FROM AUTHOR]

Background: Repeated exposure to heat (ie, plasma volume expansion) or altitude (ie, increase in total hemoglobin mass), in conjunction with exercise, induces hematological adaptations that enhance endurance performance in each respective environment. Recently, combining heat and altitude training has become increasingly common for athletes preparing to compete in temperate, sea-level conditions. Purpose: To review the physiological adaptations to training interventions combining thermal and hypoxic stimuli and summarize the implications for temperate, sea-level performance. Current Evidence: To date, research on combining heat and hypoxia has employed 2 main approaches: simultaneously combining the stressors during training or concurrently training in the heat and sleeping at altitude, sometimes with additional training in hypoxia. When environmental stimuli are combined in a training session, improvements in aerobic fitness and time-trial performance in temperate, sea-level conditions are generally similar in magnitude to those observed with heat, or altitude, training alone. Similarly, training in the heat and sleeping at altitude does not appear to provide any additional hematological or nonhematological benefits for temperate; sea-level performance relative to training in hot, hypoxic, or control conditions. Conclusions: Current research regarding combined heat and altitude interventions does not seem to indicate that it enhances temperate, sea-level performance to a greater extent than "traditional" (heat or hypoxia alone) training approaches. A major challenge in implementing combined-stressor approaches lies in the uncertainty surrounding the prescription of dosing regimens (ie, exercise and environmental stress). The potential benefits of conducting heat and altitude exposure sequentially (ie, one after the other) warrants further investigation. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate acute psychophysiological responses to repeated-sprint training in hypoxia (RSH) combined with whole-body cryotherapy (WBC). Method: Sixteen trained cyclists performed 3 sessions in randomized order: RSH, WBC-RSH (WBC pre-RSH), and RSH-WBC (WBC post-RSH). RSH consisted of 3 sets of 5 × 10-second sprints with 20-second recovery at a simulated altitude of 3000 m. Power output, muscle oxygenation (tissue saturation index), heart-rate variability, and recovery perception were analyzed. Sleep quality was assessed on the nights following test sessions and compared with a control night using nocturnal ActiGraphy and heart-rate variability. Results: Power output did not differ between the conditions (P =.27), while the decrease in tissue saturation index was reduced for WBC-RSH compared to RSH-WBC in the last set. In both conditions with WBC, the recovery perception was higher compared to RSH (WBC-RSH: +15.4%, and RSH-WBC: +21.9%, P <.05). The number of movements during the RSH-WBC night was significantly lower than for the control night (−18.7%, P <.01) and WBC-RSH (−14.9%, P <.05). RSH led to a higher root mean square of the successive differences of R-R intervals and high-frequency band during the first hour of sleep compared to the control night (P <.05) and RSH-WBC (P <.01). Conclusions: Inclusion of WBC in an RSH session did not modify the power output but could improve prolonged performance in hypoxia by maintaining muscle oxygenation. A single RSH session did not deteriorate sleep quality. WBC, particularly when performed after RSH, positively influenced recovery perception and sleep. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effect of cycling-based repeated-sprint training in hypoxia versus in normoxia on single overground running sprint performance and associated force–velocity (F–V) profile in world-class female rugby sevens players. Methods: Eighteen world-class female rugby sevens players were randomly assigned to repeated-sprint cycling training in normobaric hypoxia (n = 9) or normoxia (n = 9) groups. Training consisted of 4 sessions of repeated-sprint cycling training in normobaric hypoxia or in normoxia (4 × 5 × 5-s cycle sprints—25-s intersprint recovery performed in simulated altitude of ∼5000 m or in normoxia with 3-min interset rest in normoxia for both groups) in addition to rugby sevens training and strength and conditioning sessions within a 9-day intervention period before an international competition. Before and 1 day after the intervention, single 50-m overground running "all-out" sprint performance and associated F–V-related mechanical output were assessed. Results: No interaction (group × time; all P >.088), time effect (before vs 1 d after; all P >.296), or group effect (repeated-sprint cycling training in normobaric hypoxia vs in normoxia; all P >.325) was detected for 50-m overground running sprint performance and any derived F–V profiling variables. Conclusions: Four sessions of repeated-sprint training either in hypoxia or in normoxia performed over 9 days had no influence on single 50-m overground running sprint performance and associated F–V profile. In world-class female rugby sevens players, the intervention (training camp before an international competition) might have been too short to induce measurable changes. It is also plausible that implementing a similar program in players with likely different F–V profile may result in negligible mechanical effect. [ABSTRACT FROM AUTHOR]

