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Endoscopic retrograde cholangiopancreatography (ERCP) is an important endoscopic technology in the field of digestive endoscopy. It is mainly used to diagnose biliary diseases in the early stage, and now it has developed into the diagnosis and treatment of biliary and pancreatic diseases. Compared with the general endoscopic treatment, its operation time is longer and its anesthesia risk is greater. ERCP under sedation/anesthesia can enhance patients′ tolerance and create better diagnosis and treatment conditions for digestive endoscopists, but there is also the risk of anesthesia-related hypoxemia, so airway management during operation is particularly important. In this paper, the ventilation strategies of ERCP patients under sedation/anesthesia were reviewed in combination with the related research in recent years. [ABSTRACT FROM AUTHOR]

Iron‐rich, ferruginous waters were the dominant geochemical regime for most of Earth's history. Modern ferruginous waters are found in stratified, sulfur‐poor lakes, and serve as crucial analogs for biogeochemical cycling throughout Earth's past. Here we present the first depth‐resolved data of physical structure, nutrients and trace elements from Lake Poso (Indonesia), a deep oligotrophic ancient lake. Lake Poso is ferruginous, with anoxia below ~ 90 m depth, placing it among the world's largest ferruginous lakes. Physical stratification is weaker than other tropical anoxic lakes, indicating sensitivity for paleoclimate reconstructions. Trace elements and nutrients are predominantly shaped by the oxic–anoxic transition. Manganese– and Fe oxyhydroxide–driven biogeochemical cycling occurs at distinct depth horizons, with Co and Ni controlled by Mn and showing shallow release in anoxic waters, while V, Cr, P, and As are controlled by Fe, with release in surface sediments and diffusive transport. Chromium is nonquantitatively removed in anoxic waters, in contrast to widespread assumptions in Cr‐based paleoreconstructions. Oxycline U and Se removal corresponds to a local N minimum, suggesting biological reduction and/or uptake. These first ferruginous water Se data also show removal in sediments, indicating sediment signals reflect multiple removal processes and informing Se‐based paleoreconstructions, while the absence of sediment U removal contrasts other anoxic basins. A comparison with other ferruginous lakes demonstrates how local influences drive deviations from expectations in other systems, and highlight common, generalizable ferruginous basin features. Therefore, these data will guide research in ferruginous settings across space and time, and improve paleoreconstructions from ferruginous sediment records. [ABSTRACT FROM AUTHOR]

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]

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]

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]

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]

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]

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

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

Reactive oxygen species (ROS) production is a key event in modulating plant responses to hypoxia and post-hypoxia reoxygenation. However, the molecular mechanism by which hypoxia-associated ROS homeostasis is controlled remains largely unknown. Here, we showed that the calcium-dependent protein kinase CPK16 regulates plant hypoxia tolerance by phosphorylating the plasma membrane-anchored NADPH oxidase respiratory burst oxidase homolog D (RBOHD) to regulate ROS production in Arabidopsis (Arabidopsis thaliana). In response to hypoxia or reoxygenation, CPK16 was activated through phosphorylation of its Ser274 residue. The cpk16 knockout mutant displayed enhanced hypoxia tolerance, whereas CPK16-overexpressing (CPK16-OE) lines showed increased sensitivity to hypoxic stress. In agreement with these observations, hypoxia and reoxygenation both induced ROS accumulation in the rosettes of CPK16-OEs more strongly than in the rosettes of the cpk16-1 mutant or the wild type. Moreover, CPK16 interacted with and phosphorylated the N-terminus of RBOHD at 4 serine residues (Ser133, Ser148, Ser163, and Ser347) that were necessary for hypoxia- and reoxygenation-induced ROS accumulation. Furthermore, the hypoxia-tolerant phenotype of cpk16-1 was fully abolished in the cpk16 rbohd double mutant. Thus, we have uncovered a regulatory mechanism by which the CPK16–RBOHD module shapes the ROS production during hypoxia and reoxygenation in Arabidopsis. The calcium-dependent CPK16–RBOHD module modulates the ROS production during plant responses to hypoxia and reoxygenation. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To review the literature on the different indications and recommendations for high-flow therapy in the hospital and at home. MATERIALS AND METHODS: Retrospective study based on a review of articles published in English or Spanish and indexed in the published in English or Spanish and indexed in PubMed, SciELO and Medline databases, with MeSH: oxygen; high flow; respiratory failure; nasal cannula; hypoxaemia and ROX index. RESULTS: Seventy-eight articles were identified. The main indication for high flow therapy was found in patients with hypoxemic respiratory failure, mainly with PaO2/FiO2 less than 200 mmHg, where it was shown to reduce the risk of intubation, days on mechanical ventilation and the risk of associated infectious complications. It currently has other indications of clinical importance. CONCLUSIONS: High flow therapy has been shown to be effective in the treatment of inpatients and outpatients with hypoxemic and hypercapnic respiratory failure. Since it is a strategy that avoids escalation of oxygen treatments, the earlier it is indicated, the greater the benefits it will bring to the clinical evolution of the patient. [ABSTRACT FROM AUTHOR]

