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Recent evidence suggests that different hypoxic modalities might accelerate the rehabilitation process in injured athletes. In this review, the application of hypoxia during rehabilitation from musculoskeletal injury is explored in relation to two principles: (1) facilitating the healing of damaged tissue, and (2) mitigating detraining and inducing training adaptations with a reduced training load. Key literature that explores the underlying mechanisms for these themes is presented, and considerations for practice and future research directions are outlined. For principle (1), passive intermittent hypoxic exposures might accelerate tissue healing through angiogenic and osteogenic mechanisms. Experimental evidence is largely derived from rodent research, so further work is warranted to establish whether clinically meaningful effects can be observed in humans, before optimal protocols are determined (duration, frequency, and hypoxic severity). Regarding principle (2), a hypoxia-related increase in the cardiometabolic stimulus imposed by low-load exercise is appealing for load-compromised athletes. As rehabilitation progresses, a variety of hypoxic modalities can be implemented to enhance adaptation to energy-systems and resistance-based training, and more efficiently return the athlete to competition readiness. While hypoxic modalities seem promising for accelerating musculoskeletal injury rehabilitation in humans, and are already being widely used in practice, a significant gap remains regarding their evidence-based application. [ABSTRACT FROM AUTHOR]

\nSummary boxOver the past decade, numerous studies have investigated an innovative “live low-train high” approach based on the repetition of short (<30 s) “all-out” sprints with incomplete recoveries in hypoxia; the so-called Repeated-Sprint training in Hypoxia (RSH). The aims of the present review are therefore threefold. First, this study summarizes the available evidence on putative additional performance enhancement after RSH comparing to the same training in normoxia (RSN). Second, a critical analysis of underpinning mechanisms discusses how advantages can be obtained through RSH for sea-level performance enhancement. An enhanced microcirculatory vasodilation leading to improved muscle perfusion and/or oxygenation and an increase in muscular phosphocreatine content may help explain the superiority of RSH vs. RSN. Third, the present review aims to provide guidelines for coaches, athletes and scientists to apply RSH interventions with regard to the interval duration, exercise-to-rest ratio and training volume. In conclusion, this review supports repeated-sprint training in hypoxia as an efficient (but not magic) training intervention with 77% of the controlled studies reporting an additional benefit with added hypoxia, mainly for team-, combat- and racket-sports athletes but also for all other sports (e.g. endurance) that require repeated accelerations with lesser fatigue. This review critically analyzes the results of the studies involving repeated-sprint training in hypoxia (RSH) since 2013.10 years ago, RSH was proposed as a promising training strategy shown to delay muscle and metabolic fatigue, particularly during repeated-sprint exercises with incomplete recoveries.In the past decade, RSH has gained great popularity among athletes, coaches and scientists as an effective training reproduced in various sports with a large majority of studies reporting beneficial outcomes.RSH may improve performance in a fibre-type-selective and intensity-dependent manner, with mechanisms presumably different than those associated with other (less intense) hypoxic training methods.This review critically analyzes the results of the studies involving repeated-sprint training in hypoxia (RSH) since 2013.10 years ago, RSH was proposed as a promising training strategy shown to delay muscle and metabolic fatigue, particularly during repeated-sprint exercises with incomplete recoveries.In the past decade, RSH has gained great popularity among athletes, coaches and scientists as an effective training reproduced in various sports with a large majority of studies reporting beneficial outcomes.RSH may improve performance in a fibre-type-selective and intensity-dependent manner, with mechanisms presumably different than those associated with other (less intense) hypoxic training methods. [ABSTRACT FROM AUTHOR]

Objective: This letter to the editor presents suggestions for the therapeutic use of riboflavin in perinatal brain lesions caused by oxygen deprivation.Methods: Clinical and preclinical studies using riboflavin conjugated with other components for the treatment of cerebral oxygen deprivation were included in the discussion.Results: Oxygen deprivation is predisposed by anoxia, hypoxia, or ischemia and causes severe early central damage, including sensorimotor impairment. At the moment, these lesions lack effective and affordable therapies. We present studies demonstrating the neuroprotective effects of riboflavin–containing drugs to treat children affected by hypoxic perinatal injuries.Discussion: This article suggests conducting preclinical studies to elucidate the potential isolated effects of riboflavin on the pathogenesis of perinatal brain injury caused by oxygen deprivation, by presenting routes for future clinical strategies for the prevention or treatment of perinatal encephalopathies. [ABSTRACT FROM AUTHOR]

The timing and pattern of biotic recovery after the Late Ordovician Mass Extinction (LOME) are highly controversial. Here, we conducted a systematic investigation on ichnofossils from the lower Silurian succession of the northwestern Hunan province, middle-upper Yangtze Block, South China. Biotic recovery of marine benthic ecosystems after the LOME was analysed and discussed for the first time using multiple ichnofossil proxies. The vertical distribution and evolutional trends of trace fossil assemblages suggest that biotic recovery was significantly delayed by the widespread anoxia during the latest Hirnantian to middle Aeronian. The recovery displays a stepwise pattern and reached a relatively high stage during the late Aeronian, although a full recovery was generally not achieved during this interval as proposed elsewhere before. There is a sharp decrease in all trace fossil proxies across the Aeronian-Telychian boundary, indicating a resetting of biotic recovery back to initial stages, most likely linked to a re-onset of anoxia in shallow marine settings during the late Aeronian Event. Subsequent recovery generally followed the patterns of late Aeronian, but was hampered by a low nutrient supply during early Telychian. By the beginning of middle Telychian, a full recovery was achieved, ca. 8.8 Ma after the second pulse of the LOME. [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]

Background: Renal hypoxia plays a key role in the progression of chronic kidney disease (CKD). Shen Shuai II Recipe (SSR) has shown good results in the treatment of CKD as a common herbal formula. This study aimed to explore the effect of SSR on renal hypoxia and injury in CKD rats. Methods: Twenty-five Wistar rats underwent 5/6 renal ablation/infarction (A/I) surgery were randomly divided into three groups: 5/6 (A/I), 5/6 (A/I) + losartan (LOS), and 5/6 (A/I) + SSR groups. Another eight normal rats were used as the Sham group. After 8-week corresponding interventions, blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) was performed to evaluate renal oxygenation in all rats, and biochemical indicators were used to measure kidney and liver function, hemoglobin, and proteinuria. The expression of fibrosis and hypoxia-related proteins was analyzed using immunoblotting examination. Results: Renal oxygenation, evaluated by BOLD-fMRI as cortical and medullary T2* values (COT2* and MET2*), was decreased in 5/6 (A/I) rats, but increased after SSR treatment. SSR also downregulated the expression of hypoxia-inducible factor-1α (HIF-1α) in 5/6 (A/I) kidneys. With the improvement of renal hypoxia, renal function and fibrosis were improved in 5/6 (A/I) rats, accompanied by reduced proteinuria. Furthermore, the COT2* and MET2* were significantly positively correlated with the levels of creatinine clearance rate (Ccr) and hemoglobin, but negatively associated with the levels of serum creatinine (SCr), blood urea nitrogen (BUN), serum cystatin C (CysC), serum uric acid (UA), 24-h urinary protein (24-h Upr), and urinary albumin:creatinine ratio (UACR). Conclusion: The degree of renal oxygenation reduction is correlated with the severity of renal injury in CKD. SSR can improve renal hypoxia to attenuate renal injury in 5/6 (A/I) rats of CKD. [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]

Experimental studies on animals have demonstrated a higher neuroprotective efficacy of hypercapnic hypoxia compared to normocapnic hypoxia. Respiratory training with hypercapnic hypoxia has shown a positive impact on the functional state of the nervous system in children with cerebral palsy (CP). It can be presumed that the combined effect of moderate hypercapnia and hypoxia will be promising for clinical application within the context of early rehabilitation after ischemic stroke. A randomized triple-blind placebo-controlled study was conducted on 102 patients with ischemic stroke, aged 63.07 ± 12.1 years. All patients were diagnosed with ischemic stroke based on neuroimaging criteria and/or clinical criteria within the 48–72 hour timeframe. The experimental group (n = 50) underwent daily respiratory training with hypercapnic hypoxia (FetCO2 5–6%, FetO2 15–16%) using the 'Carbonic' device for 7–11 sessions of 20 minutes each day during the treatment process. The control group (placebo, n = 52) underwent training on a similar device modified for breathing atmospheric air. Neurological examinations were conducted on all patients before the study and on the day after completing the training course. The standard treatment demonstrated effectiveness in terms of neurological status scales in both groups. Intermittent exposure to hypercapnic hypoxia proved more effective in improving neurological function indicators in patients compared to the placebo group: NIHSS scale scores were 40% lower than in the placebo group (p < 0.001); mRS scale scores were 35% lower (p < 0.001); B-ADL-I and RMI indices were higher by 26% (p < 0.01) and 36% (p < 0.001), respectively; MoCA scale results were 13% higher (p < 0.05); HADS and BDI-II scale scores were lower by 35% (p < 0.05) and 25% (p < 0.05), respectively. The increase in MMSE scale scores in the intervention group was 54% higher (p < 0.001), and MoCA scale scores increased by 25% (p < 0.001). Respiratory training with hypercapnic hypoxia improves the functional state of the nervous system in patients with ischemic stroke. After conducting further clarifying studies, hypercapnic hypoxia can be considered as an effective method of neurorehabilitation, which can be used as early as 48–72 hours after the onset of stroke. [ABSTRACT FROM AUTHOR]

