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Purpose: We investigated the effects of manipulating running velocity and hypoxic exposure on vastus lateralis muscle oxygenation levels during treadmill running. Methods: Eleven trained male distance runners performed 7 randomized runs at different velocities (8, 10, 12, 14, 16, 18, and 20 km·h−1), each lasting 45 seconds on an instrumented treadmill in normoxia (fraction of inspired oxygen [FiO2] = 20.9%), moderate hypoxia (FiO2 = 16.1%), high hypoxia (FiO2 = 14.1%), and severe hypoxia (FiO2 = 13.0%). Continuous assessment of Tissue Saturation Index (TSI) in the vastus lateralis muscle was conducted using near-infrared spectroscopy. Subsequently, changes in TSI (ΔTSI) data over the final 20 seconds of each run were compared between velocities and conditions. Results: There was a significant velocity × condition interaction for ΔTSI% (P <.001, η p 2 =.19), with a smaller ΔTSI% decline in normoxia compared with high hypoxia and severe hypoxia at 8 km·h−1 (g = 1.30 and 1.91, respectively), 10 km·h−1 (g = 0.75 and 1.43, respectively), and 12 km·h−1 (g = 1.47 and 1.95, respectively) (pooled values for all conditions: P <.037). The ΔTSI% decline increased with each subsequent velocity increment from 8 km·h−1 (−9.2% [3.7%]) to 20 km·h−1 (−22.5% [4.1%]) irrespective of hypoxia severity (pooled values for all conditions: P <.048). Conclusions: Running at slower velocities in conjunction with high and severe hypoxia reduces vastus lateralis muscle oxygenation levels. Muscle ΔTSI% proves to be a sensitive indicator, underscoring the potential use of near-infrared spectroscopy as a reference index of internal load during treadmill runs. [ABSTRACT FROM AUTHOR]

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]

Extracorporeal membrane oxygenator (ECMO) is a well-established therapy for respiratory failure. Refractory hypoxemia, despite the use of ECMO, remains a challenging problem. The ECMO circuit may not provide enough oxygenation support in the presence of high cardiac output, increased physiologic demand, and impaired gas exchange. Adding a second ECMO oxygenator using the same pump (sometimes needing a second drainage cannula) can improve oxygenation and facilitate lung-protective ventilation in selected patients. We describe a 3-patient series with severe ARDS secondary to SARS-CoV-2 infection and refractory hypoxemia during ECMO support successfully treated with this approach. [ABSTRACT FROM AUTHOR]

Introduction: Prone position ventilation (PPV) of patients with adult respiratory distress syndrome (ARDS) supported with veno-venous extracorporeal membrane oxygenation (V-V ECMO) may improve oxygenation and alveolar recruitment and is recommended when extensive dorsal consolidations are present, but only few data regarding adverse events (AE) related to PPV in this group of patients have been published. Methods: Nationwide retrospective analysis of 68 COVID-19 patients admitted from March 2020 – December 2021 with severe ARDS and need of V-V ECMO support. The number of patients treated with PPV, number of PPV-events, timing, the time spent in prone position, number and causes of AE are reported. Causes to stop the PPV regimen and risk factors for AE were explored. Results: 44 out of 68 patients were treated with PPV, and 220 PPV events are evaluated. AE were identified in 99 out of 220 (45%) PPV events and occurred among 31 patients (71%). 1 fatal PPV related AE was registered. Acute supination occurred in 19 events (9%). Causes to stop the PPV regimen were almost equally distributed between effect (weaned from ECMO), no effect, death (of other reasons) and AE. Frequent causes of AE were pressures sores and ulcers, hypoxia, airway related and ECMO circuit related. Most AE occurred during patients first or second PPV event. Conclusions: PPV treatment was found to carry a high incidence of PPV related AE in these patients. Causes and preventive measures to reduce occurrence of PPV related AE during V-V ECMO support need further exploration. [ABSTRACT FROM AUTHOR]

Background: Nasal obstruction in humans leads to mouth breathing and subsequent hypoxia in the entire body. Furthermore, nasal obstruction in growing children affects craniofacial growth and development. Objective: To investigate the effects of unilateral nasal obstruction (UNO) on craniofacial growth in mice of different ages, particularly on the morphology of the nasomaxillary complex and mandible. Methods: Mice aged 3, 6 and 12 weeks were selected as representatives of juvenile, adolescent and adult stages, respectively. A total of 30 male C57BL/6J mice (10 mice each at the ages of 3, 6 and 12 weeks) were used in this study for a 3‐week experiment. The mice in each age stage were randomly and evenly assigned to either the control group (C3+3, C6+3 and C12+3) or the experimental group (E3+3, E6+3 and E12+3). The UNO model in experimental group was constructed by plugging the mouse's left nostril, thereby disrupting its normal nasal breathing pattern and inducing hypoxia. The control group underwent the sham procedure. After 3 weeks, the length, width and height of the cranium, nasomaxillary complex and mandible of each group were measured on two‐dimensional images constructed by micro‐computed tomography. Furthermore, the impact of UNO on mouse growth was evaluated through the measurement of femoral length. Results: In juvenile mice, UNO inhibited the growth of cranial width, cranial height and mandibular length. In adolescent mice, UNO impeded the growth of the femoral length, cranial length, nasomaxillary length and mandibular length. In adult mice, no significant negative effects of UNO on craniofacial growth were found. Conclusion: Referring to the experimental results, in addition to actively treating nasal obstruction in patients, it is important to monitor the growth of the mandible in juveniles, as well as the nasomaxillary and mandibular growth in adolescents during orthodontic clinical practice. [ABSTRACT FROM AUTHOR]

Background: Solid tumors often develop hypoxic regions, leading to aggressive behavior and increased drug resistance. Methods: The chemical composition of Cymbopogon citratus essential oil (EO) was analyzed using GC-MS. Alginate nanoparticles containing the EO and its primary component, citral, were synthesized via the ionic gelation method. Encapsulation was confirmed using ATR-FTIR analysis. The anticancer efficacy of C. citratus EO, citral, and their respective alginate nanoparticles was evaluated under normoxic (21% oxygen) and hypoxic (1% oxygen) conditions on breast cancer (MDA-MB-231) and melanoma (A-375) cell lines. Additionally, qPCR and flow cytometry were used to assess apoptosis gene expression ratios (Bax/Bcl-2) and levels of apoptosis. Results: Citral (80.98%) was identified as the major component of the EO. Alginate nanoparticles containing C. citratus EO and citral (C. citratus-AlgNPs and citral-AlgNPs) were synthesized with particle sizes of 195 ± 4 nm and 222 ± 9 nm, and zeta potentials of -22 ± 3 mV and − 17 ± 1 mV, respectively. Both samples demonstrated significantly greater efficacy under hypoxic conditions. Citral and C. citratus-AlgNPs had IC50 values of 27 (19–39) µg/mL and 25 (4-147) µg/mL, respectively, against MDA-MB-231 and A-375 cells. Flow cytometry showed increased apoptosis under hypoxic conditions, with the highest rates observed for citral-AlgNPs and C. citratus-AlgNPs (84 ± 5 and 92 ± 5% in MDA-MB-231 and A-375 cells, respectively). Conclusion: This study demonstrates that alginate nanoparticles enhance the anticancer activity of C. citratus-AlgNPs and citral, particularly under hypoxic conditions, highlighting their potential for hypoxia-targeted cancer therapies. [ABSTRACT FROM AUTHOR]

