Low Oxygen Levels Research Articles

Effects of fasting and environmental factors on appetite regulators in pond loach Misgurnus anguillicaudatus

The pond loach (Misgurnus anguillicaudatus) is an important aquaculture freshwater species, used as an ornamental fish, food source for humans and angling bait. Pond loaches are resistant to fasting and extreme environmental conditions, including temperature and low oxygen levels. Little is known about how these factors affect the feeding physiology and the endocrine regulation of feeding of loaches. In this study, we examined the effects of fasting, as well as increased temperature and decreased oxygen levels on food intake and transcript levels of appetite regulators. Fasted fish had lower blood glucose levels, and lower expression levels of intestine CCK and PYY, and brain CART1, but had higher levels of brain orexin and ghrelin than fed fish. Fish held at 30 °C had higher food intake, glucose levels, and mRNA levels of intestine CCK and PYY, and brain CART2, but lower brain orexin levels than fish at 20 °C. Fish held at low oxygen levels had a lower food intake, higher intestine CCKa and ghrelin, and brain orexin, CART2 and ghrelin mRNA expression levels than fish held at high O2 levels. Our results suggest that fasting and high temperatures increase the expression of orexigenic and anorexigenic factors respectively, whereas the increase in expression of both orexigenic and anorexigenic factors in low O2 environments might not be related to their role in feeding, but possibly to protection from tissue damage. The results of our study might shed new light on how pond loaches are able to cope with extreme environmental conditions such as low food availability, extreme temperatures and hypoxia.

Abstract PS13-04: Frequent Intra-Tumoral Hypoxia in Pregnancy-Associated Breast Cancer

Abstract Rationale: Breast cancer is the most common malignancy in pregnant women, occurring in approximately 1:3000 pregnancies. Breast cancer diagnosed during pregnancy or after childbirth is also known as Pregnancy-Associated Breast Cancer (PABC). PABC is known for exhibiting several unfavorable prognostic tumor characteristics, such as an advanced tumor stage at diagnosis, high histologic grade and frequent hormone receptor negativity. Most probably, several interplaying mechanisms may promote the tumor progression and adverse clinical outcome of PABC. One of these mechanisms may be the presence of hypoxia, a relative state of low intra-tumoral oxygen levels which is a known marker of adverse outcome in breast cancer. However, the occurrence and prognostic consequences of the presence of intra-tumoral hypoxia in PABC have not been studied yet. Methods: We constructed a cohort with histopathological, clinical, and outcome data of patients diagnosed with breast cancer during pregnancy (PrBC) or within one year after childbirth (PPBC) in the Netherlands between 1988 and 2022. Next, tissue blocks of all patients were collected from the participating Dutch pathology laboratories. Using H&E stained slides of the tumor tissue blocks, we selected suitable donor sites for a tissue micro array (TMA). Slides from these TMAs were stained for three important hypoxia-associated proteins: glucose transporter-1 (Glut-1), carbonic anhydrase IX (CAIX) and hypoxia-inducible factor-1α (HIF-1α). Expression was scored by an expert breast pathologist blinded by clinicopathologic data. Results: For a total of 195 PrBC and PPBC patients, we were able to assess the expression of Glut-1, CAIX and HIF-1α on tumor cells. Patients had a median age of 33 years at diagnosis, whilst a large majority had a Bloom & Richardson grade III tumor (76%) with frequent hormone receptor negativity (50%). Expression of hypoxia-associated proteins was frequent, with 61% of the tumors expressing Glut-1, 30% expressing CAIX and 56% expressing HIF-1α. In total, 153 (78%) of the tumors expressed at least one of the hypoxia-associated proteins. We observed a significantly worse 5-year overall survival for patients with intra-tumoral hypoxia in comparison to patients without intra-tumoral hypoxia (70% vs. 90%, p=0.046). Conclusions: We show that the presence of intra-tumoral hypoxia in PABC is common, with 78% of tumors expressing at least one of the studied hypoxia-associated proteins. Importantly, patients with tumors overexpressing hypoxia-markers have a significantly worse survival. This shows that intra-tumoral hypoxia may be an important underlying carcinogenic mechanism in PABC, and might be a promising novel therapeutic target in this patient group. Citation Format: Carsten Bakhuis, Carmen Van Dooijeweert, Britt Suelmann, Pieter Westenend, Sabine Linn, Elsken Van der Wall, Paul Van Diest. Frequent Intra-Tumoral Hypoxia in Pregnancy-Associated Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS13-04.