AbstractObjectivesMethodsKey findingsConclusionsExperimental models to test the effective protection against cardiac ischemia injury are still challenging in pre-clinical studies. The use of myocardial slices creates a special link between testing isolated cardiomyocytes and whole-heart research. In this work, we investigated the effects of oxygen deprivation in a hypoxic chamber and treatment with cobalt chloride (CoCl2) on the nucleotide profile in isolated mouse myocardial slices.200 μm-thick left ventricle myocardial slices were obtained from 3-month-old male C57Bl/6J mice using an oscillatory microtome. Slices were then exposed to 1% O2 atmosphere or 100 μM CoCl2 at 37 °C for 45 min and used for nucleotide measurements using ultra-high-performance liquid chromatography. The effects of two short-term experimental models of hypoxia were compared to 2′-deoxyglucose with oligomycin (2-DG + OLIGO) treatment, which inhibited both glycolysis and mitochondrial ATP synthesis.A significant effect of hypoxia with 1% O2 was observed on adenosine triphosphate (ATP) and total adenine nucleotide (TAN) concentrations as well as on adenylate energy charge (AEC), ATP/ADP and ATP/AMP ratios. Oxygen deprivation caused changes almost as profound as 2-DG + OLIGO, emphasizing the critical role of mitochondrial oxidative phosphorylation in the energy metabolism of cultured heart slices. CoCl2 treatment that elicits hypoxia-like responses via HIF-1α stabilization only slightly affected nucleotide levels. This suggests that mechanisms induced by cobalt ions require more time to change the cardiac energy metabolism.A short-term culture of myocardial slices in a hypoxic chamber seems to be an appropriate model of cardiac ischemia for testing new pharmacological approaches based on modulating the energy metabolism of cardiac cells. [ABSTRACT FROM AUTHOR]

We aimed to investigate the role of aerobic capacity on cognitive functions during hypoxic conditions. Possessing a mishap risk in aviation, acute hypobaric hypoxia has some negative effects on cognitive functions. Therefore, it is important to develop hypoxia tolerance to preserve the mental functions of pilots against possible hypoxic conditions during flight. A total of 25 pilot candidates were included in this study. The subjects were dichotomized into two groups as high-fit and low-fit according to aerobic capacities. Hypoxia was applied at an altitude equivalent pressure of 18,000 ft. Go/NoGo and Digit Span cognitive tests were applied in two phases before hypoxia training and during hypoxia. In the low-fit group, for the Go/NoGo test parameters, the mean R-Go reaction time increased significantly during hypoxia when compared to before hypoxia training. Additionally, in the low-fit group for the Digit Span test parameters, the memory span and the sum of correct answers both decreased significantly during hypoxia. In the high-fit group, there was no significant difference between the two test parameters during hypoxia. The results of this study indicate that physical fitness has a positive effect on the deterioration of cognitive functions during hypoxia. It could be useful to suggest regular physical exercise habits for aircrews to increase their acute hypoxia tolerance in terms of cognitive function. [ABSTRACT FROM AUTHOR]

This study aimed to characterise bilateral asymmetry in running mechanics during perceptually regulated, high-intensity intermittent running in hypoxia and normoxia and examines whether inter-limb differences in running mechanics are modified between and within intervals. Nineteen trained runners completed 4 × 4-min treadmill running bouts (3-min passive recoveries) at a perceived rating exertion of 16 on the 6–20 Borg scale in either hypoxic (FiO2 = 0.15) or normoxic (FiO2 = 0.21) conditions. Ground reaction force recordings at constant velocity (group average: 14.8 ± 1.9 km/h) allowed measurement of running kinetics/kinematics and calculation of spring-mass model characteristics at the beginning and the end of each 4-min interval. Lower limb asymmetry was assessed from the 'symmetry angle' (SA) score. There were no between intervals (P > 0.087), within intervals (P > 0.076) or FiO2 (P > 0.128) differences in SA scores for any of the 16 biomechanical variables. Mean SA scores were lower than 1.5% for spatio-temporal variables, ~1.5–3% for braking and push-off phase durations, peak forces and impulses and ~4–6% for mean loading rate and vertical stiffness. With preserved lower limb asymmetries both between and within intervals and with additional hypoxia, trained runners completing perceptually regulated interval treadmill runs may anticipate a maintained performance without heightened injury risk. [ABSTRACT FROM AUTHOR]

Several biases are often introduced in taxonomic studies due to the transformation or loss of biological information that occurs at different stages from the original depositional ecosystem to the finally selected study sample. We propose the creation of a Taphonomic Alteration Index for Fishes (TAIF) that allows an estimation of the extent of such transformation in the selected sample and its representativeness of the complete record. TAIF is designed as an easily-applicable index that can be used to rapidly assess and compare the taphonomic alteration in different taxa or localities and can also be used as a quantitative variable in other analyses (e.g. morphometrical, statistical). To test TAIF, we have used a sample of Teleostei incertae sedis (N = 190) from the Early Cretaceous of the Las Hoyas site (Cuenca, Spain). Although the obtained TAIF values show some variability, they are in general low, as would be expected for a Konservat-Lagerstätte. The low TAIF values obtained fit with the hypothesis that these fishes inhabited low energy and shallow inland waters, where the effect of anoxia and bacterial sealing would have preserved their remains from degradation. Similar indices could be designed for other taxa based on TAIF. [ABSTRACT FROM AUTHOR]

Acute respiratory distress syndrome (ARDS) is characterized by acute inflammatory injury to the lungs, alterations in vascular permeability, loss of aerated tissue, bilateral infiltrates, and refractory hypoxemia. ARDS is considered a heterogeneous syndrome, which complicates the search for effective therapies. The goal of this review is to provide an update on the pharmacological management of ARDS. The difficulties in finding effective pharmacological therapies are mainly due to the challenges in designing clinical trials for this unique, varied population of critically ill patients. Recently, some trials have been retrospectively analyzed by dividing patients into hyper-inflammatory and hypo-inflammatory sub-phenotypes. This approach has led to significant outcome improvements with some pharmacological treatments that previously failed to demonstrate efficacy, which suggests that a more precise selection of ARDS patients for clinical trials could be the key to identifying effective pharmacotherapies. This review is provided after searching the main studies on this topics on the PubMed and clinicaltrials.gov databases. The future of ARDS therapy lies in precision medicine, innovative approaches to drug delivery, immunomodulation, cell-based therapies, and robust clinical trial designs. These should lead to more effective and personalized treatments for patients with ARDS. [ABSTRACT FROM AUTHOR]

Rapid sequence intubation (RSI) is frequently performed by emergency medical services (EMS). We investigated the relationship between succinylcholine and rocuronium use and time until first laryngoscopy attempt, first-pass success, and Cormack-Lehane (CL) grades. We included adult patients for whom prehospital RSI was attempted from July 2015 through June 2022 in a retrospective, observational study with pre-post analysis. Timing was verified using recorded defibrillator audio in addition to review of continuous ECG, pulse oximetry, and end-tidal carbon dioxide waveforms. Our primary exposure was neuromuscular blocking agent (NMBA) used, either rocuronium or succinylcholine. Our prespecified primary outcome was the first attempt Cormack-Lehane view. Key secondary outcomes were first laryngoscopy attempt success rate, timing from NMBA administration to first attempt, number of attempts, and hypoxemic events. Of 5,179 patients in the EMS airway registry, 1,475 adults received an NMBA while not in cardiac arrest. Cormack-Lehane grades for succinylcholine and rocuronium were similar: grade I (64%, 59% [95% CI 0.64–1.09]), grade II (16%, 21%), grade III (18%, 16%), grade IV (3%, 3%). The median interval from NMBA administration to start of the first attempt was 57 s for succinylcholine and 83 s for rocuronium (mean difference 28 [95% CI 20–36] seconds). First attempt success was 84% for succinylcholine and 83% for rocuronium. Hypoxemic events were present in 25% of succinylcholine cases and 23% of rocuronium cases. Prehospital use of either rocuronium or succinylcholine is associated with similar Cormack-Lehane grades, first-pass success rates, and rates of peri-intubation hypoxemia. [ABSTRACT FROM AUTHOR]