Background: This narrative review was written by an expert panel to the members of the jury to help in the development of clinical practice guidelines on oxygen therapy. Results: According to the expert panel, acute hypoxemic respiratory failure was defined as PaO2 < 60 mm Hg or SpO2 < 90% on room air, or PaO2/FiO2 ≤ 300 mm Hg. Supplemental oxygen should be administered according to the monitoring of SpO2, with the aim at maintaining SpO2 above 92% and below 98%. Noninvasive respiratory supports are generally reserved for the most hypoxemic patients with the aim of relieving dyspnea. High-flow nasal cannula oxygen (HFNC) seems superior to conventional oxygen therapy (COT) as a means of avoiding intubation and may therefore be should probably be used as a first-line noninvasive respiratory support in patients requiring more than 6 L/min of oxygen or PaO2/FiO2 ≤ 200 mm Hg and a respiratory rate above 25 breaths/minute or clinical signs of respiratory distress, but with no benefits on mortality. Continuous positive airway pressure (CPAP) cannot currently be recommended as a first-line noninvasive respiratory support, since its beneficial effects on intubation remain uncertain. Despite older studies favoring noninvasive ventilation (NIV) over COT, recent clinical trials fail to show beneficial effects with NIV compared to HFNC. Therefore, there is no evidence to support the use of NIV or CPAP as first-line treatment if HFNC is available. Clinical trials do not support the hypothesis that noninvasive respiratory supports may lead to late intubation. The potential benefits of awake prone positioning on the risk of intubation in patients with COVID-19 cannot be extrapolated to patients with another etiology. Conclusions: Whereas oxygen supplementation should be initiated for patients with acute hypoxemic respiratory failure defined as PaO2 below 60 mm Hg or SpO2 < 90% on room air, HFNC should be the first-line noninvasive respiratory support in patients with PaO2/FiO2 ≤ 200 mm Hg with increased respiratory rate. Further studies are needed to assess the potential benefits of CPAP, NIV through a helmet and awake prone position in patients with acute hypoxemic respiratory failure not related to COVID-19. [ABSTRACT FROM AUTHOR]

The ocean has experienced substantial oxygen loss over recent decades, affecting marine ecosystems and fisheries. Investigating ocean deoxygenation during hyperthermal events, such as the Paleocene-Eocene Thermal Maximum (PETM), offers insights into its future dynamics. Here, sediment cores from the South Atlantic reveal a pronounced decline in foraminifera-bound δ15N, concurrent with an increase in marine barite δ34S and enhanced ocean productivity during the PETM. These findings suggest an expansion of oxygen-deficient zones (ODZs) from suboxia to anoxia in the thermocline, with ammonium and sulfide accumulation. Model simulations indicate "ammonium-type" ODZs were driven by Southern Ocean warming and elevated productivity. Intense fixed nitrogen loss at the upper boundary of these ODZs, along with increased oceanic phosphorus inventory, likely spurred a compensatory rise in N2 fixation. While the Pacific might experience different oxygenation conditions during the PETM, parts of the Atlantic thermocline became anoxic, highlighting potential spatial variabilities of ocean deoxygenation under global warming. Extreme warming 56 million years ago may have rendered parts of the subsurface Atlantic Ocean anoxic and toxic to fish due to ammonium and hydrogen sulfide accumulation – a scenario we must strive to prevent under current anthropogenic climate change. [ABSTRACT FROM AUTHOR]

Air-breathing fish risk losing aerially sourced oxygen to ambient hypoxic water since oxygenated blood from the air-breathing organ returns through the heart to the branchial basket before distribution. This loss is thought to help drive the evolutionary reduction in gill size with the advent of air-breathing. In many teleost fish, gill size is known to be highly plastic by modulation of their anatomic diffusion factor (ADF) with inter-lamellar cell mass (ILCM). In the anoxia-tolerant crucian carp, ILCM recedes with hypoxia but regrows in anoxia. The air-breathing teleost Chitala ornata has been shown to increase gill ADF from normoxic to mildly hypoxic water by reducing ILCM. Here, we test the hypothesis that ADF is modulated to minimize oxygen loss in severe aquatic hypoxia by measuring ADF, gas-exchange, and by using computed tomography scans to reveal possible trans-branchial shunt vessels. Contrary to our hypothesis, ADF does not modulate to prevent oxygen loss and despite no evident trans-branchial shunting, C. ornata loses only 3% of its aerially sourced O2 while still excreting 79% of its CO2 production to the severely hypoxic water. We propose this is achieved by ventilatory control and by compensating the minor oxygen loss by extra aerial O2 uptake. [ABSTRACT FROM AUTHOR]

Plant quiescence and seed dormancy can be triggered by reduced oxygen availability. Under water, oxygen depletion caused by flooding can culminate in a quiescent state, which is a plant strategy for energy preservation and survival. In adult plants, a quiescent state can be activated by sugar starvation, leading to metabolic depression. In seeds, secondary dormancy can be activated by reduced oxygen availability, which creates an unfavourable state for germination. The physical dormancy of some seeds and buds includes barriers to external conditions, which indirectly results in hypoxia. The molecular processes that support seed dormancy and plant survival through quiescence under hypoxia include the N-degron pathway, which enables the modulation of ethylene-responsive factors of group VII and downstream targets. This oxygen- and nitric oxide-dependent mechanism interacts with phytohormone-related pathways to control growth. [ABSTRACT FROM AUTHOR]

Background: Interatrial right-to-left shunt flow through a patent foramen ovale (PFO) can be caused by changes in heart position for anastomosis during off-pump coronary artery bypass (OPCAB). We herein present a case in which the direction of PFO shunt flow changed with heart position during OPCAB and the ventilation settings after sternal closure. Case presentation: A 66-year-old man with interstitial pneumonia underwent OPCAB. Preoperative transesophageal echocardiography revealed right-to-left shunt flow through a PFO induced by the Valsalva maneuver. During OPCAB, heart displacement resulted in right-to-left shunting and acute hypoxemia, which quickly improved with increase of inspired oxygen fraction. After chest closure, bidirectional shunt flow developed under increased airway pressure. Conclusions: Vigilant intraoperative monitoring with TEE and postoperative airway pressure management are important to address shunt flow and hypoxemia due to PFO. [ABSTRACT FROM AUTHOR]