Purpose: Total hemoglobin mass (tHbmass) and blood volume (BV) are important determinants of maximal oxygen uptake and endurance capacity. Higher-caliber endurance athletes usually possess higher tHbmass and BV values. This study aimed to compare tHbmass and BV among swimmers of diverse competitive calibers and distances. Methods: Thirty swimmers (16 female and 14 male) participated in the study: 3 were tier 5, world class (869 [59] FINA points); 15 were tier 4, elite/international (853 [38] points); and 12 were tier 3, highly trained/national (808 [35] points). They specialized in competition distances ranging from 200 m to open-water 10 km. Between February 2019 and February 2020, all swimmers had their tHbmass and BV measured by carbon monoxide rebreathing 1 to 6 times and participated in multiple competitions and race events. Results: Relative tHbmass and BV were not different (P >.05) between tiers among women or among men (pooled tHbmass values 14.5 [0.5], 12.5 [1.5], 12.6 [2.3] g/kg for tier 5, tier 4, and tier 3, respectively). No differences were observed in relative tHbmass (P =.215) and BV (P =.458) between pool and open-water swimmers or between 200-, 400-, and 1500-m specialists (P >.05). No significant correlations were found between the highest measured absolute or relative tHbmass and BV and the highest FINA points scored over the follow-up period (R = −.42–.17, P =.256–.833), irrespective of competition distance. Conclusion: tHbmass and BV values did not differ between swimmers of different calibers or among competition distances. Furthermore, these values did not correlate with FINA points, either in males or in females. The present results indicate that hematological characteristics may have a lesser impact on swimming performance than on land-based endurance sports. [ABSTRACT FROM AUTHOR]

Purpose: To compare the effects of graded hypoxia during exhaustive intermittent cycling on subsequent rapid and maximal torque-production capacity. Methods: Fifteen well-trained cyclists repeated intermittent cycling bouts (15 s at 30% of anaerobic power reserve; rest = 45 s) until exhaustion at sea level (FiO2 ∼0.21/end-exercise arterial oxygen saturation ∼96%), moderate hypoxia (FiO2 ∼0.16/∼90%), and severe hypoxia (FiO2 ∼0.12/∼79%). Rapid (rate of torque development [RTD]) and maximal isometric torque-production capacities of the knee extensors were assessed at baseline (visit 1) and exhaustion (visits 2–4). Results: Exercise capacity decreased with hypoxia severity (39 [30], 22 [13], and 13 [6] cycle efforts in sea level, moderate hypoxia, and severe hypoxia, respectively; P =.002). Changes in maximal-voluntary-contraction torque between baseline and postexercise in all conditions were not statistically significant (pooled values: −2.6% [5.7%]; P =.162). Peak RTD measured postexercise was reduced below baseline in all conditions (–21.5% [5.1%]; P ≤.015). Compared with baseline, absolute RTD values were lower at 0- to 30-millisecond (–35.1% [5.3%], P ≤.020), 0- to 50-millisecond (–40.0% [3.9%], P ≤.002), 0- to 100-millisecond (–30.7% [3.7%], P ≤.001), and 0- to 200-millisecond (–18.1% [2.4%], P ≤.004) time intervals in all conditions. Conclusions: Exhaustive intermittent cycling induces substantial yet comparable impairments in RTD of knee extensors between normoxia and moderate to severe hypoxia. [ABSTRACT FROM AUTHOR]

Objectives: Repeated-sprint training in hypoxia (RSH) is an effective way of improving physical performance compared with similar training in normoxia. RSH efficiency relies on hypoxia severity, but also on the oxidative–glycolytic balance determined by both sprint duration and exercise-to-rest ratio. This study investigated the effect of 2 types of RSH sessions during a classic altitude camp in world-class female rugby sevens players. Methods: Sixteen players performed 5 RSH sessions on a cycle ergometer (simulated altitude: 3000 m above sea level [asl]) during a 3-week natural altitude camp (1850 m asl). Players were assigned to 2 different protocols with either a high (RSH1:3, sprint duration: 8–10 s; exercise-to-rest ratios: 1:2–1:3; n = 7) or a low exercise-to-rest ratio (RSH1:5, sprint duration: 5–15 s; exercise-to-rest ratios: 1:2–1:5; n = 9). Repeated-sprint performances (maximal and mean power outputs [PPOmax, and PPOmean]) were measured before and after the intervention, along with physiological responses. Results: PPOmax (962 [100] to 1020 [143] W, P =.008, Cohen d = 0.47) and PPOmean (733 [71] to 773 [91] W, P =.008, d = 0.50) increased from before to after. A significant interaction effect (P =.048, d = 0.50) was observed for PPOmean, with a larger increase observed in RSH1:3 (P =.003). No interaction effects were observed (P >.05) for the other variables. Conclusion: A classic altitude camp with 5 RSH sessions superimposed on rugby-sevens-specific training led to an improved repeated-sprint performance, suggesting that RSH effects are not blunted by prolonged hypoxic exposure. Interestingly, using a higher exercise-to-rest ratio during RSH appears to be more effective than when applying a lower exercise-to-rest ratio. [ABSTRACT FROM AUTHOR]

Purpose: In short-track speed skating, athletes need to possess specific physiological capabilities to perform explosive starts and to finish races with faster lap times than their opponents. Repeated-sprint training in hypoxia (RSH) can enhance repeated-sprint ability and high-intensity performance. This study aimed to evaluate the relationship between on- and off-ice performance indicators for training and testing purposes and how these are optimized with RSH in world-class short-track speed skaters including world and Olympic champions. Methods: RSH training was administered for 3 consecutive weeks, 3 times per week, at 3500 m of simulated altitude. Testing sessions (on-ice: 3-lap, 27-lap; off-ice: cycling incremental test, 7-s and 30-s Wingate) were performed immediately before and 2 and 4 weeks after RSH to determine the time course of decay. Results: On-ice top speed showed a small and possibly beneficial change of ∼0.9% for the women and large and almost certain ∼0.7% improvement for the men 2 weeks post-RSH. Cycling peak power showed a moderate and probable ∼5.4% improvement for the men 2 weeks after RSH. These adaptations reverted to baseline 4 weeks post-RSH. Wingate average power showed a small and possibly beneficial gain (∼3.4%) in performance 4 weeks post-RSH. Conclusion: Although scientific controls could not be added due to the extremely high caliber of these athletes and low sample size of the national team, this study suggests that cycling RSH can be added immediately after on-ice training and can transfer into meaningful improvements on the ice in both male and female skaters. [ABSTRACT FROM AUTHOR]