Current State and Future Perspective of Diabetic Wound Healing Treatment: Present Evidence from Clinical Trials.

Diabetes is a chronic metabolic condition that is becoming more common and is characterised by sustained hyperglycaemia and long-term health effects. Diabetes-related wounds often heal slowly and are more susceptible to infection because of hyperglycaemia in the wound beds. The diabetic lesion becomes harder to heal after planktonic bacterial cells form biofilms. A potential approach is the creation of hydrogels with many functions. High priority is given to a variety of processes, such as antimicrobial, pro-angiogenesis, and general pro-healing. Diabetes problems include diabetic amputations or chronic wounds (DM). Chronic diabetes wounds that do not heal are often caused by low oxygen levels, increased reactive oxygen species, and impaired vascularization. Several types of hydrogels have been developed to get rid of contamination by pathogens; these hydrogels help to clean up the infection, reduce wound inflammation, and avoid necrosis. This review paper will focus on the most recent improvements and breakthroughs in antibacterial hydrogels for treating chronic wounds in people with diabetes. Prominent and significant side effects of diabetes mellitus include foot ulcers. Antioxidants, along with oxidative stress, are essential to promote the healing of diabetic wounds. Some of the problems that can come from a foot ulcer are neuropathic diabetes, ischemia, infection, inadequate glucose control, poor nutrition, also very high morbidity. Given the worrying rise in diabetes and, by extension, diabetic wounds, future treatments must focus on the rapid healing of diabetic wounds.

Investigating the interplay between LIGHT and HIF in inflammatory fibroblast responses

Introduction: Intestinal fibroblast differentiation into an inflammatory phenotype likely plays a key role in Inflammatory Bowel Disease (IBD). However, the mechanisms that control this process are poorly understood. The cytokine TNFSF14 (LIGHT) drives inflammatory fibroblast responses in other diseases such as Eosinophilic esophagitis. Additionally, hypoxia, defined as low cellular or tissue levels of oxygen, is a feature of IBD progression. The use of hydroxylase inhibiting drugs which exhibit hypoxia mimetic conditions have been shown in murine models to have protective effects in IBD. Here we hypothesize the role of LIGHT to be of central importance in intestinal fibroblast differentiation and test how this inflammatory phenotype may be affected by hypoxia mimetic drugs and conversely what effect LIGHT may have on the hypoxic condition. Methods: Primary human colonic fibroblasts (18CO), the hepatic stellate cell line (LX2) and the epithelial cell line (T84) were treated with LIGHT in time course studies. 18COs were also treated with hydroxylase inhibitors Dimethyloxalylglycine (DMOG), JNJ42041935 and Roxadustat. Responses were analysed using qPCR, flowcytometry and Immunoblot-analysis. Results: LIGHT-treated 18COs upregulated CCL2 (7-fold ± increase, p=<0.001, n=5), CXCL10 (14-fold ± increase, p=<0.0001, n=3) and IL34 (30-fold ± increase, p=<0.05 n=5) at transcript level, and surface protein expression of ICAM1 (15% ± increase at 24 hours compared to vehicle, n=4) and VCAM1 (18% ± increase at 24 hours compared to vehicle, n=4) displaying distinct kinetics. This response was absent or to a much less significant degree in LX2s and T84s. DMOG decreased CCL2 (4-fold ± decrease compared to LIGHT treated samples, p=<0.001, n=5) and CXCL10 (11-fold ± decrease compared to LIGHT treated samples, p=<0.0001, n=3) gene expression in 18COs when subsequently treated with LIGHT for 8 hours but did not affect other targets tested such as CSF1, CXCL5, VCAM1 and ICAM1. Immunoblot analysis of 18COs showed a decreased HIF-1α stabilization when treated with hydroxylase inhibitors in the presence of LIGHT compared to hydroxylase inhibitors alone (3 different hydroxylase inhibiting drugs n=3-4, n=11 total). Preliminary data of HIF downstream activated genes VEGFA (14-fold ± increase, p=<0.05 n=3) and GLUT1 (6-fold ± increase, p=<0.05 n=3) show increased gene expression in 18COs when treated with DMOG with noticeable decreases when treated with a LIGHT DMOG combination. Conclusions: Our current studies show that LIGHT is a potential mediator of colonic inflammatory fibroblast differentiation and a possible inhibitor of HIF-1α stabilization. The effects of LIGHT are either significantly weaker or not displayed in colonic epithelial cells or hepatic stellate cells, indicating LIGHT-specific effects on intestinal stroma. Hydroxylase inhibitors show selective effects on the LIGHT driven response. Collectively our data reveals a potential LIGHT-hypoxia network that may be amenable for therapeutic interventions. SFI/IRC Pathway Fellows Award to Dr. Manresa, 21/PATH-S/9621. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Hypoxia modulates P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) drug transporters in brain endothelial cells of the developing human blood-brain barrier