Aircraft pilots face a high mental workload (MW) under environmental constraints induced by high altitude and sometimes sleep restriction (SR). Our aim was to assess the combined effects of hypoxia and sleep restriction on cognitive and physiological responses to different MW levels using the Multi-Attribute Test Battery (MATB)-II with an additional auditory Oddball-like task. Seventeen healthy subjects were subjected in random order to three 12-min periods of increased MW level (low, medium, and high): sleep restriction (SR, <3 h of total sleep time (TST)) vs. habitual sleep (HS, >6 h TST), hypoxia (HY, 2 h, FIO2 = 13.6%, ~3500 m vs. normoxia, NO, FIO2 = 21%). Following each MW level, participants completed the NASA-TLX subjective MW scale. Increasing MW decreases performance on the MATB-II Tracking task (p = 0.001, MW difficulty main effect) and increases NASA-TLX (p = 0.001). In the combined HY/SR condition, MATB-II performance was lower, and the NASA-TLX score was higher compared with the NO/HS condition, while no effect of hypoxia alone was observed. In the accuracy of the auditory task, there is a significant interaction between hypoxia and MW difficulty (F(2–176) = 3.14, p = 0.04), with lower values at high MW under hypoxic conditions. Breathing rate, pupil size, and amplitude of pupil dilation response (PDR) to auditory stimuli are associated with increased MW. These parameters are the best predictors of increased MW, independently of physiological constraints. Adding ECG, SpO2, or electrodermal conductance does not improve model performance. In conclusion, hypoxia and sleep restriction have an additive effect on MW. Physiological and electrophysiological responses must be taken into account when designing a MW predictive model and cross-validation. [ABSTRACT FROM AUTHOR]

Understanding the factors that influence the resilience of biological systems to environmental change is a pressing concern in the face of increasing human impacts on ecosystems and the organisms that inhabit them. However, most considerations of biological resilience have focused at the community and ecosystem levels, whereas here we discuss how including consideration of processes occurring at lower levels of biological organization may provide insights into factors that influence resilience at higher levels. Specifically, we explore how processes at the genomic and epigenomic levels may cascade up to influence resilience at higher levels. We ask how the concepts of "resistance," or the capacity of a system to minimize change in response to a disturbance, and "recovery," or the ability of a system to return to its original state following a disturbance and avoid tipping points and resulting regime shifts, map to these lower levels of biological organization. Overall, we suggest that substantial changes at these lower levels may be required to support resilience at higher levels, using selected examples of genomic and epigenomic responses of fish to climate-change-related stressors such as high temperature and hypoxia at the levels of the genome, epigenome, and organism. [ABSTRACT FROM AUTHOR]

Introduction: Pulmonary hemorrhage is a life-threatening complication of VA-ECMO occasionally presenting with Harlequin syndrome. Case report: We present a case of a VA-ECMO patient complicated with pulmonary hemorrhage, complete right lung atelectasis and differential hypoxia refractory to conventional treatment including optimal mechanical ventilation and bronchoscopy interventions. Patient was successfully managed by conversion of VA to VAV-ECMO. Discussion: Pulmonary hemorrhage and atelectasis treatment in a VA-ECMO patient includes transfusion, hold and reversal of anticoagulation, bronchoscopy interventions and optimization of VA-ECMO and ventilator support. Differential hypoxia may ensue due to residual native cardiac function. If refractory to conservative treatment, a VAV-ECMO configuration may be utilized to improve upper body oxygenation by inserting an additional cannula to the superior vena cava. Conclusion: VAV-ECMO is an ECMO configuration support in patients at risk of Harlequin syndrome presenting with pulmonary hemorrhage. [ABSTRACT FROM AUTHOR]