The pathology of respiratory syncytial virus (RSV) infection remains unclear. An unbalanced immune response to RSV infection can lead to immunopathology, causing airway damage and impaired exchange of oxygen and carbon dioxide between the air and the bloodstream. We aimed to evaluate the association of the expression of inflammatory and antiviral genes in peripheral blood with severe hypoxemia in children with RSV infection seen in the hospital emergency room. We conducted a cross-sectional study on 121 RSV-infected children seen in hospital emergency rooms between 2015 and 2023. Total RNA was extracted from whole blood samples, and gene expression (IL-6, TNFa, CXCL8, ISG15, IFIT1, RIGI, IFNb, CCL5, and CXCL10) was quantified using quantitative RT-PCR. The outcome variable was having severe hypoxemia (SpO2 = 90%). The association analysis was performed using a volcano plot, adjusted logistic regression, and orthogonal partial least squares discriminant analysis (OPLSDA). We found that 26 of 121 children had severe hypoxemia (SpO2 = 90%). CXCL8 was overexpressed [fold changes (FC) > 2; q-value < 0.05], and ISG15, IFIT1, RIGI, IFNb, CCL5, and CXCL10 were underexpressed (FC <0.5; q-value <0.05) in children with severe hypoxemia. These associations were ratified using adjusted logistic regression. The OPLS-DA showed that the gene expressions of CXCL8, ISG15, IFIT1, RIGI, and CXCL10 had values of variable importance in projection (VIP) =1, being the most relevant features. In conclusion, an imbalance favoring inflammation over antiviral defense may contribute to the pathogenesis of severe hypoxemia in RSV-infected children. These findings provide valuable insights into the pathology of RSV infection. [ABSTRACT FROM AUTHOR]

Background: Pulse oximetry is a standart of anesthesia for perioperative monitoring. Due to the principles of Hb oxygen dissociation curve, peripheral oxygen saturation has an approximate sensitivity and specificity of 90% for the detection of hypoxemia. Objectives: The primary outcome of the study was to evaluate ORiⓇ as an early parameter to determine hypoxia in morbidly obese patients. The secondary outcome was to compare the effectiveness of ORiⓇ with SpO2 in non-obese patients. Design: Prospective, observational study. Setting: Department of elective operating room at tertiary hospital. Patients and methods: Observational study included written informed consent from 51 patients with 19 < BMI < 25 kg/m2 and 51 patients with BMI > 40 kg/m2 undergoing an elective surgery requiring tracheal intubation. In addition to standard monitors, an ORi sensor was placed and baseline values were recorded. The patients were preoxygenated until end tidal expiratory oxygen concentration is reached to 90%. After anesthesia induction and tracheal intubation, the breathing circuit was not connected tracheal tube until the SpO2 decreased to 95%. Shapiro-Wilk, Pearson Chi-square, t-test, and Mann Whitney U test were used for the study. Main outcome measures: Times of tolerable apnea, ORiⓇ and SpO2 values at the end of preoxygenation, beginning of intubation, beginning of the ORi alarm, when SpO2 reached 95%, and when ORi reaches a plateau. Sample size: 102 patients. Results: The alert period: time to reach ORiⓇ from 0.24 to a value of 95% SpO2 was observed as 32 s in morbidly obese patients and 94 s in patients with a normal body mass index. The SpO2 alert period was determined as time difference between 97% and 95% SpO2. The data were recorded as 15 s and 36 s, respectively. It was observed that tolerable apnea, ORiⓇ, SpO2 and added alert times were longer in patients with normal BMI compared to morbidly obese patients. Conclusions: As a result, ORiⓇ can provide an early warning to prevent unexpected hypoxia before saturation begins to decrease in morbidly obese patients. Limitations: Inability to perform arterial blood gas sampling in the time periods when we looked at the parameters to determine the relationship between ORiⓇ and PaO2. Clinical trials. gov identifier: NCT05480748 registered 2022-07-29. [ABSTRACT FROM AUTHOR]

A fundamental question in evolutionary biology concerns the relative contributions of phenotypic plasticity vs. local adaptation (genotypic specialization) in enabling wide-ranging species to inhabit diverse environmental conditions. Here, we conduct a long-term hypoxia acclimation experiment to assess the relative roles of local adaptation and plasticity in enabling highland and lowland deer mice (Peromyscus maniculatus) to sustain aerobic thermogenesis at progressively increasing elevations. We assessed the relative physiological performance capacities of highland and lowland natives as they were exposed to progressive, stepwise increases in hypoxia, simulating the gradual ascent from sea level to an elevation of 6,000 m. The final elevation of 6,000 m far exceeds the highest attainable elevations within the species' range, and therefore tests the animals' ability to tolerate levels of hypoxia that surpass the prevailing conditions within their current distributional limits. Our results demonstrate that highland natives exhibit superior thermogenic capacities at the most severe levels of hypoxia, suggesting that the species' broad fundamental niche and its ability to inhabit such a broad range of elevational zones is attributable to genetically based local adaptation, including evolved changes in plasticity. Transcriptomic and physiological measurements identify evolved changes in the acclimation response to hypoxia that contribute to the enhanced thermogenic capacity of highland natives. [ABSTRACT FROM AUTHOR]

Viscosity and hypoxia, as microenvironment parameters, play important roles in maintaining normal biological processes and homeostasis. Therefore, simultaneous and sensitive detection of these elements with simple and effective methods could offer precise information in biology. Here, we report a two-site lysosome-targeting fluorescent probe, NVP, for monitoring viscosity and nitroreductase with dual emission channels (emission shift is 86 nm). The NVP probe has displayed highly sensitive and selective responses towards viscosity and nitroreductase, respectively. Significantly, the fluctuations of viscosity and NTR have been detected in vitro and in vivo. We expect that the dual-responsive fluorescent NVP probe will become a potential molecular tool for the exploration of deeper functions of viscosity and hypoxia. [ABSTRACT FROM AUTHOR]

Background: Sigh breaths may impact outcomes in acute hypoxemic respiratory failure (AHRF) during assisted mechanical ventilation. We investigated whether sigh breaths may impact mortality in predefined subgroups of patients enrolled in the PROTECTION multicenter clinical trial according to: 1.the physiological response in oxygenation to Sigh (responders versus non-responders) and 2.the set levels of positive end-expiratory pressure (PEEP) (High vs. Low-PEEP). If mortality differed between Sigh and No Sigh, we explored physiological daily differences at 7-days. Results: Patients were randomized to pressure support ventilation (PSV) with Sigh (Sigh group) versus PSV with no sigh (No Sigh group). (1) Sighs were not associated with differences in 28-day mortality in responders to baseline sigh-test. Contrarily-in non-responders-56 patients were randomized to Sigh (55%) and 28-day mortality was lower with sighs (17%vs.36%, log-rank p = 0.031). (2) In patients with PEEP > 8cmH2O no difference in mortality was observed with sighs. With Low-PEEP, 54 patients were randomized to Sigh (48%). Mortality at 28-day was reduced in patients randomised to sighs (13%vs.31%, log-rank p = 0.021). These findings were robust to multivariable adjustments. Tidal volume, respiratory rate and ventilatory ratio decreased with Sigh as compared with No Sigh at 7-days. Ventilatory ratio was associated with mortality and successful extubation in both non-responders and Low-PEEP. Conclusions: Addition of Sigh to PSV could reduce mortality in AHRF non-responder to Sigh and exposed to Low-PEEP. Results in non-responders were not expected. Findings in the low PEEP group may indicate that insufficient PEEP was used or that Low PEEP may be used with Sigh. Sigh may reduce mortality by decreasing physiologic dead space and ventilation intensity and/or optimizing ventilation/perfusion mismatch. Clinical Trial Registration: ClinicalTrials.gov; Identifier: NCT03201263. [ABSTRACT FROM AUTHOR]