P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) multidrug resistance (MDR) transporters are localized at the luminal surface of the blood-brain barrier (BBB). They confer fetal brain protection against harmful compounds that may be circulating in the peripheral blood. The fetus develops in low oxygen levels; however, some obstetric pathologies such as pre-eclampsia, placenta accreta/previa may result in even greater fetal hypoxic states. We investigated how hypoxia impacts MDR transporters in human fetal brain endothelial cells (hfBECs) derived from early and mid-stages of pregnancy. Hypoxia decreased BCRP protein and activity in hfBECs derived in early pregnancy. In contrast, in hfBECs derived in mid-pregnancy there was an increase in P-gp and BCRP activity following hypoxia. Results suggest a hypoxia-induced reduction in fetal brain protection in early pregnancy, but a potential increase in transporter-mediated protection at the BBB during mid-gestation. This would modify accumulation of various key physiological and pharmacological substrates of P-gp and BCRP in the developing fetal brain and potentially contribute to the pathogenesis of neurodevelopmental disorders commonly associated with in utero hypoxia.

Risk Factors Associated with Mortality in Hospitalized COVID-19 Patients: A Case Study from Southeast Iran

Background: This study aimed to identify mortality risk factors among hospitalized COVID-19 patients in southeast Iran. Methods: This cross-sectional study used data from the COVID-19 patients admitted to Afzalipour teaching hospital in Kerman, Iran, from February 2020 to September 2021. The demographic and clinical data of 6,057 patients were analyzed using Bayesian network and logistic regression models. Results: Out of 6,057 patients, 333 (5.5%) died. The most important risk factors for COVID-19 mortality were age, gender, fever, headache, decreased level of consciousness (LoC), chronic liver disease, blood oxygen level (BOL), admission season, and length of stay (LoS). Fever, headache, and longer LoS were protective and mortality-reducing variables. Conclusion: Following model estimation results, it is recommended that older male patients with low oxygen levels and a lower LoC, as well as patients with chronic liver disease, receive additional medical care and not be discharged prematurely. Early medical interventions for high-risk patients may reduce COVID-19 mortality risk.

A field study of a novel permeable-reactive-biobarrier to remediate chlorinated hydrocarbons contaminated groundwater

Chlorinated hydrocarbons (CHs) pose significant health risks due to their suspected carcinogenicity, necessitating urgent remediation efforts. While the combination of zero-valent iron (Fe0) and microbial action shows promise in mitigating CH contamination, field studies on this approach are scarce. We devised a novel three-layer permeable reactive barrier (PRB) material incorporating Fe0 and coconut shell biochar, effectively implemented at a typical CH-contaminated site. Field monitoring data revealed conducive conditions for reductive dechlorination of CHs, characterized by low oxygen levels and a relatively neutral pH in the groundwater. The engineered PRB material consistently released organic carbon and iron, fostering the proliferation of CH-dechlorinating bacteria. Over a 250-day operational period, the pilot-scale PRB demonstrated remarkable efficacy in CH removal, achieving removal efficiencies ranging from 21.9% to 99.6% for various CH compounds. Initially, CHs were predominantly eliminated through adsorption and iron-mediated reductive dechlorination. However, microbial reductive dechlorination emerged as the predominant mechanism for sustained and long-term CHs removal. These findings underscore the economic viability and effectiveness of our approach in treating CH-contaminated groundwater, offering promising prospects for broader application in environmental remediation efforts.