The growth, enzyme activity, and nutritional value of Theobroma cacao L. are strongly affected under hypoxic conditions and by the toxicity of iron (Fe). It is a challenge to mitigate the stress caused by excessive levels of Fe under flooding in cocoa trees. This study evaluated the physiological response of two cocoa genotypes to different Fe concentrations and hypoxic conditions. The plants were cultivated under three Fe concentrations (44.5, 133.5, and 400.5 lmol L-1 FeSO4) and two hydroponic cultivation conditions, one with an oxygenated nutrient solution and the other solution without oxygenation (hypoxia). Growth characteristics, enzyme activity, and nutritional balance were evaluated at 116 days after planting. An increased guaiacol peroxidase activity and higher phenolic compound contents of genotype TSH 1188 were observed at the Fe concentration of 400.5 lmol L-1 under hypoxia. The genotype SIAL 70 was also recorded increased with rising Fe concentrations, even without aeration. Regardless of the hypoxic conditions, the calcium content of both genotypes decreased with increasing Fe concentrations in the nutrient solution, while the Zn concentration of genotype TSH 1188 increased, regardless of the hypoxic nutrient solution, and that of genotype SIAL 70 decreased under hypoxic conditions. The genotypes respond differently to Fe excess and hypoxia, indicating distinct tolerance mechanisms for each stress type. In general, the tolerance of genotype TSH 1188 and SIAL 70 to the combination of Fe excess and hypoxia, respectively, was high and moderate, suggesting that the two genotypes have different mechanisms to support these stress conditions. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether performing resistance exercise in hypoxia acutely reduces performance and increases markers of fatigue, and whether these responses are exaggerated if exercising at high versus low work rates (i.e., exercising to failure or volume matched non-failure). Methods: Following a within-subject design, 20 men completed two trials in hypoxia (13% oxygen) and two in normoxia (21% oxygen). The first session for hypoxic and normoxic conditions comprised six sets of bench press and shoulder press to failure (high work rate), while subsequent sessions involved the same volume distributed over 12 sets (low work rate). Physical performance (concentric velocity) and perceptual responses were measured during exercise and for 72 hr post-exercise. Neuromuscular performance (bench throw velocity) was assessed pre- and post-session. Results: Hypoxia did not affect physical performance, neuromuscular performance, and perceptual recovery when exercising at high or low work rates. Higher work rate exercise caused greater acute decrements in physical performance and post-exercise neuromuscular performance and increased perceived exertion and muscle soreness (p ≤ 0.006), irrespective of hypoxia. Conclusions: Hypoxia does not impact on resistance exercise performance or increase markers of physical and perceptual fatigue. Higher exercise work rates may impair physical performance, and exaggerate fatigue compared to low work rate exercise, irrespective of environmental condition. Practitioners can prescribe hypoxic resistance exercise without compromising physical performance or inducing greater levels of fatigue. For athletes who are required to train with high frequency, decreasing exercise work rate may reduce post-exercise markers of fatigue for the same training volume. [ABSTRACT FROM AUTHOR]

Previous studies show that spinal cord ischemia and hypoxia is an important cause of spinal cord necrosis and neurological loss. Therefore, the study aimed to identify genes related to ischemia and hypoxia after spinal cord injury (SCI) and analyze their functions, regulatory mechanism, and potential in regulating immune infiltration. The expression profiles of GSE5296, GSE47681, and GSE217797 were downloaded from the Gene Expression Omnibus database. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to determine the function and pathway enrichment of ischemia- and hypoxia-related differentially expressed genes (IAHRDEGs) in SCI. LASSO model was constructed, and support vector machine analysis was used to identify key genes. The diagnostic values of key genes were evaluated using decision curve analysis and receiver operating characteristic curve analysis. The interaction networks of miRNAs-IAHRDEGs and IAHRDEGs-transcription factors were predicted and constructed with the ENCORI database and Cytoscape software. CIBERSORT algorithm was utilized to analyze the correlation between key gene expression and immune cell infiltration. There were 27 IAHRDEGs identified to be significantly expressed in SCI at first. These genes were mostly significantly enriched in wound healing function and the pathway associated with lipid and atherosclerosis. Next, five key IAHRDEGs (Abca1, Casp1, Lpl, Procr, Tnfrsf1a) were identified and predicted to have diagnostic value. Moreover, the five key genes are closely related to immune cell infiltration. Abca1, Casp1, Lpl, Procr, and Tnfrsf1a may promote the pathogenesis of ischemic or hypoxic SCI by regulating vascular damage, inflammation, and immune infiltration. [ABSTRACT FROM AUTHOR]

Intractable nausea can occur in numerous settings. We report on a 49-year-old woman with a past medical history of cystic fibrosis (CF) with chronic hypoxia, chronic nausea, complex infection history and frequent hospitalizations who was admitted to an academic medical center with a CF exacerbation. Her chronic nausea worsened with the use of antimicrobials, and she was unable to tolerate dopamine or serotonin antagonist antiemetics. Nausea persisted despite the use of benzodiazepines and antihistamines. She was given a one-time dose of fosaprepitant 150 mg intravenously (IV) with marked improvement of her nausea. During subsequent exacerbations, she again developed severe nausea which continued to respond well to a one-time dose of fosaprepitant 150 mg IV. Fosaprepitant is a substance P/neurokinin-1 (NK1) receptor antagonist that is FDA-approved for the prevention of chemotherapy-induced nausea and vomiting and has been used to prevent post-operative nausea and vomiting. Its use in other contexts has not been well established. This case suggests a role for fosaprepitant in the management of nausea outside the context of chemotherapy or general anesthesia. [ABSTRACT FROM AUTHOR]

We investigated whether a single heart rate clamped cycling session under systemic hypoxia affects the recovery of physical and psycho-physiological responses from residual fatigue compared to normoxia. On separate occasions, twelve trained males performed a 3-d acute training camp scenario. On days 1 and 3, participants cycled for 60 min at a constant heart rate (80% of ventilatory threshold). On day 2, fatigue was induced through a simulated team game circuit (STGC), followed by a 60-min intervention of either: (1) heart rate clamped cycling in normoxia; (2) heart rate clamped cycling in hypoxia (simulated altitude ~ 3500 m); or (3) no cycling. Countermovement jump height and leg stiffness were assessed before and after every session. Perceptual fatigue was evaluated daily. Compared to baseline, jump height decreased at all timepoints following the STGC (all p < 0.05). Leg stiffness and cycling power output only decreased immediately following the STGC, with a 48% further decrease in cycling power output in hypoxia compared to normoxia (p < 0.05). Perceived fatigue, decreased sleep quality, and increased muscle soreness responses occurred on day 3 (p < 0.05). A single heart rate-clamped cycling session in hypoxia reduced mechanical output without affecting recovery of physical performance and perceptual measures from residual fatigue induced through team sport activity. [ABSTRACT FROM AUTHOR]