Background: As a supportive treatment, the effectiveness of oxygen therapy in ischemic stroke (IS) patients remains unclear. This study aimed to evaluate the relationships between arterial partial pressure of oxygen (PaO2) and both consciousness at discharge and all-cause mortality risk in ICU IS patients. Methods: Blood gas measurements for all patients diagnosed with IS were extracted from the MIMIC-IV database. Patients were classified into four groups based on their average PaO2 during the first ICU day: hypoxemia (PaO2 < 80 mmHg), normoxemia (PaO2 80–120 mmHg), mild hyperoxemia (PaO2 121–199 mmHg), and moderate/severe hyperoxemia (PaO2 ≥ 200 mmHg). The primary endpoint was 90-day all-cause mortality. Secondary outcomes included the level of consciousness at discharge, assessed by the Glasgow Coma Scale (GCS), and 30-day all-cause mortality. Multivariate Cox regression and Restricted cubic spline (RCS) analysis were used to investigate the relationship between mean PaO2 and mortality, and to assess the nonlinear association between exposure and outcomes. Results: This study included a total of 946 IS patients. The cumulative incidence of 30-day and 90-day all-cause mortality increased with decreasing PaO2 levels. RCS analysis revealed a nonlinear relationship between PaO2 and the risk of 30-day all-cause mortality (nonlinear P < 0.0001, overall P < 0.0001), as well as a nonlinear association between PaO2 and 90-day all-cause mortality (nonlinear P < 0.0001, overall P < 0.0001). The results remained consistent after excluding the small subset of patients who received reperfusion therapy. Sensitivity analysis indicated that the favorable impact on survival tends to increase with the extended duration of elevated PaO2. Conclusions: For IS patients who do not receive reperfusion therapy or whose recanalization status is unknown, a lower PaO2 early during ICU admission is considered an independent risk factor for short-term and recent mortality. Adjusting respiratory parameters to maintain supraphysiological levels of PaO2 appears to be beneficial for survival, although this finding requires further validation through additional studies. Trial registration: Not applicable. [ABSTRACT FROM AUTHOR]

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Simple Summary: Pancreatic cancer is surrounded by a dense fibrotic environment due to the activity of pancreatic stellate cells (PSCs). This hinders the effectiveness of treatment by limiting drug penetration and oxygen delivery. To better understand this, PSCs and cancer cells were studied in laboratory models using radiotracer imaging techniques. The results indicated that while glucose uptake and hypoxia were similar between cancer cells alone and in combination with PSCs, a specific marker of fibrosis (FAPα) was significantly higher in PSC-rich environments. In mice, the marker in question decreased in tumors with only PSCs, indicating that the cells had died. Conversely, the biomarker increased over time in tumors containing both cancer cells and PSCs, suggesting that mouse cells had invaded. This study sheds light on how the tumor environment influences metabolism and thus provides insights for more targeted theranostic applications. In turn, this approach supports the development of more reliable models. Background/Objective Pancreatic stellate cells (PSCs) in pancreatic adenocarcinoma (PDAC) are producing extracellular matrix, which promotes the formation of a dense fibrotic microenvironment. This makes PDAC a highly heterogeneous tumor-stroma-driven entity, associated with reduced perfusion, limited oxygen supply, high interstitial fluid pressure, and limited bioavailability of therapeutic agents. Methods In this study, spheroid and tumor xenograft models of human PSCs and PanC-1 cells were characterized radiopharmacologically using a combined positron emission tomography (PET) radiotracer approach. [18F]FDG, [18F]FMISO, and [18F]FAPI-74 were employed to monitor metabolic activity, hypoxic metabolic state, and functional expression of fibroblast activation protein alpha (FAPα), a marker of activated PSCs. Results In vitro, PanC-1 and multi-cellular tumor spheroids demonstrated comparable glucose uptake and hypoxia, whereas FAPα expression was significantly higher in PSC spheroids. In vivo, glucose uptake as well as the transition to hypoxia were comparable in PanC-1 and multi-cellular xenograft models. In mice injected with PSCs, FAPα expression decreased over a period of four weeks post-injection, which was attributed to the successive death of PSCs. In contrast, FAPα expression increased in both PanC-1 and multi-cellular xenograft models over time due to invasion of mouse fibroblasts. Conclusion The presented models are suitable for subsequently characterizing stromal cell-induced metabolic changes in tumors using noninvasive molecular imaging techniques. [ABSTRACT FROM AUTHOR]

Simple Summary: Exogenous ketone esters (KEs) are compounds that elevate blood ketones without dietary restriction and they show promise as anti-cancer agents. This study examined the effects of an exogenous ketone ester-supplemented (eKET) diet in mouse models of metastatic breast and kidney cancers. Our eKET diet slowed tumor growth and reduced metastatic spread to the lungs in both cancer types. The mechanisms behind these effects differed: the eKET diet downregulated genes involved in Wnt and TGFβ signaling in mammary cancers, whereas it downregulated genes related to hypoxia and DNA damage repair in tumor-bearing kidneys. The diet was safe for use overall but was associated with some negative physiological effects in mice with renal cancer. Thus, eKET diets could be an effective addition to current cancer treatments, but additional work is needed to fully understand their limitations. Background/Objectives: Ketone esters (KEs) exhibit promise as anti-cancer agents but their impact on spontaneous metastases remains poorly understood. Although consumption of a ketogenic diet (KD) that is low in carbohydrates and high in fats can lead to KE production in vivo, the restrictive composition of KDs may diminish adherence in cancer patients. Methods: We investigated the effects of an exogenous ketone ester-supplemented (eKET), carbohydrate-replete diet on tumor growth, metastasis, and underlying mechanisms in orthotopic models of metastatic breast (4T1-Luc) and renal (Renca-Luc) carcinomas. Mice were randomized to diet after tumor challenge. Results: Administration of KEs did not alter tumor cell growth in vitro. However, in mice, our eKET diet increased circulating β-hydroxybutyrate and inhibited primary tumor growth and lung metastasis in both models. Body composition analysis illustrated the overall safety of eKET diet use, although it was associated with a loss of fat mass in mice with renal tumors. Immunogenetic profiling revealed divergent intratumoral eKET-related changes by tumor type. In mammary tumors, Wnt and TGFβ pathways were downregulated, whereas in renal tumors, genes related to hypoxia and DNA damage repair were downregulated. Conclusions: Thus, our eKET diet exerts potent antitumor and antimetastatic effects in both breast and renal cancer models, albeit with different modes of action and physiologic effects. Its potential as an adjuvant dietary approach for patients with diverse cancer types should be explored further. [ABSTRACT FROM AUTHOR]