Hypoxia delays steroid-induced developmental maturation in Drosophila by suppressing EGF signaling.

Animals often grow and develop in unpredictable environments where factors like food availability, temperature, and oxygen levels can fluctuate dramatically. To ensure proper sexual maturation into adulthood, juvenile animals need to adapt their growth and developmental rates to these fluctuating environmental conditions. Failure to do so can result in impaired maturation and incorrect body size. Here we describe a mechanism by which Drosophila larvae adapt their development in low oxygen (hypoxia). During normal development, larvae grow and increase in mass until they reach critical weight (CW), after which point a neuroendocrine circuit triggers the production of the steroid hormone ecdysone from the prothoracic gland (PG), which promotes maturation to the pupal stage. However, when raised in hypoxia (5% oxygen), larvae slow their growth and delay their maturation to the pupal stage. We find that, although hypoxia delays the attainment of CW, the maturation delay occurs mainly because of hypoxia acting late in development to suppress ecdysone production. This suppression operates through a distinct mechanism from nutrient deprivation, occurs independently of HIF-1 alpha and does not involve dilp8 or modulation of Ptth, the main neuropeptide that initiates ecdysone production in the PG. Instead, we find that hypoxia lowers the expression of the EGF ligand, spitz, and that the delay in maturation occurs due to reduced EGFR/ERK signaling in the PG. Our study sheds light on how animals can adjust their development rate in response to changing oxygen levels in their environment. Given that hypoxia is a feature of both normal physiology and many diseases, our findings have important implications for understanding how low oxygen levels may impact animal development in both normal and pathological situations.

Characteristic of a group of genes with low level of expression in the pancreas of rats under conditions of multi-day intermittent hypoxia influence

In modern medical science great attention is paid to the clarification of the molecular mechanisms, which are the basis of adaptation to environmental factors of unusual origin and/or extraordinary strength. The aim of the study is to determine the features of a group of genes with low expression level, associated with hypoxia in the pancreas of Wistar rats under conditions of intermittent hypoxia. Materials and methods. The study was conducted on 10 white, sexually mature Wistar rats, which were divided into 2 groups (5 animals in each). Animals of group 1 were part of the control (intact) group. The animals of the 2nd group were subjected to hypoxic training according to the following scheme: for 15 days, 6 hours daily, namely on days 1–5 they simulated an ascent to a height of one to five kilometers above sea level under the conditions of a barometer, and the last 10 days 6 km above the sea level. To analyze gene expression, we used the polymerase chain reaction method with real-time reverse transcription (PCR) CFX-96 Touch™ (Bio-Rad, USA) and the RT2 Profiler™ PCR Array Rat Hypoxia Signaling Pathway kit (QIAGEN, Germany), where 84 genes were the subject of research in experimental animals. Results. According to the results of the PCR study of genes in the pancreas samples of intact animals and animals exposed to hypoxic training, it was established that out of 84 genes associated with hypoxia, a group of 5 genes with a low expression level (∆∆Ct < 30) was found. This pattern includes Bhlhe40 genes, Ctsa, Hif1a, Lox, and Slc16a3, the expression of which is statistically reduced. Thus, compared to the level of their expression in intact animals, the expression of Bhlhe40 decreased by 2.59 times, Ctsa by 6.02 times, Hif1a by 3.85 times, Lox by 3.01 times, and Slc16a3 by 2.40 times. Conclusions. Intermittent hypoxia reduces the expression of the Bhlhe40 gene by 2.59 times, which can be considered as an element of adaptation of cells to a low level of oxygen and modulation of genetic programs. The decrease in Ctsa gene expression by 6.02, Hif1a by 3.85, and Lox by 3.01 times during intermittent hypoxia demonstrates, that these effects can be used as sanogenic factors in insulin resistance and type 2 diabetes. The 2.40-fold decreased expression level of Slc16a3 is probably an element of metabolic adaptation and adaptation of the metabolic pathway of cells to hypoxia conditions.