Background: Renal hypoxia plays a key role in the progression of chronic kidney disease (CKD). Shen Shuai II Recipe (SSR) has shown good results in the treatment of CKD as a common herbal formula. This study aimed to explore the effect of SSR on renal hypoxia and injury in CKD rats. Methods: Twenty-five Wistar rats underwent 5/6 renal ablation/infarction (A/I) surgery were randomly divided into three groups: 5/6 (A/I), 5/6 (A/I) + losartan (LOS), and 5/6 (A/I) + SSR groups. Another eight normal rats were used as the Sham group. After 8-week corresponding interventions, blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) was performed to evaluate renal oxygenation in all rats, and biochemical indicators were used to measure kidney and liver function, hemoglobin, and proteinuria. The expression of fibrosis and hypoxia-related proteins was analyzed using immunoblotting examination. Results: Renal oxygenation, evaluated by BOLD-fMRI as cortical and medullary T2* values (COT2* and MET2*), was decreased in 5/6 (A/I) rats, but increased after SSR treatment. SSR also downregulated the expression of hypoxia-inducible factor-1α (HIF-1α) in 5/6 (A/I) kidneys. With the improvement of renal hypoxia, renal function and fibrosis were improved in 5/6 (A/I) rats, accompanied by reduced proteinuria. Furthermore, the COT2* and MET2* were significantly positively correlated with the levels of creatinine clearance rate (Ccr) and hemoglobin, but negatively associated with the levels of serum creatinine (SCr), blood urea nitrogen (BUN), serum cystatin C (CysC), serum uric acid (UA), 24-h urinary protein (24-h Upr), and urinary albumin:creatinine ratio (UACR). Conclusion: The degree of renal oxygenation reduction is correlated with the severity of renal injury in CKD. SSR can improve renal hypoxia to attenuate renal injury in 5/6 (A/I) rats of CKD. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is the deadliest form of malignancy and the most common subtype is non-small cell lung cancer (NSCLC). Hypoxia is a typical feature of solid tumor microenvironment. In the current study, we clarified the effects of hypoxia on stemness and metastasis and the molecular mechanism. Methods: The biological functions were assessed using the sphere formation assay, Transwell assay, and XF96 extracellular flux analyzer. The protein levels were detected by western blot. The lactylation modification was assessed by western blot and immunoprecipitation. The role of SOX9 in vivo was explored using a xenografted tumor model. Results: We observed that hypoxia promoted sphere formation, migration, invasion, glucose consumption, lactate production, glycolysis, and global lactylation. Inhibition of glycolysis suppressed cell stemness, migration, invasion, and lactylation. Moreover, hypoxia increased the levels of SOX9 and lactylation of SOX9, whereas inhibition of glycolysis reversed the increase. Additionally, knockdown of SOX9 abrogated the promotion of cell stemness, migration, and invasion. In tumor-bearing mice, overexpression of SOX9 promoted tumor growth, and inhibition of glycolysis suppressed tumor growth. Conclusion: Hypoxia induced the lactylation of SOX9 to promote stemness, migration, and invasion via promoting glycolysis. The findings suggested that targeting hypoxia may be an effective way for NSCLC treatment and reveal a new mechanism of hypoxia in NSCLC. [ABSTRACT FROM AUTHOR]

Hypoxemia as a common complication in colonoscopy under sedation and may result in serious consequences. Unfortunately, a hypoxemia prediction model for outpatient colonoscopy has not been developed. Consequently, the objective of our study was to develop a practical and accurate model to predict the risk of hypoxemia in outpatient colonoscopy under sedation. In this study, we included patients who received colonoscopy with anesthesia in Nanjing First Hospital from July to September 2021. Risk factors were selected through the least absolute shrinkage and selection operator (LASSO). Prediction models based on logistic regression (LR), random forest classifier (RFC), extreme gradient boosting (XGBoost), support vector machine (SVM), and stacking classifier (SCLF) model were implemented and assessed by standard metrics such as the area under the receiver operating characteristic curve (AUROC), sensitivity and specificity. Then choose the best model to develop an online tool for clinical use. We ultimately included 839 patients. After LASSO, body mass index (BMI) (coefficient = 0.36), obstructive sleep apnea-hypopnea syndrome (OSAHS) (coefficient = 1.32), basal oxygen saturation (coefficient = -0.14), and remifentanil dosage (coefficient = 0.04) were independent risk factors for hypoxemia. The XGBoost model with an AUROC of 0.913 showed the best performance among the five models. Our study selected the XGBoost as the first model especially for colonoscopy, with over 95% accuracy and excellent specificity. The XGBoost includes four variables that can be quickly obtained. Moreover, an online prediction practical tool has been provided, which helps screen high-risk outpatients with hypoxemia swiftly and conveniently. Colonoscopy under sedation is an effective technique for the inspection and treatment of alimentary canal diseases, but hypoxemia associated with this process cannot be ignored, since prolonged or severe hypoxemia may result in several serious consequences. We wanted to develop a practical and accurate model to predict the risk of hypoxemia for outpatient colonoscopy under sedation, which could help clinicians make more accurate and objective judgments to prevent patients from being harmed. A total of 839 patients were included in our study and we constructed five machine learning models and selected the best one, which demonstrated satisfactory performance. On this basis, a user-friendly data interface has been developed for convenient application. Clinicians can log in to this interface at any time and it will automatically calculate the patient's risk of hypoxemia when entering patient information. This study offers evidence that machine learning algorithms can accurately predict the risk of hypoxemia for outpatient colonoscopy under sedation and the model we developed is a practical and interpretable tool that could be used as a clinical decision-making aid. [ABSTRACT FROM AUTHOR]

Prehospital post-resuscitation hypotension and hypoxia have been associated with adverse outcomes in the context of out-of-hospital cardiac arrest (OHCA). We aimed to investigate the association between clinical outcomes and post-resuscitation hypoxia alone, hypotension alone, and combined hypoxia and hypotension. We used the 2018–2021 ESO annual datasets to conduct this study. All EMS-treated non-traumatic OHCA patients who had a documented prehospital return of spontaneous circulation (ROSC) and two or more SpO2 readings and systolic blood pressures recorded were evaluated for inclusion. Patients who were less than 18 years of age, pregnant, had a do-not-resuscitate order or similar, achieved ROSC after bystander CPR only, or had an EMS-witnessed cardiac arrest were excluded. Multivariable logistic regression adjusted for standard Utstein factors and highest prehospital Glasgow Coma Scale (GCS) score was used to investigate the association between hypoxia, hypotension, and outcomes. We analyzed data for 17,943 patients, of whom 3,979 had hospital disposition data. Hypotension and hypoxia were not documented in 1,343 (33.8%) patients, 1,144 (28.8%) had only hypoxia documented, 507 (12.7%) had only hypotension documented, and 985 (24.8%) had both hypoxia and hypotension documented. In comparison to patients who did not have documented hypotension or hypoxia, patients who had documented hypoxia (aOR: 1.76 [1.38, 2.24]), documented hypotension (aOR: 3.00 [2.15, 4.18]), and documented hypoxia and hypotension combined (aOR: 4.87 [3.63, 6.53]) had significantly increased mortality. The relationship between mortality and vital sign abnormalities (hypoxia and hypotension > hypotension > hypoxia) was observed in every evaluated subgroup. In this large dataset, hypotension and hypoxia were independently associated with mortality both alone and in combination. Compared to patients without documented hypotension and hypoxia, patients with documented hypotension and hypoxia had nearly five-fold greater odds of mortality. [ABSTRACT FROM AUTHOR]

Hard-to-heal wounds can be detrimental to patients' quality of life. Currently, there is scarcity of therapeutic alternatives to mainstay surgical treatment, which uses the principles of tissue debridement, temporary wound coverage, and subsequent tissue reconstruction. Here, a new approach is proposed that harnesses the regenerative power of autologous peripheral blood, through a process termed hypoxia-adjusted in vitro preconditioning. The effectiveness of this method is demonstrated with six cases of surgical wounds, including two cases of large full-thickness dermal wounds that developed as a result of skin necrosis following abdominoplasty and buttock-lift procedures in heavy smokers, as well as a case of extensive inflammatory tissue damage that occurred following breast surgery. While these wounds differed in size (4-160 cm²), geometry and location, all of them could be managed conservatively with topical application of growth factor-enriched hypoxia preconditioned serum derived from the patient's own peripheral blood. This treatment led to complete wound closure by latest 135 days. The finding of complete skin regeneration even in large (>10 cm²), full-thickness wounds, where initially no dermal tissue was available in the wound bed, strongly suggests that the treatment targeted key cellular regenerative mechanisms, including differentiation, angiogenesis, granulation tissue induction, contraction and epithelialization. The method is readily clinically applicable, cost effective, and overcomes limitations of the classic reconstructive approach. [ABSTRACT FROM AUTHOR]

As a major risk factor for cardiovascular diseases (CVD), Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH). Recent studies indicated that the increased cardiovascular risk in patients with OSA may be mediated by accelerated vascular senescence. Danggui-Buxue decoction (DBD) has been used for treating cardiovascular diseases, but its mechanism of vascular senescence regulation is still unclear. To investigate the effect of DBD on vascular senescence in mice exposed to CIH and to explore the role of the Nrf2/HO-1 pathway. C57BL/6N mice were randomly divided into Normoxia control group (CON), CIH (21%-5% O2, 20 times/h, 8 h/d) exposed group (CIH), and DBD treatment group (intragastrically treated with 2.34, 4.68, or 9.36 g/kg/day of DBD separately for 12 weeks as DBL, DBM, or DBH). Blood pressure, cardiac and vascular function, vascular senescence, inflammation response, oxidative stress, and Nrf2/HO-1 expression were determined. DBD (4.68 and 9.36 g/kg) significantly decreased Tail-cuff blood pressure, increased left ventricular systolic function, and alleviated arterial stiffness and vasorelaxation dysfunction in mice exposed to CIH. DBD treatment reduced SA-β-gal activity, decreased p16 (0.68-fold, 0.62-fold), P21 (0.58-fold, 0.52-fold), and p53 expressions (0.67-fold, 0.65-fold), and increased SIRT1 expression (2.22-fold, 2.98-fold) in the aortic. DBD treatment decreased IL-6, NF-κB, and TNF-α expressions, decreased MDA but increased SOD levels, and increased Nrf2 (1.8-fold, 1.89-fold) and HO-1 (2.25-fold, 2.43-fold) expression. DBD could attenuate vascular senescence accelerated by CIH exposure through inhibiting inflammatory response and oxidative stress by activating the Nrf2/HO-1 pathway. [ABSTRACT FROM AUTHOR]