Objective: Obstructive sleep apnea (OSA) has been associated with an elevated cardiovascular risk, increased daytime sleepiness, cognitive decline, and slower electroencephalographic activity (EEG). This study assesses EEG patterns during wakefulness in OSA patients compared to those without sleep-disordered breathing. Materials and methods: This retrospective study analyzed 30 OSA patients with an Apnea/Hypopnea Index (AHI) of 15 or higher, as well as 29 individuals without sleep-disordered breathing (AHI of 5 or lower) who underwent hospital polysomnography and met all inclusion criteria. Sociodemographic and EEG data were obtained from the sleep laboratory database. Blinded EEG analysis was conducted by two observers, assessing activity in the frontal, central, and occipital regions. Results: No significant differences were observed in EEG activity between OSA and non-OSA patients. However, a weak correlation was found between decreased C3 EEG frequency and higher AHI (p = 0.033), as well as increased total sleep time and higher O2 EEG frequency (p = 0.038). Lower amplitudes in C3 (p = 0.043) and O1 (p = 0.031) were correlated with reduced average oxygen saturation. Conclusion: Our findings suggest that OSA-related hypoxemia may impact neuronal activity, highlighting the need to address this sleep-disordered breathing in order to potentially prevent the cognitive decline observed in OSA patients. [ABSTRACT FROM AUTHOR]

Background: There is growing concern that pulse oximeters are routinely less accurate in hospitalized patients with darker skin pigmentation, in turn increasing risk of undetected (occult) hypoxemia and adverse clinical outcomes. The aim of this systematic review and meta-analysis was to synthesize evidence on racial and ethnic disparities in occult hypoxemia prevalence and clinical impacts of undetected hypoxemia. Methods: Ovid MEDLINE, Embase, and CINAHL databases were searched for relevant articles published through January 2024. Eligible studies must have been conducted among adults in inpatient or outpatient settings and report occult hypoxemia prevalence stratified by patient race or ethnicity, or clinical outcomes stratified by patient race or ethnicity and occult hypoxemia status. Screening for inclusion was conducted independently by two investigators. Data extraction and risk of bias assessment were conducted by one investigator then checked by a second. Outcome data were synthesized using random-effects meta-analyses. Results: Fifteen primary studies met eligibility criteria and reported occult hypoxemia prevalence in 732,505 paired oximetry measurements from 207,464 hospitalized patients. Compared with White patients, occult hypoxemia is likely more common among Black patients (pooled prevalence ratio = 1.67, 95% CI 1.47 to 1.90) and among patients identifying as Asian, Latinx, Indigenous, multiracial, or other race or ethnicity (pooled prevalence ratio = 1.39, 95% CI 1.19 to 1.64). Findings from studies reporting clinical outcomes suggest that Black patients with undetected hypoxemia may experience poorer treatment delivery outcomes than White patients with undetected hypoxemia. No evidence was found from outpatient settings. Discussion: This review and included primary studies rely on self-identified race or ethnicity, which may obscure variability in occult hypoxemia risk. Findings underscore that clinicians should be aware of the risk of occult hypoxemia in hospitalized patients with darker skin pigmentation. Moreover, oximetry data from included studies suggests that the accuracy of pulse oximeters could vary substantially from patient to patient and even within individual patients. Trial Registration: PROSPERO (CRD42023402152). [ABSTRACT FROM AUTHOR]

A 71-year-old man with a history of recurrent tonsillar squamous cell carcinoma was admitted to the hospital with oropharyngeal bleeding. He received high-dose radiation therapy with curative intent. On day 4 of hospitalization, he demonstrated hypoxia resulting from an airway mucus plug and was brought to the medical ICU. [ABSTRACT FROM AUTHOR]

Background: Previous studies have reported the link between hypoxic conditions and NLRP3 inflammasome-mediated pulpal inflammation in the progression of pulpitis. However, the underlying mechanism has not been fully elucidated. This study aimed to investigate the role of HIF-1α in the regulation of NLRP3 inflammasome pathway via NF-κB signaling under hypoxic conditions with or without LPS in human dental pulp fibroblasts (HDPFs) during the progression of pulpitis. Methods: HIF-1α plasmids or siRNAs were used to upregulate or downregulate HIF-1α in HDPFs, respectively. The effect of hypoxia with or without LPS on the NF-κB signaling and NLRP3 inflammasome pathway was analyzed by immunofluorescence staining, qRT-PCR, western blotting and ELISA. Results: The hypoxic conditions alone induced ASC oligomerization and NLRP3/CASP1 inflammasome pathway activation via NF-κB signaling in a time-dependent manner in HDPFs. The upregulation of HIF-1α further promoted hypoxia-induced ASC oligomerization and NLRP3/CASP1 inflammasome pathway activation via NF-κB signaling compared to the hypoxia-induced group. In comparison, downregulation of HIF-1α inhibited ASC oligomerization and NLRP3/CASP1 inflammasome pathway activation via NF-κB signaling compared to the hypoxia-induced group. Additionally, LPS plus hypoxia further promoted HIF-1α expression and NLRP3/ASC/CASP1 inflammasome pathway activation via NF-κB signaling compared to the hypoxia-induced group. Conclusions: HIF-1α served as a positive regulator of NLRP3/ASC/CASP1 inflammasome pathway activation via NF-κB signaling in HDPFs in the sterile pulpal inflammation and caries-related pulpitis microenvironment. The finding of a novel functional HIF-1α-NF-κB-NLRP3 axis provides insight into the link between the hypoxic microenvironment and pulpal inflammation, thus supporting a promising therapeutic strategy for the control of pulpal inflammation. [ABSTRACT FROM AUTHOR]