Investigation of the control of Sitophilus granarius in stored grain using vacuum packaging and the creation of an anaerobic atmospheric environment

The efficacy of vacuum and oxygen absorption-based treatments for controlling Sitophilus granarius L. damage in wheat grains was compared under laboratory conditions. The efficacy of the treatments was evaluated at different temperature ranges (−5, 26, 42 °C) and exposure times (0.5, 1, 3, 6, 24, 48, 72 h). Treatment-survived adult progeny were measured on day 45. Our studies demonstrated that the efficacy of the controlled atmosphere methods (CAs) we tested varied significantly as a function of time. While the mortality curve induced by the different temperature-controlled low-pressure vacuum packaging treatments is logarithmic, the mortality trend induced by the absorber's low oxygen levels follows an exponential slope. The hypoxia induced by low oxygen levels has a much longer duration of action. We have shown that vacuum packaging at lower and higher pessimum temperature ranges other than the thermal optimum of the insect induced significant mortality of S. granarius. The method was particularly effective when vacuum-packed items were kept at a higher pessimum temperature range. Our results confirm that vacuum packaging based on atmospheric modification, especially at elevated temperatures, can be a sustainable solution for pest control of small volume, valuable seed samples.

Habitat and Respiratory Strategy Effects on Hypoxia Performance in Anuran Tadpoles.

A critical component of animal conservation in a changing world is an understanding of the physiological resilience of animals to different conditions. In many aquatic animals, hypoxia (low environmental oxygen levels) is a regular occurrence, but the likelihood and severity of hypoxia vary across habitats. Fast-flowing, stream-like habitats are never hypoxic, so long as flow is maintained. Do animals from such habitats retain the capacity to survive hypoxic conditions? We use aquatic frog tadpoles to test the effects of natural habitat on performance in hypoxia in an experimental framework, finding that stream-living tadpoles have reduced performance in hypoxia. Tadpoles also vary in lung presence, with some species able to breathe air during hypoxia. We found that among lunged tadpoles, air-breathing rates increase in hypoxia in pond-living species but not stream-living species. Lung presence was also found to influence hypoxia performance, as lungless, stream-living tadpoles were found to be especially vulnerable to hypoxia, while pond-living, lungless tadpoles appeared largely resilient to hypoxia. We consider the ramifications of our findings on conservation outlooks and strategies for frogs and their tadpoles, suggesting that stream-living tadpoles, and especially lungless, stream-living tadpoles, may be particularly at risk to factors that reduce stream flow. Thus, a primary goal for conservation and management of species with stream-living tadpoles should be the maintenance of year-round streamflow, which oxygenates waters and prevents hypoxia.

Culture of Human Embryos at High and Low Oxygen Levels.

One of the parameters potentially affecting the in vitro growth of preimplantation embryos is the oxygen concentration in the culture environment. An increased oxygen concentration causes the generation of ROS which in turn can cause damage to the cells and seriously disrupt the embryonic development. Previous studies have assessed oxygen concentrations in the fallopian tubes of several mammals of between 5 and 8%, while the oxygen levels in the uterus were found to be even lower; similar measurements have been confirmed in humans. In addition, studies in mammalian embryos showed that low oxygen concentrations improve embryo development. Multiple studies on the effect of the oxygen concentration on human embryos have been conducted so far with diverse methodologies and objectives. Data from these have been included in three meta-analyses. All meta-analyses indicate the potential benefit in favor of a low oxygen concentration, though data are considered to be of a low methodological quality and further studies are considered necessary. However, based on the existing evidence, it is suggested that a low oxygen concentration should be adopted in the routine of the IVF laboratory, especially in the case of blastocyst culture.

Dynamic Functional Hyperconnectivity After Psilocybin Intake Is Primarily Associated With Oceanic Boundlessness