Introduction Inhaled nitric oxide (INO) is a selective pulmonary vasodilator delivered from compressed gas cylinders filled to 2,200 psig (137.8 bar) with 800 ppm of NO in a balance of nitrogen. NO is currently FDA-approved for use in term or near-term infants with hypoxemia and signs of pulmonary hypertension in the absence of cardiac disease. INO has also been shown to improve oxygenation in adults with refractory hypoxemia. Current doctrine precludes the use of NO during military aeromedical transport owing to the requirement for large compressed gas cylinders. We performed a bench evaluation of 2 delivery systems that create NO from room air without the need for pressurized cylinders, Materials and Methods We evaluated 2 portable nitric oxide INO generation systems (LungFit PH, Beyond Air Inc, Garden City, NJ and a prototype NO generator, Odic Inc, Littleton, MA) at ground level, 8,000, and 14,000 feet (2,437 and 4,267 meter) simulated altitude in an altitude chamber. The output from each device was injected into the inspiratory limb of the ventilator circuit that was attached to a test lung. A 731 ventilator (Zoll Medical, Chelmsford, MA) and T1 (Hamilton Medical, Reno, NV) were used employing 24 combinations of ventilator settings each repeated in duplicate. An INOmax DS IR was used to measure delivered INO and NO2 via a sampling line attached in the ventilator circuit inspiratory limb. A fast response oxygen analyzer (O2CAP, Oxigraf Inc, Sunnyvale, CA) was used to measure inspired FiO2. Target INO concentration was 20 ppm. Results Across all ventilator settings, the LungFit device delivered INO was 19.8 ± 1.6 ppm, 16.1 ± 1.9 ppm, and 11.6 ± 1.7 ppm at ground level, 8,000 ft (2,437 meter), and 14,000 ft (4,267 meter), respectively. The Odic device delivered INO dose was 20.6 ± 1.4 ppm, 21.3 ± 5.5 ppm, and 20.4 ± 9.1 ppm at ground level, 8,000 ft (2,437 meter), and 14,000 ft (4,267 meter), respectively. Conclusions Both devices delivered a reliable INO dose at ground level. Altitude significantly affected INO delivery accuracy at 14,000 ft (4,267 meter) (P  < 0.01) with both devices and at 8,000 ft (2,437 meter) (P  < 0.01) with LungFit. Differences in INO dosage were not statistically significant with the Odic device at 8,000 ft (2,437 meter)(P  > 0.05) although there were large variations with selected ventilator settings. With careful monitoring, devices creating INO from room air without cylinders could be used during aeromedical transport without the need for pressurized cylinders. [ABSTRACT FROM AUTHOR]

Clinical and experimental studies have been shown,that after the combined craniocerebral injury, physiological mechanisms are damaged We maintain perfusion pressure. Partially or completely disruptedShares Autoregulating the brain blood flow. In these conditions after the craniocerebral injury, the brain is not able to respond to the systemic violator Wear homeostasis. As a result, various secondary damage ariseIn the brain tissue is predominantly corridor character thatWe are curved in 80-90% of the dead patients. Is currently among the systemsviolations of homeostasis, most often as secondary damaging factors of the headthe brain. The following: hypotension, hypoxemia, sodium exchange and osmotoostomy, hypocapnia and hyperDrip, hyperthermia, extra-causal inflammatory complications, etc. [1,2,3,4,10,11]. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate the accuracy of peripheral oxygen saturation (SpO2) measurements from Polar Elixir™ pulse oximetry technology compared with arterial oxygen saturation (SaO2) measurements during acute stepwise steady-state inspired hypoxia at rest. A post hoc objective was to determine if SpO2 measurements could be improved by recalibrating the Polar Elixir™ algorithm with SaO2 values from a random subset of participants. Methods: The International Organization for Standardization (ISO) protocol (ISO 80601-2-61:2017) for evaluating the SpO2 accuracy of pulse oximeter equipment was followed whereby five plateaus of SaO2 between 70% and 100%were achieved using stepwise reductions in inspired O2 during supine rest. Blood samples drawn through a radial arterial catheter from 25 participants were first used to compare SaO2 with SpO2 measurements from Polar Elixir™. Then the Polar Elixir™ algorithm was recalibrated using SaO2 data from 13 random participants, and SpO2 estimates were recalculated for the other 12 participants. For SaO2 values between 70%and 100%, root mean square error, intraclass correlation coefficients (ICC), Pearson correlations, and Bland--Altman plots were used to assess the accuracy, agreement, and strength of relationship between SaO2 values and SpO2 values from Polar Elixir™. Results: The initial root mean square error for Polar Elixir™ was 4.13%. After recalibrating the algorithm, the RMSE was improved to 2.67%. The ICC revealed excellent levels of agreement between SaO2 and Polar Elixir™SpO2 values both before (ICC(1,3) = 0.837, df = 574, P < 0.001) and after (ICC(1,3) = 0.942, df = 287, P < 0.001) recalibration. Conclusions: Relative to ISO standards, Polar Elixir™ yielded accurate SpO2 measurements during stepwise inspired hypoxia at restwhen comparedwith SaO2 values, which were improved by recalibrating the algorithm using a subset of the SaO2 data. [ABSTRACT FROM AUTHOR]