Objective: Adrenocortical responsiveness is critical for maintaining glucocorticoids production and homeostasis during stress. We sought to investigate adrenocortical responsiveness during hypoxia in mice and the mechanisms responsible for the regulation of adrenal responsiveness. Methods: (1) Adult male WT mice were randomly divided into four groups: normoxia, hypoxia (24h), hypoxia (72h), hypoxia (72h) + GYY4137(hydrogen sulfide (H2S) donor, 133mmol/kg/day); (2) WT mice were randomly divided into four groups: sham, adrenalectomy (ADX), sham+hypoxia, ADX+hypoxia; (3) Cse-/- mice were randomly divided into two groups: Cse-/-, Cse-/- +GYY4137. Results: The circulatory level of corticosteroid induced by ACTH stimulation was significantly reduced in the mice with hypoxia compared with control mice. The mortality rate induced by lipopolysaccharide (LPS) increased during hypoxia. Cystathionine-γ-lyase (CSE) expression was significantly reduced in adrenal glands during hypoxia. GYY4137 treatment significantly increased adrenal responsiveness and attenuated NLRP3 inflammasome activation in mice treated by hypoxia and Cse-/- mice. Furthermore, The sulfhydrated level of PSMA7 in adrenal gland was decreased in the mice with hypoxia and Cse-/- mice. PSMA7 was S-sulfhydrated at cysteine 70. Blockage of S-sulfhydration of PSMA7 increased NLRP3 expression in adrenocortical cells. Conclusion: Reduced H2S production mediated hypo-adrenocortical responsiveness and NLRP3 inflammasome activation via PAMA7 S-sulfhydration during hypoxia. [ABSTRACT FROM AUTHOR]

Hypoxemia often occurs in outpatients undergoing anesthesia-assisted esophagogastroduodenoscopy (EGD). However, there is a scarcity in tools to predict the hypoxemia risk. We aimed to solve this problem by developing and validating machine learning (ML) models based on preoperative and intraoperative features. All data were retrospectively collected from June 2021 to February 2022. The most appropriate predictive features were selected by the least absolute shrinkage and selection operator, which were incorporated and modelled by 4 ML algorithms. The area under the precision-recall curve (AUPRC) was used as the main evaluation metric to select the best models, and the selected models were compared with the STOP-BANG score. Their predictive performance was visually interpreted by SHapley Additive exPlanations. The primary endpoint of this study was hypoxemia during the procedure, defined as at least one reading of pulse oximetry < 90% without probes misplacement from the anesthesia induction beginning to the end of EGD, while the secondary endpoint was hypoxemia during induction, from the induction beginning to the start of endoscopic intubation. Of 1160 patients in the derivation cohort, 112 patients (9.6%) developed intraoperative hypoxemia, of which 102 (8.8%) occurred during the induction period. In temporal and external validation, no matter whether based on preoperative variables or still based on preoperative plus intraoperative variables, our models showed excellent predictive performance for the two endpoints, significantly better than STOP-BANG score. In the model interpretation section, preoperative variables (airway assessment indicators, pulse oximeter oxygen saturation and BMI) and intraoperative variables (the induced propofol dose) made the highest contribution to the predictions. To our knowledge, our ML models were the first to predict hypoxemia risk, which achieved excellent overall predictive ability integrating various clinical indicators. These models have the potential to become an effective tool for adjusting sedation strategies flexibly and reducing the workload of anesthesiologists. This study is the first model employing ML methods based on preoperative and preoperative plus intraoperative variables for predicting the risk of hypoxemia during induction and the whole EGD procedure respectively. Our four models achieved satisfactory predictive performance and outperformed STOP-BANG score in terms of AUPRC in the temporal and external validation cohorts respectively. We found that the relevant variables of airway assessment should be fully taken into account when analyzing the risk factor of hypoxemia, and the effect of patients' age on their hypoxemia risk should be considered in conjunction with the propofol dose. [ABSTRACT FROM AUTHOR]

This study investigates how cognitive performance is affected by the combination of two stressors that are operationally relevant for helicopter pilots: heat load and hypobaric hypoxia. Fifteen participants were exposed to (1) no stressors, (2) heat load, (3) hypobaric hypoxia, and (4) combined heat load and hypobaric hypoxia. Hypobaric hypoxia (13,000 ft) was achieved in a hypobaric chamber. Heat load was induced by increasing ambient temperature to ∼28 °C. Cognitive performance was measured using two multitasks, and a vigilance task. Subjective and physiological data (oxygen saturation, heart rate, core- and skin temperature) were also collected. Mainly heat load caused cognitive performance decline. This can be explained by high subjective heat load and increased skin temperature, which takes away cognitive resources from the tasks. Only the arithmetic subtask was sensitive to hypobaric hypoxia, whereby hypobaric hypoxia caused a further performance decline in addition to the decline caused by heat load. Practitioner summary: Little is known about how multiple environmental stressors interact. This study investigates the combined effects of heat load and hypobaric hypoxia on cognitive performance. An additive effect of heat load and hypobaric hypoxia was found on a arithmetic task, which may be attributed to independent underlying mechanisms. [ABSTRACT FROM AUTHOR]

Inhalation of high concentrations of phosgene often causes pulmonary edema, which obstructs the airway and causes tissue hypoxia. There is currently no specific antidote. This study was performed to investigate the effect behind pentoxifylline (PTX) treatment for phosgene-induced lung injury in rat models. Rats were exposed to phosgene. The protein levels of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and occludin proteins in lung tissue were determined. The effect of both prophylactic and therapeutic administration of PTX (50 mg/kg and 100 mg/kg) was evaluated. The lung permeability index and HIF-1α protein level increased, the arterial blood oxygenation index (PaO2/FIO2 ratio) and occludin protein level decreased significantly 6 h after phosgene exposure (P < 0.05). PTX exerted protective effects by HIF-1α-VEGF-occludin signaling pathway to some extent. Moreover, prophylactic, but not therapeutic administration of PTX (100 mg/kg), exhibited a significant protective effect. Pretreatment with PTX protected against phosgene-induced lung injury, possibly by inhibiting differential expression of HIF-1α, VEGF, and occludin. [ABSTRACT FROM AUTHOR]

Protective effects of Leuzea uniflora (L.) Holub (Rhaponticum uniflorum (L.) DC., Asteraceae) on the white rats' brain mitochondrial function in acute hypobaric hypoxia/reoxygenation were studied. The extract of L. uniflora in the dose of 100 mg/kg was administered to animals for 14 days. The effects of the extract on the brain mitochondria respiration rate as well as on the NADH- and succinate dehydrogenase activities were determined. The extract of L. uniflora increased the oxidative phosphorylation processes coupling in brain mitochondria, namely, it significantly stimulated basal respiration, caused an increase in NADH-oxidase and succinate dehydrogenase complexes activity, increased the ATP content, reduced the lipid peroxidation intensity and improved the antioxidant state. The results obtained indicate the presence of energy-protective and antioxidant activities of L. uniflora, which are due to its ability to reduce the oxidation of biomacromolecules in hypoxia/reoxygenation. [ABSTRACT FROM AUTHOR]

Barley (Hordeum vulgare L.) growth is often inhibited under waterlogged fields. Under waterlogging, a higher C/N ratio in soil easily leads to low oxygen concentration and soil reduction. Although the tolerant varieties for waterlogging and soil reduction were previously reported, those root growth under hypoxia remains unknown. In this study, more than 90% of total leaf area in Deder 2, Hayakiso 2 and Akashinriki remained green even under waterlogged and reduced soil condition at seedling stage. The root elongation of Deder 2 and Hayakiso 2 was similar between aerobic and hypoxic conditions. In comparison, severe leaf necrosis was observed in Haruna Nijo and Houshun. Those root elongation was significantly inhibited under hypoxia, as compared with that under aerobic condition. In conclusion, it was considered that barley varieties tolerant to waterlogged reduced soil showed the better root growth in hypoxia in this study. [ABSTRACT FROM AUTHOR]