Some degree of localized hypoxia can cause varying degrees of cellular damage in tissues. Oxygen-releasing biomaterials can sustainably provide oxygen to transplanted cells. In recent years, extensive research efforts have been dedicated to developing more pratical oxygen-releasing biomaterials and systems to enhance oxygen delivery in vivo and ensure effective oxygen supply to implanted tissues. Based on the form of oxygen provision, these materials can be calssified into oxygen-carrying materials and oxygen-producing materials. The former deliver therapeutic oxygenation by binding oxygen molecules under specific conditions, while the latter incorporate oxygen source materials into polymers, achieving oxygen release through in vivo hydrolysis. This paper summarizes the current development of oxygen-carrying materials and oxygen-producing materials, including oxygen source supply, loading materials, and controlled release. It discusses practical application of oxygen-releasing biomaterials for oxygen delivery and various strategies for controlled release. [ABSTRACT FROM AUTHOR]

The 2‐nitroimidazole based 99mTc‐radiopharmaceuticals are widely explored for imaging tumor hypoxia. Radiopharmaceuticals for targeting hypoxia are often lipophilic and therefore, show significant uptake in liver and other vital organs. In this context, lipophilic radiopharmaceuticals with design features enabling faster clearance from liver may be more desirable. A dipicolylamine‐NCS bifunctional chelator that could generate a thiourea‐bridge up on conjugation to primary amine bearing molecule was used to synthesize a 2‐nitroimidazole‐dipicolyl amine ligand for radiolabeling with 99mTc(CO)3 core. Corresponding Re(CO)3‐analogue was prepared to establish the structure of 2‐nitroimidazole‐99mTc(CO)3 complex prepared in trace level. The 2‐nitroimidazole‐99mTc(CO)3 complex showed a hypoxic to normoxic ratio of ~2.5 in CHO cells at 3 h. In vivo, the complex showed accumulation and retention in tumor with high tumor to blood and tumor to muscle ratio. The study demonstrated the utility of metabolizable thiourea‐bridge in 2‐nitroimidazole‐99mTc(CO)3 complex in inducing faster clearance of the radiotracer from liver. The dipicolylamine‐NCS bifunctional chelator reported herein can also be used for radiolabeling other class of target specific molecules with 99mTc(CO)3 core. [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]

Simple Summary: Glioblastoma (GBM) appears to be a challenging malignancy to completely eradicate, with few significant improvements in treatment. This review explores the mechanisms by which GBM tumors acquire resistance to antiangiogenic therapy, which are designed to inhibit the growth of blood vessels in tumors. This study addresses numerous mechanisms of resistance, including redundant pathways, heightened invasion, hypoxia, and immune modulation. This article additionally highlights potential strategies to overcome resistance, including combination therapies, personalized medicine, immunotherapy, and drug delivery using nanoparticles, with the goal of enhancing treatment results for patients with GBM. Malignant gliomas present great difficulties in treatment, with little change over the past 30 years in the median survival time of 15 months. Current treatment options include surgery, radiotherapy (RT), and chemotherapy. New therapies aimed at suppressing the formation of new vasculature (antiangiogenic treatments) or destroying formed tumor vasculature (vascular disrupting agents) show promise. This study summarizes the existing knowledge regarding the processes by which glioblastoma (GBM) tumors acquire resistance to antiangiogenic treatments. The discussion encompasses the activation of redundant proangiogenic pathways, heightened tumor cell invasion and metastasis, resistance induced by hypoxia, creation of vascular mimicry channels, and regulation of the tumor immune microenvironment. Subsequently, we explore potential strategies to overcome this resistance, such as combining antiangiogenic therapies with other treatment methods, personalizing treatments for each patient, focusing on new therapeutic targets, incorporating immunotherapy, and utilizing drug delivery systems based on nanoparticles. Additionally, we would like to discuss the limitations of existing methods and potential future directions to enhance the beneficial effects of antiangiogenic treatments for patients with GBM. Therefore, this review aims to enhance the research outcome for GBM and provide a more promising opportunity by thoroughly exploring the mechanisms of resistance and investigating novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Identification of hypoxaemia and hypercapnia is essential for the diagnosis and treatment of acute respiratory failure. While arterial blood gas (ABG) analysis is standard for PO2 and PCO2 measurement, venous blood gas (VBG) analysis is increasingly used as an alternative. Previous systematic reviews established that VBG reporting of PO2 and PCO2 is less accurate, but the impacts on clinical management and patient outcomes are unknown. Aims: This study aimed to systematically review available evidence of the clinical impacts of using ABGs or VBGs and examine the arteriovenous difference in blood gas parameters. Methods: A comprehensive search of the MEDLINE, Embase and Cochrane Library databases since inception was conducted. Included studies were prospective or cross‐sectional studies comparing peripheral ABG to peripheral VBG in adult non‐critical care inpatients presenting with respiratory symptoms. Results: Of 15 119 articles screened, 15 were included. No studies were found that examined clinical impacts resulting from using VBG compared to ABG. Included studies focused on the agreement between ABG and VBG measurements of pH, PO2, PCO2 and HCO3−. Due to the heterogeneity of the included studies, qualitative evidence synthesis was performed. While the arteriovenous difference in pH and HCO3− was generally predictable, the difference in PO2 and PCO2 was more significant and less predictable. Conclusions: Our study reinforces the notion that VBG is not comparable to ABG for physiological measurements. However, a key revelation from our research is the significant lack of data regarding the clinical implications of using VBG instead of ABG, a common scenario in clinical practice. This highlights a critical knowledge gap. [ABSTRACT FROM AUTHOR]