Ageing is a natural ontogenetic phenomenon that entails a decrease in the adaptive capacity of the organism, as a result of which the body becomes less adaptable to stressful conditions. Nitrate and nitrite enter the body from exogenous sources and from nitrification of ammonia nitrogen by intestinal microorganisms. This review considers the mechanisms of action of l -arginine, a known inducer of nitric oxide (NO) biosynthesis, and nitrates as supplements in the processes of ageing and aggravated stress states, in which mechanisms of individual physiological reactivity play an important role. This approach can be used as an element of individual therapy or prevention of premature ageing processes depending on the different levels of initial reactivity of the functional systems. A search was performed of the PubMed, Scopus, and Google Scholar databases (n = 181 articles) and the author's own research (n = 4) up to May 5, 2023. The review presents analyses of data on targeted treatment of NO generation by supplementation with l -arginine or nitrates, which is a promising means for prevention of hypoxic conditions frequently accompanying pathological processes in an ageing organism. The review clarifies the role of the individual state of physiological reactivity, using the example of individuals with a high predominance of cholinergic regulatory mechanisms who already have a significant reserve of adaptive capacity. In studies of the predominance of adrenergic influences, a poorly trained organism as well as an elderly organism correspond to low resistance, which is an additional factor of damage at increased energy expenditure. Conclusion It is suggested that the role of NO synthesis from supplementation of dietary nitrates and nitrites increases with age rather than from oxygen-dependent biosynthetic reactions from l -arginine supplementation. [ABSTRACT FROM AUTHOR]

Cellular responses to hypoxia are crucial in various physiological and pathophysiological contexts and have thus been extensively studied. This has led to a comprehensive understanding of the transcriptional response to hypoxia, which is regulated by hypoxia-inducible factors (HIFs). However, the detailed molecular mechanisms of HIF regulation in hypoxia remain incompletely understood. In particular, there is controversy surrounding the production of mitochondrial reactive oxygen species (ROS) in hypoxia and how this affects the stabilization and activity of HIFs. This review examines this controversy and attempts to shed light on its origin. We discuss the role of physioxia versus normoxia as baseline conditions that can affect the subsequent cellular response to hypoxia and highlight the paucity of data on pericellular oxygen levels in most experiments, leading to variable levels of hypoxia that might progress to anoxia over time. We analyze the different outcomes reported in isolated mitochondria, versus intact cells or whole organisms, and evaluate the reliability of various ROS-detecting tools. Finally, we examine the cell-type and context specificity of oxygen's various effects. We conclude that while recent evidence suggests that the effect of hypoxia on ROS production is highly dependent on the cell type and the duration of exposure, efforts should be made to conduct experiments under carefully controlled, physiological microenvironmental conditions in order to rule out potential artifacts and improve reproducibility in research. [ABSTRACT FROM AUTHOR]

Clathrin-associated trafficking is a major mechanism for intracellular communication, as well as for cells to communicate with the extracellular environment. A decreased oxygen availability termed hypoxia has been described to influence this mechanism in the past. Mostly biochemical studies were applied in these analyses, which miss spatiotemporal information. We have applied live cell microscopy and a newly developed analysis script in combination with a GFP-tagged clathrin-expressing cell line to obtain insight into the dynamics of the effect of hypoxia. Number, mobility and directionality of clathrin-coated vesicles were analysed in non-stimulated cells as well as after stimulation with epidermal growth factor (EGF) or transferrin in normoxic and hypoxic conditions. These data reveal cargo-specific effects, which would not be observable with biochemical methods or with fixed cells and add to the understanding of cell physiology in hypoxia. The stimulus-dependent consequences were also reflected in the final cellular output, i.e. decreased EGF signaling and in contrast increased iron uptake in hypoxia. [ABSTRACT FROM AUTHOR]

The article comments on a study which observed the implementation of an automated oxygen control system in a tertiary care hospital. Emphasis is given on the need of automated oxygen control systems for accurate calibration to arterial oxygen saturation given the possible occurrence of software bugs. The potential benefits and potential disadvantages of routine use of automated oxygen administration systems are highlighted.