Generating highly organized skeletal muscle tissues that mimics the cellular alignment, maturation, and contraction of native skeletal muscle remains a challenge in disease modeling and regenerative therapies. Existing methodologies are constrained by complexity in fabrication and difficulty in achieving aligned 3D myofibers. Here, a functional skeletal muscle organoid‐on‐a‐chip (SMO) is engineered by establishing mechanical boundary constraints at either end of the cell‐laden extracellular matrix hydrogel within polydimethylsiloxane microstructures to promote the formation of an anisotropic biophysical microenvironment in tissues. The linearly aligned tissue, featuring multinucleated myofibers with distinct cross‐striations, exhibited a positive force‐frequency relationship and stable calcium transients under electrical stimulation. SMOs applicability is demonstrated by systematically evaluating muscle response to varying degrees of intermittent hypoxia. Murine‐ or human‐derived SMOs revealed that, with increasing hypoxia severity, muscles transitioned from a compensatory phase‐characterized by enhanced contractile function, vacuolation and hypertrophic‐like changes in myofibers, fiber type switching, and metabolic shift, to a decompensatory stage, paralleling in vivo muscle responses and highlighting interspecies differences. Human‐derived SMOs are also utilized to assess self‐repair capabilities and pharmaceuticals protective effects on damaged muscle. Together, the platform, with its simplicity of operation and reliable phenotypic readouts, demonstrates significant potential for future disease modeling and regenerative therapies. [ABSTRACT FROM AUTHOR]

Hypoxia (low-oxygen) is one of the most common characteristics of solid tumours. Exploiting tumour hypoxia to reductively activate Pt(IV) prodrugs has the potential to deliver toxic Pt(II) selectively and thus overcome the systemic toxicity issues of traditional Pt(II) therapies. However, our current understanding of the behaviour of Pt(IV) prodrugs in hypoxia is limited. Here, we evaluated and compared the aryl carbamate fluorogenic Pt(IV) complexes, CisNap and CarboNap, as well as the previously reported OxaliNap, as potential hypoxia-activated Pt(IV) (HAPt) prodrugs. Low intracellular oxygen concentrations (<0.1%) induced the greatest changes in the respective fluorescence emission channels. However, no correlation between reduction under hypoxic conditions and toxicity was observed, except in the case for CarboNap, which displayed significant hypoxia-dependent toxicity. Other aryl carbamate Pt(IV) derivatives (including non-fluorescent analogues) mirrored these observations, where carboplatin(IV) derivative CarboPhen displayed a hypoxia-selective cytotoxicity similar to that of CarboNap. These findings underscore the need to perform extensive structure activity relationship studies on the cytotoxicity of Pt(IV) complexes under normoxic and hypoxic conditions. [ABSTRACT FROM AUTHOR]

Simple Summary: Head and neck squamous cell carcinoma (HNSC) is the most common type of cancer in the head and neck region, affecting areas like the mouth and throat. Understanding how these cancers grow and spread is crucial for developing better treatments. This study focuses on a group of proteins called solute carrier (SLC) transporters, which help cancer cells survive and grow by moving nutrients and other molecules in and out of cells. We investigated the levels of these transporters in cancerous tissues compared to normal tissues and found that certain SLC transporters are much more active in tumors. These transporters are linked to worse outcomes for patients. By targeting these specific transporters with new drugs, we hope to create more effective treatments that can block cancer growth and improve survival rates for patients with HNSC. Background: Head and neck squamous cell carcinoma (HNSC) is the most prevalent cancer in the head and neck region, originating from the mucosal epithelium of the oral cavity, pharynx, and larynx. The solute carrier (SLC) transporter superfamily, consisting of over 400 proteins across 65 families, plays a crucial role in cellular functions and presents promising targets in precision oncology. This study aims to analyze the expression of SLC transporters in HNSC and their potential as biomarkers and therapeutic targets. Methods: We leveraged mRNA and protein expression data from The Cancer Genome Atlas (TCGA) and The Human Protein Atlas (HPA) to examine SLC transporter expression in HNSC. Gene Set Enrichment Analysis (GSEA) was conducted to assess the involvement of SLC transporters in various oncogenic pathways. Results: Significant upregulation of SLC transporters was observed in tumor tissues compared to normal tissues, with notable increases in SLC16A3, SLC53A1, SLC25A32, and SLC2A3. This upregulation correlated with poorer overall survival (OS) and disease-specific survival (DSS). GSEA revealed that these transporters are significantly involved in critical oncogenic pathways, including epithelial-mesenchymal transition (EMT), angiogenesis, and hypoxia, which are vital for cancer progression and metastasis. Conclusions: The study identifies SLC transporters as potential biomarkers and therapeutic targets in HNSC. Targeting these transporters with small molecule inhibitors could disrupt essential supply routes for cancer cells, enhancing treatment efficacy and improving patient outcomes. This study paves the way for developing SLC-based target therapies in precision oncology, with the goal of improving survival rates for patients with HNSC. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Modern Medicine & Health is the property of Journal of Modern Medicine & Health and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background/Objectives: The present study examined the effect of 12-week combined exercise training in normobaric hypoxia on arterial stiffness, inflammatory biomarkers, and red blood cell (RBC) hemorheological function in 24 obese older women (mean age: 67.96 ± 0.96 years). Methods: Subjects were randomly divided into two groups (normoxia (NMX; n = 12) and hypoxia (HPX; n = 12)). Both groups performed aerobic and resistance exercise training programs three times per week for 12 weeks, and the HPX group performed exercise programs in hypoxic environment chambers during the intervention period. Body composition was estimated using bioelectrical impedance analysis equipment. Arterial stiffness was measured using an automatic waveform analyzer. Biomarkers of inflammation and oxygen transport (tumor necrosis factor alpha, interleukin 6 (IL-6), erythropoietin (EPO), and vascular endothelial growth factor (VEGF)), and RBC hemorheological parameters (RBC deformability and aggregation) were analyzed. Results: All variables showed significantly more beneficial changes in the HPX group than in the NMX group during the intervention. The combined exercise training in normobaric hypoxia significantly reduced blood pressure (systolic blood pressure: p < 0.001, diastolic blood pressure: p < 0.001, mean arterial pressure: p < 0.001, pulse pressure: p < 0.05) and brachial–ankle pulse wave velocity (p < 0.001). IL-6 was significantly lower in the HPX group than in the NMX group post-test (p < 0.001). Also, EPO (p < 0.01) and VEGF (p < 0.01) were significantly higher in the HPX group than in the NMX group post-test. Both groups showed significantly improved RBC deformability (RBC EI_3Pa) (p < 0.001) and aggregation (RBC AI_3Pa) (p < 0.001). Conclusions: The present study suggests that combined exercise training in normobaric hypoxia can improve inflammatory biomarkers and RBC hemorheological parameters in obese older women and may help prevent cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Background: Research on a health-related event at the stage of labour and the occurrence of adverse outcomes at the school age has provided inconclusive results. Thus far, no systematic reviews have been conducted. Thus, the objective of this study is to investigate the association between hypoxia during pregnancy or delivery and the subsequent occurrence of a developmental dyslexia in school-age children. Methods: We used a standard search strategy of electronic databases (PubMed, PsycINFO, Web of Science, EMBASE, and Cochrane Library) and handsearching. We included observational studies (cohort studies, case-control studies) that consider as an exposure the presence of hypoxia during pregnancy or delivery, and as an outcome, developmental dyslexia in school-age children. Two reviewers independently conducted the search and determined eligibility, which was not restricted by language or year of publication. Results: The search took place until 1 April 2023. Of the 1,336 abstracts screened, 6 were assessed for eligibility. Of the six eligible studies, no studies met the pre-specified eligibly criteria. Conclusions: We were unable to assess the association between hypoxia and developmental dyslexia, as no eligible studies were found. Thus, the association between hypoxia during pregnancy or delivery and dyslexia in school-age children remains unknown. [ABSTRACT FROM AUTHOR]