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

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

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

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]

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

Purpose: We hypothesised that during a rest-to-exercise transient in hypoxia (H), compared to normoxia (N), (i) the initial baroreflex sensitivity (BRS) decrease would be slower and (ii) the fast heart rate (HR) and cardiac output (CO) response would have smaller amplitude (A1) due to lower vagal activity in H than N. Methods: Ten participants performed three rest-to-50 W exercise transients on a cycle-ergometer in N (ambient air) and three in H (inspired fraction of O2 = 0.11). R-to-R interval (RRi, by electrocardiography) and blood pressure profile (by photo-plethysmography) were recorded non-invasively. Analysis of the latter provided mean arterial pressure (MAP) and stroke volume (SV). CO = HR·SV. BRS was calculated by modified sequence method. Results: Upon exercise onset in N, MAP fell to a minimum (MAPmin) then recovered. BRS decreased immediately from 14.7 ± 3.6 at rest to 7.0 ± 3.0 ms mmHg−1 at 50 W (p < 0.01). The first BRS sequence detected at 50 W was 8.9 ± 4.8 ms mmHg−1 (p < 0.05 vs. rest). In H, MAP showed several oscillations until reaching a new steady state. BRS decreased rapidly from 10.6 ± 2.8 at rest to 2.9 ± 1.5 ms mmHg−1 at 50 W (p < 0.01), as the first BRS sequence at 50 W was 5.8 ± 2.6 ms mmHg−1 (p < 0.01 vs. rest). CO-A1 was 2.96 ± 1.51 and 2.31 ± 0.94 l min−1 in N and H, respectively (p = 0.06). HR-A1 was 7.7 ± 4.6 and 7.1 ± 5.9 min−1 in N and H, respectively (p = 0.81). Conclusion: The immediate BRS decrease in H, coupled with similar rapid HR and CO responses, is compatible with a withdrawal of residual vagal activity in H associated with increased sympathetic drive. [ABSTRACT FROM AUTHOR]