BACKGROUND: The ratio of oxygen saturation index (ROX index; or .../.../breathing frequency) has been shown to predict risk of intubation after high-flow nasal cannula (HFNC) support among adults with acute hypoxemic respiratory failure primarily due to pneumonia. However, its predictive value for other subtypes of respiratory failure is unknown. This study investigated whether the ROX index predicts liberation from HFNC or noninvasive ventilation (NIV), intubation with mechanical ventilation, or death in adults admitted for respiratory failure due to an exacerbation of COPD. METHODS: We performed a retrospective study of 260 adults hospitalized with a COPD exacerbation and treated with HFNC and/or NIV (continuous or bi-level). ROX index scores were collected at treatment initiation and predefined time intervals throughout HFNC and/or NIV treatment or until the subject was intubated or died. A ROX index score of ≥ 4.88 was applied to the cohort to determine if the same score would perform similarly in this different cohort. Accuracy of the ROX index was determined by calculating the area under the receiver operator curve. RESULTS: A total of 47 subjects (18%) required invasive mechanical ventilation or died while on HFNC/NIV. The ROX index at treatment initiation, 1 h, and 6 h demonstrated the best prediction accuracy for avoidance of invasive mechanical ventilation or death (area under the receiver operator curve 0.73 [95% CI 0.66-0.80], 0.72 [95% CI 0.65-0.79], and 0.72 [95% CI 0.63-0.82], respectively). The optimal cutoff value for sensitivity (Sn) and specificity (Sp) was a ROX index score > 6.88 (sensitivity 62%, specificity 57%). CONCLUSIONS: The ROX index applied to adults with COPD exacerbations treated with HFNC and/or NIV required higher scores to achieve similar prediction of low risk of treatment failure when compared to subjects with hypoxemic respiratory failure/pneumonia. ROX scores < 4.88 did not accurately predict intubation or death. [ABSTRACT FROM AUTHOR]

BACKGROUND: When treating acute respiratory failure, both hypoxemia and hyperoxemia should be avoided. ... should be monitored closely and O2 flows adjusted accordingly. Achieving this goal might be easier with automated O2 titration compared with manual titration of fixed-flow O2. We evaluated the feasibility of using an automated O2 titration device in subjects treated for acute hypoxemic respiratory failure in a tertiary care hospital. METHODS: Health-care workers received education and training about oxygen therapy, and were familiarized with an automated O2 titration device (FreeO2,). A coordinator was available from 8:00 AM to 5:00 PM during weekdays to provide technical assistance. The ability of the device to maintain ... within the prescribed therapeutic window was recorded. Basic clinical information was recorded. RESULTS: Subjects were enrolled from November 2020 to August 2022. We trained 508 health-care workers on the use of automated O2 titration, which was finally used on 872 occasions in 763 subjects, distributed on the respiratory, COVID-19, and thoracic surgery wards, and in the emergency department. Clinical information could be retrieved for 609 subjects (80%) who were on the system for a median (interquartile range) of 3 (2-6) d, which represented 2,567 subject-days of clinical experience with the device. In the 82 subjects (14%) for whom this information was available, the system maintained ... within the prescribed targets 89% of the time. Ninety-six subjects experienced clinical deterioration as defined by the need to be transferred to the ICU and/or requirement of high flow nasal oxygen but none of these events were judged to be related to the O2 device. CONCLUSIONS: Automated O2 titration could be successfully implemented in hospitalized subjects with hypoxemic respiratory failure from various causes. This experience should foster further improvement of the device and recommendations for an optimized utilization. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether Buthus martensii karsch (Scorpiones), Scolopendra subspinipes mutilans L. Koch (Scolopendra) and Gekko gecko Linnaeus (Gekko) could ameliorate the hypoxic tumor microenvironment and inhibit lung cancer growth and metastasis by regulating phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin/hypoxia-inducible factor-1α (PI3K/AKT/mTOR/HIF-1α) signaling pathway. Methods: Male C57BL/6J mice were inoculated with luciferase labeled LL/2-luc-M38 cell suspension to develop lung cancer models, with rapamycin and cyclophosphamide as positive controls. Carboxy methyl cellulose solutions of Scorpiones, Scolopendra and Gekko were administered intragastrically as 0.33, 0.33, and 0.83 g/kg, respectively once daily for 21 days. Fluorescent expression were detected every 7 days after inoculation, and tumor growth curves were plotted. Immunohistochemistry was performed to determine CD31 and HIF-1α expressions in tumor tissue and microvessel density (MVD) was analyzed. Western blot was performed to detect the expression of PI3K/AKT/mTOR/HIF-1α signaling pathway-related proteins. Enzyme-linked immunosorbent assay was performed to detect serum basic fibroblast growth factor (bFGF), transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor (VEGF) in mice. Results: Scorpiones, Scolopendra and Gekko prolonged the survival time and inhibited lung cancer metastasis and expression of HIF-1α (all P<0.01). Moreover, Scorpiones, Scolopendra and Gekko inhibited the phosphorylation of AKT and ribosomal protein S6 kinase (p70S6K) (P<0.05 or P<0.01). In addition, they also decreased the expression of CD31, MVD, bFGF, TGF-β1 and VEGF compared with the model group (P<0.05 or P<0.01). Conclusion: Scorpiones, Scolopendra and Gekko all showed beneficial effects on lung cancer by ameliorating the hypoxic tumor microenvironment via PI3K/AKT/mTOR/HIF-1α signaling pathway. [ABSTRACT FROM AUTHOR]