Egl-9 family hypoxia-inducible factor (egln), an oxygen-sensing enzyme family, has been thoroughly characterized in mammals and certain fishes, but there is few research on its involvement in reproductive development and hypoxic stress in rainbow trout. In this study, we investigated the gene structure, physicochemical properties, and evolutionary connection of the egln gene family. The expression profile of egln gene family and their regulatory mechanism were explored using bioinformatics analysis and hypoxia treatment experiments. Five egln genes were discovered in the rainbow trout genome in this investigation (egln1, egln2a, egln2b, egln3a, and egln3b). Domain prediction revealed that all egln proteins have p4hc conserved domains, and phylogenetic analysis revealed that rainbow trout egln2 and egln3 were closely related to Atlantic salmon. The results of real-time quantitative PCR (RT-qPCR) showed that egln genes were generally expressed in all detected tissues, and higher in the ovary, testis, and brain in normoxia. Under hypoxia, the expression level of eglns was significantly down-regulated in most tissues except the liver. Our research contributes to future research on the functional properties of egln genes, as well as the evolution of teleosts and the impact of hypoxia on biological immunity. [ABSTRACT FROM AUTHOR]

To determine the anatomical proximity of the vestibular nuclei to the respiratory nuclei and the effect of susceptibility of the posterior labyrinth to a hypoxic state on the vestibular system. It was aimed to evaluate the possible effects of periodic hypoxia on vestibular reflexes and proprioceptive perception in patients with obstructive sleep apnea syndrome (OSAS). The study was conducted with 40 patients diagnosed with moderate and severe OSAS and 21 healthy individuals. All individuals were evaluated with Dizziness Handicap Inventory, ocular vestibular evoked myogenic potential (oVEMP), cervical vestibular evoked myogenic potential (cVEMP), video head impulse test (vHIT), videonystagmography (VNG) and sportKAT 3000. In the vHIT, a statistically significant difference was found between the groups in terms of anterior and posterior semicircular canal vestibulo-ocular reflex gains (p <.05). A negative correlation was found between the lateral gain asymmetry and RALP gain asymmetry and the awake blood oxygen level in the OSAS groups. There was a statistically significant difference between the groups in terms of wave response rates cVEMP 100 dB nHL and oVEMP 100–110 dB nHL (p <.05). It was concluded that vestibular reflexes and proprioceptive perception were affected due to periodic/chronic hypoxia in patients with moderate and severe OSAS. [ABSTRACT FROM AUTHOR]

Green abalone (Haliotis fulgens) experienced severe biomass losses and massive mortality due to short-term marine climatic extremes. We studied green abalone behavior and energy expenditure in response to environmental stress. Acclimatized juveniles were subjected to hyperthermia (26°C), hypoxia (1.0 mg O2 L-1), the combination of both, and control conditions (18°C and oxygen saturation) using an automated system. The movement parameters of organisms were recorded by labeling and filming them, and the respiration rate was measured in hermetic chambers. There were differences in gross and net distance and velocity between the control and the combined stressors. Respiration was raised by hyperthermia, lowered by hypoxia, and further reduced by the combined stressors. All abalone that left the shelter during the night returned by daylight, while hypoxia and hyperthermia reduced this number. Research on environmental stress and movement strategies could lead to a more objective stress proxy. [ABSTRACT FROM AUTHOR]

Screening for congenital heart diseases by pulse oximetry is used for the initial assessment of the neonate. Variants of hemoglobin F can compromise light absorbance, inducing erroneous results. Two infants screened for congenital heart disease showed an asymptomatic low peripheral oxygen saturation. Arterial blood gases analysis revealed a normal arterial pressure of oxygen and oxygen saturation. More likely and/or severe causes of hypoxemia were ruled out. This "artifact" with SpO2-SaO2 dissociation, and after exclusion of other common etiologies of hypoxemia, raised the clinical suspicion of hemoglobinopathy. Hemoglobin molecular and genetic studies identified specific mutations in gamma chains from hemoglobin F, named hemoglobin F Sardinia. Hemoglobin F variants may result in low peripheral oxygen saturation readings by pulse oximetry, explaining the discordance in the clinical appearance and low peripheral oxygen saturation readings. [ABSTRACT FROM AUTHOR]

This study evaluated various biological parameters in subjects exposed to hypoxia, to verify effective monitoring for early hypoxia detection. Hypoxic-hypoxia is a life-threatening condition, but no method of early detection in flight has been established. Six healthy male subjects underwent 2 experiments at different oxygen concentrations (O2) during hypoxic exposure on different days. Subjects inhaled approximately 21% O2 for 3 minutes, hypoxia using approximately 14% O2 in Experiment 1 and 7% O2 in Experiment 2 for 3.5 minutes using a reduced oxygen breathing device. During the experiments, pupil diameter (PD), cerebral oxygenated hemoglobin (O2Hb), peripheral tissue oxygen saturation (SpO2), heart rate (HR), and blood pressure (BP) were measured. All 6 subjects completed both Experiments 1 and 2. ΔO2Hb showed significant correlations with %HR (r = −0.6005, P <.0001), %PD (r = −0.5227, P =.0001), and %SpO2 (r = 0.8281, P <.0001) in Experiment 1. ΔO2Hb also showed significant correlations with %HR (r = −0.7904, P <.0001), %PD (r = −0.7933, P <.0001), and %SpO2 (r = 0.7240, P <.0001) in Experiment 2. Rapid hypoxic exposure caused increase in %PD and decrease in ΔO2Hb, followed by immediate increase in %HR, and then decrease in %SpO2. The present study suggested that monitoring of HR, PD, and O2Hb were earlier parameters to detect hypoxia than SpO2. [ABSTRACT FROM AUTHOR]

Amphibians are believed to be sensitive to hypoxia, and in terms of this ability, they are between mammals with poor toleranсе to hypoxia and some turtles and fish with good tolerance to variable oxygen availability. However, we found that the Pallas' spadefoot, Pelobates vespertinus (Pallas, 1771), a Eurasian anuran burrowing amphibian species, is capable of surviving in harsh hypoxia during wintering. This species can tolerate over long-term vital oxygen concentration of almost 10 times lower than the normal atmospheric air concentration (about 2%). The lethal oxygen concentration was about 1% (from 0.6 to 1.8% for different individuals), i.e. 20 times lower than the atmospheric concentration. The Pallas' spadefoots overwinters in soils for more than half a year, having small sizes of storage organs (fat bodies and liver) and low content of lipids and glycogen in them, which are consumed at a low rate in normoxia at 3°С. Under hypoxic conditions, lipid consumption stops, and glycogen consumption increases, indicating a shift from aerobic to anaerobic metabolism. The cumulative effect of the reduced metabolic rate due to low wintering temperatures and the activation of glycolysis allows the Pallas's spadefoot to be considered as one of the most hypoxia-resistant burrowing amphibian species studied. [ABSTRACT FROM AUTHOR]

The main objective of this study was to compare the physical response of para-footballers with cerebral palsy (CP) in official international football matches played at moderate altitude and sea level locations. Eighty-seven international CP footballers participated in this study. We divided participants according to the place of the international competition [sea level group (SLG) and moderate altitude group (MAG)], sport classes (i.e., FT1, FT2, and FT3), and match playing time (i.e., <20 min, 20‒40 min, and >40 min). We recorded the physical response using global position system devices during matches. This study showed that MAG described a lower physical response than SLG on total distance, distance covered at different intensities, and the number of accelerations and decelerations. FT2 and FT3 presented a similar pattern, where we found significant differences for total distance, distance covered at lower and high intensities and moderate accelerations, and decelerations. Considering the playing time during altitude matches, the 20‒40 min and >40 min groups obtained more marked differences in the physical response variables. Para-footballers with CP who competed under altitude conditions showed a lower physical response during football matches, suggesting the implementation of specific preparation and training strategies to face the demanding environmental conditions. [ABSTRACT FROM AUTHOR]