Our group previously showed that genetic or pharmacological inhibition of the cystine/glutamate antiporter, system xc−, mitigates excitotoxicity after anoxia by increasing latency to anoxic depolarization, thus attenuating the ischaemic core. Hypoxia, however, which prevails in the ischaemic penumbra, is a condition where neurotransmission is altered, but excitotoxicity is not triggered. The present study employed mild hypoxia to further probe ischaemia‐induced changes in neuronal responsiveness from wild‐type and xCT KO (xCT−/−) mice. Synaptic transmission was monitored in hippocampal slices from both genotypes before, during and after a hypoxic episode. Although wild‐type and xCT−/− slices showed equal suppression of synaptic transmission during hypoxia, mutant slices exhibited a persistent potentiation upon re‐oxygenation, an effect we termed 'post‐hypoxic long‐term potentiation (LTP)'. Blocking synaptic suppression during hypoxia by antagonizing adenosine A1 receptors did not preclude post‐hypoxic LTP. Further examination of the induction and expression mechanisms of this plasticity revealed that post‐hypoxic LTP was driven by NMDA receptor activation, as well as increased calcium influx, with no change in paired‐pulse facilitation. Hence, the observed phenomenon engaged similar mechanisms as classical LTP. This was a remarkable finding as theta‐burst stimulation‐induced LTP was equivalent between genotypes. Importantly, post‐hypoxic LTP was generated in wild‐type slices pretreated with system xc− inhibitor, S‐4‐carboxyphenylglycine, thereby confirming the antiporter's role in this phenomenon. Collectively, these data indicate that system xc− interference enables neuroplasticity in response to mild hypoxia, and, together with its regulation of cellular damage in the ischaemic core, suggest a role for the antiporter in post‐ischaemic recovery of the penumbra. What is the central question of this study?Does glutamate antiporter system xc− influence recovery in the ischemic penumbra?What is the main finding and its importance?Our data reveal that mild hypoxia elicits a persistent potentiation of synaptic transmission in hippocampus when system xc− is genetically deleted or pharmacologically inhibited. This 'post‐hypoxic long‐term potentiation (LTP)' engages similar mechanims as classical NMDAR‐dependent LTP induced by theta‐burst stimulation (TBS). Because this neuroplasticity potentially fosters recovery in penumbral tissue, these findings portend system xc− antagonism as a post‐stroke therapeutic intervention. [ABSTRACT FROM AUTHOR]

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

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

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

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]

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]

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

Objective: This study delves into the implications of adenoidectomy for scoliosis progression, investigating the intricate nexus of hypoxia, spinal curvature, and surgical intervention. With adenoidectomy being a common procedure for addressing pediatric sleep-disordered breathing, this research study explores its potential impact on spinal health. Patients and Methods: Employing a retrospective cohort design, this study gathered data from patients who underwent adenoidectomy, including those with scoliosis, between January 2017 and March 2023. Initial and follow-up evaluations involved clinical and radiological assessments, notably measuring the Cobb angle to quantify spinal curvature. Results: This study enrolled 218 patients under 10 years old. Among them, 18 exhibited Cobb angles of 10° or more, with a mean Cobb angle of 12.8°. In the follow-up evaluation, 83% of patients with initial Cobb angles of 10° or more were reached out to, along with 84.6% of those with Cobb angles below 10°. The postoperative follow-up revealed a notable decrease in Cobb angles for most patients, particularly those with an initial Cobb angle exceeding 10°. Conclusions: This study underscores the potential connection between adenoidectomy, hypoxia, and scoliosis regression, highlighting the importance of early intervention for scoliosis management. Despite certain limitations, this investigation lays the foundation for future research involving larger patient cohorts and multifaceted analyses. The observed interactions between airway function, hypoxia, and spinal health open avenues for refining clinical strategies in scoliosis treatment. [ABSTRACT FROM AUTHOR]

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

Rationale: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. Our previous studies have identified that nocturnal hypoxemia causes skeletal muscle loss (i.e., sarcopenia) in in vitro models of COPD. Objectives: We aimed to extend our preclinical mechanistic findings by analyzing a large sleep registry to determine whether nocturnal hypoxemia is associated with sarcopenia in patients with COPD. Methods: Sleep studies from patients with COPD (n = 479) and control subjects without COPD (n = 275) were analyzed. Patients with obstructive sleep apnea, as defined by apnea–hypopnea index ⩾ 5, were excluded. Pectoralis muscle cross-sectional area (PMcsa) was quantified using computed tomography scans performed within 1 year of the sleep study. We defined sarcopenia as less than the lowest 20% residuals for PMcsa of control subjects, which was adjusted for age and body mass index (BMI) and stratified by sex. Youden's optimal cut-point criteria were used to predict sarcopenia based on mean oxygen saturation during sleep. Additional measures of nocturnal hypoxemia were analyzed. The pectoralis muscle index (PMI) was defined as PMcsa normalized to BMI. Results: On average, males with COPD had a 16.6% lower PMI than control males (1.41 ± 0.44 vs. 1.69 ± 0.56 cm2/BMI; P < 0.001), whereas females with COPD had a 9.4% lower PMI than control females (0.96 ± 0.27 vs. 1.06 ± 0.33 cm2/BMI; P < 0.001). Males with COPD with nocturnal hypoxemia had a 9.5% decrease in PMI versus COPD with normal O2 (1.33 ± 0.39 vs. 1.47 ± 0.46 cm2/BMI; P < 0.05) and a 23.6% decrease compared with control subjects (1.33 ± 0.39 vs. 1.74 ± 0.56 cm2/BMI; P < 0.001). Females with COPD with nocturnal hypoxemia had an 11.2% decrease versus COPD with normal O2 (0.87 ± 0.26 vs. 0.98 ± 0.28 cm2/BMI; P < 0.05) and a 17.9% decrease compared with control subjects (0.87 ± 0.26 vs. 1.06 ± 0.33 cm2/BMI; P < 0.001). These findings were largely replicated using multiple measures of nocturnal hypoxemia. Conclusions: We defined sarcopenia in the pectoralis muscle using residuals that take into account age, BMI, and sex. We found that patients with COPD have a lower PMI than patients without COPD and that nocturnal hypoxemia was associated with an additional decrease in the PMI of patients with COPD. Additional prospective analyses are needed to determine a protective threshold of oxygen saturation to prevent or reverse sarcopenia due to nocturnal hypoxemia in COPD. [ABSTRACT FROM AUTHOR]