Objective: Identification of at risk patients before surgery could facilitate improved clinical communication, care pathways and postoperative pain management Design: A retrospective cohort study was performed in all infants who had undergone cleft palate repair. Setting: Tertiary Institutional Participants: Infants < 36 months of age who underwent primary repair of cleft palate between March 2016 and July 2022 Intervention: Requirement for analgesic intervention in the post operative care unit Main outcome measure: Adverse perioperative event defined as pain or distress. Secondary outcomes were the incidence of airway obstruction, hypoxemia or unplanned intensive care admission. Results: Two hundred and ninety one patients (14.6 months,10.1 kg weight) were included. Cleft distribution included submucous (5.2%), Veau I (23.4%), Veau 2 (38.1%), Veau 3 (24.4%), and Veau 4 (8.9%). Overall 35% of 291 infants undergoing cleft palate repair experienced pain or distress requiring opiate intervention in the first hour after surgery. Infants with a Veau 4 cleft palate had 1.8 times and Veau 2 cleft palate had 1.5 times the risk of postoperative pain compared to infants with Veau 1 cleft palate (relative risk 1.82, 95%CI 1.04−3.18 and 1.49, 95%CI 0.96−2.32 respectively). The use of bilateral above elbow arm splints was significantly associated with postoperative pain or distress (odds ratio 2.23, 95%CI 1.01−5.16). Conclusions: Post operative pain requiring intervention in PACU is common despite adequate intraoperative multimodal analgesia, local anaesthesia infiltration and postoperative opiate infusions. Infants undergoing soft palate alone or submucous palate repair may require less perioperative opiates. [ABSTRACT FROM AUTHOR]

Varying rates of complications have been reported for prehospital sedation with ketamine, and the relationship to dosing has not been studied on a large scale. We evaluated the association between prehospital ketamine dosing and rates of intubations and other adverse events in patients with behavioral emergencies. Using the 2018/2019 ESO public-use research datasets, we included all non-traumatic, adult behavioral and drug-related EMS encounters with ketamine administration. Based on consensus guidelines, we stratified patients into "above" and "at/below" the maximum dosing for sedation (2 mg/kg IV/IO or 5 mg/kg IM) using the highest single dose of ketamine given. We created propensity scores for matched subjects using 1:1 propensity score matching. Using logistic regression, we compared rates of intubation and other airway interventions, antipsychotic coadministration, improvement reported by EMS, hypoxia, hypotension, and cardiac arrest between the two groups. We included 2383 patients: 478 in the above and 1905 in the at/below dose group. Above-dose ketamine was associated with a higher rate of intubation or supraglottic airway placement (6.4% v 3.3%, OR 2.0, 95% CI 1.00–3.90). Other airway interventions were similar (40.0% v 40.0%, OR 1, 95% CI 0.80–1.30). The above-dose group also showed a higher rate of improvement noted by EMS clinicians (92.5% v 88.7%, OR 1.6, 95% CI 1.01–2.40). The rates of antipsychotic coadministration, hypoxia, hypotension, and cardiac arrest were similar between the cohorts. Patients given ketamine doses above consensus recommendations for sedation appeared more likely to receive prehospital intubation but not more likely to experience other adverse events. [ABSTRACT FROM AUTHOR]

Hypoxia is one of the predominant water quality issues affecting estuaries and coastal ecosystems, and its impact is often monitored using benthic macroinvertebrates. The M-AMBI (Multivariate AZTI Marine Biotic Index) is an index that meets the needs of small and large-scale monitoring as it is scalable. However, gaps remain as to the sensitivity of M-AMBI to hypoxia as few studies are available. Using Pensacola Bay in the northern Gulf of Mexico (USA) as a case study, we sought to evaluate the time scales over which benthic macrofauna respond to dissolved oxygen conditions from May through September 2017. Combined continuous DO monitoring and benthic sampling identified important differences in DO exposure on benthic habitat condition based on both the duration and frequency of low oxygen. We identified periods of 7 to 31 days as critical windows of exposure prior to a measurable benthic response, and that both duration and exposure to varying low oxygen conditions as well as the recovery period of oxygen to > 5 mg L−1 are important to benthic habitat health. While the duration of exposure to DO from < 2 mg L−1 to near anoxia remains an important factor in benthic health, benthic organisms can better tolerate periods of low oxygen when reoxygenation occurs after a short time interval. More research is needed to better quantify the relationship between oxygen stress and recovery on benthic habitats, particularly in systems where low DO exposure and recovery can vary over timescales of hours to days. [ABSTRACT FROM AUTHOR]

Fractionation of sediment-bound nitrogen (N) in Thrissur Kole wetland was carried out to assess the mobility, bioavailability, and nutrient contamination status. Various N fractions were extracted using KCl equilibrium extraction method, and the concentration of each N fraction was analyzed by spectrophotometric method. Dominance of ammonia during all seasons was due to dissimilatory NO3− reduction to NH4+ and direct inputs from agriculture fields. Enrichment of urea during post-monsoon (181.78 ± 8.47 ppm) was attributed to fertilizer sources. NO3−-N deficit at central zone of the study area (monsoon and post-monsoon) was due to the anoxia. Comparatively higher values of NO2−-N during monsoon (0.07 ± 0.02 ppm) was due to the land run-off, leaching of fertilizers from agriculture fields, and higher rate of denitrification. Elevated content of total N [1819.94 ± 40.20 ppm (pre-monsoon); 3061.62 ± 13.21 ppm (monsoon); 2763.44 ± 9.65 ppm (post-monsoon)] reflected the inputs from in-situ production, agriculture, terrestrial run-off, waste disposal, and guano as well as carcass of birds. Average contribution of bioavailable N to total N was higher (36.16%) indicated the possibility for eutrophication risk during pre-monsoon. Agriculture dominated regions recorded severe contamination and eutrophication risk as indicated by organic pollution index, organic nitrogen index, and phosphorous pollution index. [ABSTRACT FROM AUTHOR]