The Changjiang Estuary and adjacent East China Sea are well-known hypoxic aquatic environments. Eutrophication-driven hypoxia frequently occurs in coastal areas, posing a major threat to the ecological environment, including altering community structure and metabolic processes of marine organisms, and enhancing diversion of energy shunt into microbial communities. However, the responses of microbial communities and their metabolic pathways to coastal hypoxia remain poorly understood. Here, we studied the microbial communities collected from spatiotemporal samplings using metagenomic sequencing in the Changjiang Estuary and adjacent East China Sea. This generated 1.31 Tbp of metagenomics data, distributed across 103 samples corresponding to 8 vertical profiles. We further reported 1,559 metagenome-assembled genomes (MAGs), of which 508 were high-quality MAGs (Completeness > 90% and Contamination < 10%). Phylogenomic analysis classified them into 181 archaeal and 1,378 bacterial MAGs. These results provided a valuable metagenomic dataset available for further investigation of the effects of hypoxia on marine microorganisms. [ABSTRACT FROM AUTHOR]

The clinical translation of tumor hypoxia intervention modalities still falls short of expectation, restricted by poor biocompatibility of oxygen‐carrying materials, unsatisfactory oxygen loading performance, and abnormally high cellular oxygen consumption‐caused insufficient hypoxia relief. Herein, a carrier‐free oxygen nano‐tank based on modular fluorination prodrug design and co‐assembly nanotechnology is elaborately exploited, which is facilely fabricated through the molecular nanoassembly of a fluorinated prodrug (FSSP) of pyropheophorbide a (PPa) and an oxygen consumption inhibitor (atovaquone, ATO). The nano‐tank adeptly achieves sufficient oxygen enrichment while simultaneously suppressing oxygen consumption within tumors for complete tumor hypoxia alleviation. Significant, the fluorination module in FSSP not only confers favorable co‐assemblage of FSSP and ATO, but also empowers the nanoassembly to readily carry oxygen. As expected, it displays excellent oxygen carrying capacity, favorable pharmacokinetics, on‐demand laser‐triggerable ATO release, closed‐loop tumor hypoxia relief, and significant enhancement to PPa‐mediated PDT in vitro and in vivo. This study provides a novel nanotherapeutic paradigm for tumor hypoxia intervention‐enhanced cancer therapy. [ABSTRACT FROM AUTHOR]

Corneal diseases represent 5.1% of all eye defects and are the fourth leading cause of blindness globally. Corneal neovascularization can arise from all conditions of chronic irritation or hypoxia, which disrupts the immune‐privileged state of the healthy cornea, increases the risk of rejection after keratoplasty, and leads to opacity. In the past decades, significant progress has been made for neovascular diseases of the retina and choroid, with plenty of drugs getting commercialized. In addition, to overcome the barriers of the short duration and inadequate penetration of conventional formulations of antivascular endothelial growth factor (VEGF), multiple novel drug delivery systems, including adeno‐associated virus (AAV)‐mediated transfer have gone through the full process of bench‐to‐bedside translation. Like retina neovascular diseases, corneal neovascularization also suffers from chronicity and a high risk of recurrence, necessitating sustained and efficient delivery across the epithelial barrier to reach deep layers of the corneal stroma. Among the explored methods, adeno‐associated virus‐mediated delivery of anti‐VEGF to treat corneal neovascularization is the most extensively researched and most promising strategy for clinical translation although currently although, it remains predominantly at the preclinical stage. This review comprehensively examines the necessity, benefits, and risks of applying AAV vectors for anti‐VEGF drug delivery in corneal vascularization, including its current progress and challenges in clinical translation. [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]

The newly developed portable oxygen concentrator with an auto-demand oxygen delivery system (auto-DODS) automatically switches between 3 sensitivities according to the negative pressure gradient of inhalation and supplies oxygen only during inhalation. The aim of this study was to verify the effectiveness and safety of auto-demand devices compared with a continuous flow oxygen concentrator, during sleep, in a randomized crossover noninferiority trial. We alternatively used an auto-DODS or a continuous-flow oxygen concentrator, all night on separate days for HOT (Home Oxygen Therapy) patients with nocturnal hypoxemic symptoms. The primary endpoints were the mean value of oxygen saturation (SpO2) over the total sleep time. The secondary endpoints included the efficacy endpoints and the safety endpoints. Regarding the primary endpoint, the difference in SpO2 between the auto-DODS and continuous flow was 0.835%. Since the upper limit of this difference did not exceed 2.8, which was set as the noninferiority margin, it was shown that the auto-DODS did not reduce SpO2 by at least 2.8% on average compared to continuous flow. No equipment failure or exacerbation of disease was observed, confirming the safety of the auto-DODS during the night. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of cancer-related death globally. Metastasis is the most common reason of mortality in which hypoxia is suggested to have a pivotal role. However, the effect of hypoxia on the metastatic potential and migratory activity of cancer cells is largely unexplored and warrants detailed scientific investigations. Accordingly, we analyzed changes on cell proliferation and migratory activity both in single-cell migration and invasion under normoxic and hypoxic conditions in lung adenocarcinoma cell lines. Alterations in crucial genes and proteins associated with cellular response to hypoxia, epithelial-mesenchymal transition, proliferation and apoptosis were also analyzed. Generally, we observed no change in proliferation upon hypoxic conditions and no detectable induction of apoptosis. Interestingly, we observed that single-cell motility was generally reduced while invasion under confluent conditions using scratch assay was enhanced by hypoxia in most of the cell lines. Furthermore, we detected changes in the expression of EMT markers that are consistent with enhanced motility and metastasis-promoting effect of hypoxia. In summary, our study indicated cell line-, time of exposure- and migrational type-dependent effects of hypoxia in cellular proliferation, motility and gene expression. Our results contribute to better understanding and tackling cancer metastasis. [ABSTRACT FROM AUTHOR]