Penaeus vannamei, experiences hypoxia in its natural habitat and in aquaculture. Under hypoxia, cells enhance anaerobic energy production through glycolysis dependent on the up-regulation of glycolytic enzymes including glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in gills. In vertebrates, GAPDH translocates into the nucleus and displays "moonlighting" functions including apoptosis. These alternative localizations and functions have not been described in crustaceans. We examined the effect of severe hypoxia and GAPDH silencing by RNA interference (RNAi) on its mRNA expression localization and glycolytic activity in P. vannamei gills. Expression and cytosolic activity were up-regulated only in hypoxia-exposed shrimp, but not in hypoxia-silenced specimens. GAPDH was immunodetected in cytosol and nucleus regardless of oxygen conditions. Hypoxia and RNAi decreased activity in cytosol and nucleus without affecting protein abundance, which suggests that nuclear GAPDH may have non-glycolytic functions. Moreover, Caspase-3 (Casp-3) expression increased with GAPDH silencing, suggesting alternative roles for GAPDH in apoptosis evasion. [ABSTRACT FROM AUTHOR]

Prone positioning during mechanical ventilation in patients with severe respiratory failure is an important intervention with both physiologic and empiric rationale for its use. This study describes a consecutive cohort of patients with severe hypoxemic respiratory failure due to COVID-19 who were transported in the prone position in order to determine the incidence of serious adverse events (SAEs) during transport. This retrospective study used prospectively collected data from a provincial air and land critical care transport system where specially trained critical care paramedic crews transported intubated and mechanically ventilated patients with COVID-19 in the prone position. SAEs were determined a priori, and included markers of new hemodynamic or respiratory instability, new resuscitative measures, and equipment or vehicle malfunction. Two authors independently reviewed each patient care record to identify SAEs during transport, and the ability of the crews to successfully manage such events. From April 2020 to June 2021, 127 intubated and mechanically ventilated patients were transported in the prone position. Of these, 117 were transported by land vehicle, 7 by rotor-wing, and 3 by fixed wing aircraft. 67 (52.8%) were vasopressor-dependent, 5 (3.9%) were receiving inhaled vasodilators, 9 (7.1%) were hypoxic (SpO2 < 88%), and 3 (2.4%) were hypotensive (SBP < 90 or MAP < 65 mm Hg) when the transport crew made patient contact at the sending hospital. Of the 122 (96.1%) patients in which a pre-transport PaO2/FiO2 ratio was available, the mean (median; range) was 86.7 (81; 47–144), with 27 patients greater having a ratio greater than 100. The mean (median; range) transport time was 49 (45; 14–176) minutes. There were 19 SAEs in 18 (14.2%) patients during transport, the most common of which was new hypoxia requiring ventilator adjustments (15 of 18 patients). All SAEs were successfully managed by the transport crews. No patient experienced tracheal tube obstruction, unintentional extubation, cardiac arrest, or died during transport. Patients with severe hypoxemic respiratory failure due to COVID-19 can be safely transported in the prone position by specially trained critical care paramedic crews. [ABSTRACT FROM AUTHOR]

Gliomas are brain tumors associated with high morbidity, relapse and lethality despite improvement in therapeutic regimes. The hypoxic tumor microenvironment is a key feature associated with such poor outcomes in gliomas. The Hypoxia Inducible Factor (HIF) family of transcription factors are master regulators of cellular proliferation, high metabolic rates and angiogenesis via aberrant expression of downstream genes. Recent studies have implicated long non-coding RNAs (lncRNAs) as potential prognostic and diagnostic biomarkers. In this study, identification of hypoxia regulated lncRNA with a bioinformatic pipeline consisting of a newly developed tool "GenOx" was utilized for the identification of Hypoxia Response Element (HRE) and Hypoxia Ancillary Sequence (HAS) motifs in the promoter regions of lncRNAs. This was coupled with molecular, functional and interactome-based analyses of these hypoxia-relevant lncRNAs in primary tumors and cell-line models. We report on the identification of novel hypoxia regulated lncRNAs SNHG12, CASC7 and MF12-AS1. A strong association of RNA splicing mechanisms was observed with enriched lncRNAs. Several lncRNAs have emerged as prognostic biomarkers, of which TP53TG1 and SNHG1 were identified as highly relevant lncRNAs in glioma progression and validated in hypoxia cultured cells. Significantly, we determined that SNHG1 expression in tumor (vs. normal) is different from glioma stem cells, GSC (vs. tumors) and in hypoxia (vs. normoxia), positioning downregulation of SNHG1 to be associated with worsened prognosis. [ABSTRACT FROM AUTHOR]

Highly dynamic oxygen gradients occur within tumors that can result in a hypoxic response, contributing to tumor progression and metastasis. Evidence in uveal melanoma (UM) suggests an upregulated hypoxia response in some poor prognosis UM characterized by HIF1α signaling. We aimed to investigate the effects of exposure to hypoxia on tumor growth and dissemination in the chick embryo chorioallantoic membrane (CAM) model. UM cell lines (MP41, 92.1, MP46, and OMM1) were grown in two-dimensional culture and pre-exposed to hypoxic (1% O2) conditions for 72 h. The effects of this hypoxia pre-conditioning on cell number and clonogenicity as compared with 21% O2 ("normoxia") were investigated prior to transplantation of the cells onto the CAM. Nodule-forming efficiency (NFE), nodule size, and the presence/absence of tumor cell dissemination were determined macroscopically and histologically. Exposure of UM cell lines to hypoxia upregulated HIF1α expression compared to cells cultured in normoxia. A 72-h pre-exposure to hypoxia significantly reduced cell number and clonogenicity in the MP41 and OMM1 cell lines while it had little effect in 92.1 and MP46 cells. When 72-h hypoxia pre-conditioned cells were grown in three-dimensions on the CAM, a reduction in NFE and nodule size was observed when compared with normoxic UM cells. All nodules were composed of proliferating (Ki-67+) Melan-A + cells and displayed chick blood vessel recruitment. Spread of UM cells into the adjacent CAM was observed; however, dissemination to the chick liver was only seen with 92.1 cells grown under normoxia. Hypoxia pre-conditioning does not appear to drive a metastatic phenotype in UM; however, further understanding of how oxygen dynamics within the tumor microenvironment regulates HIF1 signaling is needed to determine whether inhibitors of HIF signaling represent a therapeutic option in metastatic UM. [ABSTRACT FROM AUTHOR]

Nowadays the most effective way to cure myocardial infarction (MI) is reperfusion, which inevitably leads to cardiomyocyte apoptosis. In this study, we discussed the functions of SNHG15 in regulating cardiomyocyte apoptosis through the modulation of miR-188-5p/PTEN axis. We examined the links between SNHG15 and miR-188-5p/PTEN in mice with MI. Extensive experiments, measurements and comparisons were performed, including RT-PCR, western blotting, luciferase reporter assay, flow cytometry analysis etc. Through a series of comparisons and analysis, we discovered that SNHG15 could interact with the miR-188-5p/PTEN axis and impact the cellular physiology of cardiomyocyte apoptosis. PTEN was upregulated in hypoxia cells, but this effect was attenuated by miR-188-5p. MiR-188-5p could combine with SNHG15 and PTEN, and form a SNHG15-miR-188-5p-PTEN axis, which regulated the apoptosis of MCs. These results suggest that LncRNA SNHG15 regulates cardiomyocyte apoptosis induced by hypoxia or reperfusion injury through modulating of miR-188-5p/PTEN axis. [ABSTRACT FROM AUTHOR]

The paleo-ecological settings of Burgess Shale-type (BST) fossils have been the subject of extensive investigations, particularly with regard to the role of anoxia in their exceptional preservation. Our understanding of the complexity of both paleontological and geochemical environmental proxies has evolved with increased knowledge of niche communities and marine geochemical and biogeochemical processes. Accordingly, dated approaches should be reevaluated. The commonly applied paleoredox proxies V/Cr, Ni/Co, and V/(V + Ni), as well as the redox proxy V/Al2O3 and productivity proxy Ba/Al2O3, were all tested on the Wheeler Formation (Utah, USA) for which a fluctuating oxycline environment has been well established based on paleontological features. Subsequently, these proxies were applied to three additional BST fossil-bearing deposits: the Emigsville Member of the Kinzers Formation (Pennsylvania, USA), the Burgess Shale (British Columbia, CA) and the Emu Bay Shale (South Australia, AU). Their host shales lack perceptible V of marine origin, indicative of oxic conditions, in contrast to the Wheeler and brine-related strata from the Burgess Shale which include additional marine input of V in some beds, consistent with varying redox conditions. The black shales of the Longs Park Member (Kinzers) have elevated V/Al2O3 indicative of anoxic conditions. Molybdenum concentrations are relatively low in most samples, but minor variations tend to correlate with V/Al2O3 patterns. Ba/Al2O3 indicates high productivity with deposition of BST fossils in the Wheeler Formation, and diagenetic remobilisation of Ba owing to sediment anoxia in the Burgess Shale. Our findings show that redox proxy V/Al2O3 can be effectively applied to BST samples, whereas Ba/Al is a reliable proxy for low to moderate paleoproductivity levels and may be useful as a secondary or tangential proxy for redox conditions. Taphonomic processes leading to BST preservation occur in a variety of environments characterised by oxyclines, matgrounds, variable sedimentation rates, hypersalinity and/or anoxia. V/Al2O3 and Ba/Al2O3 are effective proxies for anoxia and productivity in BST deposits. BST preservation can occur in a variety of depositional environments. Marine anoxia is not required for BST preservation. [ABSTRACT FROM AUTHOR]