Denitrification – a key process in the global nitrogen cycle and main source of the greenhouse gas N2O – is intricately controlled by O2. While the transition from aerobic respiration to denitrification is well-studied, our understanding of denitrifier communities' responses to cyclic oxic/anoxic shifts, prevalent in natural and engineered systems, is limited. Here, agricultural soil is exposed to repeated cycles of long or short anoxic spells (LA; SA) or constant oxic conditions (Ox). Surprisingly, denitrification and N2O reduction rates are three times greater in Ox than in LA and SA during a final anoxic incubation, despite comparable bacterial biomass and denitrification gene abundances. Metatranscriptomics indicate that LA favors canonical denitrifiers carrying nosZ clade I. Ox instead favors nosZ clade II-carrying partial- or non-denitrifiers, suggesting efficient partnering of the reduction steps among organisms. SA has the slowest denitrification progression and highest accumulation of intermediates, indicating less functional coordination. The findings demonstrate how adaptations of denitrifier communities to varying O2 conditions are tightly linked to the duration of anoxic episodes, emphasizing the importance of knowing an environment's O2 legacy for accurately predicting N2O emissions originating from denitrification. A soil history of constant oxygen exposure enhances N2O reduction rates under anoxia compared to a history of long or short anoxic pulses, highlighting the importance of knowing the oxygen legacy of a soil for accurate N2O emission predictions. [ABSTRACT FROM AUTHOR]

L-type amino acid transporter 1 (LAT1) is upregulated in various cancer types and contributes to disease progression. Previous studies have demonstrated or suggested that hypoxia-inducible factors (HIFs), the key transcription factors in hypoxic responses, control the expression of LAT1 gene in several types of cancer cells. However, this regulatory relationship has not been investigated yet in colorectal cancer (CRC), one of the cancer types in which the increased LAT1 expression holds prognostic significance. In this study, we found that neither LAT1 mRNA nor protein is induced under hypoxic condition (1% O2) in CRC HT-29 cells in vitro, regardless of the prominent HIF-1/2α accumulation and HIFs-dependent upregulation of glucose transporter 1. The hypoxic treatment generally did not increase either the mRNA or protein expression of LAT1 in eight CRC cell lines tested, in contrast to the pronounced upregulation by amino acid restriction. Interestingly, knockdown of von Hippel-Lindau ubiquitin ligase to inhibit the proteasomal degradation of HIFs caused an accumulation of HIF-2α and increased the LAT1 expression in certain CRC cell lines. This study contributes to delineating the molecular mechanisms responsible for the pathological expression of LAT1 in CRC cells, emphasizing the ambiguity of HIFs-dependent transcriptional upregulation of LAT1 across cancer cells. [ABSTRACT FROM AUTHOR]

Background: By controlling hypercapnia, respiratory acidosis, and associated consequences, extracorporeal CO2 removal (ECCO2R) has the potential to facilitate ultra-protective lung ventilation (UPLV) strategies and to decrease injury from mechanical ventilation. We convened a meeting of European intensivists and nephrologists and used a modified Delphi process to provide updated insights into the role of ECCO2R in acute respiratory distress syndrome (ARDS) and to identify recommendations for a future randomized controlled trial. Results: The group agreed that lung protective ventilation and UPLV should have distinct definitions, with UPLV primarily defined by a tidal volume (VT) of 4–6 mL/kg predicted body weight with a driving pressure (ΔP) ≤ 14–15 cmH2O. Fourteen (93%) participants agreed that ECCO2R would be needed in the majority of patients to implement UPLV. Furthermore, 10 participants (majority, 63%) would select patients with PaO2:FiO2 > 100 mmHg (> 13.3 kPa) and 14 (consensus, 88%) would select patients with a ventilatory ratio of > 2.5–3. A minimum CO2 removal rate of 80 mL/min delivered by continuous renal support machines was suggested (11/14 participants, 79%) for this objective, using a short, double-lumen catheter inserted into the right internal jugular vein as the preferred vascular access. Of the participants, 14/15 (93%, consensus) stated that a new randomized trial of ECCO2R is needed in patients with ARDS. A ΔP of ≥ 14–15 cmH2O was suggested by 12/14 participants (86%) as the primary inclusion criterion. Conclusions: ECCO2R may facilitate UPLV with lower volume and pressures provided by the ventilator, while controlling respiratory acidosis. Since recent European Society of Intensive Care Medicine guidelines on ARDS recommended against the use of ECCO2R for the treatment of ARDS outside of randomized controlled trials, new trials of ECCO2R are urgently needed, with a ΔP of ≥ 14–15 cmH2O suggested as the primary inclusion criterion. [ABSTRACT FROM AUTHOR]