BackgroundPsilocybin is a widely studied psychedelic substance that leads to the psychedelic state, a specific altered state of consciousness. To date, the relationship between the psychedelic state’s neurobiological and experiential patterns remains undercharacterized because they are often analyzed separately. We investigated the relationship between neurobiological and experiential patterns after psilocybin by focusing on the link between dynamic cerebral connectivity and retrospective questionnaire assessment. MethodsHealthy participants were randomized to receive either psilocybin (n = 22) or placebo (n = 27) and scanned for 6 minutes in an eyes-open resting state during the peak subjective drug effect (102 minutes posttreatment) in ultrahigh field 7T magnetic resonance imaging. The 5-Dimensional Altered States of Consciousness Rating Scale was administered 360 minutes after drug intake. ResultsUnder psilocybin, there were alterations across all dimensions of the 5-Dimensional Altered States of Consciousness Rating Scale and widespread increases in averaged brain functional connectivity. Time-varying functional connectivity analysis unveiled a recurrent hyperconnected pattern characterized by low blood oxygen level–dependent signal amplitude, suggesting heightened cortical arousal. In terms of neuroexperiential links, canonical correlation analysis showed higher transition probabilities to the hyperconnected pattern with feelings of oceanic boundlessness and secondly with visionary restructuralization. ConclusionsPsilocybin generates profound alterations at both the brain and the experiential levels. We suggest that the brain’s tendency to enter a hyperconnected-hyperarousal pattern under psilocybin represents the potential to entertain variant mental associations. These findings illuminate the intricate interplay between brain dynamics and subjective experience under psilocybin, thereby providing insights into the neurophysiology and neuroexperiential qualities of the psychedelic state.

Intensive feeding alters the rumen microbiota and its fermentation parameters in natural grazing yaks.

Amidst the challenging environmental conditions characterized by low oxygen levels and cold temperatures on the plateau, alterations in nutrient supply emerge as pivotal factors influencing the survival and reproduction of yaks. Intensive feeding stands out as a substantial mechanism for nutrient provision, initiating discernible changes in the host's rumen flora. Within the extreme natural conditions prevailing in the plateau area of northwest Yunnan, China, there exists a con-strained comprehension of the variations in rumen microflora, fermentation parameters, and growth responses exhibited by yaks subjected to intensive feeding. This study employs 16S rRNA and ITS sequencing methods to scrutinize the rumen flora of yaks engaged in both natural grazing (G) and intensive feeding (F) on the plateau. The outcomes unveil that, during the severe winter season, yaks adeptly modulate the abundance and diversity of rumen flora in response to dietary modifications under intensive feeding, aiming to optimize the efficient utilization of dietary fiber and energy. Principal Coordinate Analysis (PCoA) illustrates a substantial alteration in the rumen microbial community of naturally grazing yaks when exposed to intensive feeding. The natural grazing group manifests a higher prevalence of Firmicutes and Bacteroidetes, while the intensive feeding group exhibits heightened levels of Prevotella in the rumen. The Rikenellaceae _ RC9 _ gut_ group, associated with mycobacteria, prevails more abundantly in the natural grazing setting. PICRUSt2 analysis indicates that intensive feeding induces bacterial gene overexpression linked to protein metabolism. Rumen fungi showcase heightened diversity under intensification. Intensive feeding results in an augmented abundance of non-fiber-degrading bacteria and semi-fiber-degrading bacteria, accompanied by elevated concentrations of Volatile Fatty Acids (VFA). These findings yield novel insights into the shifts in the rumen microflora of yaks acclimated to intensive feeding in high-altitude environments, provide an important reference for the nutritional regulation of supplemental feeding of natural grazing yaks in the cold season, ultimately contributing to their enhanced growth.

Does the use of higher versus lower oxygen concentration improve neurodevelopmental outcomes at 18–24 months in very low birthweight infants?