The blood–brain barrier is essential for maintaining the stability of the central nervous system and is also crucial for regulating drug metabolism, changes of blood–brain barrier's structure and function can influence how drugs are delivered to the brain. In high-altitude hypoxia, the central nervous system's function is drastically altered, which can cause disease and modify the metabolism of drugs in vivo. Changes in the structure and function of the blood–brain barrier and the transport of the drug across the blood-brain barrier under high-altitude hypoxia, are regulated by changes in brain microvascular endothelial cells, astrocytes, and pericytes, either regulated by drug metabolism factors such as drug transporters and drug-metabolizing enzymes. This article aims to review the effects of high-altitude hypoxia on the structure and function of the blood–brain barrier as well as the effects of changes in the blood-brain barrier on drug metabolism. We also hypothesized and explore the regulation and potential mechanisms of the blood-brain barrier and associated pathways, such as transcription factors, inflammatory factors, and nuclear receptors, in regulating drug transport under high-altitude hypoxia. [ABSTRACT FROM AUTHOR]

Background: Familiarity breeds complacency. One case of sore throat can start to sound like another. However, even common viral and bacterial infections can lead to serious sequelae. Clinicians cannot make a diagnosis if they do not consider it in their differential. Case: The presentation – and subsequent hospitalization – of a septic 19 year-old male college student is described. Despite brief interval improvement, he became hypoxic one week after developing a sore throat and was ultimately diagnosed with Lemierre's syndrome (septic thrombophlebitis of the internal jugular vein) via blood cultures and advanced imaging. Conclusions: Though rare, Lemierre's syndrome carries a high mortality rate. It should be considered an emergent complication of head and neck infections, particularly in young adults. [ABSTRACT FROM AUTHOR]

Aim: To highlight the role of secondary aeromedical services and required knowledge of Critical Care Flight Nurses (CCFN), in facilitating the safe inter-hospital transfer of patients with acute Spinal Cord Impairment (SCI) from a Major Trauma Centre (MTC) to a specialist SCI centre. Method: Literature search. Results: There is significant demand for secondary aeromedical services in order for patients with acute SCI to be transferred to a SCI centre within 24 h of injury. CCFN play an important role in triaging patients, coordinating patient care, arranging logistics of transport as well as providing direct clinical care inflight. CCFN must have knowledge regarding the pathophysiology of acute SCI, altitude physiology and interventions to manage stressors of flight in the aeromedical environment. Specific clinical challenges encountered by CCFN include the prevention of hypobaric hypoxic hypoxia and achieving appropriate immobilisation of the spine. Conclusion: Mitigating the increased risk associated with transporting critically unwell patients with SCI in the aeromedical environment, relies on aeromedical clinicians with education and training within the clinical specialty of aeromedical retrieval. The availability of secondary aeromedical services to undertake urgent inter-hospital retrieval of patients with acute SCI will be promoted by the continued development of Retrieval Nurse Practitioner (RNP) roles. [ABSTRACT FROM AUTHOR]

Background and aim: Pulmonary hypertension (PH) is a serious and even fatal disorder with limited treatment strategies. The hypoxia-induced pulmonary hypertension (HPH) rat model is commonly used in this field. While the HPH rat model has strong predictability and repeatability, the model is a chronic model, making it time-consuming, costly, and complicated and limiting the progress of the experiments. Currently, there is no uniform international standard for the HPH model. Our study aimed to find a relatively effective and efficient HPH modeling protocol. Methods: We established HPH rat models with different total hypoxia periods and different daily hypoxia times, and assessed different hypoxia modeling modes in multiple dimensions, such as haemodynamics, right ventricular (RV) hypertrophy, pulmonary arterial remodeling, muscularization, inflammation, and collagen deposition. Results: Longer daily hypoxia time resulted in higher mean pulmonary arterial pressure (mPAP)/right ventricular systolic pressure (RVSP) and more obvious RV hypertrophy, as well as more severe pulmonary arterial remodeling and muscularization, regardless of the total period of hypoxia (3- or 4-week). Moreover, pulmonary perivascular macrophages and collagen deposition showed daily hypoxia time-dependent increases, both in 3- and 4-week hypoxia groups. Conclusion: Our findings showed that the 3-week continuous hypoxia mode was a relatively efficient way to reduce the time needed to induce significant disease phenotypes, which offered methodological evidence for future studies in building HPH models. [ABSTRACT FROM AUTHOR]

As T cells transit between blood, lymphoid organs, and peripheral tissues, they experience varied levels of oxygen/hypoxia in inflamed tissues, skin, intestinal lining, and secondary lymphoid organs. Critical illness among COVID-19 patients is also associated with transient hypoxia and attenuation of T cell responses. Hypoxia is the fulcrum of altered metabolism, impaired functions, and cessation of growth of a subset of T cells. However, the restoration of normal T cell functions following transient hypoxia and kinetics of their phenotype-redistribution is not completely understood. Here, we sought to understand kinetics and reversibility of dichotomous T cell responses under sustained and transient hypoxia. We found that a subset of activated T cells accumulated as lymphoblasts under hypoxia. Further, T cells showed the normal expression of activation markers CD25 and CD69 and inflammatory cytokine secretion but a subset exhibited delayed cell proliferation under hypoxia. Increased levels of reactive oxygen species (ROS) in cytosol and mitochondria were seen during dichotomous and reversible attenuation of T cell response under hypoxia. Cell cycle analysis revealed maximum levels of cytosolic and mitochondrial ROS in dividing T cells (in S, G2, or M phase). Hypoxic T cells also showed specific attenuation of activation induced memory phenotype conversion without affecting naïve and activated T cells. Hypoxia-related attenuation of T cell proliferation was also found to be reversible in an allogeneic leukocyte specific mixed lymphocyte reaction assay. In summary, our results show that hypoxia induces a reversible delay in proliferation of a subset of T cells which is associated with obliteration of memory phenotype and specific increase in cytosolic/mitochondrial ROS levels in actively dividing subpopulation. Thus, the transient reoxygenation of hypoxic patients may restore normal T cell responses. Activated T cells cultured under hypoxic conditions show increased cellular ROS and mitochondrial ROS levels and there is limited expansion of memory phenotype T cells under as compared to activated T cells cultured under normoxia. [ABSTRACT FROM AUTHOR]

Neuroblastoma (NB) is the most common extracranial solid tumor of childhood, and high-risk disease is resistant to intensive treatment. Histotripsy is a focused ultrasound therapy under development for tissue ablation via bubble activity. The goal of this study was to assess outcomes of histotripsy ablation in a xenograft model of high-risk NB. Female NCr nude mice received NGP-luciferase cells intrarenally. Under ultrasound image guidance, histotripsy pulses were applied over a distance of 4–6 mm within the tumors. Bioluminescence indicative of tumor viability was quantified before, immediately after, and 24 h after histotripsy exposure. Tumors were immunostained to assess apoptosis (TUNEL), endothelium (endomucin), pericytes (αSMA), hypoxia (pimonidazole), vascular endothelial growth factor A (VEGFA), and platelet-derived growth factor-B (PDGF-B). The apoptotic cytokine TNFα and its downstream effector cleaved caspase-3 (c-casp-3) were assessed with SDS-PAGE. Histotripsy induced a 50% reduction in bioluminescence compared to untreated controls, with an absence of nuclei in the treatment core surrounded by a dense rim of TUNEL-positive cells. Tumor regions not targeted by histotripsy also showed an increase in TUNEL staining density. Increased apoptosis in histotripsy samples was consistent with increases in TNFα and c-casp-3 relative to controls. Treated tumors exhibited a decrease in hypoxia, VEGF, PDGF-B, and pericyte coverage of vasculature compared to control samples. Further, increases in vasodilation were found in histotripsy-treated specimens. In addition to ablative effects, histotripsy was found to drive tumor apoptosis through intrinsic pathways, altering blood vessel architecture, and reducing hypoxia. [ABSTRACT FROM AUTHOR]