To evaluate the prognostic significance of the maximum standardized uptake value (SUVmax) in nasopharyngeal carcinoma (NPC), establish a gene signature that correlates with SUVmax, and explore the underlying biological behaviors associated with these correlations for the prediction of clinical outcomes. A cohort of 726 patients with NPC was examined to identify correlations between SUVmax and various clinical variables. RNA sequencing was performed to identify genes related to SUVmax, and these genes were used to develop an SUV signature. Additionally, transcriptome enrichment analysis was conducted to investigate the potential biological behaviors underlying the observed correlations. Higher SUVmax was associated with an increased tumor burden and worse prognosis. The SUV signature, which consisted of 10 genes, was positively correlated with SUVmax, and it predicted worse survival outcomes. This signature was highly expressed in malignant epithelial cells and associated with hypoxia and resistance to radiotherapy. Additionally, the signature was negatively correlated with immune function. SUVmax is a valuable prognostic indicator in NPC, with higher values predicting worse outcomes. The SUV signature offers further prognostic insights, linking glucose metabolism to tumor aggressiveness, treatment resistance, and immune function, and it could represent a potential biomarker for NPC. [ABSTRACT FROM AUTHOR]

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Pericytes line the microvasculature throughout the body and play a key role in regulating blood flow by constricting and dilating vessels. However, the biophysical mechanisms through which pericytes transduce microenvironmental chemical and mechanical cues to mediate vessel diameter, thereby impacting oxygen and nutrient delivery, remain largely unknown. This knowledge gap is clinically relevant as numerous diseases are associated with the aberrant contraction of pericytes, which are unusually susceptible to injury. Here, we report the development of a high-throughput hydrogel-based pericyte contraction cytometer that quantifies single-cell contraction forces from murine and human pericytes in different microvascular microenvironments and in the presence of competing vasoconstricting and vasodilating stimuli. We further show that murine pericyte survival in hypoxia is mediated by the mechanical microenvironment and that, paradoxically, pre-treating pericytes to reduce contraction increases hypoxic cell death. Moreover, using the contraction cytometer as a drug-screening tool, we found that cofilin-1 could be applied extracellularly to release murine pericytes from hypoxia-induced contractile rigor mortis and, therefore, may represent a novel approach for mitigating the long-lasting decrease in blood flow that occurs after hypoxic injury. [ABSTRACT FROM AUTHOR]

The third-degree burns pose a severe public health issue. They often require autologous skin grafting, which faces limitations such as donor scarcity, resulting in graft failures and delayed wound closure. Secretomes derived from hypoxia-preconditioned mesenchymal stem cells (SH-MSCs) enriched with antiinflammatory cytokines and growth factors are explored as an alternative therapy. This study investigates the therapeutic potential of SH-MSCs in accelerating wound healing for thirddegree burns. Rat umbilical cord-derived mesenchymal stem cells (MSCs) were isolated, characterized, and subjected to hypoxic preconditioning to produce SH-MSCs. The secretome was obtained from SH-MSCs using tangential flow filtration. In a third-degree burn rat model, reduced levels of inflammatory markers, including IL-1ß and p65, reduced burn wound size, and enhanced tissue regeneration were found after SH-MSCs treatment compared to control groups. Histopathological examination further supports the efficacy of SH-MSCs in minimizing inflammatory cells. Overall, this study demonstrates the potential of SH-MSCs in accelerating wound healing in the third-degree burns. [ABSTRACT FROM AUTHOR]

Simple Summary: The YAP/TAZ signaling pathways, which is involved in tumor development and proliferation in a variety of solid tumors, inhibits hypoxia-induced cell death, increases and stabilizes angiogenesis, and activates tumor proliferation, both independently and in conjunction with HIF in hypoxic tumors. It also promotes tumor metastasis by regulating different TME environments. Therefore, understanding the activity of YAP/TAZ as a mechanism of tumor development may lead to the development of novel therapeutic strategies. In solid tumors such as hepatocellular carcinoma (HCC), hypoxia is one of the important mechanisms of cancer development that closely influences cancer development, survival, and metastasis. The development of treatments for cancer was temporarily revolutionized by immunotherapy but continues to be constrained by limited response rates and the resistance and high costs required for the development of new and innovative strategies. In particular, solid tumors, including HCC, a multi-vascular tumor type, are sensitive to hypoxia and generate many blood vessels for metastasis and development, making it difficult to treat HCC, not only with immunotherapy but also with drugs targeting blood vessels. Therefore, in order to develop a treatment strategy for hypoxic tumors, various mechanisms must be explored and analyzed to treat these impregnable solid tumors. To date, tumor growth mechanisms linked to hypoxia are known to be complex and coexist with various signal pathways, but recently, mechanisms related to the Hippo signal pathway are emerging. Interestingly, Hippo YAP/TAZ, which appear during early tumor and normal tumor growth, and YAP/TAZ, which appear during hypoxia, help tumor growth and proliferation in different directions. Peculiarly, YAP/TAZ, which have different phosphorylation directions in the hypoxic environment of tumors, are involved in cancer proliferation and metastasis in various carcinomas, including HCC. Analyzing the mechanisms that regulate the function and expression of YAP in addition to HIF in the complex hypoxic environment of tumors may lead to a variety of anti-cancer strategies and combining HIF and YAP/TAZ may develop the potential to change the landscape of cancer treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Intratumoral hypoxia is associated with poor prognosis and therapeutic resistance by modifying the tumor microenvironment in several cancers. MTH1, a member of the Nudix family, maintains the genomic integrity and viability of tumor cells under hypoxic conditions. This study aimed to investigate whether the antitumor activity of immune cells is effective under hypoxia and whether hypoxia-induced MTH1 could be a target for immunotherapy. We found that MTH1 expression is elevated in hypoxic head and neck cancer cell lines and tissues. A novel MTH1 epitope peptide activates CD4+ helper T cells with cytotoxic activity, and is effective even under hypoxic conditions. Combining MTH1-targeted immunotherapy with PD-1 blockade enhances cytotoxicity. These results suggest that MTH1-targeted immunotherapy combined with checkpoint blockade could effectively treat hypoxic tumors by maintaining T-cell activity and increasing cytotoxicity under hypoxic conditions. Intratumoral hypoxia is associated with tumor progression, aggressiveness, and therapeutic resistance in several cancers. Hypoxia causes cancer cells to experience replication stress, thereby activating DNA damage and repair pathways. MutT homologue-1 (MTH1, also known as NUDT1), a member of the Nudix family, maintains the genomic integrity and viability of tumor cells in the hypoxic tumor microenvironment. Although hypoxia is associated with poor prognosis and can cause therapeutic resistance by regulating the microenvironment, it has not been considered a treatable target in cancer. This study aimed to investigate whether hypoxia-induced MTH1 is a useful target for immunotherapy and whether hypoxic conditions influence the antitumor activity of immune cells. Our results showed that MTH1 expression was elevated under hypoxic conditions in head and neck cancer cell lines. Furthermore, we identified a novel MTH1-targeting epitope peptide that can activate peptide-specific CD4+ helper T cells with cytotoxic activity. The proliferation and cytotoxic activity of T cells were maintained under hypoxic conditions, and PD-1 blockade further augmented the cytotoxicity. These results indicate that MTH1-targeted immunotherapy combined with checkpoint blockade can be an effective strategy for the treatment of hypoxic tumors. [ABSTRACT FROM AUTHOR]