BackgroundImmediately after birth, the oxygen saturation is between 30 and 50%, which then increases to 85–95% within the first 10 min. Over the last 10 years, recommendations regarding the ideal level of the initial fraction of inspired oxygen (FiO2) for resuscitation in preterm infants have changed from 1.0, to room air to low levels of oxygen (< 0.3), up to moderate concentrations (0.3–0.65). This leaves clinicians in a challenging position, and a large multi-center international trial of sufficient sample size that is powered to look at safety outcomes such as mortality and adverse neurodevelopmental outcomes is required to provide the necessary evidence to guide clinical practice with confidence.MethodsAn international cluster, cross-over randomized trial of initial FiO2 of 0.3 or 0.6 during neonatal resuscitation in preterm infants at birth to increase survival free of major neurodevelopmental outcomes at 18 and 24 months corrected age will be conducted. Preterm infants born between 230/7 and 286/7 weeks’ gestation will be eligible. Each participating hospital will be randomized to either an initial FiO2 concentration of either 0.3 or 0.6 to recruit for up to 12 months’ and then crossed over to the other concentration for up to 12 months. The intervention will be initial FiO2 of 0.6, and the comparator will be initial FiO2 of 0.3 during respiratory support in the delivery room. The sample size will be 1200 preterm infants. This will yield 80% power, assuming a type 1 error of 5% to detect a 25% reduction in relative risk of the primary outcome from 35 to 26.5%. The primary outcome will be a composite of all-cause mortality or the presence of a major neurodevelopmental outcome between 18 and 24 months corrected age. Secondary outcomes will include the components of the primary outcome (death, cerebral palsy, major developmental delay involving cognition, speech, visual, or hearing impairment) in addition to neonatal morbidities (severe brain injury, bronchopulmonary dysplasia; and severe retinopathy of prematurity).DiscussionThe use of supplementary oxygen may be crucial but also potentially detrimental to preterm infants at birth. The HiLo trial is powered for the primary outcome and will address gaps in the evidence due to its pragmatic and inclusive design, targeting all extremely preterm infants. Should 60% initial oxygen concertation increase survival free of major neurodevelopmental outcomes at 18–24 months corrected age, without severe adverse effects, this readily available intervention could be introduced immediately into clinical practice.Trial registrationThe trial was registered on January 31, 2019, at ClinicalTrials.gov with the Identifier: NCT03825835.

Data mining approaches to pneumothorax detection: Integrating mask-RCNN and medical transfer learning techniques

With the medical condition of pneumothorax, also known as collapsed lung, air builds up in the pleural cavity and causes the lung to collapse. It is a critical disorder that needs to be identified and treated right as it can cause breathing difficulties, low blood oxygen levels, and, in extreme circumstances, death. Chest X-rays are frequently used to diagnose pneumothorax. Using the Mask R-CNN model and medical transfer learning, the proposed work offers•A novel method for pneumothorax segmentation from chest X-rays.•A method that takes advantage of the Mask R-CNN architecture's for object recognition and segmentation.•A modified model to address the issue of segmenting pneumothoraxes and then polish it using a sizable dataset of chest X-rays.The proposed method is tested against other pneumothorax segmentation techniques using a dataset of ‘chest X-rays’ with ‘pneumothorax annotations. The test findings demonstrate that proposed method outperforms other cutting-edge techniques in terms of segmentation accuracy and speed. The proposed method could lead to better patient outcomes by increasing the precision and effectiveness of pneumothorax diagnosis and therapy. Proposed method also benefits other medical imaging activities by using the medical transfer learning approaches which increases the precision of computer-aided diagnosis and treatment planning.

1.44 Ga Oxygenation Event: Evidence From the Southern Margin of North China

AbstractPrevious studies suggest that the atmospheric and shallow seawater oxygen levels during the mid‐Proterozoic may have remained persistently unbalanced due to the low atmospheric oxygen levels and that, under these conditions, the oxygen concentrations of shallow seawater would largely reflect local oxygenation caused by primary productivity. As a result, in a microbialite‐rich setting, it may be difficult to differentiate oxygenation caused by local primary productivity from overall oxygenation of the surface environment. To address this issue, we conducted an integrative study of the ∼1.44 Ga stromatolitic carbonates of the Fengjiawan Formation in the Xiong’er Basin, southern North China, using techniques of sedimentology, mineralogy and geochemistry. The results show that the Fengjiawan Formation is dominated by water‐column precipitated carbonate mud (now dolomitized), pointing to moderately oxidized marine conditions. A significant and stable negative Cerium (Ce) anomaly (as low as 0.42) is identified in a long interval (&gt;50 m in thickness) of this formation. This Ce anomaly is lower than the minimum values both recorded in the Great Oxidation Event (GOE; minimum 0.76) and in the Neoproterozoic Oxygenation Event (NOE; minimum 0.52), suggesting a significant oxygenation process rather than an oxygen oasis. Some intervals in this formation show I/(Ca + Mg) values higher than the Precambrian background value of 0.5 μmol/mol, providing a further support for shallow seawater oxygenation. This study, together with the enhanced oxygenation identified in the time‐equivalent Tieling Formation, indicates a multi‐basin oxygenation event in North China at ∼1.44 Ga.