Tumor hypoxia is a negative prognostic factor in many tumors and is predictive of metastatic spread and poor responsiveness to both chemotherapy and radiotherapy. Purpose: To assess the feasibility of using 18F-Fluoroazomycin arabinoside (FAZA) PET/MR to image tumor hypoxia in patients with locally advanced rectal cancer (LARC) prior to and following neoadjuvant chemoradiotherapy (nCRT). The secondary objective was to compare different reference tissues and thresholds for tumor hypoxia quantification. Patients and Methods: Eight patients with histologically proven LARC were included. All patients underwent 18F-FAZA PET/MR prior to initiation of nCRT, four of whom also had a second scan following completion of nCRT and prior to surgery. Tumors were segmented using T2-weighted MR. Each voxel within the segmented tumor was defined as hypoxic or oxic using thresholds derived from various references: ×1.0 or ×1.2 SUVmean of blood pool [BP] or left ventricle [LV] and SUVmean +3SD for gluteus maximus. Correlation coefficient (CoC) between HF and tumor SUVmax/reference SUVmean TRR for the various thresholds was calculated. Hypoxic fraction (HF), defined as the % hypoxic voxels within the tumor volume was calculated for each reference/threshold. Results: For all cases, baseline and follow-up, the CoCs for gluteus maximus and for BP and LV (×1.0) were 0.241, 0.344, and 0.499, respectively, and HFs were (median; range) 16.6% (2.4–33.8), 36.8% (0.3–72.9), and 30.7% (0.8–55.5), respectively. For a threshold of ×1.2, the CoCs for BP and LV as references were 0.611 and 0.838, respectively, and HFs were (median; range) 10.4% (0–47.6), and 4.3% (0–20.1%), respectively. The change in HF following nCRT ranged from (−18.9%) to (+54%). Conclusions: Imaging of hypoxia in LARC with 18F-FAZA PET/MR is feasible. Blood pool as measured in the LV appears to be the most reliable reference for calculating the HF. There is a wide range of HF and variable change in HF before and after nCRT. [ABSTRACT FROM AUTHOR]

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

Anemia and hypoxemia are common clinical conditions that are difficult to study and may impact pulse oximeter performance. Utilizing an in vitro circulation system, we studied performance of three pulse oximeters during hypoxemia and severe anemia. Three oximeters including one benchtop, one handheld, and one fingertip device were selected to reflect a range of cost and device types. Human blood was diluted to generate four hematocrit levels (40%, 30%, 20%, and 10%). Oxygen and nitrogen were bubbled through the blood to generate a range of oxygen saturations (O2Hb) and the blood was cycled through the in vitro circulation system. Pulse oximeter saturations (SpO2) were paired with simultaneously-measured O2Hb readings from a reference CO-oximeter. Data for each hematocrit level and each device were least-squares fit to a 2nd-order equation with quality of each curve fit evaluated using standard error of the estimate. Bias and average root mean square error were calculated after correcting for the calibration difference between human and in vitro circulation system calibration. The benchtop oximeter maintained good accuracy at all but the most extreme level of anemia. The handheld device was not as accurate as the benchtop, and inaccuracies increased at lower hematocrit levels. The fingertip device was the least accurate of the three oximeters. Pulse oximeter performance is impacted by severe anemia in vitro. The use of in vitro calibration systems may play an important role in augmenting in vivo performance studies evaluating pulse oximeter performance in challenging conditions.