SUMMARY Calcium (Ca2+) is essential for plant growth and cellular homeostasis, with cation exchangers (CAXs) regulating Ca2+ transport into plant vacuoles. In Arabidopsis, multiple CAXs feature a common structural arrangement, comprising an N‐terminal autoinhibitory domain followed by two pseudosymmetrical modules. Mutations in CAX1 enhance stress tolerance, notably tolerance to anoxia (a condition marked by oxygen depletion), crucial for flood resilience. Here we engineered a dominant‐negative CAX1 variant, named ½N‐CAX1, incorporating the autoinhibitory domain and the N‐terminal pseudosymmetrical module, which, when expressed in wild‐type Arabidopsis plants, phenocopied the anoxia tolerance of cax1. Physiological evaluations, yeast assays, and calcium imaging demonstrated that wild‐type plants expressing ½N‐CAX1 have phenotypes consistent with inhibition of CAX1, which is likely through direct interaction of ½N‐CAX1 with CAX1. Eliminating segments within the N‐terminal pseudosymmetrical module, as well as incorporating modules from other plant CAXs and expressing these variants into wild‐type plants, failed to produce anoxia tolerance. This underscores the requirement for both the CAX1 autoinhibitory domain and the intact pseudosymmetrical module to produce the dominant‐negative phenotype. Our study elucidates the interaction of this ½N‐CAX1 variant with CAX1 and its impact on anoxia tolerance, offering insights into further approaches for engineering plant stress tolerance. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusions To quantify the magnitude and recovery of central and limbal corneal oedema induced by short‐term unilateral eyelid closure without contact lens wear.The left eye of 10 adults with healthy corneas was patched using a folded eye pad for 30 min. High‐resolution optical coherence tomography images (which captured the limbal and central corneal regions simultaneously) were obtained before patching, immediately after eye opening and again at 1, 2, 5, 6, 9, 10, 14 and 15 mins after eyelid opening. Oedema was measured from the limbus (scleral spur) to the central cornea (thinnest corneal location) along the horizontal meridian.A greater amount of limbal oedema was noted (mean [SD] 3.84 [1.79] %) compared to the central cornea (2.48 [0.61] %; p = 0.04) after 30 mins of unilateral eyelid closure. Both central and limbal corneal oedema recovered rapidly following eyelid opening, with no significant differences in the rate of corneal recovery between corneal locations (p = 0.90).Short‐term unilateral eyelid closure resulted in ~55% more relative oedema in the limbal region compared to the central cornea. Rapid recovery of oedema and corneal overshoot (thinning beyond the baseline corneal thickness) was observed within 1–2 min of eyelid opening for both central and peripheral regions. [ABSTRACT FROM AUTHOR]

As natural living substances, microorganisms have emerged as useful resources in medicine for creating microbe-material hybrids ranging from nano to macro dimensions. The engineering of microbe-involved nanomedicine capitalizes on the distinctive physiological attributes of microbes, particularly their intrinsic "living" properties such as hypoxia tendency and oxygen production capabilities. Exploiting these remarkable characteristics in combination with other functional materials or molecules enables synergistic enhancements that hold tremendous promise for improved drug delivery, site-specific therapy, and enhanced monitoring of treatment outcomes, presenting substantial opportunities for amplifying the efficacy of disease treatments. This comprehensive review outlines the microorganisms and microbial derivatives used in biomedicine and their specific advantages for therapeutic application. In addition, we delineate the fundamental strategies and mechanisms employed for constructing microbe-material hybrids. The diverse biomedical applications of the constructed microbe-material hybrids, encompassing bioimaging, anti-tumor, anti-bacteria, anti-inflammation and other diseases therapy are exhaustively illustrated. We also discuss the current challenges and prospects associated with the clinical translation of microbe-material hybrid platforms. Therefore, the unique versatility and potential exhibited by microbe-material hybrids position them as promising candidates for the development of next-generation nanomedicine and biomaterials with unique theranostic properties and functionalities. [ABSTRACT FROM AUTHOR]

Dysregulated autophagy/mitophagy is one of the major causes of cardiac injury in ischemic conditions. Glycogen synthase kinase-3alpha (GSK-3α) has been shown to play a crucial role in the pathophysiology of cardiac diseases. However, the precise role of GSK-3α in cardiac mitophagy remains unknown. Herein, we investigated the role of GSK-3α in cardiac mitophagy by employing AC16 human cardiomyocytes under the condition of acute hypoxia. We observed that the gain-of-GSK-3α function profoundly induced mitophagy in the AC16 cardiomyocytes post-hypoxia. Moreover, GSK-3α overexpression led to increased ROS generation and mitochondrial dysfunction in cardiomyocytes, accompanied by enhanced mitophagy displayed by increased mt-mKeima intensity under hypoxia. Mechanistically, we identified that GSK-3α promotes mitophagy through upregulation of BNIP3, caused by GSK-3α-mediated increase in expression of HIF-1α and FOXO3a in cardiomyocytes post-hypoxia. Moreover, GSK-3α displayed a physical interaction with BNIP3 and, inhibited PINK1 and Parkin recruitment to mitochondria was observed specifically under hypoxia. Taken together, we identified a novel mechanism of mitophagy in human cardiomyocytes. GSK-3α promotes mitochondrial dysfunction and regulates FOXO3a -mediated BNIP3 overexpression in cardiomyocytes to facilitate mitophagy following hypoxia. An interaction between GSK-3α and BNIP3 suggests a role of GSK-3α in BNIP3 recruitment to the mitochondrial membrane where it enhances mitophagy in stressed cardiomyocytes independent of the PINK1/Parkin. [Display omitted] • GSK-3a promotes oxidative stress and mitochondrial dysfunction under hypoxia. • Gain-of-GSK-3α function activates hypoxia-induced mitophagy in cardiomyocytes. • GSK-3α physically interacts with BNIP3 specifically under hypoxia. • GSK-3α inhibits PINK1/Parkin recruitment to mitochondria post-hypoxia. • GSK-3α promotes hypoxia-induces mitophagy through FOXO3a-mediated BNIP3 upregulation. [ABSTRACT FROM AUTHOR]