Anterior palatoplasty as a treatment for mild and moderate obstructive sleep apnea: our experience

Abstract BACKGROUND. Obstructive sleep apnea (OSA) is characterized by frequent episodes of breathing cessation during sleep, resulting in low oxygen and high carbon dioxide levels, leading to daytime sleepnes, cognitive issues, and increased cardiovascular risk. The objective of this study was to assess the effectiveness of the anterior palatoplasty (AP) procedure in the treatment of patients with mild and moderate obstructive sleep apnea. MATERIAL AND METHODS. Sixteen patients diagnosed with mild and moderate OSA underwent AP in our clinic between 2021-2023. All patients were &gt; 18 years old, body mass index &lt; 30, with an apnea-hypopnea index (AHI) from 10 to 40 and disfunction of the velopharyngeal or of the retropalatal space. Patients underwent a one-night polysomnography examination prior to the surgical procedure, as well as six months after the procedure. Additionally, patients were asked to complete the Epworth Sleepiness Scale (ESS) both prior to and six months following the surgery. The procedure was done under general anaesthesia and involved AP surgery with or without reducing of the uvula. RESULTS. The average of total AHI values decreased from 28.89 per hour prior to surgery to 11.14 per hour six months after surgery. The oxygen desaturation index decreased after surgery with 2.57%. ESS scores of patients also decreased from 10.40 to 7.80 and all patients felt less tired. CONCLUSION. We believe that AP is an effective technique in the treatment of mild and moderate OSA caused by a disfunction of the velopharyngeal or retropalatal space. Additionally, we consider that AP is linked with a lower incidence of post-surgical complications compared to other surgical options.

Fuel-use strategies at ultrahigh elevations on the Tibetan Plateau since the last deglaciation

Often referred to as the “Third Pole”, the Tibetan Plateau combines high elevation, extreme cold temperatures, hyper-aridity, and low oxygen levels. The strategy that early populations adopted to adapt to the harsh environment of the Tibetan Plateau has always attracted much attention. However, relevant studies have predominantly focused on the relatively lower elevation northeastern part of the Tibetan Plateau (<3000 m a.s.l.), with limited study in areas of ultrahigh elevation (>3500 m a.s.l.). This paper employed the flotation method and charcoal analysis of survey profiles from thirteen archaeological sites in the ultrahigh-elevation region of the middle Yarlung Zangbo River basin on the southern Tibetan Plateau, and finds that ancient people have been active in this region since the last deglaciation. The primary fuel sources used by ancient populations were small trees such as sea buckthorn (Hippophae gyantsensis) and shrubs such as juniper (Juniperus). The widespread use of undesirable wood (dwarf thorny shrub) like Sophora moorcroftiana and Caragana, along with the phenomenon of many sites relying on a single taxon, reflects the prevalent issue of fuel scarcity in this ultrahigh-elevation region. This might have been a driving factor for the early adoption of animal dung as a primary fuel source by ancient populations on the southern Tibetan Plateau.

Sensing and Imaging Molecular Oxygen in Mammals with Spin Lattice Relaxation Electron Paramagnetic Resonance.

Molecular oxygen and its thermodynamic transformation drive nearly all life processes. Quantitative measurement and imaging of oxygen in living systems is of fundamental importance for the study of life processes and their aberrations-disease- many of which are affected by hypoxia, or low levels of oxygen. Cancer is among the disease processes profoundly affected by hypoxia. Electron paramagnetic resonance has been shown to provide remarkably accurate images of normal and cancerous tissue. In this review, we emphasize the reactivity of molecular oxygen particularly highlighting the metabolic processes of living systems to store free energy in the reactants. The history of hypoxic resistance of living systems to cytotoxic therapy, particularly radiation therapy is also reviewed. The measurement and imaging of molecular oxygen with pulse spin lattice relaxation (SLR) electron paramagnetic resonance (EPR) is reviewed briefly. This emphasizes the advantages of the spin lattice relaxation based measurement paradigm to reduce the sensitivity of the measurement to the presence of the oxygen sensing probe itself. The involvement of a novel small mammal external beam radiation delivery system is described. This enables an experimental paradigm based on control by radiation of the last resistant clonogen. This is much more specific for tumor cure than growth delay assays which primarily reflects control of tumor cells most sensitive to therapy.