Abstract 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.

Muammar M Kabir,1,2,&ast; Atousa Assadi,1– 3,&ast; Shumit Saha,4 Bojan Gavrilovic,1 Kaiyin Zhu,1 Susanna Mak,5 Azadeh Yadollahi1,2 1KITE-Toronto Rehabilitation Institute, University Health Network, Toronto, ON, Canada; 2Institute for Biomedical Engineering, University of Toronto, Toronto, ON, Canada; 3Temerty Center for AI Research and Education in Medicine, University of Toronto, Toronto, ON, Canada; 4Department of Biomedical Data Science, School of Applied Computational Sciences (SACS), Meharry Medical College, Nashville, TN, USA; 5Department of Medicine, Division of Cardiology, University of Toronto, Toronto, ON, Canada&ast;These authors contributed equally to this workCorrespondence: Azadeh Yadollahi, KITE-Toronto Rehabilitation Institute, University Health Network, Room 12-106, 550 University Ave., Toronto, ON, M5G 2A2, Canada, Tel +1 416 597 3422 x 7936, Fax +1 416 597 8959, Email azadeh.yadollahi@uhn.caPurpose: Cardiovascular disorders are the leading cause of mortality worldwide with obstructive sleep apnea (OSA) as the independent risk factor. Heart sounds are strong modalities to obtain clinically relevant information regarding the functioning of the heart valves and blood flow. The objective of this study was to use a small wearable device to record and investigate the changes in heart sounds during respiratory events (reduction and cessation of breathings) and their association with oxyhemoglobin desaturation (hypoxemia).Patients and Methods: Sleep assessment and tracheal respiratory and heart sounds were recorded simultaneously from 58 individuals who were suspected of having OSA. Sleep assessment was performed using in-laboratory polysomnography. Tracheal respiratory and heart sounds were recorded over the suprasternal notch using a small device with embedded microphone and accelerometer called the Patch. Heart sounds were extracted from bandpass filtered tracheal sounds using smoothed Hilbert envelope on decomposed signal. For each individual, data from 20 obstructive events during Non-Rapid Eye Movement stage-2 of sleep were randomly selected for analysis.Results: A significant increase in heart sounds’ intensities from before to after the termination of respiratory events was observed. Also, there was a significant positive correlation between the magnitude of hypoxemia and the increase in heart sounds’ intensities (r> 0.82, p< 0.001). In addition, the changes in heart sounds were significantly correlated with heart rate and blood pressure.Conclusion: Our results indicate that heart sound analysis can be used as an alternative modality for assessing the cardiovascular burden of sleep apnea, which may indicate the risk of cardiovascular disorders. Keywords: heart sounds, obstructive sleep apnea, sympathetic nervous activity, hypoxemia, blood pressure

Abstract 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 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.

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

Background: Altitude training is often regarded as an indispensable tool for the success of elite endurance athletes. Historically, altitude training emerged as a key strategy to prepare for the 1968 Olympics, held at 2300 m in Mexico City, and was limited to the "Live High-Train High" method for endurance athletes aiming for performance gains through improved oxygen transport. This "classical" intervention was modified in 1997 by the "Live High-Train Low" (LHTL) model wherein athletes supplemented acclimatization to chronic hypoxia with high-intensity training at low altitude. Purpose: This review discusses important considerations for successful implementation of LHTL camps in elite athletes based on experiences, both published and unpublished, of the authors. Approach: The originality of our approach is to discuss 10 key "lessons learned," since the seminal work by Levine and Stray-Gundersen was published in 1997, and focusing on (1) optimal dose, (2) individual responses, (3) iron status, (4) training-load monitoring, (5) wellness and well-being monitoring, (6) timing of the intervention, (7) use of natural versus simulated hypoxia, (8) robustness of adaptative mechanisms versus performance benefits, (9) application for a broad range of athletes, and (10) combination of methods. Successful LHTL strategies implemented by Team USA athletes for podium performance at Olympic Games and/or World Championships are presented. Conclusions: The evolution of the LHTL model represents an essential framework for sport science, in which field-driven questions about performance led to critical scientific investigation and subsequent practical implementation of a unique approach to altitude training. [ABSTRACT FROM AUTHOR]